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Patterns of Heredity and Human Genetics
A Look at Genetic Complexities Chapter 12 Notes
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What happens when heredity follows different rules?
The Exceptions to Mendel’s Rules Section 12.2
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Section Objectives At the end of this lesson, YOU will be able to:
Distinguish between alleles for incomplete dominance and codominance. Explain the patterns of multiple allelic and polygenic inheritance. Analyze the pattern of sex-linked inheritance. Summarize how internal and external environments affect gene expression.
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Remember Punnett Squares
dd Heterozygous Chin Dimple (male) X No Chin Dimple (female) d d D Dd d
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Remember Mendel? His 4 conclusions were: The Rule of Unit Factors
His 4 conclusions were: The Rule of Unit Factors The Rule of Dominance The Law of Segregation The Law of Independent Assortment In genetics, dominance describes a specific relationship between the effects of different versions of a gene (alleles) on a trait or phenotype. Animals (including humans) and plants are diploid (see ploidy), with two copies of each gene, one inherited from each parent. If the two copies are not identical (not the same allele), their combined effect may be different than the effect of having two identical copies of one or the other allele. But if the combined effect is the same as the effect of having two copies of one of the alleles, we say that allele's effect is dominant over the other. For example, having two copies of one allele of the EYCL3 gene causes the eye's iris to be brown, and having two copies of another allele causes the iris to be blue. But having one copy of each allele leads to a brown iris, thus the brown allele is said to be dominant over the blue allele (and the blue allele is said to be recessive to the brown allele). We now know that in most cases a dominance relationship is seen when the recessive allele is defective. In these cases a single copy of the normal allele produces enough of the gene’s product to give the same effect as two normal copies, and so the normal allele is described as being dominant to the defective allele. This is the case for the eye color alleles described above, where a single functional copy of the ‘brown’ allele causes enough melanin to be made in the iris that the eyes appear brown even when paired with the non-melanin-producing ‘blue’ allele. Dominance was discovered by Mendel, who introduced the use of uppercase letters to denote dominant alleles and lowercase to denote recessive alleles, as is still commonly used in introductory genetics courses (e.g. B b for alleles causing brown and blue eyes). Although this usage is convenient it is misleading, because dominance is not a property of an allele considered in isolation but of a relationship between the effects of two alleles. When geneticists loosely refer to a dominant allele or a recessive allele, they mean that the allele is dominant or recessive to the standard allele. Geneticists often use the term dominance in other contexts, distinguishing between simple or complete dominance as described above, and other relationships. Relationships described as incomplete or partial dominance are usually more accurately described as giving an intermediate or blended phenotype. The relationship described as codominance describes a relationship where the distinct phenotypes caused by each allele are both seen when both alleles are present.
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Exceptions to Mendel’s Rules
Sometimes, patterns of inheritance are not as simple as Mendel’s Rules imply. The exceptions to Mendel’s Rules are when nature uses a different method of determining traits.
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Gene Linkage The Law of Independent Assortment can be broken when genes are found close together on the same chromosome. The genes will appear linked, or show up together. The closer the genes are to each other the more they will be inherited together. Physical Mapping is the process of determining how DNA contained in a group of clones overlap without having to sequence all the DNA in the clones. Once the map is determined, we can use the clones as a resource to efficiently contain stretches of genome in large quantity. This type of mapping is more accurate than genetic maps. In maps based on a genetic fingerprinting of the clones, the stretches of DNA are identified according to how they are cut by a restriction enzyme. Once cut, the DNA fragments are separated by electrophoresis. The resulting pattern of DNA migration (ie. its fingerprint) is used to identify what stretch of DNA is in the clone. By analysing the fingerprints, contigs are assembled by automated (FPC) or manual means (Pathfinders) into overlapping DNA stretches. Now a good choice of clones can be made to efficiently sequence the clones to determine the DNA sequence of the organism under study (seed picking). Macrorestriction is a type of physical mapping wherein the high molecular weight DNA is digested with a restriction enzyme having a low number of restriction sites. Outlined above are alternative ways to investigate to create genetic maps (radiation hybrids, STS,...). Genes can be mapped prior to the complete sequencing of a by independent approaches like in situ hybridization. Once the genome has been sequenced, in-silico approaches perform the gene finding. The such suggested genes are compared with the experimental evidence for the respective gene.
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Breaking the Rule of Dominance
DNA Usually, a dominant gene produces a protein for the trait. The recessive allele either produces a nonfunctional protein or no protein at all. So we see the dominant trait in hybrids because it is the only trait expressing a protein. mRNA mRNA Protein Many genes code for enzymes. Consider the case where someone is homozygous for some trait. Both alleles code for the same enzyme, which causes a trait. Only a small amount of that enzyme may be necessary for a given phenotype. The individual therefore has a surplus of the necessary enzyme. Let's call this case "normal". Individuals without any functional copies cannot produce the enzyme at all, and their phenotype reflects that. Consider a heterozygous individual. Since only a small amount of the normal enzyme is needed, there is still enough enzyme to show the phenotype. This is why some alleles are dominant over others. In the case of incomplete dominance, the single dominant allele does not produce enough enzyme, so the heterozygotes show some different phenotype. For example, fruit color in eggplants is inherited in this manner. A purple color is caused by two functional copies of the enzyme, with a white color resulting from two non-functional copies. With only one functional copy, there is not enough purple pigment, and the color of the fruit is a lighter shade, called violet. Some non-normal alleles can be dominant. The mechanisms for this are varied, but one simple example is when the functional enzyme is composed of several subunits. In this case, if any of the subunits are nonfunctional, the entire enzyme is nonfunctional. In the case of a single subunit with a functional and nonfunctional allele (heterozygous individual), the concentration of functional enzymes is 50% of normal. If the enzyme has two identical subunits, the concentration of functional enzyme is 25% of normal. For four subunits, the concentration of functional enzyme is about 6% of normal. This may not be enough to produce the wild type phenotype. There are other mechanisms for dominant mutants.
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Incomplete Dominance When heterozygous individuals show an intermediate phenotype between the two homozygous phenotypes. Having one copy of a gene does not produce enough protein to completely mask the recessive allele. Discovered by Karl Correns, incomplete dominance (sometimes called partial dominance) is a heterozygous genotype that creates an intermediate phenotype. In this case, only one allele (usually the wild type) at the single locus is expressed, and the expression is doseage dependent. Two copies of the gene produce full expression, while one copy of the gene produces partial expression in an intermediate phenotype. A cross of two intermediate phenotypes (= monohybrid heterozygotes) will result in the reappearance of both parent phenotypes and the intermediate phenotype. There is a 1:2:1 phenotype ratio instead of the 3:1 phenotype ratio found when one allele is dominant and the other is recessive. This lets an organism's genotype be diagnosed from its phenotype without time-consuming breeding tests.
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r R Rr R r R r RR Rr rr Incomplete Dominance Snapdragons
If you cross a red flower and a white flower, the resulting hybrid will be pink. RR = red flower rr = white flower Rr = pink flower If you cross two pink flowers (Rr), you get: 25% Red Flowers 50% Pink Flowers 25% White Flowers R Rr R r The taxonomy of this genus is disputed at present. At one extreme, ITIS recognises only the Old World species of sect. Antirrhinum in the genus, listing only the Garden Snapdragon A. majus (the only species in the section naturalised in North America). At the other, Thompson (1988) places 36 species in the genus; many modern botanists accept this circumscription. New species also continue to be discovered (see e.g. Romo et al., 1995). Recent research in the molecular systematics of this group, and related species, by Oyama and Baum (2004), has confirmed that the genus as described by Thompson is monophyletic, provided that one species (A. cyathiferum) is removed to a separate genus, and two others (previously listed as Mohavea confertiflora and M. breviflora) are included. The species list at the right follows these conclusions. It is widely agreed that this broad group should be subdivided into three or four subgroups, but the level at which this should be done, and exactly which species should be grouped together, remain unclear. Some authors continue to follow Thompson in using a large genus Antirrhinum, which is then divided into several sections; others treat Thompson's genus as a tribe or subtribe, and divide it into several genera. If the broad circumscription is accepted, its sections are as follows: Section Antirrhinum: about 20 Old World species of perennial plants, the type Antirrhinum majus, mostly native to the western Mediterranean region with a focus on the Iberian Peninsula. Section Orontium: two to six species, also Mediterranean. The species in this section, including the type Lesser Snapdragon A. orontium, are often treated in the genus Misopates. Section Saerorhinum: about 16 New World species, mostly annual plants and mostly native to California, though species are found from Oregon to Baja California Sur and as far east as Utah. Like other authors, Thompson placed A. cyathiferum in this section, but Oyama and Baum, following earlier authors, suggest that it should be reclassified in genus Pseudorontium, while Mohavea confertiflora and M. breviflora should be included. Some authors classify the species in this section into the genera Sairocarpus, Howelliella and Neogaerrhinum. The Garden Snapdragon is an important garden plant; cultivars of this species have showy white, crimson, or yellow bilabiate flowers. It is also important as a model organism in botanical research, and its genome has been studied in detail. While Antirrhinum majus is the plant that is usually meant if the word "snapdragon" is used on its own, many other species in the genus, and in the family Scrophulariaceae more widely, have common names that include the word "snapdragon". R r RR Rr rr
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Incomplete Dominance Hair Straight (HH) Wavy (Hh) Curly (hh)
Head hair is a type of hair that is grown on the head (sometimes referring directly to the scalp). The most noticeable part of human hair is the hair on the head, which can grow longer than on most mammals and is more dense than most hair found elsewhere on the body. The average human head has about 100,000 hair follicles. [1] Its absence is termed alopecia, commonly known as baldness. Anthropologists speculate that the functional significance of long head hair may be adornment, a by-product of secondary natural selection once other somatic hair had been lost. Another possibility is that long head hair is a result of Fisherian runaway sexual selection, where long lustrous hair is a visible marker for a healthy individual (with good nutrition, waist length hair—approximately 1 meter or 39 inches long—would take around 84 months, or about 7 years, to grow). Each follicle can grow about 20 individual hairs in a person's lifetime. [2] Average hair loss is about 100 strands a day. The average human scalp measures approximately 120 square inches (770 cm²). These values are also reported by Desmond Morris[4] although it is not clear if these apply to both men and women. Average number of head hairs (Caucasian) [3] color number of hairs diameter Blonde 146,000 1⁄1500th to 1⁄500th inch 17 to 51 micrometers Black 110,000 1⁄400th to 1⁄250th inch 64 to 100 micrometers Brunette 100,000 variable variable Red 86,000 variable variable
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Codominance When a heterozygous individual shows the phenotypic traits of both alleles. Both alleles produce a protein, which are seen in the hybrids. The traits do not blend! In codominance, neither phenotype is recessive. Instead, the heterozygous individual expresses both phenotypes. A common example is the ABO blood group system. The gene for blood types has three alleles: A, B, and i. i causes O type and is recessive to both A and B. The A and B alleles are codominant with each other. When a person has both an A and a B allele, the person has type AB blood. When two persons with AB blood type have children, the children can be type A, type B, or type AB. There is a 1A:2AB:1B phenotype ratio instead of the 3:1 phenotype ratio found when one allele is dominant and the other is recessive. This is the same phenotype ratio found in matings of two organisms that are heterozygous for incomplete dominant alleles. Roan, caused by the roan gene, (R), consists of single white hairs intermingled with the base color of a horse. Roaning gives the horse a lightened appearance, while the mane, tail, head and legs tend to remain darker, close to the original base color. It is a dominant gene, meaning that any individual with at least one copy of the R gene trait will be roan. An implication of the gene's dominance is that at least one parent must be a roan in order to pass the gene on — it cannot appear in offspring of two non-roan parents, even if they have roan ancestors. Roan horses are born roan and stay that way throughout life. Though there may be some changes in coat color when a foal sheds out its first "baby" coat, and color variation from summer to winter, but the horse will not progressively lighten each year the way a gray does. A roan and a gray can be distinguished from one another because a gray is born dark, and lightens more each year, usually on the head first, while a roan is born with intermixed hairs, and the head stays darker than the body.
