Abstract:
:Meiotic crossovers in the human genome cluster into highly localized hotspots identifiable indirectly from patterns of DNA diversity and directly by high-resolution sperm typing. Little is known about factors that control hotspot activity and the apparently rapid turnover of hotspots during recent evolution. Clues can, however, be gained by characterizing variation in sperm crossover activity between men. Previous studies have identified single nucleotide polymorphisms within hotspots that appear to suppress crossover activity and which may be involved in hotspot attenuation/extinction. We now analyse a closely spaced pair of hotspots (MSTM1a, MSTM1b) on chromosome 1q42.3, the former being a candidate for a young hotspot that has failed to leave a significant mark on haplotype diversity. Extensive surveys of different men revealed substantial polymorphism in sperm crossover frequencies at both hotspots, but with very different patterns of variation. Hotspot MSTM1b was active in all men tested but with widely differing crossover frequencies. In contrast, MSTM1a was active in only a few men and appeared to be recombinationally inert in the remainder, providing the first example of presence/absence polymorphism of a human hotspot. Haplotype analysis around both hotspots identified active and suppressed men sharing identical haplotypes, establishing that these major variations in the presence/absence of a hotspot and in quantitative activity are not caused by local DNA sequence variation. These findings suggest a role for distal regulators or epigenetic factors in hotspot activity and provide the first direct evidence for the rapid evolution of recombination hotspots in humans.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Neumann R,Jeffreys AJdoi
10.1093/hmg/ddl063subject
Has Abstractpub_date
2006-05-01 00:00:00pages
1401-11issue
9eissn
0964-6906issn
1460-2083pii
ddl063journal_volume
15pub_type
杂志文章abstract::Loss-of-function mutations of the X-chromosome gene UPF3B cause male neurodevelopmental disorders (NDDs) via largely unknown mechanisms. We investigated initially by interrogating a novel synonymous UPF3B variant in a male with absent speech. In silico and functional studies using cell lines derived from this individu...
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pub_type: 杂志文章
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journal_title:Human molecular genetics
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