The Chromosomal Basis of Inheritance

1. The Chromosomal Basis of Inheritance

2. Review • Mendel used the scientific approach to identify the two laws of inheritance • Law of Segregation: the 2 alleles for a heritable character separate during gamete formation • Involves behavior of homologous chromosomes • Law of Independent Assortment: each pair of alleles separate independently of each other pair of alleles during gamete formation • Involves behavior of nonhomologous chromosomes

3. Review • The laws of probability govern Mendelian Inheritance • Instead of doing crazy big punnett squares to determine the probability that two traits will be inherited together, simply multiply the probability that one trait will be inherited with the probability that the second trait will be inherited

4. Review • Inheritance patterns are often more complex than predicted by simple Mendelian genetics • Codominance in heterozygotes both traits are expressed • Ex. red + white = red & white • Incomplete dominance  heterozygotes express a 3rd phenotype different from either homozygote • Ex. red + white = pink • Pleiotropy 1 gene affects multiple things • ex. Cystic fibrosis affects both lung function and nutrient absorption in intestines • Epistasis the expression of one gene affects the expression of another gene • Ex. Bombay blood type • Polygenic inheritance  height & skin color

5. Key Concepts • Mendelian inheritance has its physical basis in the behavior of chromosomes • Sex Linked genes exhibit unique patterns of inheritance • Linked genes tend to be inherited together because they are located near each other on the same chromosome • Alterations of chromosome number or structure cause some genetic disorders • Some inheritance patterns are exceptions to the standard chromosome theory

6. Time Line • 1866- Mendel's Paper • 1875- Mitosis worked out • 1890's- Meiosis worked out • 1902- Sutton, Boveriet. al. connect chromosomes to Meiosis. • 1907- Morgans “fly room” provides support for chromosomes as the hereditary material

7. Chromosome Theory of Inheritance • Developed in 1902 by Walter Sutton & Theodor Boveri • States: Genes have specific loci (locations) along chromosomes, and it is the chromosomes that undergo segregation and independent assortment, rather than the individual genes

9. Thomas Morgan Hunt • Chose to use fruit flies as a test organism in genetics. • Allowed the first tracing of traits to specific chromosomes

10. Drosophila melanogaster • Early test organism for genetic studies. • Reasons: • Small • Cheap to house and feed • Short generation time • Prolific breeders, (a single mating produces upwards of 200 offspring) • New generation can be bred every two weeks • Few chromosomes 3 pairs of autosomes & 1 pair of sex chromosomes

11. Thomas Hunt Morgan • Unlike peas, fruit flies did not come in many varieties, so Morgan spent over two years breeding them in what became known as “the fly room” in attempt to find one with an observable mutation • Eventually he found one variation, a single male fly born with white eyes instead of traditional red

12. New Vocab • Wild Type: the phenotype for a character most commonly observed in a population • Just because a trait is wild type does not mean it is dominant! For example, blue eyes is recessive but also the wild type for people of Dutch heritage • In fruit flies wild type is red eyes • Use a superscript + to identify a wild type trait • Mutant Phenotypes: traits that are alternatives to the wild type • In fruit flies white eyes

13. Genetic Symbols • Mendel - use of uppercase or lowercase letters. T = tall t = short • Morgan: symbol from the mutant phenotype. + = wild phenotype

14. Genetic Symbol Examples • Recessive mutation: • w = white eyes • w+ = red eyes • Dominant Mutation • Cy = Curly wings • Cy+ = Normal wings

15. What Did Morgan do With His Mutant? • Morgan crossed the white eye male with a normal red eye female. • The F1 offspring all had red eyes suggesting white eyes are Dominant / Recessive • What ratio would you expect the F2 generation to have?

16. Quiz Time! • Morgan expected the F2 to have a 3:1 ratio of red:white • He got this ratio, however, all of the white eyed flies were MALE. • Therefore, the eye color trait appeared to be linked to sex. • Do you think this eye color gene is on the X chromosome or the Y chromosome? Explain

17. Fruit Fly Chromosomes

18. Chromosomal Basis of Sex • Obviously the one we are most familiar is the XY system used by mammals • XX = girl • XY = boy • 3 other systems for gender determination • XO • ZW • Haplo-diploid

19. XO System for Gender Determination • Grasshoppers, cockroaches, other insects • Only 1 type ofs an sex chromosome, the X • XX = female • X = male • Gender is determined by whether the sperm has an X chromosome or not

20. ZW System for Gender Determination • Birds, fish, and some insects • Sex chromosome present in the egg and not the sperm determines the gender of the offspring • Sex chromosomes are designated Z & W • ZW = females • ZZ = males

21. Haplo-Diploid System for Gender Determination • There are no sex chromosomes in most species of bees & ants • Females develop from fertilized eggs and are thus diploid • Males develop from unfertilized eggs and are thus haploid • They don’t have daddys

22. Variations on the XY System for Gender Determination in Fruit Flies • Male fruit flies are XY BUT…. • Sex depends on the number of X chromosomes and the number of autosome sets • Sex is not determined only by the presence of a Y chromosome

23. Chromosomal Basis of Gender Determination in Humans • X chromosome - medium sized chromosome with a large number of traits. • Y chromosome - much smaller chromosome with only a few traits • The X and Y chromosomes are a homologous pair, but only for a small region at one tip.

