tailieunhanh - Báo cáo y học: " Detecting sequence polymorphisms associated with meiotic recombination hotspots in the human genome"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Detecting sequence polymorphisms associated with meiotic recombination hotspots in the human genome. | Zheng et al. Genome Biology 2010 11 R103 http 2010 11 10 R103 Genome Biology RESEARCH Open Access Detecting sequence polymorphisms associated with meiotic recombination hotspots in the human genome Jie Zheng1 Pavel P Khil2 R Daniel Camerini-Otero2 Teresa M Przytycka1 Abstract Background Meiotic recombination events tend to cluster into narrow spans of a few kilobases long called recombination hotspots. Such hotspots are not conserved between human and chimpanzee and vary between different human ethnic groups. At the same time recombination hotspots are heritable. Previous studies showed instances where differences in recombination rate could be associated with sequence polymorphisms. Results In this work we developed a novel computational approach LDsplit to perform a large-scale association study of recombination hotspots with genetic polymorphisms. LDsplit was able to correctly predict the association between the FG11 SNP and the DNA2 hotspot observed by sperm typing. Extensive simulation demonstrated the accuracy of LDsplit under various conditions. Applying LDsplit to human chromosome 6 we found that for a significant fraction of hotspots there is an association between variations in intensity of historical recombination and sequence polymorphisms. From flanking regions of the SNPs output by LDsplit we identified a conserved 11-mer motif GGNGGNAGGGG whose complement partially matches 13-mer CCNCCNTNNCCNC a critical motif for the regulation of recombination hotspots. Conclusions Our result suggests that computational approaches based on historical recombination events are likely to be more powerful than previously anticipated. The putative associations we identified may be a promising step toward uncovering the mechanisms of recombination hotspots. Background Meiotic recombination is an important cellular process. Errors in meiotic recombination can result in chromosomal abnormalities that underlie diseases and aneuploidy 1 2 . A main driving .