Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes.
We carried out a resequencing project that examined 552 kb of sequence from each of 46 individual HLA haplotypes representing a diversity of HLA allele types, generating nearly 27 Mb of fully phased genomic sequence. Haplotype blocks were defined extending from telomeric of HLA-F to centromeric of HLA-DP including in total 5186 MHC SNPs. To investigate basic questions about the evolutionary origin of common HLA haplotypes, and to obtain an estimate of rare variation in the MHC, we similarly examined two additional sets of samples. In 19 independent HLA-A1, B8, DR3 chromosomes, the most common HLA haplotype in Northern European Caucasians, variation was found at 11 SNP positions in the 3600-kb region from HLA-A to DR. Partial resequencing of 282 individuals in the gene-dense class III region identified significant variability beyond what could have been detected by linkage to common SNPs.
Smith
Wade P
WP
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA.
Vu
Quyen
Q
Li
Shuying Sue
SS
Hansen
John A
JA
Zhao
Lue Ping
LP
Geraghty
Daniel E
DE
D002461:Cell Line, Transformed; D017124:Conserved Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D006680:HLA Antigens / Q000235:genetics*; D015788:HLA-A1 Antigen / Q000235:genetics; D015795:HLA-B8 Antigen / Q000235:genetics; D015803:HLA-DR3 Antigen / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics*; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D006680:HLA Antigens; D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen