Localization of Type 1 Diabetes susceptibility in the ancestral haplotype 18.2 by high density SNP mapping.
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.
Santiago
Jose Luis
JL
Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY, USA. jlsantial@gmail.com
Li
Wentian
W
Lee
Annette
A
Martinez
Alfonso
A
Chandrasekaran
Alamelu
A
Fernandez-Arquero
Miguel
M
Khalili
Houman
H
de la Concha
Emilio G
EG
Urcelay
Elena
E
Gregersen
Peter K
PK
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
D005819:Genetic Markers; D015235:HLA-B Antigens; D059911:HLA-B18 Antigen; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human