NOTES: Ch 15 - Chromosomes, Sex Determination & Sex Linkage

1. NOTES: Ch 15 - Chromosomes, Sex Determination & Sex Linkage

2. Overview: Locating Genes on Chromosomes ● A century ago the relationship between genes and chromosomes was not obvious ● Today we can show that genes are located on chromosomes ● The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

3. The Chromosome Theory of Inheritance states that: ● Mendelian genes have specific loci (positions) on chromosomes ● It is the chromosomes that undergo segregation and independent assortment!

4. P Generation Yellow-round seeds (YYRR) Green-wrinkled seeds (yyrr) Meiosis Fertilization Gametes All F1 plants produce yellow-round seeds (YyRr) F1 Generation Meiosis LAW OF SEGREGATION LAW OF INDEPENDENT ASSORTMENT Two equally probable arrangements of chromosomes at metaphase I Anaphase I Metaphase II Gametes F2 Generation Fertilization among the F1 plants

5. Morgan’s Experimental Evidence: Scientific Inquiry ● The first solid evidence associating a specific gene with a a specific chromosome came from Thomas Hunt Morgan, an embryologist

6. Morgan’s Choice of Experimental Organism: Fruit Flies! ● Characteristics that make fruit flies a convenient organism for genetic studies: -They breed at a high rate -A generation can be bred every two weeks -They have only four pairs of chromosomes

8. ● Morgan noted WILD TYPE, or normal, phenotypes that were common in the fly populations ● Traits alternative to the wild type are called mutant phenotypes

10. Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair ● In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type) -The F1 generation all had red eyes -The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes ● Morgan determined that the white-eye mutant allele must be located on the X chromosome ● Morgan’s finding supported the chromosome theory of inheritance!

11. P Generation F1 Generation F2 Generation P Generation Ova (eggs) Sperm F1 Generation Ova (eggs) Sperm F2 Generation

12. Linkage & Gene Maps

13. The Big Question… ● It may be easy to see that genes located on DIFFERENT chromosomes assort independently but what about genes located on the SAME chromosome?

14. Thomas Morgan’s Research ● Morgan identified more than 50 genes on Drosophila’s 4 chromosomes. ● He discovered that many seemed to be “linked” together • They are almost always inherited together & only rarely become separated ● Grouped genes into 4 linkage groups

15. Hmmm... 4 chromosomes & 4 linkage groups

16. Morgan’s Conclusion: ● Each chromosome is actually a group of linked genes ● BUT Mendel’s principle of independent assortment still holds true ● It is the chromosomes that assort independently!! • Mendel missed this because 6 of the 7 traits he studied were on different chromosomes.

17. So… ● If 2 genes are found on the same chromosome are they linked forever? • NO!! ●CROSSING OVER during Meiosis can separate linked genes

18. Black body, vestigial wings (double mutant) Testcross parents Gray body, normal wings (F1 dihybrid) Replication of chromosomes Replication of chromosomes Meiosis I: Crossing over between b and vg loci produces new allele combinations. Meiosis I and II: No new allele combinations are produced. Meiosis II: Separation of chromatids produces recombinant gametes with the new allele combinations. Recombinant chromosomes Sperm Ova Gametes Ova Testcross offspring 965 Wild type (gray-normal) 944 Black- vestigial 206 Gray- vestigial 185 Black- normal Sperm Recombination frequency 391 recombinants =  100 = 17% 2,300 total offspring Parental-type offspring Recombinant offspring

19. Gene Maps ● Alfred Sturtevant was a graduate student working in Morgan’s lab part-time in 1911 ● He hypothesized that the farther apart 2 genes are on a chromosome the more likely they are to be separated by crossing-over ● The rate of at which linked genes are separated can be used to produce a “map” of distances between genes Alfred Sturtevant 1891-1970

