title: Multi-SNP analysis of MHC region: remarkable conservation of HLA-A1-B8-DR3 haplotype.
abstract: Technology has become available to cost-effectively analyze thousands of single nucleotide polymorphisms (SNPs). We recently confirmed by genotyping a small series of class I alleles and microsatellite markers that the extended haplotype HLA-A1-B8-DR3 (8.1 AH) at the major histocompatibility complex (MHC) is a common and conserved haplotype. To further evaluate the region of conservation of the DR3 haplotypes, we genotyped 31 8.1 AHs and 29 other DR3 haplotypes with a panel of 656 SNPs spanning 4.8 Mb in the MHC region. This multi-SNP evaluation revealed a 2.9-Mb region that was essentially invariable for all 31 8.1 AHs. The 31 8.1 AHs were >99.9% identical for 384 consecutive SNPs of the 656 SNPs analyzed. Future association studies of MHC-linked susceptibility to type 1 diabetes will need to account for the extensive conservation of the 8.1 AH, since individuals who carry this haplotype provide no information about the differential effects of the alleles that are present on this haplotype.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Mail Stop B140, P.O. Box 6511, Aurora, CO 80045-6511, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Aly
authors.forename: Elise
authors.initials: E
authors.lastname: Eller
authors.forename: Akane
authors.initials: A
authors.lastname: Ide
authors.forename: Katherine
authors.initials: K
authors.lastname: Gowan
authors.forename: Sunanda R
authors.initials: SR
authors.lastname: Babu
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Rewers
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D015788:HLA-A1 Antigen / Q000235:genetics*; D015795:HLA-B8 Antigen / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008285:Major Histocompatibility Complex; D020641:Polymorphism, Single Nucleotide
chemical_list: D015788:HLA-A1 Antigen; D015795:HLA-B8 Antigen; D015803:HLA-DR3 Antigen