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Codominance B BW W W B BW BB WW W B Feather Color in Chickens
A black chicken would be BB. A white chicken would be WW. A hybrid, BW, would have a checkered appearance. Both white and black pigments are seen in the offspring. BW W W B BW BB WW W B
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Codominance Sickle Cell Inheritance
Sickle-cell conditions are inherited from parents in much the same way as blood type, hair color and texture, eye color and other physical traits. The types of haemoglobin a person makes in the red blood cells depend upon what haemoglobin genes the person anaemia ("SS" in the diagram) and the other is Normal (AA), all of their children will have sickle cell trait (AS). If one parent has sickle-cell anaemia (SS) and the other has Sickle Cell Trait (AS), there is a 50% chance (or 1 out of 2) of a child having sickle cell disease (SS) and a 50% chance of a child having sickle cell trait (AS). When both parents have sickle cell trait (AS), they have a 25% chance (1 of 4) of a child having sickle cell disease (SS), as shown in the diagram. Sickle-cell anemia appears to be caused by a recessive allele. Two carrier parents have a one in four chance of having a child with the disease. The child will be homozygous recessive. However, it has been argued that the allele, although appearing outwardly recessive, is in fact co-dominant, due to the resistance to a malaria which is obtained by those of the AS genotype. Since a separate phenotype from that of Normal (AA) has therefore been expressed, it is impossible to argue that the S allele is homozygous recessive.
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Multiple Alleles When a trait is controlled by more than two alleles.
Each individual only owns two alleles, but others in the population may possess different types. An allele (pronounced /ˈæliːl/ (UK), /əˈliːl/ (US)) (from the Greek αλληλος, meaning each other) is one member of a pair or series of different forms of a gene. Usually alleles are coding sequences, but sometimes the term is used to refer to a non-coding sequence. An individual's genotype for that gene is the set of alleles it happens to possess. In a diploid organism, one that has two copies of each chromosome, two alleles make up the individual's genotype. An example is the gene for blossom colour in many species of flower — a single gene controls the colour of the petals, but there may be several different versions (or alleles) of the gene. One version might result in red petals, while another might result in white petals. The resulting colour of an individual flower will depend on which two alleles it possesses for the gene and how the two interact.
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Multiple Alleles C ch ca cch Fur Color in Rabbits C = Dominant allele
ch = Himalayan fur cch = Chinchilla fur ca = Albino fur cbcb- Bugs Bunny ch Bugs is noted for his feuds with Elmer Fudd, Yosemite Sam, Marvin the Martian, Beaky Buzzard, Daffy Duck, Witch Hazel, Rocky and Mugsy, Wile E. Coyote and a host of others. Bugs is the traditional winner of these conflicts, a plot pattern which recurs in Looney Toons films directed by Chuck Jones. Concerned that viewers would lose sympathy for an invariably triumphant protagonist, Jones had the antagonist characters repeatedly bully, cheat or threaten Bugs. When offended by the antagonism, Bugs' catchline was "Of course you realize, dis means war!" (this line was taken from Groucho Marx)[2] or, alternatively, "You realize this is not going to go unchallenged!". Other directors, such as Friz Freleng, characterized Bugs as altruistic. When Bugs meets other successful characters, (such as Cecil Turtle in Tortoise Beats Hare, or, in World War II, the Gremlin of Falling Hare) his overconfidence becomes a disadvantage. Bugs Bunny's nonchalant carrot-chewing standing position, as explained by Chuck Jones, Friz Freleng, and Bob Clampett, originated from a scene in the film It Happened One Night, in which Clark Gable's character leans against a fence, eating carrots rapidly and talking with his mouth full to Claudette Colbert's character. This scene was well-known while the film was popular, and viewers at the time likely recognized Bugs Bunny's behavior as satire.[6] The carrot-chewing scenes are generally followed by Bugs Bunny's most well-known catchphrase, "What's up, Doc?". The phrase was written by director Tex Avery for his first Bugs Bunny short, 1940's A Wild Hare. Avery explained later that it was a common expression in Texas, where he was from, and that he did not think much of the phrase. When the short was first screened in theaters, the "What's up, Doc?" scene received a tremendously positive audience reaction.[7] As a result, the scene became a recurring element in subsequent films and cartoons. However, the phrase is not beyond editing, the most notable of which being whenever Bugs greets Daffy: "What's up, Duck?" Several Chuck Jones shorts in the late 1940s and 1950s depict Bugs travelling via cross-country (and, in some cases, intercontinental) tunnel-digging, ending up in places as varied as Mexico (Bully For Bugs, 1953), the Himalayas (The Abominable Snow Rabbit, 1960) and Antarctica (Frigid Hare, 1949) all because he "should'a taken that left toin at Albukoikee." He first utters that phrase in Herr Meets Hare (1945), when he emerges in the Black Forest, a cartoon seldom seen today due to its blatantly topical subject matter. When Goering says to Bugs, "There is no Las Vegas in 'Chermany'" and takes a potshot at Bugs, Bugs dives into his hole and says, "Joimany! Yipe!", as Bugs realizes he's behind enemy lines. The confused response to his "left toin" comment also followed a pattern. For example, when he tunnels into Scotland in 1948's My Bunny Lies Over The Sea, while thinking he's heading for the La Brea Tar Pits in Los Angeles, California, it provides another chance for an ethnic stereotype: "Therrre's no La Brrrea Tarrr Pits in Scotland!" (to which Bugs responds, "Uh...what's up, Mac-doc?"). A couple of late-1950s shorts of this ilk also featured Daffy Duck travelling with Bugs. Bugs Bunny has some similarities to figures from mythology and folklore, such as Br'er Rabbit, Nanabozho, or Anansi, and might be seen as a modern trickster (for example, he repeatedly uses cross-dressing mischievously). Unlike most cartoon characters, however, Bugs Bunny is rarely defeated in his own games of trickery. One exception to this is in the short Hare Brush in which Elmer Fudd ultimately carries the day at the end—however critics note that in this short Elmer had become Bugs Bunny and Bugs had become Elmer, and it is only by becoming Bugs that Elmer can win. The name "Bugs" or "Bugsy" as a nickname means "crazy" (or "loopy"). ca cch
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Multiple Alleles IAIA or IAi IBIB or IBi IAIB ii Blood Types
IA, IB, or i IAIA or IAi IBIB or IBi IAIB ii
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Polygenic Traits When one trait is controlled by more than one gene.
The genes may be on the same or different chromosomes. Both genes have a single phenotypic effect. Polygenic inheritance, also known as quantitative or multifactorial inheritance refers to inheritance of a phenotypic characteristic (trait) that is attributable to two or more genes and their interaction with the environment. Unlike monogenic traits, polygenic traits do not follow patterns of Mendelian inheritance (qualitative traits). Instead, their phenotypes typically vary along a continuous gradient depicted by a bell curve.[1] An example of a polygenic trait is human skin color. Many genes factor into determining a person's natural skin color, so modifying only one of those genes changes the color only slightly. Many disorders with genetic components are polygenic, including autism, cancer, diabetes and numerous others. Most phenotypic characteristics are the result of the interaction of multiple genes. Examples of disease processes generally considered to be results of multifactorial etiology: Diabetes Mellitus[2] Cancer[2] Cleft palate[3] [2] Multifactorially inherited diseases are said to constitute the majority of all genetic disorders affecting humans which will result in hospitalization or special care of some kind[4] [5].
