1. The X and Y Chromosomes

2. From a comparison of the genes on the X and Y chromosomes, we can infer that, even though the X is now much larger than the Y, 300 million years ago they were essentially identical.

3. --X and Y pair in meiosis and have crossing over in PARs There are 19 known X/Y gene pairs in man (these are pseudo autosomal genes). They are grouped in the X in four groups of differing ages due to a series of inversions that occurred on the Y during the past 300+ million years of mammalian evolution.

4. PAR: PAR: pseudo-autosomal regions on tips of X and Y: homologous, contain some genes. PAR1 has a required cross over for successful sperm development.

5. X: very similar to autosomes; many genes, mostly un-related to sex. X is more evolutionarily conserved than autosomes: genes on X in one species usually on X in others, although often rearranged by inversions

6. X-inactivation: X-inactivation: Lyon hypothesis: placental mammals randomly inactivate all but 1 X at the 200- 400 cell embryo stage (blastocyst).

7. The inactivated X's become Barr bodies: late-replicating condensed chromatin sitting on the nuclear membrane (heterochromatin). Seen in XXY, XXX, etc.

8. Each cell inactivates one X at random. Descendant cells keep same X inactive. Mosaics: example Mosaics: example glucose 6- phosphate dehydrogenase mosaics: 2 alleles, only 1 active in each cell.

9. Mechanism of inactivation: Mechanism of inactivation: XIC (X inactivation center) first seen as a spot where the inactive X first folds after mitosis in Xq13.

10. XIST XIST is a gene in the XIC region which is expressed only from the INACTIVE X. It has 8 exons, but it codes for structural RNA (not mRNA).

11. XIST XIST encodes a large molecule of RNA Barr bodies are inactive X chromosomes "painted" with XIST RNA.

12. Some genes on X are not inactivated. Genes in pseudo-autosomal regions PAR1 and PAR2. XIST XIST, active only on the Inactive X.

13. Y-chromosome --mostly inert, very few genes, mostly repeat sequence DNA (high and middle).

14. Origin of Y: started out as normal chromosome with many genes. But, without crossing over, mutations built up and inactivated most genes (Muller's ratchet).

15. -HY antigen: cell surface antigen marking male cells only: gene on Y.

16. Sex Chromosome Aneuploidies nondisjunctions

17. HUMAN TRISOMY Except for the sex chromosomes, only three trisomies are compatible with life.

18. PATAU PATAU syndrome = trisomy 13 - facial defects, polydactyly, heart defects, die within a few months of birth EDWARDS EDWARDS syndrome = trisomy 18 - small + muliple defects, usually die in first year of life DOWN DOWN syndrome = trisomy 21

19. Most fetuses with abnormal chromosome complements spontaneously abort, accounting for 20% to 50% of all miscarriages. The most common cause of miscarriage is X0.

21. Klinefelter’s syndrome 47, XXY (Klinefelter’s syndrome) extra X chromosomes predispose to azoo and female phenotype development (micropenis, etc.), mental retardation, disproportionate growth of the legs, and other somatic anomalies, with estimated incidence of 1:500 in newborns. X chromosome polyploidy

22. Klinefelter patients may occasionally demonstrate motile sperms in the ejaculate which is speculated to be due to a mosaic 46, XY cell line.

23. Turner’s Syndrome XO 1/2500 live births Female, but sterile, often no breast development, short stature, some distinctive physical features ("webbed neck"). Generally normal intelligence.

24. Estimated incidence is 1:750 newborns, may be fertile with frequent miscarriage of their wives, perinatal death and chromosomal anomalies of their children. Y chromosome polyploidy:

25. There are men who appear to be normal men, but have an XX chromosomal combination (about 1 out of every 20,000 males), and women who appear to be normal women but have the XY combination.

26. In every Olympics since sex testing was initiated, several women have been disqualified because they were identified as XY.

27. Deletion mapping of the gene for the testis- determining factor(s) in humans

28. Subtractive hybridization Deletion mapping

29. In 1990, Sinclair and colleagues narrowed the region to a 35,000 base-pair domain of the small arm of the Y chromosome. http://zygote.swarthmore.edu/sex2.html

30. SRY includes a single exon that acts as a transcription factor…..a protein product recognizes and binds specifically to the DNA sequence: AACAAT

31. Four siblings with testicular feminization syndrome. All four subjects in this photograph have 44 autosomes plus an X and a Y, (so they are genotypically MALES (!)) but they have inherited the recessive sex-linked allele conferring insensitivity to androgens (male hormones). http://www.cbs.dtu.dk/dave/roanoke/bio101ch15.htm