2Mendel working in his garden Pea Plants!Mendel grew and tended the pea plants he used for his experiments. For each experiment, he observed as many offspring as possible. For a cross that required him to count the number of round seeds to wrinkled seeds, he observed and counted a total of 7,324 peas.
3Gregor MendelGregor Mendel combined his farmer’s skills with his training in mathematics.Mendel’s law of segregation states that each individual has two factors (called genes today) for each trait.Alternative forms of a gene having the same position on a pair of homologous chromosomes and affecting the same trait are now referred to as alleles.
4Today we know that alleles occur at the same loci (position) on a chromosome. The factors segregate during the formation of the gametes and each gamete has only one factor from each pair.Fertilization gives each new individual two factors again.
5Gene locus (locus = location) Each allelic pair, such as Gg or Zz, is located on homologous chromosomes at a particular gene locus, shown at the left. Following replication, each sister chromatid carries the same alleles in the same order, as shown at the right.
6The Inheritance of a Single Trait A capital letter indicates a dominant allele, which is expressed when present.An example is W for widow’s peak.A lowercase letter indicates a recessive allele, which is only expressed in the absence of a dominant allele.An example is w for continuous hairline.
7Widow’s peakIn humans, widow’s peak (top) is dominant over straight hairline (bottom).
8Genotype and Phenotype Genotype refers to the genes of an individual which can be represented by two letters or by a short descriptive phrase.Homozygous means that both alleles are the same; for example, WW stands for homozygous dominant and ww stands for homozygous recessive.Phenotype refers to the physical appearance of the genotype!
9Gamete Formation (sperm and eggs) Because homologous pairs separate during meiosis, a gamete has only one allele from each pair of alleles.If the allelic pair is Ww, a gamete would contain either a W or a w, but not both.Ww represents the genotype of an individual.Gametes are represented by W or w.
10One-Trait Crosses (let’s breed!) In one-trait crosses, only one trait such as type of hairline is being considered.When performing crosses, the original parents are called the parental generation, or the P generation.All of their children are the filial generation, or F generation.Children are monohydrids when they are heterozygous for one pair of alleles.
11P stands for the parental generation; F for the filial generation P stands for the parental generation; F for the filial generation. The F generation from this cross are all monohybrids.
12When a monohybrid reproduces with a monohybrid, the results are 3 : 1. If you know the genotype of the parents, it is possible to determine the gametes and use a Punnett square to determine the phenotypic ratio among the offspring.When a monohybrid reproduces with a monohybrid, the results are 3 : 1.This ratio is used to state the chances of a particular phenotype.A 3 : 1 ratio means that there is a 75% chance of the dominant phenotype and a 25% chance of the recessive phenotype.The 3:1 phenotypic ratio indicates three offspring with the dominant phenotype and 1 with the recessive phenotype. (The genotypic ratio would be 1:2:1.)
13Monohybrid crossA Punnett square diagrams the results of a cross. When the parents are heterozygous, each child has a 75% chance of having the dominant phenotype and a 25% chance of having the recessive phenotype.It is important to realize that chance has no memory; for example, if two heterozygous parents already have three children with a widow’s peak and are expecting a fourth child, this child still has a 75% chance of having a widow’s peak and a 25% chance of having a straight hairline.
14One-Trait Crosses and Probability Laws of probability alone can be used to determine results of a cross.The laws are:(1) the probability that two or more independent events will occur together is the product of their chances occurring separately, and(2) the chance that an event that can occur in two or more independent ways is the sum of the individual chances.
15In the cross of Ww x Ww, what is the chance of obtaining either a W or a w from a parent? Chance of W = ½, or chance of w = ½The probability of these genotypes is:The chance of WW = ½ x ½ = ¼The chance of Ww = ½ x ½ = ¼The chance of wW = ½ x ½ = ¼The chance of ww = ½ x ½ = ¼The chance of widow’s peak (WW, Ww, wW) is ¼ + ¼ + ¼ = ¾ or 75%.
16The One-Trait Testcross It is not always possible to discern a homozygous dominant from a heterozygous individual by inspection of phenotype.A testcross crosses the dominant phenotype with the recessive phenotype.If a homozygous recessive phenotype is among the offspring, the parent must be heterozygous.