21. Gene Maps ● This map shows the relative locations of each known gene on a chromosome

22. Linkage Maps ● A linkage map is a genetic map of a chromosome based on recombination frequencies ● Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency ● Map units indicate relative distance and order, not precise locations of genes

23. Recombination frequencies 9% 9.5% 17% vg b cn Chromosome

24. I IV X II Y III Mutant phenotypes Short aristae Vestigial wings Cinnabar eyes Brown eyes Black body 67.0 104.5 0 48.5 57.5 Gray body Long aristae (appendages on head) Red eyes Red eyes Normal wings Wild-type phenotypes

25. Sex-linked genes exhibit unique patterns of inheritance ● In humans and other animals, there is a chromosomal basis of sex determination

26. ● Human somatic cells contain 23 pairs of chromosomes -22 pairs of autosomes (same in males & females) -1 pair of sex chromosomes (XX or XY) -Females have 2 matching sex chromosomes: XX -Males are XY XX XY

27. Inheritance of Sex-Linked Genes ● The sex chromosomes have genes for many characters unrelated to sex ● A gene located on either sex chromosome is called a SEX-LINKED gene ● Sex-linked genes follow specific patterns of inheritance

28. Sperm Sperm Sperm Ova Ova Ova

29. ● Some disorders caused by recessive alleles on the X chromosome in humans: -Color blindness -Duchenne muscular dystrophy -Hemophilia

31. ● When a gene is located on the X chromosome, females receive 2 copies of the gene, and males receive only 1 copy • Example: Color-blindness (c) is recessive to normal vision (C), and it is located on the X chromosome; hemophilia

33. EXAMPLE PROBLEM: ● A female heterozygous for normal vision: (we say she has normal vision, but is a carrier of the colorblindness allele) ● A male who is colorblind: XC Xc Xc Y

34. What is the probability that: a) they will have a son who is colorblind? b) they will have a daughter who is colorblind? c) their first son will be colorblind? d) their first daughter will be carrier? XC Xc • 1/4 (25%) • 1/4 (25%) • 1/2 (50%) • 1/2 (50%) Xc Y Xc Xc XC Xc XC Y Xc Y

35. EXAMPLE PROBLEM: ● Hemophilia is a hereditary disease in which the blood clotting process if defective. Classic hemophilia results from an abnormal or missing clotting factor VIII; it is inherited as an X-linked recessive disorder (h). ● If a man without hemophilia and a woman who is a carrier of the hemophilia allele have children, what is the probability that… XH Y XH Xh x

36. what is the probability that: a) they will have a daughter with hemophilia? b) they will have a son with hemophilia? c) their first son will have hemophilia? d) their first daughter will be a carrier? XH Xh • 0/4 (0%) • 1/4 (25%) • 1/2 (50%) • 1/2 (50%) XH Y XH Xh XH XH XH Y Xh Y

37. Pedigree Charts

38. Queen Victoria’s Legacy in Royal Families of Europe

40. X-inactivation in Female Mammals ● In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development ● If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

41. Two cell populations in adult cat: Active X Early embryo: Orange fur X chromosomes Cell division and X chromosome inactivation Inactive X Inactive X Black fur Allele for orange fur Active X Allele for black fur

42. Tortoise-shell cats! (a.k.a. “Torties”) XBXb

43. So, what about the Y chromosome?

47. Alterations of chromosome number or structure cause some genetic disorders ● Large-scale chromosomal alterations often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders

48. Abnormal Chromosome Number ● In NONDISJUNCTION, pairs of homologous chromosomes do not separate normally during meiosis ● As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy

49. Meiosis I Nondisjunction Meiosis II Nondisjunction Gametes n + 1 n – 1 n n n + 1 n – 1 n + 1 n – 1 Number of chromosomes Nondisjunction of homologous chromosomes in meiosis I Nondisjunction of sister chromatids in meiosis I

50. ● Aneuploidy results from the fertilization of gametes in which nondisjunction occurred ● Offspring with this condition have an abnormal number of a particular chromosome