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Polygenic Traits Coat Color in Labrador Retrievers
Controlled by two different genes, the B gene and the E gene. A dihybrid cross of two black labs (BbEe x BbEe) results in: 9 Black Pups 3 Chocolate Pups 3 Golden Pups 1 Golden Pup with a brown nose and light eyes. Color There are three recognized colors for Labs:[7] black (a solid black color), yellow (anything from light cream to gold to "fox-red"), and chocolate (medium to dark brown). Puppies of all colors can potentially occur in the same litter. Color is determined primarily by two genes. The first gene (the B locus) determines the density of the coat's pigment granules: dense granules result in a black coat, sparse ones give a chocolate coat. The second (E) locus determines whether the pigment is produced at all. A dog with the recessive e allele will produce little pigment and will be yellow regardless of its genotype at the B locus.[10] Variations in numerous other genes control the subtler details of the coat's coloration, which in yellow Labs varies from white to light gold to a fox red. Chocolate and black Labs' noses will match the coat color. The Labrador is an exceptionally popular dog. For example as of 2006: Widely considered the most popular breed in the world.[42][43][3] Most popular dog by ownership in USA (since 1991),[44][45] UK,[46] Australia,[47] New Zealand[48] and Canada.[49] In both the UK and USA, there are well over twice as many Labradors registered as the next most popular breed.[44][46] If the comparison is limited to dog breeds of a similar size, then there are around times as many Labradors registered in both countries as the next most popular breeds, the German Shepherd and Golden Retriever.[44][46] Most popular breed of assistance dog in the United States, Australia and many other countries, as well as being widely used by police and other official bodies for their detection and working abilities.[4] Approximately 60–70% of all guide dogs in the United States are Labradors (see below).[28] Seven out of 13 of the Australian National Kennel Council "Outstanding Gundogs" Hall of Fame appointees are Labradors (list covers ).[50]
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Polygenic Traits Eye Color Brown Gene Green Gene
Eye color is an inherited trait influenced by more than one gene.[6][7] There are two major genes and other minor ones that account for the tremendous variation of human eye color.[8] In humans, three genes associated with eye color are currently known: EYCL1, EYCL2, and EYCL3.[9][10] These genes account for three phenotypic eye colors (brown, green, and blue) in humans.[3] Eye color usually stabilizes when an infant is around 6 months old.[11] In 2006, the molecular basis of the EYCL3 locus was resolved.[12] In a study of 3839 people, researchers reported that 74% of total variation in eye color was explained by a number of single nucleotide polymorphisms (SNPs) near the OCA2 gene (OMIM: ). OCA2 was previously known because, when mutated, the gene can result in a type of albinism. The recent study showed that different SNPs strongly associate with blue and green eyes as well as variations in freckling, mole counts, hair and skin tone. The authors speculate that the SNPs may be in an OCA2 regulatory sequence and thus influence the expression of the gene product, which in turn affects pigmentation.[13] A 2008 study demonstrated that a specific mutation within the HERC2 gene that regulates OCA2 expression is responsible for blue eyes[14] (see below). Blue eyes with brown spot, Green eyes and Gray eyes are caused by an entirely different part of the genome. As Eiberg said: "The SNP rs is found to be associated with the brown and blue eye color, but this single DNA variation cannot explain all the brown eye color variation from dark brown over hazel to blue eyes with brown spots". "Behind Blue Eyes" is a song written by Pete Townshend of The Who for his Lifehouse project. It first appeared on The Who's 1971 Who's Next album, along with a number of other remnants from the project. The song is one of the most well-known of The Who's recordings. It starts off with a solo voice singing over a finger-picked guitar, later adds in bass guitar and ethereal harmonies, eventually breaks out into full-scale rock anthem when a second theme is introduced near the end, and wraps up by a brief reprise of the quieter first theme. Songs written in alternating sections were something of a trademark of Townshend's writing of the period, going back at least to Tommy, where it was used in "Christmas" and "Go to the Mirror!" The guitar riff at the end of the rock anthem section is also used after the bridge during the song Won't Get Fooled Again, perhaps serving as a link between the two songs when Who's Next was intended to be a rock opera. (Some musical themes from Tommy and Quadrophenia appear in multiple places.) The lyrics are a first-person lament from a man in the Lifehouse story, variously identified as 'Brick' or 'Jumbo', who is always angry and full of angst because of all the pressure and temptation that surrounds him, and the song was intended to be his "theme song" had the project been successful. (The lyrics of the rocking section near the end were actually written by Townshend as a prayer when he was a disciple of Meher Baba after being tempted by a groupie, and incorporated into the song when it was written.) The version of "Behind Blue Eyes" on the original Who's Next album was actually the second version the band recorded; the earlier version appears as a bonus track on the remastered CD release, which features Al Kooper on Hammond Organ.
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Multifactorial Traits
When traits are determined by several factors from the genetic makeup and the organism’s environment. The genes only represent the potential. Environmental influences turn on the genes at different times and in different amounts. Generally, multifactorial traits outside of illness contribute to what we see as continuous characteristics in organisms, such as height[4], skin color, and body mass[6]. All of these phenotypes are complicated by a great deal of interplay between genes and environment[4]. While some authors[4] [6] include intelligence in the same vein, and it is tempting to do so, the problem with intelligence is that it is so ill-defined. Indeed, the entry on intelligence offers so many definitions, that the point is easily made that there is no single, agreed-upon entity that one could say amounts to a definable cluster of heritable traits. The continuous distribution of traits such as height and skin colour described above reflects the action of genes that do not quite show typical patterns of dominance and recessiveness. Instead the contributions of each involved locus are thought to be additive. Writers have distinguished this kind of inheritance as polygenic, or quantitative inheritance[7]. Thus, due to the nature of polygenic traits, inheritance will not follow the same pattern as a simple monohybrid or dihybrid cross[5]. Polygenic inheritance can be explained as Mendelian inheritance at many loci[4], resulting in a trait which is normally-distributed. If n is the number of involved loci, then the coefficients of the binomial expansion of (a + b)2n will give the frequency of distribution of all n allele combinations. For a sufficiently high n, this binomial distribution will begin to resemble a normal distribution. From this viewpoint, a disease state will become apparent at one of the tails of the distribution, past some threshold value. Disease states of increasing severity will be expected the further one goes past the threshold and away from the mean[7]. There are, however, many traits and disease states where many genes are involved, but their contribution is not equal, or additive.
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Multifactorial Traits
Temperature, nutrition, light, chemicals, and infections can influence gene expression. Arctic Foxes have coats that change color due to temperature. The Arctic fox has a circumpolar range, meaning that it is found throughout the entire Arctic, including the outer edges of Greenland, Russia, Canada, Alaska, and Svalbard, as well as in sub-Arctic and alpine areas, such as Iceland and mainland alpine Scandinavia. The conservation status of the species is good, except for the Scandinavian mainland population. It is acutely endangered there, despite decades of legal protection from hunting and persecution. The total population estimate in all of Norway, Sweden and Finland is a mere 120 adult individuals. The arctic fox is the only native land mammal to Iceland. It came to the isolated North Atlantic island at the end of the last ice age, walking over the frozen sea. The abundance of the Arctic fox species tends to fluctuate in a cycle along with the population of lemmings. Because the fox reproduces very quickly and often dies young, population levels are not seriously impacted by trapping. The Arctic fox has, nonetheless, been eradicated from many areas where humans are settled. The Arctic fox is losing ground to the larger red fox. Historically, the gray wolf has kept red fox numbers down, but as the wolf has been hunted to near extinction in much of its former range, the red fox population has grown larger, and it has taken over the niche of top predator. In areas of northern Europe there are programs in place that allow hunting of the red fox in the Arctic fox's previous range. As with many other game species, the best sources of historical and large scale population data are hunting bag records and questionnaires. There are several potential sources of error in such data collections (Garrott and Eberhardt 1987). In addition, numbers vary widely between years due to the large population fluctuations. However, the total population of Arctic foxes must be in the order of several hundred thousand animals (Tannerfeldt 1997). The world population is thus not endangered, but two Arctic fox subpopulations are. One is the subspecies Alopex lagopus semenovi on Mednyi Island (Commander Islands, Russia), which was reduced by some 85-90%, to around 90 animals, as a result of mange caused by an ear tick introduced by dogs in the 1970’s (Goltsman et al. 1996). The population is currently under treatment with antiparasitic drugs, but the result is still uncertain. The other threatened population is the one in Fennoscandia (Norway, Sweden, Finland and Kola Peninsula). This population decreased drastically around the turn of the century as a result of extreme fur prices which caused severe hunting also during population lows (Lönnberg 1927, Zetterberg 1927). The population has remained at a low density for more than 90 years, with additional reductions during the last decade (Angerbjörn et al. 1995). The total population estimate for 1997 is around 60 adults in Sweden, 11 adults in Finland and 50 in Norway. From Kola, there are indications of a similar situation, suggesting a population of around 20 adults. The Fennoscandian population thus numbers a total of 140 breeding adults. Even after local lemming peaks, the Arctic fox population tends to collapse back to levels dangerously close to non-viability (Tannerfeldt 1997).
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Multifactorial Traits
Height, Intelligence, Cholesterol, Weight, Mental Illness, etc.
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How do our chromosomes determine our sex?
Sex Determination and Sex-linked Traits Section 12.2
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Sex Determination Humans have a total of 46 chromosomes, or 23 pairs:
22 pairs of autosomes 1 pair of sex chromosomes Autosomes All of the chromosomes that determine the traits other than sex. Come in different sizes with different genes on them. Pairs 1-22
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Sex Determination Sex Chromosomes Determine the sex of the individual.
Pair 23 In females, these chromosomes match in the form of XX. In males, these chromosomes are different, as in XY.
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X X XX XX X Y XY XY Sex Determination
The combination of sex chromosomes decides if you are a boy or a girl. A mother (XX) can only supply eggs that have an X chromosome. The father (XY) has some sperm with a X chromosome and some with a Y chromosome. X X XX XX X Y XY XY G- 50% XX; 50% XY P- 50% female; 50% male
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Comparing the X and the Y
Other proposed genes on the Y chromosome:
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Sex-Linked Traits Genes that are located on the sex chromosomes.
The X chromosome contain many important genes that are necessary for survival. The Y chromosome contains the SRY gene which determines maleness. Impact upon anatomical sex Since its discovery, the importance of the SRY gene in sex determination has been extensively documented: Humans with one Y chromosome and multiple X chromosomes (XXY, XXXY etc.) are usually males. Individuals with a male phenotype and an XX (female) genotype have been observed; these males have the SRY gene in one or both X chromosomes, moved there by chromosomal translocation. (However, these males are infertile.) Similarly, there are females with an XXY or XY genotype. These females have no SRY gene in their Y chromosome, or the SRY gene exists but is defective (mutated). SRY and the Olympics One of the most controversial uses of this discovery was as a means for gender verification at the Olympic Games, under a system implemented by the International Olympic Committee in Athletes with a SRY gene were not permitted to participate as females, although all athletes in whom this was "detected" at the 1996 Summer Olympics were ruled false positives and were not disqualified. In the late 1990s, a number of relevant professional societies in United States called for elimination of gender verification, including the American Medical Association, the American Academy of Pediatrics, the American College of Physicians, the American College of Obstetricians and Gynecologists, the Endocrine Society and the American Society of Human Genetics, stating that the method used was uncertain and ineffective.[2] The screening was eliminated as of the 2000 Summer Olympics.[2][3][4] SRY-related diseases and defects Individuals with XY genotype and functional SRY gene can have a female phenotype, where the underlying cause is androgen insensitivity syndrome (AIS). SRY has been linked to the fact that men are more likely than women to develop dopamine-related diseases such as schizophrenia and Parkinson's disease. SRY makes a protein that controls concentrations of dopamine, the neurotransmitter that carries signals from the brain that control movement and coordination.[5][6]
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Sex-Linked Traits First observed in fruit flies (Drosophila).
Fruit flies have either red or white eyes. Thomas Hunt Morgan noticed that all of the white-eyed flies were male. Therefore, eye-color in flies is a sex-linked trait.