17One-trait testcrossA testcross determines if an individual with the dominant phenotype is homozygous or heterozygous. Because all offspring show the dominant characteristic, the individual is most likely homozygous as shown.
18Because the offspring show a 1:1 phenotypic ratio, the individual is heterozygous as shown.
19The Inheritance of Many Traits Independent AssortmentThe law of independent assortment states that each pair of alleles segregates independently of the other pairs and all possible combinations of alleles can occur in the gametes.This law is dependent on the random arrangement of homologous pairs at metaphase.
20Segregation and independent assortment Segregation occurs because the homologous chromosomes separate during meiosis I. Also, independent assortment occurs. The homologous chromosomes line up randomly at the metaphase plate; therefore, the homologous chromosomes, and the alleles they carry, segregate independently during gamete formation. All possible combinations of chromosomes and alleles occur in the gametes.
21Two-Trait CrossesIn two-trait crosses, genotypes of the parents require four letters because there is an allelic pair for each trait.Gametes will contain one letter of each kind in every possible combination.When a dihybrid reproduces with a dihybrid the results are 9 : 3 : 3 : 1.
22Dihybrid crossF1 is the first filial generation, offspring of the parental cross. F2, or second filial generation, is the offspring of the cross of two F1 individuals.Since each F1 parent can form four possible types of gametes, four different phenotypes occur among the offspring in the proportions shown.The expected F2 phenotypic ratio is:9 widow’s peak and short fingers3 window’s peak and long fingers3 straight hairline and short fingers1 straight hairline and long fingers
23Two-Trait Crosses and Probability It is possible to use the two laws of probability to arrive at a phenotypic ratio for a two-trait cross without using a Punnett square.The results for two separate monohybrid crosses are as follows:Probability of widow’s peak = ¾Probability of short fingers = ¾Probability of straight hairline = ¼Probability of long fingers = ¼
24The probabilities for the dihybrid cross: Probability of widow’s peak and short fingers = ¾ x ¾ = 9/16Probability of widow’s peak and long fingers = ¾ x ¼ = 3/16Probability of straight hairline and short fingers = ¼ x ¾ = 3/16Probability of straight hairline and long fingers = ¼ x ¼ = 1/16
25The Two-Trait Testcross A testcross is done when it is not known whether a dihybrid individual is homozygous dominant or heterozygous for both or one of the traits under consideration.A cross of a person heterozygous for both traits with a homozygous recessive person produces a 1 : 1 : 1 : 1 ratio.
26Two-trait testcrossA testcross determines if the individual with a dominant phenotype is homozygous or heterozygous. If the individual is heterozygous as shown, there is a 25% chance for each possible genotype.
27Pedigree charts represent males as squares and females as circles. Recessive and dominant alleles have different patterns of inheritance.Genetic counselors construct pedigree charts to determine the mode of inheritance of a condition.
28Autosomal recessive pedigree chart Autosomal recessive disorders have these characteristics:Affected children can have unaffected parents.Heterozygotes (Aa) have a normal phenotype.Two affected parents will always have affected children.Affected individuals with homozygous dominant mates will have unaffected children.Close unaffected relatives who reproduce are more likely to have affected children if they have joint affected relatives.Both males ad females are affected with equal frequency.How would you know the individual at the asterisk is heterozygous?
29Autosomal dominant pedigree chart Autosomal dominant disorders have these characteristics:Affected children will have at least one affected parent.Heterozygotes (Aa) are affected.Two affected parents can produce an unaffected child.Two unaffected parents will not have affected children.Both males and females are affected with equal frequency.How would you know the individual at the asterisk is heterozygous?
30Autosomal Recessive Disorders Tay-Sachs DiseaseTay-Sachs disease is common among United States Jews of central and eastern European descent.An affected infant develops neurological impairments and dies by the age of three or four.Tay-Sachs results from a lack of hexosaminidase A and the storage of its substrate in lysosomes.Prenatal diagnosis of Tay-Sachs is possible following
31Cystic FibrosisCystic fibrosis is the most common lethal genetic disorder among Caucasians.A chloride ion transport protein is defective in affected individuals.Normally when chloride ion passes through a membrane, water follows.In cystic fibrosis patients, a reduction in water results in a thick mucus which accumulates in bronchial passageways and pancreatic ducts.Genetic testing for the CF gene is possible.
