title: Localization of Type 1 Diabetes susceptibility in the ancestral haplotype 18.2 by high density SNP mapping.
abstract: Previous studies have suggested that the ancestral haplotype 18.2 (AH18.2) carries additional susceptibility gene to Type 1 Diabetes (T1D) on the Major Histocompatibility Complex (MHC). We analyzed 10 DR3/TNFa1b5 homozygous subjects in order to establish the conservation of the AH18.2 and then compared this conserved region with other DR3 haplotype, the AH8.1. The Illumina's HumanHap550 Bead chip was used to perform an extensive genotyping of the MHC region. The AH18.2 was highly conserved between DDR1 and HLA-DQA1 genes; therefore most probably the second susceptibility gene is located within this region. We can exclude the region centromeric to HLA-DRA gene and telomeric to DDR1 gene. A comparison between the AH18.2 and AH8.1 haplotypes showed that 233 SNPs were different in the aforementioned conserved region. These data suggest that the 1.65 Mb MHC region between DDR1 and HLA-DRA genes is likely to carry additional susceptibility alleles for T1D on the AH18.2 haplotype.
authors: Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY, USA. jlsantial@gmail.com
authors: Jose Luis
authors: JL
authors: Santiago
authors: Wentian
authors: W
authors: Li
authors: Annette
authors: A
authors: Lee
authors: Alfonso
authors: A
authors: Martinez
authors: Alamelu
authors: A
authors: Chandrasekaran
authors: Miguel
authors: M
authors: Fernandez-Arquero
authors: Houman
authors: H
authors: Khalili
authors: Emilio G
authors: EG
authors: de la Concha
authors: Elena
authors: E
authors: Urcelay
authors: Peter K
authors: PK
authors: Gregersen
mesh_terms: D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics; D013030:Spain
chemical_list: D005819:Genetic Markers; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human