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Y XR Xr Sex-Linked Traits
Because the X chromosome is much larger than the Y, most sex-linked traits are on the X. When writing the alleles for these traits, you must include the chromosomes that the individual has: Y Y Chromosome (no alleles) XR X Chromosome (red-eyed allele) Xr (white-eyed allele)
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XRY XrY Sex-Linked Traits
Because males have only one X chromosome, they are more likely to get a single defective copy. XRY- red-eyed male XrY- white-eyed male XrY
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XRXR XRXr XrXr Sex-Linked Traits
Because females receive two X chromosomes, they are more likely to get a dominant allele that can cover the effects of the recessive trait. A carrier female has a recessive allele but does not show the trait (heterozygous) XRXR Homozygous Red-eyed Female XRXr Carrier Female XrXr White-eyed female (rare)
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Sex-Linked Punnett Squares
Homozygous Red-eyed Female x White-eyed Male XRXR XrY Xr Y G- 50% XRXr 50% XRY XR XR Xr XR Y P- 50% red-eyed female 50% red-eyed male XR Xr XR Y
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Sex-Linked Punnett Squares
Heterozygous Red-eyed Female x Red-eyed Male XRXr XRY XR Y G- 25% XRXR 25% XRXr 25% XRY 25% XrY XR Xr XR XR Y P- 50% red-eyed female 25% red-eyed male 25% white-eyed male XR Xr Xr Y
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How do pedigrees show inherited traits within families?
Understanding Pedigrees Section 12.1
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Pedigrees A graphic representation of traits inherited within a family. Allows scientists to trace the history of a genetic disorder. Uses symbols to represent individuals. Circles represent females Squares represent males If the symbol is shaded, the individual is affected by the trait. Normal Female Normal Male Affected Female Affected Male
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Pedigrees Inherited traits can be followed from generation to generation. Horizontal lines connect two individuals who have mated. Vertical lines represent the offspring of a union. I Bb Bb 1 2 Bb bb BB Bb II 1 2 3 4 5
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Rules of Pedigrees Sex-Linked vs. Autosomal
If more males are affected by a trait than females, it is probably sex-linked. If it affects males and females equally, it is probably autosomal.
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Rules of Pedigrees Dominant vs. Recessive
If a trait skips a generation, it is recessive. If the trait is found in each generation, it is probably dominant.
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Rules of Pedigrees Identifying Genotypes
If any males are carriers, the trait is autosomal. If a male has a sex- linked trait, his mother was probably a carrier.
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Autosomal Recessive Affects males and females equally.
Skips generations (appears in some generations but not in others). Males can be carriers
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Autosomal Dominant Affects males and females equally
Does not skip any generations.
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Sex-Linked Recessive Affects males more than females.
Skips generations. Must use the chromosomes (XY or XX)
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Example #1: Albinism Assign codes for the alleles.
Are males affected more frequently that females? NO Autosomal Disorder Does the disorder skip generations? YES (P1) Recessive Disorder A- normal a - albino Autosomal Recessive Assign codes for the alleles. Code “A” for the dominant normal allele. Code “a” for the recessive allele for albinism. Affected individuals must be homozygous for “a.” First generation parents must be “Aa” because they have normal phenotypes, but affected offspring. Normal individuals must have at least one “A.” #1 must transmit “a” to each offspring. The “A” in the offspring must come from the father. Normal father could be either heterozygous or homozygous for an “A.” Both parents are heterozygous. Normal offspring could have received an “A” from either parent, or from both. Only the genotype of the offspring expressing albinism are known. Normal offspring must have received an “a” from their affected father.
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Example #2: Hemophilia Assign codes for the alleles.
Are males affected more frequently that females? YES Sex-Linked Disorder Does the disorder skip generations? YES + = normal H = hemophilia Recessive Disorder Sex-Linked Recessive All females are XX All males are XY. Assign codes for the alleles. Code “H” for the recessive hemophilia allele. Code “+” for the wild-type normal allele. Affected individuals must have an “H” on an X chromosome. All daughters of an affected father receive an X chromosome with the “H” allele. Normal individuals must have at least one X chromosome with the wild-type allele, “+.”
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Pedigree Practice A B C D Genetic Trait: ACHOO
(Sneezes in response to light) #1- Is this trait sex-linked or autosomal? #2- Is this trait dominant or recessive? #3- What is the genotype of individual A? #4- What is the genotype of individual B? #5- What is the genotype of individual C? A B C D #6- What is the genotype of individual D?
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Karyotype A picture of an individuals chromosomes.
Homologous chromosomes are paired up. Pairs are arranged by size. Karyotypes can help diagnose chromosomal disorders. Six different characteristics of karyotypes are usually observed and compared: [4] differences in absolute sizes of chromosomes. Chromosomes can vary in absolute size by as much as twenty-fold between genera of the same family: Lotus tenuis and Vicia faba (legumes), both have six pairs of chromosomes (n=6) yet V. faba chromosomes are many times larger. This feature probably reflects different amounts of DNA duplication. differences in the position of centromeres. This is brought about by translocations. differences in relative size of chromosomes can only be caused by segmental interchange of unequal lengths. differences in basic number of chromosomes may occur due to successive unequal translocations which finally remove all the essential genetic material from a chromosome, permitting its loss without penalty to the organism (the dislocation hypothesis). Humans have one pair fewer chromosomes than the great apes, but the genes have been mostly translocated (added) to other chromosomes. differences in number and position of satellites, which (when they occur) are small bodies attached to a chromosome by a thin thread. differences in degree and distribution of heterochromatic regions. Heterochromatin stains darker than euchromatin, indicating tighter packing, and mainly consists of genetically inactive repetitive DNA sequences. A full account of a karyotype may therefore include the number, type, shape and banding of the chromosomes, as well as other cytogenetic information. Variation is often found: between the two sexes between the germ-line and soma (between gametes and the rest of the body) between members of a population (chromosome polymorphism) geographical variation between races mosaics or otherwise abnormal individuals. [5]
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Karyotypes When arranging the chromosomes:
Autosomal Chromosomes are placed in order by size. The Sex Chromosomes are pair 23. Number of chromosomes in a set A spectacular example of variability between closely related species is the muntjac, which was investigated by Kurt Benirschke and his colleague Doris Wurster. The diploid number of the Chinese muntjac, Muntiacus reevesi, was found to be 46, all telocentric. When they looked at the karyotype of the closely related Indian muntjac, Muntiacus muntjak, they were astonished to find it had female = 6, male = 7 chromosomes.[21] "They simply could not believe what they saw... They kept quiet for two or three years because they thought something was wrong with their tissue culture... But when they obtained a couple more specimens they confirmed [their findings]" [22] The number of chromosomes in the karyotype between (relatively) unrelated species is hugely variable. The low record is held by the nematode Parascaris univalens, where the haploid n = 1; the high record would be somewhere amongst the ferns, with the Adder's Tongue Fern Ophioglossum ahead with an average of 1262 chromosomes.[23] Top score for animals might be the common hermit crab Eupagurus at a mere 127 chromosomes.[24] The existence of supernumerary or B chromosomes means that chromosome number can vary even within one interbreeding population; and aneuploids are another example, though in this case they would not be regarded as normal members of the population.
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Karyotypes What to look for: The Sex Chromosomes: The Autosomes
Male (XY) or Female (XX) Is there an odd number (XXY, XYY, XO, XXX) The Autosomes Are there two or three chromosomes for pair 21? Trisomy 21 Down Syndrome Down syndrome or trisomy 21 (or Down's Syndrome in British English[1] and WHO ICD) is a chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British doctor who described the syndrome in The disorder was identified as a chromosome 21 trisomy by Jérôme Lejeune in The condition is characterized by a combination of major and minor differences in structure. Often Down syndrome is associated with some impairment of cognitive ability and physical growth as well as facial appearance. Down syndrome can be identified during pregnancy or at birth. Individuals with Down syndrome tend to have a lower than average cognitive ability, often ranging from mild to moderate learning disabilities. A small number have severe to profound mental disability. The incidence of Down syndrome is estimated at 1 per 800 to 1,000 births, although these statistics are heavily influenced by the age of the mother. Other factors may also play a role. Many of the common physical features of Down syndrome also appear in people with a standard set of chromosomes. They may include a single transverse palmar crease (a single instead of a double crease across one or both palms, also called the Simian crease), an almond shape to the eyes caused by an epicanthic fold of the eyelid, upslanting palpebral fissures, shorter limbs, poor muscle tone, a larger than normal space between the big and second toes, and protruding tongue. Health concerns for individuals with Down syndrome include a higher risk for congenital heart defects, gastroesophageal reflux disease, recurrent ear infections, obstructive sleep apnea, and thyroid dysfunctions. Early childhood intervention, screening for common problems, medical treatment where indicated, a conducive family environment, and vocational training can improve the overall development of children with Down syndrome. Although some of the physical genetic limitations of Down syndrome cannot be overcome, education and proper care will improve quality of life.[2]
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44 1 45 (X) Female- Example #1 Turner Syndrome Number of Autosomes:
Number of Sex-Chromosomes: Karyotype: Phenotype: 44 1 45 (X) Turner syndrome or Ullrich-Turner syndrome encompasses several chromosomal conditions, of which monosomy X is the most common. It occurs in about 1 out of every 2500 female births.[1] Instead of the normal XX sex chromosomes for a female, only one X chromosome is present and fully functional; in rarer cases a second X chromosome is present but abnormal, while others with the condition have some cells with a second X and other cells without it (mosaicism). A normal female karyotype is labeled 46,XX; individuals with Turner syndrome are 45,X0. In Turner syndrome, female sexual characteristics are present but generally underdeveloped. Common symptoms of Turner syndrome include: Short stature Lymphoedema (swelling) of the hands and feet Broad chest (shield chest) and widely-spaced nipples Low hairline Low-set ears Reproductive sterility Rudimentary ovaries Gonadal Streak (underdeveloped gonadal structures) Amenorrhea, or the absence of a menstrual period Increased weight, obesity Shield shaped thorax of heart Shortened metacarpal IV (of hand) Small fingernails Characteristic facial features Webbing of the neck (webbed neck) Coarctation of the aorta Poor Breast Development Horseshoe kidney Other symptoms may include a small lower jaw (micrognathia), cubitus valgus (turned-out elbows), soft upturned nails, palmar crease and drooping eyelids. Less common are pigmented moles, hearing loss, and a high-arch palate (narrow maxilla). Turner syndrome manifests itself differently in each female affected by the condition, and no two individuals will share the same symptoms. Female- Turner Syndrome
