1. Sex determination Jonathan Wolfe http://www.ucl.ac.uk/~ucbhjow

2. Objectives At the end of this lecture you should: know in outline the developmental steps in human sex determination be able to describe the evolution of the mammalian Y chromosome and the SRY gene. be able to describe the roles of the genes SRY, DAX1, and SOX9. Be able to describe the genes involved in sex determination in Drosophila Be able to describe the gene DMRT1 and its relatives

3. Reading http://www.hgmp.mrc.ac.uk/omim/searchomim.html Search here for any of the genes mentioned. Goodfellow, P. N.; Lovell-Badge, R. 1993: SRY and sex determination in mammals. Ann. Rev. Genet. 27 71-92 Koopman, P.; Gubbay, J.; Vivian, N.; Goodfellow, P.; Lovell-Badge, R. 1991: Male development of chromosomally female mice transgenic for Sry. Nature 351 117-121. Wunderle, V. M.; et al. 1998: Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia. Proc. Nat. Acad. Sci. 95: 10649-10654. Jennifer A. Marshall Graves 2002: The rise and fall of SRY Trends in Genetics 18: 259- 264 David Zarkower 2001 Establishing sexual dimorphism: conservation amidst diversity? Nature Reviews Genetics 2 175-185 Peter Koopman and Kelly A. Loffler, 2003, Sex Determination: The Fishy Tale of Dmrt1 Current Biology, 13: R177 - R179 Haag ES, Doty AV (2005) Sex Determination across Evolution: Connecting the Dots. PLoS Biol 3(1): e21

4. Comparison between Drosophila and Humans karyotypeDrosophilaHuman 2A XXfemale 2A XYmale 2A XOmalefemale 2A XXXfemale 2A XXYfemalemale

7. Gonadal differentiation

9. Y chromosomal genes

10. Genomic structure of SRY genes

11. Evolution of the Y chromosome and SRY

12. The loss of Y chromosomal genes

13. Sex determination in Drosophila

14. Another human gene

15. DMRT1 expression

16. Chicken Z = Human chr.9

17. DMRT1 expression in alligator