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PubMed · 16632595

Long-range multilocus haplotype phasing of the MHC.

Zhen Guo·Leroy Hood·Mari Malkki·Effie W Petersdorf
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Abstract

Haplotypes are a powerful tool for identifying the genetic basis of common complex diseases. Disease-association mapping requires molecular methods for haplotyping biallelic SNP variation and highly complex polymorphisms. We developed a method for phasing HLA-A, HLA-B, and HLA-DRB1 alleles on chromosome 6 in unrelated individuals. This method uses the highly polymorphic HLA-B locus to discriminate the two HLA haplotypes in heterozygous individuals and its ideal location 1.4 Mbp telomeric to HLA-DRB1 and 1.2 Mbp centromeric to HLA-A to capture 2-Mbp-long genomic DNA. Genomic DNA representing a single HLA-B-captured haplotype is genotyped for HLA-A and HLA-DRB1 alleles and linkage to HLA-B is established. Proof of principle was established in a large blinded study of phase-known samples. Availability of an efficient method for MHC haplotype phase determination will facilitate the mapping of causative MHC-resident genes in many human diseases and has the potential to be broadened to other polymorphic gene complexes.

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Genes, MHC Class IGenes, MHC Class IIGenetic Predisposition to DiseaseGenetic VariationHLA AntigensHaplotypesHumansMajor Histocompatibility ComplexOligonucleotide Array Sequence AnalysisJournal ArticleResearch Support, N.I.H., Extramural

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Zhen Guo, Leroy Hood, Mari Malkki, Effie W Petersdorf. 2006-04-21. Long-range multilocus haplotype phasing of the MHC.. https://doi.org/10.1073/pnas.0602286103

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