Human Genetics

1. Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

2. Chapter 6 Matters of Sex

3. Sexual Development • In early embryos unspecialized gonads and two sets of reproductive ducts exist until week 6 • An embryo develops as a male or female using information from the Y chromosome Figure 6.1

4. Male or Female? • Gender is ultimately a genetic phenomenon • It also has psychological and sociological components • Males have 22 pairs of autosomes and X and Y chromosomes • Females have 22 pairs of autosomes and two X chromosomes

5. Sex Chromosomes Determine Gender • Human males are the heterogametic sex with different sex chromosomes, (XY) • Human females are the homogametic sex (XX) • In other species sex can be determined in many ways For example, in birds and snakes • males are homogametic ZZ • females are heterogametic ZW

6. X and Y Chromosomes • X chromosome • contains more than 1,500 genes • larger than the Y chromosome • acts as a homolog to Y chromosome in males • Y chromosome • contains 231 genes • many DNA segments are palindromes and may destabilize DNA Figure 6.2

7. Genes on the Y Chromosome Genes shared with X chromosome define the pseudoautosomal regions (PAR1 and PAR2) • Male specific (MSY) including SRY gene • SRY gene is important in determining sex Figure 6.3

8. SRY Gene • Encodes a transcription factor protein • Controls the expression of other genes • Stimulates male development • Developing testes secrete anti-Mullerian hormone and destroy female structures • Testosterone and DHT are secreted and stimulate male structures

9. Mutations that Disrupt Normal Sexual Development Figure 6.4

10. Table 6.1

11. Sex ratios • Mendel’s laws predict an equal number of males and females • Calculated by # of males / # of females x 1,000 • Primary sex ratio – conceptions • Secondary – births • Bias in China and India • Changes with age

12. Figure 6.6

13. Y-linked Traits • Genes on the Y chromosome • Very rare • Transmitted male to male • No affected females • Currently, identified Y-linked traits involve infertility and are not transmitted

14. Possible genotypes X+Y  Hemizygouswild type male XmY Hemizygous mutant male X+X+ Homozyogus wild female X+Xm Heterozygous female carrier XmXm Homozygous mutant female X-linked Traits

15. X-linked Recessive Traits • Always expressed in hemizygous males • Female homozygotes show the trait but female heterozygotes do not • Affected males: Inherited from affected or heterozygous mother • Affected females: affected fathers and affected or heterozygous mothers

16. X-linked Recessive InheritanceIchthyosis Figure 6.7

17. Figure 6.8- Queen Victoria’s Family- Hemophilia

18. X-linked Dominant Inheritance • Expressed with one copy • Males are often more severely affected • Typically associated with miscarriage or lethality in males • Passed from father to all his daughters but none of his sons

19. X-linked Dominant Inheritance: Congenital Generalized Hypertrichosis Figure 6.10

20. Genetics Problems • Look at inheritance pattern • Draw pedigree • List genotypes and phenotypes and their probabilities • Assign genotypes and phenotypes • Determine alleles into gametes • Punnett square – ratios • Repeat for next generation

21. Homosexuality • Same genotype and phenotype • Physical attraction to same sex. • Homosexuality-all cultures,thousands of years • Found in > 500 animal species. • Evidence may suggest a genetic component • Twin/sibling studies- more likely in identical twins. • Brain areas different in homosexual men. • Hamer 1993- Identifying possible markers • studied 40 pairs of homosexual brothers • 5 identical genetic markers on the X chromosome found in 33 of the pairs. • Markers not found in heterosexual brothers. • Research in this area is controversial- • No gene identified. • Altered gene expression in male Drosophila • Mutant white gene expressed in all cells caused decreased serotonin levels and homosexual behavior

22. 6-3 X Inactivation • The XIST gene encodes an RNAthat binds to andinactivates the X chromosome • Inactivated X chromosome forms a Barr body • Manifesting heterozygotes

23. 6.3 - X Inactivation • Females have two alleles for X chromosome genes but males have only one • In mammals, X inactivation balances this inequality. • Early in embryonic development one X chromosome is randomly inactivated in each cell. • Which X chromosome is inactivated is random. • Some cells express the father’s X chromosome genes, some cells express the mother’s X chromosome genes. • Results in mosiac expression.

24. Figure 6.12

25. Specific region on X chromosome • X inactivation center. • XIST gene- controls inactivation process. • XIST gene encodes an RNA that binds to a specific site on the same chromosome inactivating the X chromosome. • All daughter cells will have inactivated X chromosomes. • Adult females- patches of tissue- phenotypically different in X-linked gene expression. • Genotype not altered. • Inactivation is reversed in germline cells that become oocytes. • Inactivated X chromosome- visualized in interphase as a dark staining Barr body. ( absorbs stain faster due to methyl groups on DNA) • No Barr bodies found in males.

26. Heterozygotes and X Inactivation • Homozygous X-linked genotypes-X inactivation-no effect. • Heterozygous- X inactivation-has an effect. • Expression of 1 allele or the other. • Not usually a health problem- enough cells produce gene product. • Examples • incontinentia pigmenti-swirls of skin color- melanin • Anhidrotic ectodermal dysplasia- patches lacking sweat glands and hair. • Manifesting heterozygote- X linked carrier who expresses the phenotype. • Rarely observed in humans.

27. Cats Heterozygous for the Coat Color Gene- females Tortoiseshell Calico Brownish/black & yellow patches against a white (epistasis) background

28. 6.4- Gender Effects on Phenotype Sex-limited Traits: • Traits that affect a structure or function in only one sex. • May be autosomal or X linked • Affects one sex; genes transmitted by both Examples: • Beard growth-hormones • Breast size • Milk production and horn development –cattle • Preeclampsia- elevated blood pressure. • Sperm production levels

29. Sex-influenced Traits: • Traits in which the phenotype expressed by a heterozygote is influenced by gender. • Allele appears dominant in one gender and recessive in the other Example: • Pattern baldness is a sex-influenced trait: • dominant in men- BB or Bb • Recessive in females bb menwomen m/m bald bald m/+ bald unaffected +/+ unaffected unaffected

30. Male pattern baldness- Adams family

31. Genomic Imprinting • 1% of our genes exhibit • “parent of origin” effect –silencing expression from one parent • Function unknown, may play a role in development • Genes silenced by an epigenetic event, DNA methylation • Imprints maintained in mitotic divisions but lost in meiosis

32. Genomic Imprinting Figure 6.16

33. Importance of Genomic Imprinting • Experiments suggest that it takes two opposite sex parents to produce a healthy embryo • Genes from female parent direct embryo development, • Genes from the male parent-placental development. • May explain incomplete penetrance- • polydactyl- silencing of mutant allele.

34. Imprinting and Human Disease Deletion on chromosome 15 reveals imprinting Figure 6.17 • Inherited paternally • Prader-Willi syndrome • Inherited maternally • Angelmansyndrome

35. Callipyge (“beautiful buttock”) Sheep Is Caused by Genomic Imprinting • Over-muscled hindquarters • Autosomal dominant • Trait only passed if it came from the father and the female may not carry the trait • Seven other genes are overexpessed on chromosome 18

36. Figure 6.18