32Cystic fibrosis therapy Antibiotic therapy is used to control lung infections of cystic fibrosis patients. The antibiotic tobramycin can be aerosolized and administered using a nebulizer. It is inhaled twice daily for about fifteen minutes.
33Phenylketonuria (PKU) Individuals with phenylketonuria lack an enzyme needed for the normal metabolism of phenylalanine, coded by an allele on chromosome 12.Newborns are regularly tested for elevated phenylalanine in the urine.If the infant is not put on a phenylalanine-restrictive diet in infancy until age seven when the brain is fully developed, brain damage and severe mental retardation result.
34Autosomal Dominant Disorders NeurofibromatosisSmall benign tumors, made up largely of nerve cells, occur under skin or on various organs.The effects can range from mild to severe, and some neurological impairment is possible; this disorder is variably expressive.The gene for this trait is on chromosome 17.Neurofibromatosis is variably expressive; most individuals have mild symptoms, but some have severe symptoms.
35Huntington DiseaseIndividuals with Huntington disease experience progressive degeneration of the nervous system and no treatment is presently known.Most patients appear normal until middle age.The gene coding for the protein huntingtin contains many more repeats of glutamines than normal.The gene for Huntington disease is located on chromosome 4.
36Huntington diseasePersons with this condition gradually lose psychomotor control of the body. At first, the disturbances are only minor, but the symptoms become worse with time.
37Polygenic inheritance When you record the heights of a large group of young men, the values follow a bell-shaped curve. Such a continuous distribution is due to control of a trait by several sets of alleles. Environmental effects (i.e., differences in nutrition) are also involved.
38Skin ColorThe inheritance of skin color, determined by an unknown number of gene pairs, is a classic example of polygenic inheritance.A range of phenotypes exist and several possible phenotypes fall between the two extremes of very dark and very light.The distribution of these phenotypes follows a bell-shaped curve.
39Polygenic DisordersMany human traits, like allergies, schizophrenia, hypertension, diabetes, cancers, and cleft lip, appear to be due to the combined action of many genes plus environmental influences.Many behaviors, such as phobias, are also likely due to the combination of genes and the effects of the environment.
40Multiple Allelic Traits Inheritance by multiple alleles occurs when more than two alternative alleles exist for a particular gene locus.A person’s blood type is an example of a trait determined by multiple alleles.Each individual inherits only two alleles for these genes.
41ABO Blood TypesA person can have an allele for an A antigen (blood type A) or a B antigen (blood type B), both A and B antigens (blood type AB), or no antigen (blood type O) on the red blood cells.Human blood types can be type A (IAIA or IA i), type B (IBIB or IBi), type AB (IAIB), or type 0 (ii).The Rh factor is inherited separately from ABO blood types. When you are Rh positive, your red blood cells have a particular antigen, and when you are Rh negative, that antigen is absent. The Rh-positive allele is dominant over the Rh-negative allele.
42Inheritance of blood type A mating between blood type A and blood type B can result in any one of four blood types.
43Incompletely Dominant Traits Codominance means that both alleles are equally expressed in a heterozygote.Incomplete dominance is exhibited when the heterozygote shows not the dominant trait but an intermediate phenotype, representing a blending of traits.Such a cross would produce a phenotypic ratio of 1 : 2 : 1.The alleles A and B in ABO blood groupings are codominant. An example of incomplete dominance is seen in degree of hair curliness.
44Incomplete dominanceAmong Caucasians, neither straight nor curly hair is dominant. When two wavy-haired individuals reproduce, each offspring has a 25% chance of having either straight or curly hair and a 50% chance of having wavy hair, the intermediate phenotype.
45Sickle-Cell DiseaseSickle-cell disease is an example of a human disorder controlled by incompletely dominant alleles.Sickle cell disease involves irregular, sickle shaped red blood cells caused by abnormal hemoglobin.HbA represents normal hemoglobin; and HbS represents the sickled condition.Individuals with sickle cell trait survive malaria because the sickling of some red blood cells causes a leakage of potassium, which is toxic to the malarial parasite.
