Evidence of a novel type 2 diabetes locus 50 cM centromeric to NIDDM2 on chromosome 12q.
To replicate the recent finding of a type 2 diabetes locus (NIDDM2) on 12q, families segregating early-onset autosomal-dominant type 2 diabetes were screened for linkage. Included were 26 Caucasian and 6 non-Caucasian pedigrees with an average age at diabetes diagnosis of 37 +/- 18 years. Affected (n = 233) and nonaffected (n = 152) family members were genotyped for 17 markers covering 90 cM on chromosome 12q. While no evidence for linkage was detected at the NIDDM2 locus, a linkage peak was observed 50 cM centromeric to NIDDM2 at markers D12S375 and D12S1052. In a nonparametric analysis, the Z(all) score was 2.9 (P = 0.015) at D12S375, and increased to 3.8 (P = 0.007) among Caucasian families. Further increase in significance was observed in pedigrees with poor insulin response, with a maximum Z(all) of 6.2 (P = 0.002) at D12S375. Suggestive evidence of linkage was also detected by the parametric analysis, with the heterogeneity logarithm of odds score peaking at 2.5 (alpha = 0.15) between D12S375 and D12S1052. In summary, our data indicate that the NIDDM2 locus does not play a major role in early-onset autosomal-dominant type 2 diabetes. Rather, they strongly suggest that a previously undetected type 2 diabetes locus exists 50 cM from NIDDM2 on 12q.
Bektas
A
A
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Suprenant
M E
ME
Wogan
L T
LT
Plengvidhya
N
N
Rich
S S
SS
Warram
J H
JH
Krolewski
A S
AS
Doria
A
A
D000328:Adult; D017668:Age of Onset; D044383:Black People / Q000235:genetics; D002503:Centromere / Q000235:genetics*; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
D005819:Genetic Markers