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Additional resources for [Article] Score tests of genetic association in the presence of linkage based on the additive genetic gamma frailty model
WT1 mutations and urogenital abnormalities WT1 has been identi¢ed as a gene mutated in Wilms’ tumour, an embryonic kidney tumour a¡ecting 1 in 10 000 children (Haber et al 1990, Gessler et al 1990). Soon after cloning it became clear that in addition to being a tumour suppressor, WT1 ful¢ls additional functions during development. Firstly, patients with heterozygous EARLY GONADAL DEVELOPMENT 25 FIG. 1. Structure of WT1 and its various isoforms. (A) Through a combination of alternative splicing (exon 5 and exon 9) RNA editing (exon 6) and three alternative translation start sites, as many as 24 di¡erent isoforms of WT1 can be produced.
It seems to be involved in fertility. Our own unpublished data suggest that mice with low levels of Wt1 expression in the adult testis are initially fertile and then become quite rapidly infertile. Sertoli cells are supporting cells, and they are important for getting the germ cells to develop into sperm. Lovell-Badge: What is the role of Wt1 in apoptosis? Schedl: Again, we don’t really know much about this. About 50 target genes have been identi¢ed in vitro using transfection assays of cells. But I don’t believe most of them.
Cell 74:679^691 Ladomery M 1997 Multifunctional proteins suggest connections between transcriptional and post-transcriptional processes. BioEssays 19:903^909 Laity JH, Dyson HJ, Wright PE 2000 Molecular basis for modulation of biological function by alternate splicing of the Wilms’ tumor suppressor protein. Proc Natl Acad Sci USA 97:11932^ 11935 Larsson SH, Charlieu JP, Miyagawa K et al 1995 Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing.