1. Chapter 14 - Mendel
14.1 – 14.4

2. Overview
Every day we observe heritable variations (eye color) among individuals in a population.
These traits are transmitted from parents to offspring.
The “blending” hypothesis:
Genetic material contributed by each parent mixes (eg. Blue + yellow = green).
With blending inheritance, a freely mating population will eventually give rise to a uniform population of individuals.
Everyday observations and the results of breeding experiments show that heritable traits do not blend to become uniform.
The “particulate” inheritance:
Parents pass on discrete genes that retain their separate identities in offspring.
Genes can be sorted and passed on generation after generation in undiluted form.
Modern genetics began in an abbey garden, where a monk named Gregor Mendel documented a particulate mechanism of inheritance.

4. 14.1 Mendel Used the Scientific Approach to Identify Two Laws of Inheritance.

5. Some History
Mendel discovered the basic principles f heredity by breeding garden peas in carefully planned experiments.
Mendel grow up on a small farm in what is today the Czech Republic.
1843: Mendel entered an Augustinian monastery.
: He studied at the U of Vienna, influenced by a physicist who encouraged experimentation and the application of mathematics to science and a botanist who stimulated Mendel’s interest in plant variation.
After university, Mendel taught at the Brunn Modern School and lived at the local monetary where the monks had a traditional interest in the breeding of plants, including peas.
1857: Mendel began breeding garden peas to study inheritance.

6. Peas Pea plants have several advantages for genetic study.
They are available in many varieties with distinct heritable characters with different variant traits.
Mendel could control which plant mated with which.
Each pea plant has male (stamens) and female (carpal) sexual organs.
In nature pea plants typically self-fertilize but Mendel could also use pollen from another plant for cross-pollination.
Mendel tracked only those characters that had clear variations.
Eg. He worked with flowers that were either purple or white.
He avoided traits such as seed weight that varied on a continuum.

8. True-Breeding
True-breeding: plants that when self-pollinated have offspring that express all the same traits.
In a typical breeding experiment, Mendel would cross-pollinate (hybridize) two contrasting, true-breeding pea varieties.
The true-breeding parents are the P generation, and their hybrid offspring are the F1 generation.
Mendel would allow the F1 hybrids to self-pollinate to produce an F2 generation.
It was mainly Mendel’s analysis of F2 plants that revealed two fundamental principles of heredity: the law of segregation and the law of independent assortment.

9. Pea Weirdness
If the blending model was correct, the F1 hybrids from a cross between purple-flowered and white-flowered pea plants would have pale purple flowers.
Instead, the F1 hybrids all have purple flowers, just as purple as their purple-flowered parents.
When Mendel allowed the F1 plants to self-fertilize, the F2 generation included both purple-flowered and white-flowered plants.
The white trait, absent in F1, reappeared in F2.
Mendel used very large sample sizes and kept accurate records of his results.
He recorded 705 purple-flowered F2 plants and 224 white-flowered F2 plants.
This cross produced a 3:1 ratio of purple:white in the F2 offspring.

10. Heritable Factors
Mendel reasoned that the heritable factor for white flowers was present in the F1 plants, but did not affect flower color.
Purple flower color is a dominant trait, and white flower color is a recessive trait.
The reappearance of white-flowered plants in the F2 generation indicated the heritable factor for the white trait was not diluted or “blended” by coexisting with the purple-flower factor in the F1 hybrids.
Mendel found similar 3:1 ratios of two traits among F2 offspring when he conducted crosses for six other characters, each represented by two traits.
Eg. When he crossed two true-breeding plants, one for round seeds and the other for wrinkled seeds, all the F1 offspring had round seeds.
In the F2, 75% of the seeds were round and 25% were wrinkled  3:1.

11. A Hypothesis is Born
Mendel developed a hypothesis to explain these results that consisted of four related ideas. His ideas now are understood through modern genetics.
1. Alternative versions of genes account for variations in inherited characters.
The gene for flower color in pea plants exists in two versions: purple and white.
These alternate versions are called alleles.
Each gene resides at a specific locus on a specific chromosome, and the DNA sequence at that locus can vary.
The purple-flower and white-flower alleles are two DNA variations at the flower-color locus.

