Long-range Multilocus Haplotype Phasing of the MHC

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Apr 25

PMID 16632595

Citations 17

Authors

Zhen Guo

Leroy Hood

Mari Malkki

Effie W Petersdorf

Affiliations

Soon will be listed here.

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.

Citing Articles

Haplotypes analysis reveals the genetic basis of type I CD36 deficiency.

Xia W, Chen D, Li X, Liu J, Xu X, Ye X Sci Rep. 2024; 14(1):23977.

PMID: 39402159 PMC: 11473821. DOI: 10.1038/s41598-024-74917-0.

Estimating HLA haplotype frequencies from homozygous individuals - A Technical Report.

Seitz S, Lange V, Norman P, Sauter J, Schmidt A Int J Immunogenet. 2021; 48(6):490-495.

PMID: 34570965 PMC: 9131737. DOI: 10.1111/iji.12553.

SNP-Density Crossover Maps of Polymorphic Transposable Elements and HLA Genes Within MHC Class I Haplotype Blocks and Junction.

Kulski J, Suzuki S, Shiina T Front Genet. 2021; 11:594318.

PMID: 33537058 PMC: 7848197. DOI: 10.3389/fgene.2020.594318.

Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation.

Petersdorf E F1000Res. 2017; 6:617.

PMID: 28529723 PMC: 5419254. DOI: 10.12688/f1000research.10990.1.

Complete haplotype phasing of the MHC and KIR loci with targeted HaploSeq.

Selvaraj S, Schmitt A, Dixon J, Ren B BMC Genomics. 2015; 16:900.

PMID: 26541200 PMC: 4636068. DOI: 10.1186/s12864-015-1949-7.

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