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44 3 47 (XYY) Male Example #2 Jacob’s Syndrome Number of Autosomes:
Number of Sex-Chromosomes: Karyotype: Phenotype: 44 3 47 (XYY) Most males have the 46-XY karyotype, but about 1 guy in 1000 has two Y chromosomes, and is an XYY ("diplo-Y", "diplo Y", "YY", "polysomy Y", "Jacob's syndrome"). If XYY men are at any greater "risk" of fathering XYY or XXY sons, the increase is small (Zygote 7: 131, 1999; <=1% Reproduction 121: 655, 2001). When first discovered, popular science writers speculated that the extra "Y" would make owners act more masculine -- i.e., more aggressive, irresponsible, and criminal. Uh-huh. Richard Speck, the killer of eight student nurses, pretended (falsely) to be an XYY to obtain leniency, thus popularizing the "XYY's are criminals" story. The famous Nielsen letter in Lancet Sept 7, 1968 claiming that the prevalence of XYY men in prison was "25-60 times as high as the prevalence in the general population" remains a shocking example of how to mislead the public using small-sample statistics -- there were only two XYY's identified in the study. Aliens 3 was set in an offworld "penal colony for XYY's", and folklore continues to this day. There's no question that XYY's average substantially taller, tend to be wiry-built, and tend to have severe acne. Minor birth defects -- like pectus, crooked eye, and minor outturning of the elbows, are supposed to be common in XYY's. It will probably not surprise any adult visitor to this site that the average blood testosterone (the rocket-fuel that drives male sexual characteristics and behaviors) averages much higher in some men than in others. XYY's average higher than XY men. Men in prison average higher than men not in prison. When you control for the high testosterone levels, the most recent published study (Arch. Gen. Psych. 41: 93, 1984, from Copenhagen) showed there is no over-representation of XYY men in prison. ("Information from social records, a structured psychological interview, and projective tests did not support the notion that men with sex chrmosome anomalies are particularly violent or aggressive.") XYY's average only slightly lower intelligence than XY's, and the range is the same for both groups. If XYY's really exhibit severe behavior problems, it has resisted demonstration by the best scientific minds in the field of genetics. Here's why -- it's something called "ascertainment bias". Kids who are screened for chromosomal problems tend to be learning and/or behavior problems. If they come up with XYY, it's easy to blame the karyotype. What's more, somebody doing bad science can get up a series: "Look at all the XYY's I've discovered, and most of them have mental problems!" (See the fallacy?) But to date, nobody's shown that XYY's are more common among kids who are screened for these problems than in the general population. And if XYY was itself a major problem, you'd think this would have been accomplished long ago. Now, XXYY boys traditionally been considered at increased risk for emotional and cognitive problems. (For an update on XXYY from a parents' group, see The condition is rare enough that we're still in the "single case report" stage; the most recent work seems to confirm the prevailing wisdom, but once again, we don't see the picture of violent criminals (Arch. Gen. Psych. 56: 194, 1999), and one always wonders about ascertainment bais. The extra "Y" in an XYY is obviously not silent (as is the extra "X" in a XXX woman). It seems likely that the second "Y" adds a bit more aggressiveness to a man's overall personality. And I don't know that this is necessarily a bad thing. Despite decades of male-bashing from the Left, I think most people still like a man (or woman) who is responsibly aggressive. Male Jacob’s Syndrome
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44 3 47 (XXY) Male Example #3 Klinefelter Syndrome
Number of Autosomes: Number of Sex-Chromosomes: Karyotype: Phenotype: 44 3 47 (XXY) Affected males are almost always effectively sterile, although advanced reproductive assistance is sometimes possible.[4] Some degree of language learning impairment may be present,[5] and neuropsychological testing often reveals deficits in executive functions[6]. In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue).[7] Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population, but only about 10% of XXY males' gynecomastia is noticeable enough to require surgery.[8] The term "hypogonadism" in XXY symptoms is often misinterpreted to mean "small testicles" or "small penis". In fact, it means decreased testicular hormone/endocrine function. Because of this hypogonadism, patients will often have a low serum testosterone level but high serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels.[9] Despite this misunderstanding of the term, however, it is true that XXY men often also have "microorchidism" (i.e. small testicles).[9] The more severe end of the spectrum of symptom expression is also associated with an increased risk of germ cell tumors,[10] breast cancer,[11] and osteoporosis,[2] risks shared to varying degrees[12] with females. Additionally, extant medical literature shows some individual case studies of Klinefelter's syndrome coexisting with other disorders, such as pulmonary disease, varicose veins, diabetes mellitus, and rheumatoid arthritis, but the etiologies (understanding of any potential causation relationship) between Klinefelter's and these other conditions are not well characterized or understood. In contrast to these potentially increased risks, it is currently thought that rare X-linked recessive conditions occur even less frequently in XXY males than in normal XY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically only carriers rather than affected by these X-linked recessive conditions. There are many variances within the XXY population, just as in the most common 46,XY population. While it is possible to characterise 47,XXY males with certain body types, that in itself should not be the method of identification as to whether or not someone has 47,XXY. The only reliable method of identification is karyotype testing. Male Klinefelter Syndrome
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What is the genetic basis for determining blood types?
Understanding Blood Types
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Blood Types in Humans Your body produces antibodies that attack any foreign objects within you. Usually, this fights bacteria, viruses, or fungi. All of your cells have antigens on their surface. Antigens are cellular nametags. Your body makes antibodies to fight off anything without your particular antigen. Antibodies (also known as immunoglobulins[1]) are proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses. They are made of a few basic structural units called chains; each antibody has two large heavy chains H and two small light chains L. Antibodies are produced by a kind of white blood cell called a B cell. There are several different types of antibody heavy chain, and several different kinds of antibodies, which are grouped into different isotypes based on which heavy chain they possess. Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter.[2] Although the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures to exist. This region is known as the hypervariable region. Each of these variants can bind to a different target, known as an antigen.[3] This huge diversity of antibodies allows the immune system to recognize an equally wide diversity of antigens. The unique part of the antigen recognized by an antibody is called an epitope. These epitopes bind with their antibody in a highly specific interaction, called induced fit, that allows antibodies to identify and bind only their unique antigen in the midst of the millions of different molecules that make up an organism. Recognition of an antigen by an antibody tags it for attack by other parts of the immune system. Antibodies can also neutralize targets directly by, for example, binding to a part of a pathogen that it needs to cause an infection.[4] The large and diverse population of antibodies is generated by random combinations of a set of gene segments that encode different antigen binding sites (or paratopes), followed by random mutations in this area of the antibody gene, which create further diversity.[2][5] Antibody genes also re-organize in a process called class switching that changes the base of the heavy chain to another, creating a different isotype of the antibody that retains the antigen specific variable region. This allows a single antibody to be used by several different parts of the immune system. Production of antibodies is the main function of the humoral immune system.[6]
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Blood Types in Humans Your special antigens are made by your DNA.
The antigens found on the red blood cells determine your blood type. Type A Type B Type AB Type O
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Type A Blood IAIA or IAi A antigens Anti-B antibodies Genotype
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Type B Blood IBIB or IBi B antigens Anti-A antibodies Genotype
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A antigens and B antigens
Type AB Blood Genotype IAIB Antigens A antigens and B antigens Antibodies No Antibodies
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Anti-A and Anti-B antibodies
Type O Blood Genotype ii Antigens No antigens Antibodies Anti-A and Anti-B antibodies
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Rh Factor Another antigen on the surface of the RBC, is the Rhesus Factor. Named after it was discovered in Rhesus Monkeys People who have the Rh factor are positive. People without the Rh factor are negative. Antibodies are produced when the body is exposed to an antigen foreign to the make-up of the body. If a mother is exposed to an alien antigen and produces IgG (as opposed to IgM which does not cross the placenta), the IgG will target the antigen, if present in the fetus, and may affect it in utero and persist after delivery. The three most common models in which a woman becomes sensitized toward (i.e., produces IgG antibodies against) a particular blood type are: Fetal-maternal hemorrhage can occur due to trauma, abortion, childbirth, ruptures in the placenta during pregnancy, or medical procedures carried out during pregnancy that breach the uterine wall. In subsequent pregnancies, if there is a similar incompatibility in the fetus, these antibodies are then able to cross the placenta into the fetal bloodstream to attach to the red blood cells and cause hemolysis. In other words, if a mother has anti-RhD (D being the major Rhesus antigen) IgG antibodies as a result of previously carrying a RhD-positive fetus, this antibody will only affect a fetus with RhD-positive blood. The woman may receive a therapeutic blood transfusion with an incompatible blood type. ABO blood group system and Rhesus blood group system typing are routine prior to transfusion. Suggestions have been made that women of child bearing age or young girls should not be given a transfusion with Rhc-positive blood or Kell1-positive blood to avoid possible sensitization, but this would strain the resources of blood transfusion services, and it is currently considered uneconomical to screen for these blood groups. The third sensitization model can occur in women of blood type O. The immune response to A and B antigens, that are widespread in the environment, usually leads to the production of IgM anti-A and IgM anti-B antibodies early in life. On rare occasions, IgG antibodies are produced. In contrast, Rhesus antibodies are generally not produced from exposure to environmental antigens.