12. A Hypothesis is Born
2. For each character, an organism inherits two alleles, one from each parent.
A diploid organism inherits one set of chromosomes from each parent.
Each diploid organism has a pair of homologous chromosomes  two copies of the gene.
These homologous loci may be identical, as in true-breeding plants, or the alleles may differ.
3. If the two alleles at a locus differ, the one (the dominant allele) determines the organism’s appearance. The other (the recessive allele) has no noticeable effect on the appearance.
In the flower-color example, the F1 plants inherited a purple-flower allele from one parent and white-flower allele from the other.
They had purple flowers because the purple allele is dominant.

13. A Hypothesis is Born
4. Mendel’s law of segregation states that the two alleles for a heritable character separate and segregate during gamete production and end up in different gametes.
This segregation of alleles corresponds to the distribution of homologous chromosomes to different gametes during meiosis.
If an organism has two identical alleles for a particular character, then that allele is present as a single copy in al gametes.
If different alleles are present, then 50% of the gametes will receives one allele and 50% will receive the other.

14. Law of Segregation
Mendel’s law of segregation accounts for the 3:1 ratio that he observed in the F2 generation.
The F1 hybrids produce two classes of gametes, half with the purple-flower allele and half with the white-flower allele.
During self-pollination, the gametes of these two classes unite randomly.
This produces four equally likely combinations of sperm and ovum.
A Punnett square predicts the results of a genetic cross between individuals of known genotype.

15. Punnett Square
In Punnett squares, capital letters are dominant, lowercase letters are recessive.
P is the purple allele, p is the white allele.
All inherit on white-flower allele and one purple-flower allele  all purple.
In the F2 offspring:
¼ will inherit two white-flower alleles and be white
½ will inherit one white-flower and one purple-flower allele and be purple.
¼ will inherit two purple-flower alleles and be purple.

18. Terms
An organism with two identical alleles for a character is homozygous for that character.
Organisms with two different alleles for a character are heterozygous for the character.
The physical representation of an organism’s traits is called its phenotype.
The genetic makeup of an organism is its genotype.
Two organisms can have the same phenotype but have different genotypes  one is homozygous dominant, the other is heterozygous.

20. Testcross
It is easy to tell the genotype of a recessive trait, but it is not easy to know exactly the genotype from a dominant phenotype.
Purple plants could be PP or Pp.
In order to figure out whether the organism is homozygous or heterozygous for that trait, a testcross is done.
The mystery individual is bred with a homozygous recessive individual.
If any of the offspring display the recessive phenotype, the mystery parent must be heterozygous.

22. Getting Crazy with Peas
Mendel’s first experiments followed only a single character (eg. flower color).
All F1 progeny produced in these crosses were monohybrids, heterozygous for one character.
A cross between two heterozygotes is a monohybrid cross.
Mendel identified the second law of inheritance by following two characters at the same time.
In one dihybrid cross Mendel studied the inheritance of seed color and seed shape.
The allele for yellow seeds (Y) is dominant while the allele for green seeds (y) is recessive.
The allele for round seeds (R ) is dominant while the allele for wrinkled seeds (r) is recessive.

24. One Hypothesis…
Mendel crossed true-breeding plants that had yellow, round seeds (YYRR) with true-breeding plants that had green, wrinkled seeds (yyrr).
One possibility is that the two characters are transmitted from parents to offspring as a package.
The Y and R alleles stay together, the y and r alleles stay together.
If this were the case, the F1 offspring would produce yellow, round seeds.
The F2 offspring would produce two phenotypes (yellow/round and green/wrinkled) in a 3:1 ratio, just like a monohybrid cross.
This was not consistent.

25. …And the Alternate
The two pairs of alleles segregate independently of each other.
The presence of a specific allele for one trait in a gamete has no impact on the presence of a specific allele for the second trait.
In the example, the F1 offspring would still produce yellow, round seeds.
However, when the F1s produce gametes, genes would be packaged into gametes with all possible allelic combinations.
Four classes of gametes (YR, Yr, yR, yr) would produced in equal amounts.

