A genomewide search for type 2 diabetes-susceptibility genes in indigenous Australians.
The prevalence of type 2 diabetes among Australian residents is 7.5%; however, prevalence rates up to six times higher have been reported for indigenous Australian communities. Epidemiological evidence implicates genetic factors in the susceptibility of indigenous Australians to type 2 diabetes and supports the hypothesis of the "thrifty genotype," but, to date, the nature of the genetic predisposition is unknown. We have ascertained clinical details from a community of indigenous Australian descent in North Stradbroke Island, Queensland. In this population, the phenotype is characterized by severe insulin resistance. We have conducted a genomewide scan, at an average resolution of 10 cM, for type 2 diabetes-susceptibility genes in a large multigeneration pedigree from this community. Parametric linkage analysis undertaken using FASTLINK version 4.1p yielded a maximum two-point LOD score of +2.97 at marker D2S2345. Multipoint analysis yielded a peak LOD score of +3.9 <1 cM from marker D2S2345, with an 18-cM 3-LOD support interval. Secondary peak LOD scores were noted on chromosome 3 (+1.8 at recombination fraction [theta] 0.05, at marker D3S1311) and chromosome 8 (+1.77 at theta=0.0, at marker D8S549). These chromosomal regions are likely to harbor novel susceptibility genes for type 2 diabetes in the indigenous Australian population.
Busfield
Frances
F
Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Duffy
David L
DL
Kesting
Janine B
JB
Walker
Shelley M
SM
Lovelock
Paul K
PK
Good
David
D
Tate
Heather
H
Watego
Denise
D
Marczak
Maureen
M
Hayman
Noel
N
Shaw
Joanne T E
JT
D001315:Australia / Q000453:epidemiology / Q000208:ethnology; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree
D005819:Genetic Markers