Author:
Stewart C. Andrew,Horton Roger,Allcock Richard J.N.,Ashurst Jennifer L.,Atrazhev Alexey M.,Coggill Penny,Dunham Ian,Forbes Simon,Halls Karen,Howson Joanna M.M.,Humphray Sean J.,Hunt Sarah,Mungall Andrew J.,Osoegawa Kazutoyo,Palmer Sophie,Roberts Anne N.,Rogers Jane,Sims Sarah,Wang Yu,Wilming Laurens G.,Elliott John F.,de Jong Pieter J.,Sawcer Stephen,Todd John A.,Trowsdale John,Beck Stephan
Abstract
The future systematic mapping of variants that confer susceptibility to common diseases requires the construction of a fully informative polymorphism map. Ideally, every base pair of the genome would be sequenced in many individuals. Here, we report 4.75 Mb of contiguous sequence for each of two common haplotypes of the major histocompatibility complex (MHC), to which susceptibility to >100 diseases has been mapped. The autoimmune disease-associated-haplotypes HLA-A3-B7-Cw7-DR15 and HLA-A1-B8-Cw7-DR3 were sequenced in their entirety through a bacterial artificial chromosome (BAC) cloning strategy using the consanguineous cell lines PGF and COX, respectively. The two sequences were annotated to encompass all described splice variants of expressed genes. We defined the complete variation content of the two haplotypes, revealing >18,000 variations between them. Average SNP densities ranged from less than one SNP per kilobase to >60. Acquisition of complete and accurate sequence data over polymorphic regions such as the MHC from large-insert cloned DNA provides a definitive resource for the construction of informative genetic maps, and avoids the limitation of chromosome regions that are refractory to PCR amplification.
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics(clinical),Genetics
Cited by
253 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献