26. Sperm and Ova
Both the sperm and ova cells have four possible combinations, so together there would be 16 equally probable ways the alleles could combine in the F2 generation.
These combinations produce four distinct phenotypes in a 9:3:3:1 ratio.
If only one character is followed in the crosses, the 3:1 ratio is still apparent.
The independent assortment of each pair of alleles during gamete formation is now called Mendel’s Law of Independent Assortment.
This law only applies to genes located on different, non-homologous chromosomes.
Genes located near each other on the same chromosome tend to be inherited together and have move complex inheritance patterns.

27. 14.2 The Laws of Probability Govern Mendelian Inheritance.

28. Tossing Coins, Rolling Dice, Swapping Chromosomes
The probability scale ranges from 0 (never ever happening) to 1 (certain to happen).
Getting heads on normal coin is ½.
Getting a 3 on a normal 6-sided die is 1/6.
The outcome of the toss of a coin or the roll of a die have no impact on the outcome of the next toss or roll. The same goes for the distribution of the alleles.
Math rules apply to probability, and they apply to genetics.

29. Multiplication Rule
Determines the chance that two or more independent events will occur together.
The probability of each individual event is multiplied together.
Getting heads twice in a row: ½ * ½ = ¼
The probability a heterozygous pea plant (Pp) will self-fertilize to produce a white offspring (pp) = the chance a sperm with a white allele will fertilize and ovum with a white allele: ½ * ½ = ¼
Dihybrid crosses:
For a heterozygous parent (YyRr) the probability of producing a YR gamete is ½ * ½ = ¼
The probability that and F2 plant from heterozygous parents will have YYRR is 1/16: ¼ from YR ovum and ¼ from YR sperm.

31. Addition Rule
The probability of an event that can occur two or more different ways is the sum of separate probabilities of those ways.
Eg. Two ways F1 gametes can combine to form a heterozygote.
Dominant from the sperm, recessive from the ovum: ¼
Dominant from the ovum, recessive from the sperm: ¼
¼ + ¼ = ½

32. Combining the Two
The rules of multiplication and addition can be used to solve even more complex problems, like trihybrid crosses.
Determine the probability of an offspring having two recessive phenotypes for at least two of the three traits resulting from parents PpYyRr and Ppyyrr.
5 possible genotypes: ppyyRr, ppYyrr, Ppyyrr, PPyyrr, and ppyyrr.
Where do we start?
Start with just one option: ppyyRr
Calculate the probability of getting each gene combination (multiplication) and combine the probabilities (addition).
Try it.

33. Calculating ppyyRr Parents = PpYyRr x Ppyyrr
To get a ppyyRr offspring:
Prob of pp = ½ * ½ = ¼
Prob of yy = ½ *1 = ½
Prob of Rr = ½ * 1 = ½
Total prob of ppyyRr = ¼ * ½ * ½ = 1/16
For ppYyrr: ¼ * ½ * ½ = 1/16
For Ppyyrr: ½ * ½ * ½ = 1/8, or 2/16
For PPyyrr: ¼ * ½ * ½ = 1/16
For ppyyrr: ¼ * ½ * ½ = 1/16
Total chance of an offspring having at least two recessive traits is 1/16 + 1/16 + 2/16 + 1/16 + 1/16 = 6/16

34. Review: Gene Behavior
While we cannot predict with certainty the genotype or phenotype of any particular seed from the F2 generation of a dihybrid cross, we can predict the probability that it will have a specific genotype or phenotype.
Mendel’s experiments succeeded because he counted so many offspring, was able to discern the statistical nature of inheritance, and had a keen sense of the rules of chance.
Mendel’s laws of independent assortment and segregation explain heritable variation in terms of alternative forms of genes that are passed along according to simple rules of probability.
These laws apply to all diploid organisms that reproduce by sexual reproduction.

35. 14.3 Inheritance Patterns are Often More Complex Than Predicted by Simple Mendelian Genetics

36. Science Can’t Be Simple. That’s Just Silly.
Mendel was lucky: he chose a genetically simple system.
Each character was controlled by a single gene, and each gene only had two alleles with one completely dominant to the other.
The relationship between genotype and phenotype is rarely so simple.
Genes may not be completely dominant, they may have more than two alleles, or one gene may produce more than one phenotype.
Craziness!

