1. Influence of Sex on Genetics Chapter Six

2. Humans 23 Autosomes –Chromosomal abnormalities very severe –Often fatal All have at least one X –Deletion of X chromosome is fatal Males = heterogametic sex –XY Females = homogametic sex –XX

3. Sex Chromosomes Y chromosome: –Contains ~90 genes –Majority of genes = Male Specific Region (MSR) –SRY gene – determines “maleness” X chromosome: –Contains ~1500 genes –Some dealing with sexual development –Most genes encoding proteins that have nothing to do with sex

4. Y Chromosome

5. SRY Gene SRY = Sex-determining Region of Y A transcription factor (TF) –TF’s are genes that control the expression of other genes (turn on/off) SRY turns on “male” genes “Male” genes activate male hormones Male hormones (testosterone) end up producing male structures Also, destroy female structures

6. Sex Chromosomal Abnormalities XX – males –Will be carrying a small piece of Y (crossing over) that contains the SRY gene XY – females –Deletion of SRY region XO – Turner Syndrome –Females; short, sterile, lack of female features XXY – Klinefelter Syndrome –Males; feminization, infertility

7. XY Females Much more common than XX males 1.Y has a deletion removing SRY gene 2.Genes that SRY gene activates are deleted/not responding 3.Genes encoding hormones are deleted/not responding 4.Structures do not respond to hormones Lacking receptors

8. Genetics of Homosexuality How genetic is any trait? Examine sharing trait between relatives who also share genes: MZ vs. DZ twins –Concordance rate Siblings/relatives of individual with trait vs. general population –Trait Prevalence Transgenic Animal Models

9. Genetics of Homosexuality Examine sharing trait between relatives who also share genes: Concordance rate: 52 % MZ vs. 20% DZ twins Trait Prevalence: 9-15% siblings vs. 2-5% general population Animal Models: Fruit flies and honey bees

10. For Comparison: Autism: –90% MZ concordance vs. 2% DZ –Relative risk is 50-100 times greater than general population risk –Heritability = ~ 90% Depression: –46% MZ vs. 20% DZ –Relative risk is ~ 9 times general population –Heritability = ~ 50%

11. Autosomal Disorders: Both Males and Females affected, and both transmit to both sexes of offspring Recessive – usually rare in population –Skips Generations –Inbreeding increases risk of recessive traits Dominant –Doesn’t skip generations

12. Y-Linked Disorders Rare because there are only a few genes Always inherited from father to son only Most common “disorder”? –Maleness

13. X-Linked Recessive Gene on X chromosome is carrying trait Recessive –More males are affected –Passed from affected mothers to all sons –Affected fathers will only transmit to heterozygous, unaffected daughters –Very rare to see homozygous recessive females

14. X-Linked Dominant Gene on X chromosome is carrying trait Dominant –Males and females both affected –Can be passed to both offspring, however often see more females affected because of male lethality –Affected fathers to every single daughter

15. Mitochondrial Disorders Not to be confused with X-linked disorders, but they do show a “sex” difference Affected mothers pass disorder onto every single child Affected fathers NEVER pass disorder on

16. X-Linked Recessive

17. X-Linked Dominant

18. Mitochondrial

19. X-Inactivation In order for females to not have 1,500 more genes than males have, mammals undergo X-inactivation Early in development One X randomly inactivated in each cell Every cell derived from that 1 st cell has same identical X inactivated Therefore females are “mosaics”

20. X-Inactivation

21. Calico Cats Cat coat color is on X chromosome Alleles: –Tabby (stripes) and white –Black and white –Orange/Red and white –White (actually a recessive trait that lacks any other colors) Additional genes will control amount, positions of colors, and “pointing” (Siamese)

22. Calico Cats Male cats have one X (inherited from their mothers) and so can only have two colors at most Female cats have two X’s and so can have three colors at most –Because of X-inactivation ends showing “patches” of colors –Calico or Tortoiseshell

23. Traits with “sex differences” 1.X-linked genes Already covered 2.Sex limited traits Affect a trait/phenotype that is only present in one sex 3.Sex influenced traits Differences in hormones affect gene 4.Imprinted genes Depends on the parent of origin

24. Sex Limited Traits Genes are inherited from both parents Either autosomal or X chromosome Yet, affect a structure that is only present in one sex, therefore phenotype shows a sex “difference” –Horns –Milk production –Genitalia anatomy/function

25. Sex Influenced Traits Genes are inherited from both parents Either autosomal or X chromosome Yet the affect of differences in sex hormones causes differences in phenotype –Male pattern baldness Often dominant in one sex, and recessive in the other

26. Genetic Imprinting When parent of origin for a gene affects the expression/phenotype of that gene Specific genes are silenced in either the mother’s or father’s chromosomes If an individual receives a silenced gene the individual will not express that allele of the gene Effectively end up hemizygous (only one copy rather than two)

27. Genetic Imprinting Imprinted gene = silenced gene Silencing occurs by an epigenetic process Epigenetic = altering genetics Process = methylation of the gene –Adding Methyl groups to the DNA structure –Does NOT change DNA sequence Silences one allele, therefore individual only shows phenotype of other allele –Hemizygous

28. Effect of Imprinting Imagine a case where an imprinted gene has a dominant mutation in the mother, but completely normal in the father: What if child inherits mother’s version and father’s version is silenced? –Child shows phenotype What if child inherits father’s version and mother’s version is silenced… –Child has normal phenotype What if gene was not imprinted?

29. Human Imprinting Humans carry an “imprinting cluster” on chromosome 15q11-13 If child inherits mutated father’s 15q: –Prader-Willi Syndrome If child inherits mutated mother’s 15q: –Angelman Syndrome Because other allele of 15q is imprinted child cannot hide these normally recessive mutations

30. About Imprinting This is a normal process in mammalian embryos Function is not exactly known Theories are: –Used for exact timing/regulation of development –Arose in evolution of multi-fathered litters Only with mutations do you see “detrimental” effects of imprinting

31. Next Class: Read Chapter Seven Homework – Chapter Six Problems; –Review: 1,3,6,7,8,9,10 –Applied:1,4,5,8,910,12