1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-1 Human Genetics Concepts and Applications Eighth Edition Powerpoint Lecture Outline Ricki Lewis Prepared by Dubear Kroening University of Wisconsin-Fox Valley

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-2 Chapter 6 Matters of Sex

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-3 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-4 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-5 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 heterogameticZW

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-6 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-7 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-8 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-9 Mutations that Disrupt Normal Sexual Development Figure 6.4

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-10 Table 6.1

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-11 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-12 Figure 6.6

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-14 X-linked Traits Possible genotypes X + Y  Hemizygous wild type male X m Y  Hemizygous mutant male X + X +  Homozyogus wild female X + X m  Heterozygous female carrier X m X m  Homozygous mutant female

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-15 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-16 X-linked Recessive Inheritance Ichthyosis Figure 6.7

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-17 Figure 6.8- Queen Victoria’s Family- Hemophilia

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-18 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-19 X-linked Dominant Inheritance: Congenital Generalized Hypertrichosis Figure 6.10

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-20 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-21 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-22 6-3 X Inactivation The XIST gene encodes an RNA that binds to and inactivates the X chromosome Inactivated X chromosome forms a Barr body Manifesting heterozygotes

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-23 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 Xchromosome 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-24 Figure 6.12

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-25 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-26 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-27 Cats Heterozygous for the Coat Color Gene- females Tortoiseshell Calico Brownish/black & yellow patches against a white (epistasis) background

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-28 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-29 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 men women m/m bald bald m/+ bald unaffected +/+ unaffected unaffected

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-30 Male pattern baldness- Adams family

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-31 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-32 Genomic Imprinting Figure 6.16

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-33 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-34 Imprinting and Human Disease Inherited paternally Prader-Willi syndrome Deletion on chromosome 15 reveals imprinting Inherited maternally Angelman syndrome Figure 6.17

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-35 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. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 6-36 Figure 6.18