37. Codominance
Two alleles affect the phenotype in separate, distinguishable ways.
Eg. Blood types
There are A, B, and AB blood phenotypes, based on the presence of two specific molecules on the surface of red blood cells.
Type O is separate and is normal Mendelian inheritance.
People with A have one protein while people with B have the other protein.
The AB phenotype is NOT intermediate between A and B because both are displayed.

39. Incomplete Dominance
The heterozygotes show a distinct intermediate phenotype not seen in homozygotes.
NOT BLENDING – the traits are particulate (separate).
There are three phenotypes, and the phenotypic and genotypic ratios from a heterozygous cross are identical: 1:2:1.
Eg. Snapdragons
A cross between a white and red flowered plants produces all pink F1 offspring.
In codominance, the F1 flowers would be red and white spotted.

40. Range of Effects
The effects of two alleles range from complete dominance of one allele, through incomplete dominance of either allele, to codominance of both alleles.
Alleles are simply variations in a gene’s nucleotide sequence, so when a dominant allele coexists with a recessive allele in a heterozygotes, they do not interact at all.
Eg. Round vs wrinkled pea seed shape
Wrinkled is recessive.
They accumulate monosaccharaides because they lack an enzyme that converts them to starch.
Excess water enters the seed due to the accumulation of monosaccharides.

41. Relationships
Dominance/recessiveness relationships depend on the level we examine the phenotype.
Eg. Tay-Sachs disease.
Individuals with Tay-Sachs lack a functioning enzyme to metabolize certain lipids, which accumulate in the brain. This harms the brain cells and eventually kills them.
A child has to be homozygous to have the disease.
Homozygotes with two normal alleles and heterozygotes are healthy.
The activity level of the lipid-metabolizing enzyme is reduced in heterozygotes  at the biochemical level, the alleles show incomplete dominance.
Heterozygotes produce equal numbers of normal and dysfunctional enzyme molecules. At the molecules level, the Tay-Sachs and functional alleles are codominant.

42. Polygenic Inheritance
Blood type is a common example for polygenic traits.
The ABO blood groups are determine by three alleles: IA, IB, and i.
The IA and IB alleles are dominant to the i allele.
The IA and IB alleles are codominant to each other.
Each individual carries two alleles  6 possible genotypes, 4 possible blood types.
IAIA or IAi are type A (type A carbohydrates on red blood cells).
IBIB or IBi are type B (type B carbohydrate on red blood cells).
IAIB are type AB (both carbohydrates).
ii are type O (neither carbohydrates).

43. Pleiotropic and Epistasis
Pleiotropic: genes that affect more than one phenotypic character by controlling more than one ‘unrelated’ pathways.
Eg. Sickle-cell diseases, albinism, PKU (phenylketonuria)
Epistasis: a gene at one locus alters the phenotypic expression of a gene at a second locus.
Eg. Coat color
The epistatic gene determines whether pigment will be deposited in hair or not.
Presence (C) is dominant to absence (c) of pigment.
The second gene determines whether the pigment to be deposited is black (B) or brown (b).
The black allele is dominant to the brown allele.
An individual that is cc is albino regardless of the genotype of the second gene.

45. Nature vs. Nurture Phenotype also depends on environment.
Tanning; leaves of different sizes/shapes/color; nutrition; experience; temperature in the womb/nest; personality traits.
Identical twins accumulate phenotypic differences as a result of their unique experiences  fingerprints!
This is a hotly debated argument.
The product of a genotype is not a rigidly defined phenotype, but a range of possibilities.
Sometimes, a genotype specifies a particular phenotype (blood type).
However a person’s red and white blood cell count varies with factors such as altitude, exercise, and infection.

46. 14.4 Many Human Traits Follow Mendelian Patterns of Inheritance

47. Peas vs. Humans
Peas are convenient subjects for genetic research  humans are NOT.
Generation time is too long, fecundity is too low, and breeding experiments are morally unacceptable.
Humans are still subject to the same rules governing inheritance as other organisms.
We’re not special.
New techniques in molecular biology have led to many breakthrough discoveries in the study of human genetics.

48. Pedigrees
Rather than manipulate mating patterns of people, geneticists analyze the results of matings that have already occurred.
In a pedigree analysis, information about the presence or absence of a particular phenotypic trait is collected from as many individuals in a family as possible.
We can use the normal Mendelian rules of multiplication and addition of probability to calculate the probability of specific phenotypes.