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Blood Donations Type A+ Type AB-
Anti-A Anti-B Anti-Rh Commonly, a person’s blood type combines their ABO type and Rh factor. Type A neg. Type O pos. rh Type A+ A blood type (also called a blood group) is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins or glycolipids, depending on the blood group system, and some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens, that stem from one allele (or very closely linked genes), collectively form a blood group system. Blood types are inherited and represent contributions from both parents. A total of 29 human blood group systems are now recognized by the International Society of Blood Transfusion (ISBT).[1] Many pregnant women carry a fetus with a different blood type from their own, and the mother can form antibodies against fetal RBCs. Sometimes these maternal antibodies are IgG, a small immunoglobulin, which can cross the placenta and cause hemolysis of fetal RBCs, which in turn can lead to hemolytic disease of the newborn, an illness of low fetal blood counts that is usually temporary or treatable. Type AB-
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Blood Donations A person cannot receive any blood that contains an antigen that they posses the antibody for. Type A individuals produce anti-B antibodies. Giving that person type B blood can have dangerous effects. The anti-B antibodies will cause the Type B blood to stick together. This is called clumping. The white blood cells of your immune system recognise agglutinogens (antigens) of your own blood type as belonging inside your body, and therefore do not attack your own blood cells. However, what would happen is a physician accidentally transfuses type B blood into a person with blood type A? In this case, the immune system of a person with type A blood would respond by attacking the ‘foreign’ type B blood cells. The immune response would involve the production of antibodies. There are a number of ways the antibodies can attack an invader, but the most common is for antibodies to chain invading cells or viruses together in large clumps. These clumps are then easily attacked and destroyed by phagocytic white blood cells. In the case of the mismatched blood transfusion above, antibodies in the type A person would attack and clump together the foreign type B blood cells. This reaction, where foreign cells are chained together by antibodies and form clumps, is called agglutination. Antibodies that attack foreign red blood cells also have a special name called agglutinins. A person’s blood type will determine what types of agglutinins (antibodies) are present in the body. The B-lymphocytes of the immune system will not produce agglutinins (antibodies) that attack the agglutinogens (antigens) found on your own red blood cells. Blood type A anti-B agglutinins (which would attack the type B agglutinogen) Blood type B anti-A agglutinins (which would attack the type A agglutinogen) Blood type AB does not produce anti-A or anti-B agglutinins (because either would attack the person’s own red blood cells) Blood type O produces both anti-A and anti-B agglutinins (because any cell with type A or type B antigen would be considered foreign)
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Blood Donations The Universal Recipient The Universal Donor
Produces no antibodies Can receive all types of blood Type AB+ The Universal Donor RBC’s have no antigens. Can give blood to anyone Type O- Development of blood banking See also: Blood bank While the first transfusions had to be made directly from donor to receiver before coagulation, in the 1910s it was discovered that by adding anticoagulant and refrigerating the blood it was possible to store it for some days, thus opening the way for blood banks. The first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, who used sodium citrate as an anticoagulant. The first blood transfusion using blood that had been stored and cooled was performed on January 1, Oswald Hope Robertson, a medical researcher and U.S. Army officer, is generally credited with establishing the first blood bank while serving in France during World War I. The first academic institution devoted to the science of blood transfusion was founded by Alexander Bogdanov in Moscow in Bogdanov was motivated, at least in part, by a search for eternal youth, and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of whole blood. In fact, following the death of Vladimir Lenin, Bogdanov was entrusted with the study of Lenin's brain, with a view toward resuscitating the deceased Bolshevik leader. Tragically, but perhaps not unforeseeably, Bogdanov lost his life in 1928 as a result of one of his experiments, when the blood of a student suffering from malaria and tuberculosis was given to him in a transfusion. Some scholars (e.g. Loren Graham) have speculated that his death may have been a suicide, while others attribute it to blood type incompatibility, which was still incompletely understood at the time.[1] [edit] The modern era Following Bogdanov's lead, the Soviet Union set up a national system of blood banks in the 1930s. News of the Soviet experience traveled to America, where in 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the first hospital blood bank in the United States. In creating a hospital laboratory that preserved and stored donor blood, Fantus originated the term "blood bank". Within a few years, hospital and community blood banks were established across the United States. In the late 1930s and early 1940s, Dr. Charles R. Drew's research led to the discovery that blood could be separated into blood plasma and red blood cells, and that the components could be frozen separately. Blood stored in this way lasted longer and was less likely to become contaminated. Another important breakthrough came in when Karl Landsteiner, Alex Wiener, Philip Levine, and R.E. Stetson discovered the Rhesus blood group system, which was found to be the cause of the majority of transfusion reactions up to that time. Three years later, the introduction by J.F. Loutit and Patrick L. Mollison of acid-citrate-dextrose (ACD) solution, which reduces the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer term storage. Carl Walter and W.P. Murphy, Jr., introduced the plastic bag for blood collection in Replacing breakable glass bottles with durable plastic bags allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood. Further extending the shelf life of stored blood was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks.
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Determining Blood Types
IAIA x IBIB Type A Type B IB IB IAIB IAIB G: 100% IAIB IA IAIB IAIB IA P: 100% AB
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Determining Blood Types
Type AB x Type O IAIB ii i i IAi IAi G: 50% IAi 50% IBi IA IBi IBi IB P: 50% Type A 50% Type B
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Determining Blood Types
Hospital Mix-Up On a busy night at the Plainsboro Hospital, three families delivered three healthy baby boys. Unfortunately, the babies became mixed up during a rush and no one knows which baby belongs to which family. The nurses were able to take blood samples from each parent and each baby. Use your knowledge of blood type genetics to figure out which baby belongs to each family. Parent Blood Type Mr. Robinson AB Mrs. Robinson B Mr. Jones O Ms. Jones Mr. Jackson Ms. Jackson Baby Blood Type Baby #1 O Baby #2 AB Baby #3 A Baby #1 belongs to the Jacksons Baby #2 belongs to the Robinsons Baby #3 belongs to the Jones
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Characteristics of Blood System
Codominance Both A and B are dominant. In a hybrid (AB) both types of antigen will be present. Multiple Alleles The ABO blood group has three alleles that produce four phenotypes. Polygenic Two genes control blood type: ABO and Rh factor
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How do scientists follow genetic disorders in our genome?
When Genetics Goes Wrong
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Cystic Fibrosis Inheritance Symptoms Autosomal Recessive Chromosome #7
Abnormally thick mucous clogs pores in lungs, liver, pancreas. Cystic fibrosis (CF), mucoviscoidosis, or mucoviscidosis, is a hereditary disease that affects mainly the lungs and digestive system, causing progressive disability. Thick mucus production, as well as a less competent immune system, results in frequent lung infections. Diminished secretion of pancreatic enzymes is the main cause of poor growth, fatty diarrhea and deficiency in fat-soluble vitamins. Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF. Individuals with cystic fibrosis can be diagnosed prior to birth by genetic testing. Newborn screening tests are increasingly common and effective. The diagnosis of CF is confirmed if high levels of salt are found during a sweat test. There is no cure for CF, and most individuals with cystic fibrosis die young: many in their 20s and 30s from lung failure. However, with the continuous introduction of many new treatments, the life expectancy of a person with CF is increasing. Lung transplantation is often necessary as CF worsens. Cystic fibrosis is one of the most common life-shortening, childhood-onset inherited diseases. In the United States, 1 in 3900 children are born with CF.[1] It is most common among Europeans and Ashkenazi Jews; one in twenty-two people of European descent carry one gene for CF, making it the most common genetic disease in these populations. CF is caused by a mutation in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices, and mucus. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither gene works normally. Therefore, CF is considered an autosomal recessive disease.
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What would be one potential downside to using gene therapy?
Cystic Fibrosis Gene Therapy is a hopeful avenue of treatment for those with cystic fibrosis. Here’s how it works: Insert a working copy of the gene into a virus. Load the virus into an inhaler. Have the patient breath in the virus with the working copy. The virus then injects its DNA and the working CF gene into the patient’s cells "65 Roses" is what some children with cystic fibrosis (CF) call their disease because the words are much easier for them to pronounce. Mary G. Weiss became a volunteer for the Cystic Fibrosis Foundation in 1965 after learning that her three little boys had CF. Her duty was to call every civic club, social and service organization seeking financial support for CF research. Mary's 4-year-old son, Richard, listened closely to his mother as she made each call. After several calls, Richard came into the room and told his Mom, "I know what you are working for." Mary was dumbstruck because Richard did not know what she was doing, nor did he know that he had cystic fibrosis. With some trepidation, Mary asked, "What am I working for, Richard?" He answered, "You are working for 65 Roses." Mary was speechless. He could not see the tears running down Mary's cheeks as she stammered, "Yes Richard, I'm working for 65 Roses." Since 1965, the term "65 Roses" has been used by children of all ages to describe their disease. But, making it easier to say does not make CF any easier to live with. The "65 Roses" story has captured the hearts and emotions of all who have heard it. The rose, appropriately the ancient symbol of love, has become a symbol of the Cystic Fibrosis Foundation. What would be one potential downside to using gene therapy?
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Phenylketoneuria (PKU)
Inheritance Autosomal Recessive Chromosome # 12 Symptoms Victims are unable to metabolize phenylalanine properly. Leads to mental retardation. PKU is defined as a complete absence or profound deficiency of phenylalanine hydroxylase (PAH) activity that typically results in high elevations of blood phenylalanine (greater than 20 mg/dL or 1200 micromol/L)) and accumulation of phenylketones in the urine. Partial deficiency of the enzyme results in hyperphenylalaninemia, characterized by lower elevation of blood phe and no phenylketone accumulation. PKU has a reported incidence in the U.S. of about 1 in 13,500 to 1 in 19,000 live births. For hyperphenylalaninemia, the estimate is approximately 1 in 48,000 newborns. But definitions of PKU and hyperphenyl-alaninemia vary from state to state. The incidence varies according to ethnic background of the child, with a higher incidence in White and Native American populations and lower incidence in African American, Hispanic, and Asian populations. There is great genetic and clinical variability among persons with PKU, as there is for all genetic diseases. More than 400 different mutations in the phenylalanine hydroxylase gene have now been identified. Since most people with PKU have two distinct mutations (that is, they are "compound heterozygotes"), there are a huge number of possible genetic combinations that contribute to clinical and biochemical variations. Certain mutations are associated with PKU while others are associated with hyperphenylalaninemia. In some cases, predicting enzyme activity in PKU may be possible if the genetic mutation is known. But the relationship between the mutation and the clinical expression is not always constant or easy to predict. Modifier genes may influence the expression of the mutant PAH gene, but so far such genes have not been identified. Also, there is individual variation in the transport of phe into the brain, which may explain some of the variation in clinical course among treated persons with PKU, as well as severity of the outcome in those off-diet. The physiological mechanisms that account for the mental retardation in PKU are still not well understood, but phenylalanine itself is thought to be the major toxic agent. In addition to genetic factors that contribute to variability among persons with PKU, environmental and lifestyle factors also contribute to the variations. For example, age when treatment is started and degree of diet control can explain differences in outcome between two people with the same genetic mutations. There are no data on early treated people with PKU who are beyond early adulthood since few are past 40 years of age. Thus, we have no scientific basis on which to base predictions of clinical outcomes beyond this age for early-treated persons.
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Phenylketoneuria (PKU)
All babies are tested for PKU in the first few days. How would being diagnosed with PKU affect your life? Since the early 1960’s newborn infants in the U.S. have been screened for PKU through collection of blood samples within the first days of life. Infants who have elevated levels are referred to PKU treatment centers for diagnostic evaluation and treatment as needed. The three main laboratory methods used in the U.S. are the Guthrie Bacterial Inhibition Assay (BIA), fluorometric analysis, and tandem mass spectrometry. Each of these methods can reliably detect PKU. U.S. screening programs have been very effective, but PKU is still being missed on rare occasion. There are few recent data to determine the magnitude of missed cases. Home births and early hospital discharge may contribute to missed cases, but errors can occur in any part of the screening process including specimen collection, lab testing and reporting of results. All states screen for PKU, but there is great variation in the screening protocols from state to state, including different criteria for defining a positive PKU screening test. Follow-up services also vary greatly. Not all newborns and their families have access to the same level of care.