24. G-Banding for a Human Female

25. G-Banding for a Human Male

26. Chromosomal Basis of Gender Determination in Humans • Anatomical signs of gender begin to develop about 2 months into gestation • Earlier then 2 months the gonads are generic and can turn into either ovaries or testes • In 1990 a British research team identified a a gene on the Y chromosome required for development of testes • Named this region SRY • Sex Determining Region of the Y chromosome

27. SRY • In the absence of SRY, the gonads develop into ovaries • SRY codes for a protein that regulates other genes involved in the development of sex characteristics • Critical Thinking: What do you think would be the outcome of an embryo conceived from the fusion of a normal egg with a sperm containing a Y chromosome with a mutated SRY gene?

28. The Human Y Chromosome • Contains about 75 genes • Codes for 25 proteins • Some genes redundant • About half of the genes expressed in the testes only • In the absence of any of these genes an XY individual is typically male but not able to produce sperm • Many of the genes are necessary for normal testicular function

29. Back to Morgans Discoveries • There are many genes, but only a few chromosomes. • Therefore, each chromosome must carry a number of genes together as a “package”.

30. Linked Genes • Traits that are located on the same chromosome, and so tend to be inherited together • Result: • Failure of Mendel's Law of Independent Assortment. • Ratios mimic monohybrid crosses.

31. Example of Linked Genes in Fruit Flies • Body Color (b) & wings (vg) • Body Color • b+ = gray body • b = black body • Wings • vg + = normal wings • vg = vestigial wings (too small, not functional)

32. Test Cross b+bvg+vg X bb vgvg (b+ linked to vg+) (b linked to vg) If unlinked: 1:1:1:1 ratio If linked: ratio will be altered

34. Linked genes • All genes found on the same chromosome are said to be linked • If genes on the same chromosome are 100% linked, you would only produce the parental phenotype for that chromosome, and as you can see in the previous picture, that is not the case

35. Genetic Recombination • The production of offspring with combinations of traits that differ from those found in either parent • 2 Types of Genetic Recombination • Recombination of unlinked genes due to independent assortment • Recombination of linked genes due to crossing over

36. Recombination of unlinked genes due to independent assortment • Offspring that resemble one of the two parents phenotypically are called parental types • non-parental phenotypes in offspring re called recombinant types or recombinant

37. Example • If you cross a heterozygous pea plant for seed color and shape with a homozygous pea plant for seed color and shape, what will the F1 generation look like? • 1st figure out your parental genotypes

38. Example • If you cross a heterozygous pea plant for seed color and shape with a homozygous pea plant for seed color and shape, what will the F1 generation look like? • Now figure out your possible gamete genotypes

39. Example • If you cross a heterozygous pea plant for seed color and shape with a homozygous pea plant for seed color and shape, what will the F1 generation look like? • Now fill it in & count

40. Example • Your two parental phenotypes were • YyRr X yyrr • What % of the offspring are YyRr____ • What % of the offspring are yyrr____ • So what % have a parental genotype?________

41. Frequency of Recombination • When 50% of the offspring are recombinants, genetecists say there is a 50% frequency of recombination • When there is a 50% frequency of recombination, it indicates that the two genes are located on different chromosomes and are thus unlinked • The physical basis of recombination between unlinked genes is the random orientation of homologous chromosomes at metaphase, which leads to independent assortment

42. Recombination of linked genes due to crossing over • The occurrence of parental phenotypes with a frequency greater then 50% indicates the genes are linked, and thus on the same chromosome • Crossing over accounts for the recombination of linked genes • Crossing over is when portions of nonsister chromatids exchange portions of DNA • Recombinant chromosomes resulting from crossing over may result in new combinations of alleles

43. Recombination of linked genes due to crossing over

44. Gene Linkage If genes are linked Linkage Strength Degree of strength related to how close the traits are on the chromosome. Weak - farther apart Strong - closer together • Independent Assortment of traits fails. • Linkage may be “strong” or “weak”.

45. Mapping the Distance Between Genes using Recombination Data • Sturtevant, a student of Morgan, developed a method to construct a genetic map • Genetic map: an ordered list of genetic loci along a chromosome • Constructed from crossing-over frequencies. • 1 map unit = 1% recombination frequency.

46. Sturtevants Hypothesis • The farther apart 2 genes are, the higher the probability that a crossover will occur between them, and there • Common Sense: the greater the distance between two genes, the more locations there are that crossing over can occur • Linkage Map: genetic map based on recombination frequencies • Distance between genes expressed in map units

47. Gene Maps Gene Linkage Maps Cytogenetic Maps Locate genes with respect to chromosomal features such as stained bands which can be seen under a microscope • Map units do NOT correspond to actual physical distances • Linkage maps DO portray the order or sequence of genes on a chromosome

48. Gene Mapping

50. Inheritance of Sex Linked Genes • Sex chromosomes, especially the X chromosome have genes for characteristics unrelated to sex • A gene located on either sex chromosome is called a sex-linked gene • In humans the term sex linked gene (a.k.a. sex linked trait) historically has specifically referred to a gene on the X chromosomes • Not to be confused with gene linkage in general!