50. Human Disorders
Many genetic disorders are inherited as simple recessive traits.
They range from relatively mild (albinism) to life-threatening (cystic fibrosis).
The recessive behavior of the alleles causing these conditions occurs because the allele codes for a malfunctioning protein or for no protein at all.
Heterozygotes have a normal phenotype because one normal allele produces enough of the required protein.

51. More Human Disorders
A recessively inherited disorder shows up only in homozygous individuals who inherit a recessive allele from each parent.
Individuals who lack the disorder are either homozygous dominant or heterozygotes.
While heterozygotes may lack phenotypic effects, they are carriers who may transmit a recessive allele to their offspring.
Most people with recessive disorders are born carriers with normal phenotypes.
Two carriers have a ¼ chance of having a child with the disorder, ½ chance of having a child who is a carrier, and ¼ chance of having a child without a defective allele.

52. Distribution
Genetic disorders are not evenly distributed among all groups of humans.
Different genetic histories of the world’s people during times when populations were more geographically and genetically isolated.
Cystic fibrosis strikes one of every 2,500 whites of European descent.
1/25 people of European descent is a carrier.
The normal allele for this gene codes for a membrane protein that transports Cl- between cells.
Defective channels cause a buildup of mucus in many organs and causes poor absorption of nutrients, chronic bronchitis, and bacterial infections.

53. Distribution Tay-Sachs (lethal recessive)
Ashkenazic Jews: 1/3,600 births. This is 100x greater than the incidence among non-Jews or Mediterranean Jews.
Dysfunctional enzyme that fails to break down specific brain lipids.
Sickle-cell anemia (lethal recessive)
African descendents: 1/400.
Normally unlikely two carriers will meet, mate, and pass it on, but individuals that share a recent common ancestor are more likely to.
Malformed red blood cells  heterozygotes have natural immunity to malaria.
Achondroplasia (harmful dominant)
1/25,000.
Form of dwarfism, even heterozygotes are dwarf.
Huntington’s (lethal dominant)
1/10,000 in the US.
Degenerative disease of the nervous system. Late onset.
Tracked to the tip of chromosome 4 by pedigree analysis.

55. Technology
Preventative measures to simple Mendelian disorders are sometimes possible.
The risk that a child will have a lethal trait can be assessed before conception or during pregnancy (pedigrees).
Most hospitals have genetic counselors.

56. Hypothetical Couple
John and Carol want to have a child, but in both of their families a recessive lethal disorder and each lost a brother to the disease.
Their parents didn’t have it, but they must have been carriers (Aa * Aa).
John and Carol each have a 2/3 chance of being carriers and a 1/3 chance of being homozygous dominant.
The probability their first child will have the disease is 2/3 (John’s carrier) * 2/3 (Carol’s carrier) * ¼ (chance the offspring of two carriers is homozygous recessive) = 1/9.
If their first child has the disease, John and Carol are carriers.
The chance their next child with also have the disease is ¼.

57. The Rules
Mendel’s laws are simply the laws of probability applied to heredity.
Chance has no memory, so the genotype of one child has no affect on the genotype of the other children.
The chance that John and Carol’s first three children will have the disorder is ¼ * ¼ * ¼ = 1/64. If this happens, their fourth child still has a ¼ chance of having the disease.
Most children with recessive disorders are born to parents with a normal phenotype so the key to assessing risk is identifying whether prospective parents are carriers of the recessive trait  probability.

58. Options
Tests are available to determine in utero if a child has a particular disorder.
Amniocentesis can be used form the 14th-16th week of pregnancy.
Fetal cells extracted from amniotic fluid are cultured and karyotyped to identify some disorders.
Other disorders can be identified from chemical in the amniotic fluids.
Chorinic villus sampling (CVS) allows for faster karyotyping and can be performed earlier (8th-10th week).
Fetal tissue from the chorionic villi of the placenta is taken  no amniotic fluid.
Ultrasounds and fetoscopy.
Complications and fetal death in 1% of trials.
If a test comes back positive (accounting for false positives and false negatives), the parents can chose to either terminate the pregnancy or prepare to care for a child with a serious genetic condition.

59. Nerd Alert! http://safeshare.tv/w/wEtMuInJwV
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