46HbAHbA individuals are normal; HbSHbS individuals have sickle-cell disease and HbAHbS individuals have the intermediate condition called sickle-cell trait.Heterozygotes have an advantage in malaria-infested Africa because the pathogen for malaria cannot exist in their blood cells.This evolutionary selection accounts for the prevalence of the allele among African Americans.
47Many genetic disorders and other traits are inherited according to laws first established by Gregor Mendel.Inheritance is often more complex, providing exceptions to Mendel’s laws but helping to explain an even wider variety in patterns of gene inheritance.
49AmniocentesisAmniocentesis uses a needle to extract amniotic fluid from the uterus of a pregnant woman from the 14th to 17th week of pregnancy.Up to 400 chromosome and biochemical problems can be detected by culturing fetal cells that are in the amniotic fluid.There is a slight risk of spontaneous abortion with this procedure.
50AmniocentesisDuring amniocentesis, a long needle is use to withdraw amniotic fluid containing fetal cells. Biochemical tests can also be run on the amniotic fluid.
51Chorionic Villi Sampling Chorionic villi sampling (CVS) uses a thin suction tube to sample chorionic cells from the placenta as early as the fifth week of pregnancy.The cells do not have to be cultured, and karyotyping can be done immediately.CVS carries a slightly greater risk of spontaneous abortion but can be performed earlier than amniocentesis.
52Chorionic villi sampling During chorionic villi sampling, a suction tube is used to remove cells from the chorion, where the placenta will develop.
53KaryotypingSampled fetal cells are stimulated to divide in culture medium and another chemical stops division during metaphase when chromosomes are highly condensed.The stained cells are photographed and can be paired based on stained cross-bands, and size and shape.
54Human karyotype preparation Cells are microscopically examined and photographed. A computer arranges the chromosomes into pairs based on size, shape, and banding patterns.
55Normal male karyotypeHere is a karyotype of a normal male with 46 chromosomes.
56Down syndrome karyotype This karyotype shows an individual (male) with Down syndrome having an extra chromosome 21.
57Nondisjunction in meiosis I Nondisjunction can occur during meiosis I. The result is abnormal eggs with either one too many or one too few chromosomes. Fertilization with a normal sperm results in an abnormal number of chromosomes in the zygote. Note that two of the eggs could potentially have the correct number of chromosomes.
58Nondisjunction in meiosis II Nondisjunction can occur during meiosis II if the sister chromatids separate but the resulting chromosomes go into the same daughter cell. The egg has 24 chromosomes; after fertilization with normal sperm, the zygote would have 47 instead of the normal 46 chromosomes. Alternatively, the egg could have 22 chromosomes, so after fertilization, the zygote has 45 rather than 46 chromosomes.
59Normal development depends on the presence of two of each kind of chromosome, but an extra chromosome is tolerated more than a missing chromosome.The Barr body is an inactive X chromosome and is seen whenever more than one X chromosome is present (i.e., XX, XXY, XXX).Cells of females function with a single chromosome just as those of males do.
60Down SyndromeDown syndrome is caused by trisomy 21, three copies of chromosome 21 as a result of nondisjunction.Symptoms include mental retardation, short stature, eyelid fold, flatter face, a palm creases, and stubby fingers, among others.Nondisjunction usually occurred in producing the mother’s egg and risk increases at age 40.
61Abnormal autosomal chromosome number Persons with Down syndrome have an extra chromosome 21. Common characteristics include a wide, round face, and a fold on the upper eyelids. Mental retardation, along with an enlarged tongue, make it difficult for a person with Down syndrome to speak distinctly.
62The genes causing Down syndrome are located on the bottom third of chromosome 21. In particular, the Gart gene leads to a high level of purines, which contribute to mental impairment but may allow future preventive treatment.
63Changes in Sex Chromosome Number The presence of a Y chromosome determines maleness.The SRY gene on the short arm of the Y produces a testis-determining factor that begins the development of a male; otherwise an embryo develops as a female.An abnormal number of sex chromosomes is the result of inheriting to many or too few X or Y chromosomes.
