Sex determination
Jonathan Wolfe
http://www.ucl.ac.uk/~ucbhjow
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
Reading
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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: 259264
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
Comparison between Drosophila and Humans
karyotype
2A XX
Drosophila
female
Human
female
2A XY
2A XO
2A XXX
male
male
female
male
female
female
2A XXY
female
male
Gonadal differentiation
Y chromosomal genes
Genomic structure of SRY genes
Evolution of the Y chromosome and SRY
The loss of Y chromosomal genes
Sex determination in Drosophila
Another human gene
DMRT1 expression
Chicken Z = Human chr.9
DMRT1 expression in alligator