Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family.
Based on a genomic search for linkage, a locus contributing to type 1 diabetes in a large Bedouin Arab family (19 affected relatives) maps to the long arm of chromosome 10 (10q25; nonparametric linkage = 4.99; P = 0.00004). All affected relatives carry one or two high-risk HLA-DR3 haplotypes that are rarely found in other family members. One chromosome 10 haplotype, the B haplotype, was transmitted from a heterozygous parent to 13 of 13 affected offspring compared to 10 of 23 unaffected siblings. Recombination events occurring on this haplotype place the susceptibility locus in an 8-cM interval between markers D10S1750 and D10S1773. Two adjacent markers, D10S592 and D10S554, showed evidence of linkage disequilibrium with the disease locus. A 273-bp allele at D10S592 was transmitted to 8 of 10 affected offspring compared to 3 of 14 unaffected siblings, and a 151-bp allele at D10S554 was transmitted to 15 of 15 affected offspring compared with 10 of 24 unaffected siblings. D10S554 and D10S592 and the closest flanking markers are contained in a 1,240-kb yeast artificial chromosome, a region small enough to proceed with positional cloning.
Verge
C F
CF
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado 80262-0001, USA.
Vardi
P
P
Babu
S
S
Bao
F
F
Erlich
H A
HA
Bugawan
T
T
Tiosano
D
D
Yu
L
L
Eisenbarth
G S
GS
Fain
P R
PR
D018912:Arabs; D002874:Chromosome Mapping / Q000379:methods; D002879:Chromosomes, Human, Pair 10; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015803:HLA-DR3 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007557:Israel; D010375:Pedigree; D044465:White People / Q000235:genetics*
D005819:Genetic Markers; D015803:HLA-DR3 Antigen