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Sickle Cell Inheritance Symptoms Autosomal Codominant Chromosome # 11
Defective hemoglobin becomes sickle- shaped Pain crises result when, cells clog blood vessels. Figure 3. Top left. Sickle-cell anemia results from a "missense" mutation, called HbS, or simply s, in the DNA coding for b-globin, one of the two types of polypeptides in hemoglobin. Top right. Schematic diagram of hemoglobin molecule showing the four polypeptide chains, each of which is organized about a heme group. Middle left. Normal erthrocyte. Middle right. Erythrocyte of an individual with sickle-cell anemia manifesting characteristic "sickling." Red blood cell collapse is characteristic of the disease and especially common under conditions of low oxygen tension, e.g., in muscles following exercise. Collapsed erythrocytes manifest a reduced capacity to transport oxygen. In addition, and such cells can block small blood vessels causing pain, fever, swelling and tissue damage. Individuals with two copies of HbS often die as a result. Individuals with a single copy (so-called sickle-cell trait) experience far milder symptoms. Moreover, in the presence of the blood parasite, falciparum malaria, a single dose of HbS actually confers an advantage: RBCs infected with the parasite are more likely to "sickle" than uninfected cells and whereupon they are removed from the blood by the spleen. Sickling in response to infection thus serves to fight malaria, and as a result, heterozygous individuals are more likely to survive malarial infection than "wild-type" homozygotes, i.e., individuals with two copies of the "normal" gene. Currently, malaria infects some 300 million souls and kills 1-2 million of them yearly, most in sub-Sahara Africa. Sadly, the much of this suffering is a direct result of the banning of DDT in the name of "saving the environment." Bottom left. Distribution of malaria in the Old-World tropics. Bottom right. Frequency of HbS in human populations in Africa and Asia.
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Sickle Cell AA Normal RBC/ Susceptible to Malaria AS Normal RBC and Sickle Cells/ Resistant to Malaria SS Sickle Cells/ Resistant to Malaria The best-studied influence of the malaria parasite upon the human genome is the blood disease, sickle-cell disease. In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta globin protein, while the sickle-cell allele encodes a valine. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling. In the merozoite stage of its life cycle the malaria parasite lives inside red blood cells, and its metabolism changes the internal chemistry of the red blood cell. Infected cells normally survive until the parasite reproduces, but if the red cell contains a mixture of sickle and normal haemoglobin, it is likely to become deformed and be destroyed before the daughter parasites emerge. Thus, individuals heterozygous for the mutated allele, known as sickle-cell trait, may have a low and usually unimportant level of anaemia, but also have a greatly reduced chance of serious malaria infection. This is a classic example of heterozygote advantage. Individuals homozygous for the mutation have full sickle-cell disease and in traditional societies rarely live beyond adolescence. However, in populations where malaria is endemic, the frequency of sickle-cell genes is around 10%. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC which are common in Southeast Asia and Western Africa, respectively. If sickle-cell is so bad, why has the gene not been taken out of the genome?
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Huntington’s Disease Inheritance Symptoms Autosomal Dominant
Chromosome # 4 Symptoms Progressive neurological disorder. Nerve cells begin to deteriorate resulting in a loss of coordination. Begins in late 40’s or early 50’s. Huntington's disease (HD), known historically as Huntington's chorea and chorea maior, is a rare inherited neurological disorder affecting up to approximately 1 person per 10,000 people of Western European descent and 1 per 1,000,000 of Asian and African descent. The name is derived from the physician, George Huntington, who described it precisely in The disorder has been heavily researched in the last few decades and it was one of the first inherited genetic disorders for which an accurate test could be performed. Huntington's disease is caused by a trinucleotide repeat expansion in the gene coding for Huntingtin protein, which is denoted "Htt". Note that the protein name is "Huntingtin". Huntington's disease is one of several polyglutamine diseases. This expansion produces an altered form of the Htt protein, called mutant Huntingtin (mHtt), resulting in neuronal cell death in select areas of the brain. Huntington's disease itself isn't a terminal illness, but complications caused by it reduce life expectancy. Huntington's disease's most obvious symptoms are abnormal body movements called chorea and a lack of coordination, but it also affects a number of mental abilities and some aspects of behavior. Physical symptoms occur in a large range of ages around a mean occurrence of late forties/early fifties. If the age of onset is below 20 years then it is known as Juvenile HD. As there is currently no proven cure, symptoms are managed with various medications and supportive services. Research and discovery c. 300: Along with other conditions with abnormal movements, it may have been referred to as St Vitus' dance. St Vitus is the Christian patron saint of epileptics who was martyred in 303. Middle Ages: People with the condition were probably persecuted as being witches or as being possessed by spirits, and were shunned, exiled or worse. Some speculate that the "witches" in the Salem Witch Trials in 1692 had HD.[44] 1860: One of the early medical descriptions of HD was made in 1860 by a Norwegian district physician, Johan Christian Lund. He noted that in Setesdalen, a remote and rather secluded area, there was a high prevalence of dementia associated with a pattern of jerking movement disorders that tended to run in families. This is the reason for the disease being commonly referred to as Setesdalsrykkja (Setesdalen=the location, rykkja=jerking movements) in Norwegian. 1872: George Huntington was the third generation of a family medical practice in Long Island. With their combined experience of several generations of a family with the same symptoms, he realised their conditions were linked and set about describing it. A year after leaving medical school, in 1872, he presented his accurate definition of the disease to a medical society in Middleport, Ohio. c. 1923: Smith Ely Jelliffe (1866–1945) and Frederick Tilney (1875–1938) began analyzing the history of HD sufferers in New England. 1932: P. R. Vessie expanded Jelliffe and Tilney's work, tracing about a thousand people with HD back to two brothers and their families who left Bures in Essex for Suffolk bound for Boston in 1630. 1979: The U.S-Venezuela Huntington's Disease Collaborative Research Project began an extensive study which gave the basis for the gene to be discovered. This was conducted in the small and isolated Venezuelan fishing villages of Barranquitas and Lagunetas. Families there have a high presence of the disease, which has proved invaluable in the research of the disease. 1983: James Gusella, David Housman, P. Michael Conneally, Nancy Wexler, and their colleagues find the general location of the gene, using DNA marking methods for the first time—an important first step toward the Human Genome Project. 1992: Anita Harding, et al., find that trinucleotide repeats affect disease severity[45] 1993: The Huntington's Disease Collaborative Research Group isolates the precise gene at 4p16.3. 1996: A transgenic mouse ([the R6 line]) was created that could be made to exhibit HD, greatly advancing how much experimentation can be achieved. 1997: DiFiglia M, Sapp E, Chase KO, et al., discover that mHtt aggregates (misfolds) to form nuclear inclusions.[17] The full record of research is extensive.[46][47][48]
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Huntington’s Disease is autosomal dominant.
If one of your parents have it, you have a 50% chance of inheriting this progressive disorder. Question #1 Genetic testing can determine if you have inherited the dominant allele or not. If one of your parent’s had it, would you want to know if you have the disease or not? H h Hh hh Question #2 Should the results of genetic testing be given to employers by insurance companies? Is having the trait cause for firing somebody, even if they have not shown any symptoms?
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Color Blindness Inheritance Symptoms Sex-linked Recessive X Chromosome
Unable to distinguish between red and green colors. Color blindness, or color vision deficiency, in humans is the inability to perceive differences between some of the colors that other people can distinguish. It is most often of genetic nature, but may also occur because of eye, nerve, or brain damage, or due to exposure to certain chemicals. The English chemist John Dalton in 1798 published the first scientific paper on the subject, "Extraordinary facts relating to the vision of colours",[1] after the realization of his own color blindness; because of Dalton's work, the condition is sometimes called Daltonism, although this term is now used for a type of color blindness called deuteranopia. Color blindness is usually classed as disability; however, in selected situations color blind people may have advantages over people with normal color vision. There are some studies which conclude that color blind individuals are better at penetrating certain camouflages.[2] Monochromats may have a minor advantage in dark vision, but only in the first five and a half minutes of dark adaptation.
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How would colorblindness affect the way you see the world?
