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Transcription mapping and comparative analysis of the distal mouse x chromosome


Abstract The distal short arm of the human X chromosome (Xp22.3) which includes the pseudoautosomal region, appears to be highly divergent from its alleged murine counterpart. Genes isolated from this region of the human X are either not conserved in mouse, or they show an autosomal location in the mouse genome. Most strikingly, the CLCN4 gene is X-linked in human and Mus spretus but maps to chromosome 7 in C57BL/6 laboratory mice. The high evolutionary divergence of this region in eutherian mammals may be in part due to the occurrence of obligatory crossing-over events in the pseudoautosomal region during male meiosis, which leads to a higher frequency of double strand breakage and repair and subsequently to a high mutation rate.
The region of the mouse X chromosome syntenic to human Xp22.3 is poorly characterised. We propose to construct a transcription map of this region, characterise the cloned genes, and subsequently identify any homologues of human genes through the comparison of protein sequences. We are particularly interested in isolating the murine homologue of the Kallmann syndrome gene (KAL) as this will aid colleagues at the host institute in their study of the role of the KAL protein in mammalian neuronal migration. Comparison of the mouse and human maps of this region, particularly around the pseudoautosomal boundaries, will provide valuable insights into eutherian sex chromosome evolution.

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Comitato Promotore Telethon
Via olgettina 58
20132 Milano

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