Journal article
Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9
B Croft, T Ohnesorg, J Hewitt, J Bowles, A Quinn, J Tan, V Corbin, E Pelosi, J van den Bergen, R Sreenivasan, I Knarston, G Robevska, DC Vu, J Hutson, V Harley, K Ayers, P Koopman, A Sinclair
Nature Communications | NATURE PUBLISHING GROUP | Published : 2018
Abstract
Disorders of sex development (DSDs) are conditions affecting development of the gonads or genitalia. Variants in two key genes, SRY and its target SOX9, are an established cause of 46,XY DSD, but the genetic basis of many DSDs remains unknown. SRY-mediated SOX9 upregulation in the early gonad is crucial for testis development, yet the regulatory elements underlying this have not been identified in humans. Here, we identified four DSD patients with overlapping duplications or deletions upstream of SOX9. Bioinformatic analysis identified three putative enhancers for SOX9 that responded to different combinations of testis-specific regulators. All three enhancers showed synergistic activity and ..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by a National Health and Medical Research Council (NHMRC) Program grant 1074258 to AS, PK, VH and an NHMRC Project grant 1031214 to A.S., T.O.. ARC grants DP150102120 and DP160104948 to P.K. B.C. was supported by an Australian Government Research Training Program Scholarship. R.S. was supported by NHMRC Early Career Fellowship No. 1126995. NHMRC Fellowships supported A.S. (1062854), P.K. (1059006) and V.H. (1020034). Thanks to Dan Belluoccio for assistance with design and analysis of the custom CGH-array and the Victorian Government's Operational Infrastructure Support Program.