64Turner SyndromeIndividuals with Turner syndrome are females that have only one X chromosome; therefore they are XO.They are short, with a broad chest, and webbed neck.They do not undergo puberty or menstruate, and there is a lack of breast development.Intelligence is normal and individuals can lead normal lives.XO signifies the lack of a second X chromosome. Although their reproductive organs are underdeveloped, some females with Turner syndrome have given birth following in vitro fertilization using donor eggs.
65Klinefelter SyndromeIndividuals with Klinefelter syndrome are males that have two or more X chromosomes in addition to a Y chromosome.The Y chromosome drives development as a male but gonads are underdeveloped and breasts develop.Klinefelter males are usually slow to learn but are not mentally retarded.Individuals with Klinefelter syndrome have large hands and feet and very long arms and legs.
66Abnormal sex chromosome number On the left is a female with Turner (XO) syndrome. She has a short, thick neck, short stature, and a lack of breast development. On the right is a male with Klinefelter (XXY) syndrome. He has immature sex organs and some development of the breasts.
67Poly-X FemalesA poly-X female has more than two X chromosomes and extra Barr bodies in the nucleus.An XXX female has a normal phenotype except there may be menstrual difficulties, but she is fertile; her children usually have normal karyotypes.Females with XXXX are usually tall and severely retarded; they may menstruate normally.
68Jacobs SyndromeJacobs syndrome males are XYY which can only result from nondisjuction during spermatogenesis.They tend to be tall, have persistent acne, and have speech and reading problems.At one time it was suggested that XYY males were unusually aggressive, but this was found not to be true.
69Deletions and Duplications Deletions occur when a single break causes a lost end piece, or two breaks result in a loss in the interior.An individual who inherits a normal chromosome from one parent and a chromosome with a deletion from the other parent no longer has a pair of alleles for each trait, and a syndrome can result.
70In Williams syndrome, chromosome 7 loses an end piece and children have a pixie look and the skin ages prematurely from lack of the gene that governs elastin production.An end piece of chromosome 5 produces cri du chat syndrome where larynx is abnormal and the infant’s cry is like that of a cat, the head is small, and there are facial abnormalities.
71DeletionWhen chromosome 7 loses an end piece, the result is Williams syndrome. These children, although unrelated, have the same appearance, health, and behavioral problems. Children with this syndrome look like pixies because they have turned-up noses, wide mouths, a small chin, and large ears. Although their academic skills are poor, they exhibit excellent verbal and musical abilities.
72Duplication results in a chromosome segment being repeated in the same chromosome or in a nonhomologous chromosome, producing extra alleles for a trait.An inverted duplication in chromosome 15 causes inv dup 15 syndrome with poor muscle tone, mental retardation, and related symptoms.Inverted means that the duplicated segment joins in the direction opposite from normal.
73DuplicationWhen a piece of chromosome 15 is present in inverted sequence, a syndrome results in which the child has poor muscle tone and autistic characteristics.
74TranslocationTranslocation is exchange of chromosomal segments between two, nonhomologous chromosomes.In a small percent of cases, a translocation between chromosomes 21 and 14 causes Down syndrome.The tendency for this particular translocation can run in the family of either the mother or father of affected individuals.A person who has both of the involved chromosomes has the normal amount of genetic material and is healthy, unless the chromosome exchange breaks an allele into two pieces.The person who inherits only one of the translocated chromosomes will no doubt have only one copy of certain alleles and three copies of certain other alleles. A genetic counselor begins to suspect a translocation has occurred when spontaneous abortions are commonplace and family members suffer from various syndromes.
75Alagille syndrome results from a deletion of chromosome 20 or a translocation that disrupts an allele on chromosome 20.The symptoms for Alagille syndrome range from mild to severe, so people may not be aware they have the syndrome.
76TranslocationWhen chromosomes 2 and 20 exchange segments, Alagille syndrome, with distinctive facial features, results. Here we see a father and son with Alagille syndrome. This father did not realize it until he had a child with the syndrome.
77InversionInversion involves a segment of a chromosome being turned 180 degrees; the reverse sequence of alleles can alter gene activity.Crossing-over between inverted and normal chromosomes can cause recombinant chromosomes due to the inverted chromosome needing to form a loop to align.