Tritanopia Deuteranopia Protanopia Normal Vision Those with protanomaly, deuteranomaly, or tritanomaly are trichromats, but the color matches they make differ from the normal. They are called anomalous trichromats. In order to match a given spectral yellow light, protanomalous observers need more red light in a red/green mixture than a normal observer, and deuteranomalous observers need more green. From a practical stand point though, many protanomalous and deuteranomalous people breeze through life with very little difficulty doing tasks that require normal color vision. Some may not even be aware that their color perception is in any way different from normal. The only problem they have is passing a color vision test. Protanomaly and deuteranomaly can be readily observed using an instrument called an anomaloscope, which mixes spectral red and green lights in variable proportions, for comparison with a fixed spectral yellow. If this is done in front of a large audience of men, as the proportion of red is increased from a low value, first a small proportion of people will declare a match, while most of the audience sees the mixed light as greenish. These are the deuteranomalous observers. Next, as more red is added the majority will say that a match has been achieved. Finally, as yet more red is added, the remaining, protanomalous, observers will declare a match at a point where everyone else is seeing the mixed light as definitely reddish. Protanomaly (1% of males, 0.01% of females):[14] Having a mutated form of the long-wavelength (red) pigment, whose peak sensitivity is at a shorter wavelength than in the normal retina, protanomalous individuals are less sensitive to red light than normal. This means that they are less able to discriminate colors, and they do not see mixed lights as having the same colors as normal observers. They also suffer from a darkening of the red end of the spectrum. This causes reds to reduce in intensity to the point where they can be mistaken for black. Protanomaly is a fairly rare form of color blindness, making up about 1% of the male population. Both protanomaly and deuteranomaly are carried on the X chromosome. Deuteranomaly (most common - 6% of males, 0.4% of females):[14] Having a mutated form of the medium-wavelength (green) pigment. The medium-wavelength pigment is shifted towards the red end of the spectrum resulting in a reduction in sensitivity to the green area of the spectrum. Unlike protanomaly the intensity of colors is unchanged. This is the most common form of color blindness, making up about 6% of the male population. The deuteranomalous person is considered "green weak". For example, in the evening, dark green cars appear to be black to Deuteranomalous people. Similar to the protanomates, deuteranomates are poor at discriminating small differences in hues in the red, orange, yellow, green region of the spectrum. They make errors in the naming of hues in this region because the hues appear somewhat shifted towards red. One very important difference between deuteranomalous individuals and protanomalous individuals is deuteranomalous individuals do not have the loss of "brightness" problem. Tritanomaly (equally rare for males and females):[14] Having a mutated form of the short-wavelength (blue) pigment. The short-wavelength pigment is shifted towards the green area of the spectrum. This is the rarest form of anomalous trichromacy color blindness. Unlike the other anomalous trichromasy color deficiencies, the mutation for this color blindness is carried on chromosome 7.[15] Therefore it is equally prevalent in both male & female populations. The OMIM gene code for this mutation is “Colorblindness, Partial Tritanomaly”.[16]
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Hemophilia Inheritance Symptoms Sex-linked Recessive X Chromosome
Unable to clot properly because of missing Factor VII. Seen in the Royal family of Britain Hemophilia Tsar Nicholas II and Tsarevich Alexei chop wood in captivity at Tobolsk during the winter of Courtesy: Beinecke Library. He had inherited hemophilia from his mother Alexandra, a condition which could be traced back to her maternal grandmother Queen Victoria. His hemophilia led to controversy, as it led to gossip that his mother was having an affair with the Russian starets, Grigori Rasputin. Rasputin claimed to be able to "heal" Alexei when he was on the brink of death after spells of hemophilia-related complications. There are various explanations for Rasputin's ability, such as that Rasputin hypnotized Alexei, administered herbs to him, or that his advice to the Tsarina not to let the doctors bother Alexei too much aided the boy's healing. Others believe he truly possessed a supernatural healing ability or that his prayers to God saved the boy. [16] Alexei and his sisters were taught to view Rasputin as "Our Friend" and to exchange confidences with him. Alexei was well aware that he might not live to adulthood. When he was ten, his older sister Olga found him lying on his back looking at the clouds and asked him what he was doing. "I like to think and wonder," Alexei replied. Olga asked him what he liked to think about. "Oh, so many things," the boy responded. "I enjoy the sun and the beauty of summer as long as I can. Who knows whether one of these days I shall not be prevented from doing it?" [17] During World War I, Alexei briefly joined his father to live at the Headquarters of the Russian army in the field. Alexei enjoyed these trips immensely, and he was promoted to the rank of corporal in When he was in captivity at Tobolsk following the Russian Revolution of 1917, Alexei complained in his diary about how bored he was and begged God to have mercy upon him. He was permitted to play occasionally with Kolya, the son of one of his doctors, and with a kitchen boy named Leonid Sednev. As he became older, Alexei seemed to tempt fate and injure himself on purpose. While in Siberia, he rode a sled down the stairs of the prison house and injured himself in the groin. The hemorrhage was very bad, and he was so ill that he could not be moved immediately when the Bolsheviks moved his parents and older sister Maria to Yekaterinburg in April Alexei and his three other sisters joined the rest of the family weeks later. [18] He was confined to a wheelchair for the remaining weeks of his life. Death Tsarevich Alexei, left, and Grand Duchess Olga, right, aboard a train that took them to Yekaterinburg in May This is the last known photo of Alexei and Olga. He was two weeks shy of his fourteenth birthday when he was murdered on July 17, 1918 in the cellar room of the Ipatiev House in Yekaterinburg. The assassination was carried out by forces of the Bolshevik secret police under Yakov Yurovsky. According to one account of the murder, the family was told to get up and get dressed in the middle of the night because they were going to be moved. Nicholas II carried Alexei to the cellar room. His mother asked for chairs to be brought so that she and Alexei could sit down. When the family and their servants were settled, Yurovsky announced that they were to be executed. The firing squad killed Nicholas, the Tsarina, and two of the servants first. Alexei remained sitting in the chair, "terrified," before the assassins turned on him and shot. The boy remained alive and the killers tried to stab him multiple times with bayonets. "Nothing seemed to work," wrote Yurovsky later. "Though injured, he continued to live." Unbeknownst to the killing squad, the Tsarevich's torso was protected by a shirt wrapped in precious gems that he wore beneath his tunic. Finally Yurovsky shot the boy again and he fell silent. [19] Rumors of Alexei's survival began to circulate when the bodies of his family and the royal servants were located. Alexei's was missing, along with that of one of his sisters (generally thought to be Maria or Anastasia). As a result of this, there have been people who have pretended to be the Tsarevich; these people are Alexei Poutziato, Joseph Veres, Heino Temmet, Michael Goleniewski and Vassili Filatov. However, scientists considered it extremely unlikely that he escaped death, due to his lifelong hemophilia. The missing bodies were said to have been cremated, though scientists believe it would have been impossible to completely cremate the bodies given the short amount of time and the materials the killing squad had to work with. Numerous searches of the forest surrounding Yekaterinburg since 1991 failed to turn up the cremation site or the remains of Alexei and his sister. [20]
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Hemophilia Genetics Plays a Role in History
Queen Victoria’s daughter, Alice, married a German prince, Louis, and converted to Lutheranism. Their daughter, Queen Victoria’s granddaughter, Alexandra was, thus, a German princess, grew up in Germany, and was raised in the Lutheran church. Alexandra, married Tsar Nicholas, the last tsar of Russia, and they had four daughters: Olga, Tatiana, Marie, and Anastasia. Many people in Russia didn’t like Tsarina Alexandra because she was German, not Russian, and Lutheran, not Russian Orthodox. Her mannerisms, speech, and dress were not what many people in Russia thought of as appropriate for the Tsar’s wife. Also, in Russia at that time, only a male could be tsar, so unless Alexandra and Nicholas had a son, the leadership would pass to another of Nicholas’ relatives when he died. Finally, however, they had a son who they named Alexei. Unfortunately, however, they soon discovered that he had inherited the hemophilia allele from Alexandra, from Alice, and from Queen Victoria. Realizing that chances were very slim that Alexei would survive to adulthood, Tsar Nicholas and his family became very withdrawn to try to keep that a secret (Alexandra was not very outgoing, anyway, which the people didn’t like). However, at that time, there was much social unrest in Russia, and the general public mistook the royal family’s withdrawl for aloofness and as a sign that they didn’t care about the poor living conditions of their people. Thus, Alexei’s hemophilia was probably a major contributing factor in the Russian revolution. On several occasions, Alexei had severe internal bleeding, and a rather disreputable man named Rasputin was somehow able to stop the bleeding. Because of his inexplicable ability to help Alexei, Rasputin became part of the “inner circle” and close confidant of the royal family, which also angered many people who did not trust him. Thus, when the Russian Revolution began, Rasputin was among the first to be executed. Eventually, Tsar Nicholas and his family were put under house arrest in Siberia. On 18 June 1918, Anastasia, the youngest of the daughters, turned 17 while the family was still under house arrest, and about a month later, just after midnight on 16 July, the royal family and several of their servants were all ordered down into the basement of the house, and the soldiers who had been guarding them shot and killed them all. Then, their remains were taken out of town, burned in a bonfire, then buried, together, in an unmarked grave. For years, no one knew where that grave was until, when Communist rule ended, records became available. In 1991, what was thought to, perhaps, be that grave was found, the bones were carefully removed, and as much as possible, the skeletons were reconstructed. Through the use of modern DNA technology, DNA samples from the bones were compared to DNA from the Tsar’s brother’s body (buried in a crypt in a church in St. Petersburg) and to DNA from someone in the English royal family. On that basis, one adult male skeleton was identified as the Tsar, several young adult female skeletons were identified as several of the daughters, and the DNA of several of the other skeletons didn’t match, showing that they were unrelated, family servants. The skeletons of Alexei and one of the four daughters were not with the rest, and are still unaccounted for. After the bones were studied and identified, a few years ago, the remains of the last Tsar of Russia and his family were given a proper funeral and burial. In 1919, a young woman jumped off a bridge in Berlin, Germany and was rescued and hospitalized. While in the hospital, on one occasion she showed a magazine article with a photo of the Russian royal family to a nurse, pointing out to the nurse how much she thought she looked like Anastasia. After that, she claimed to be Anastasia and claimed to have escaped and survived. She later moved to the U. S. and went by the name of Anna Anderson. The rest of her life, she stuck to her story that she was Anastasia, but people were dubious and tried everything they could think of (including things like comparing pictures of ear lobes) to figure out whether she was Anastasia, or not. When she died and was cremated in 1984, no one still knew if she was really Anastasia or not. At some point before her death, she had had surgery, and the hospital had kept the removed tissue preserved in formaldehyde. Again in the 1990s, with the advent of modern DNA technology, scientists were also able to test DNA samples from her preserved tissue and compare those to the other DNA samples, with the result that there were no similarities - she was not related. Another possible use for DNA technology has been suggested. The big question in all of this is, “From where did Victoria get the hemophilia allele?” Neither her mother, Victoria, nor her father, King Edward showed any signs of having that allele. The “standard” explanation which, for many years, has been offered to freshman biology students is that there was a chance, random mutation in that allele on one of Queen Victoria’s X chromosomes. More recently, however, I have heard suggestions that, at that time, if the royal couple was having trouble conceiving a child, it would not have been out of the question to quietly, unobtrusively “loan” the Queen out. People have raised the suggestion that maybe King Edward is not Victoria’s biological father. It has been suggested that perhaps there was not a chance mutation in one of Queen Victoria’s X chromosomes, but that, perhaps, that was inherited from another man. Since the bodies of deceased members of the royal family are in crypts in Westminster Abbey, it would be fairly easy to lift the lids on a couple of crypts to get DNA samples for comparison, but needless to say, the British royal family probably isn’t very enthused about that idea.
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Down Syndrome Inheritance Symptoms Chromosomal Nondisjunction
Trisomy 21 Symptoms Mild mental retardation Simian Crease, Epicanthal fold, shorter limbs, poor muscle tone, protruding tongue
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An amniocentesis extracts some fetal cells to prepare a karyotype.
Down Syndrome Women over the age of 35 increase the chances of a DS child up to 1 in 378 (over 45 is 1 in 30). An amniocentesis extracts some fetal cells to prepare a karyotype. If you found out that your child would be born with Trisomy 21 (Down Syndrome), would you support terminating the pregnancy? Amniocentesis is a prenatal test that allows your healthcare practitioner to gather information about your baby's health and development from a sample of your amniotic fluid. This is the fluid that surrounds your baby in the uterus. The most common reason to have an "amnio" is to determine whether a baby has a genetic disorder or a chromosomal abnormality, such as Down syndrome. Only amniocentesis or chorionic villus sampling (CVS) can diagnose these problems in the womb. Amniocentesis is usually done when a woman is between 16 and 20 weeks pregnant. Women who choose to have this test are primarily those at increased risk for genetic and chromosomal problems, in part because the test is invasive and carries a small risk of miscarriage. Here are a few other reasons that amniocentesis may be done: • To determine whether your baby's lungs are mature enough for an early delivery if you appear to be in premature labor or require an early delivery for any reason. • To diagnose or rule out a uterine infection if, for instance, your water has broken prematurely. • To check on the well-being of your baby if you have a blood sensitization, such as Rh sensitization. This is a complex condition that can occur if your blood is a different type than your baby's. (Note: Obstetricians are increasingly using Doppler ultrasound for this purpose instead of amnio.)
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Other Traits in Humans Polygenic Traits Multifactorial
Eye Color- 2 genes Skin Color- 3 genes Multifactorial Height Cholesterol Behavioral Traits
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