78InversionA segment of one homologue is inverted. When crossing-over occurs during meiosis, both chromosomes end up having a duplication of some segments and a deletion of other segments.
79X-Linked AllelesThe key for an X-linked problem shows the allele attached to the X as in:XB = normal visionXb = color blindness.Females with the genotype XBXb are carriers because they appear to be normal but each son has a 50% chance of being color blind depending on which allele the son receives.XbXb and XbY are both colorblind.The inheritance from their father cannot offset the recessive allele because the Y chromosome does not carry X-linked alleles.
80Cross involving an X-linked allele The male parent is normal, but the female parent is a carrier; an allele for colorblindness is located on one of her X chromosomes. Therefore, each son stands a 50% chance of being color blind. The daughters will appear normal, but each one stands a 50% chance of being a carrier.
81X-Linked DisordersIn pedigree charts that show the inheritance pattern for X-linked recessive disorders, more males than females have the trait because recessive alleles on the X chromosome are expressed in males.A grandfather passes an X-linked recessive disorder to a grandson through a carrier daughter.X-linked recessive disorders include red-green color blindness, muscular dystrophy, and hemophilia.
82X-linked recessive pedigree chart Pedigree charts of X-linked recessive disorders show:Males more than females are affected.An affected son can have parents who have the normal phenotype.For a female to have the characteristic, her father must also have it, and her mother either has it or is a carrier.The characteristic often skips a generation from the grandfather to the grandson.If a woman has the characteristic, all of her sons will have it.
83Color BlindnessThree types of cones are in the retina detecting red, green, or blue.Genes for blue cones are autosomal; those for red and green cones are on the X chromosome.Males are much more likely to have red-green color blindness than females.About 8% of Caucasian men have red-green color blindness.
84Muscular DystrophyMuscular dystrophy is characterized by the wasting of muscles.The most common form is Duchenne muscular dystrophy; this is an X-linked disorder, occurring in 1 of 3,600 males.Muscles weaken, frequent falls and difficulty in rising occur early; death occurs by age 20.
85Duchenne muscular dystrophy involves the absence of a protein called dystrophin that is involved in the release of calcium from the sarcoplasmic reticulum of muscle cells.The lack of dystrophin causes calcium to leak into the cell, which promotes the action of an enzyme that dissolves muscle fibers.A test is now available to determine the carriers of Duchenne muscular dystrophy.
86HemophiliaHemophilia refers to the lack of one of several clotting factors that leads to excessive bleeding in affected individuals.Hemophiliacs bleed externally after injury, but also bleed internally around joints.Hemorrhages can be stopped with blood transfusions or a biotechnology clotting factor.
87Fragile X SyndromeFragile X syndrome is an X-linked genetic disorder with an unusual pattern of inheritance.Individuals with this syndrome (one in 1,500 males and one in 2,500 females) have a base triplet repeat (CGG) in a gene on the X chromosome.Children may be autistic or hyperactive with speech difficulties.
88Adults have large testes if male, and big protruding ears. They are short in stature and the face is long with a prominent jaw.A person with a smaller number of CGG repeats and minor or no symptoms is said to have a premutation and can pass it to their children where the number increases and the condition is severe.
89Linkage groupIn this individual, alleles A and B are on one member of a homologous pair, and alleles a and b are on the other member. In complete linkage, the dihybrid produces only two types of gametes in equal proportion.
90When linkage is incomplete, this dihybrid produces four types of gametes because crossing-over has occurred. The recombinant gametes occur in reduced proportion because crossing-over occurs infrequently.
91The frequency of recombinant gametes that occurs due to the process of crossing-over has been used to map chromosomes.Crossing-over data is used to map the chromosomes of animals, such as fruit flies, but is limited in mapping human chromosomes because we do not control the crosses.
92Cross involving linked genes Linked genes reduce the number of expected phenotypes among the offspring.
93Abnormalities arise when humans inherit an incorrect number of sex chromosomes. Traits unrelated to the gender of an individual are controlled by genes located on the sex chromosomes.Males express X-linked recessive disorders because they inherit only one X chromosome.Genes that occur on the same chromosome form a linkage group and tend to be inherited together.