Confirmation of susceptibility gene loci on chromosome 1 in northern China Han families with type 2 diabetes.
OBJECTIVE
To confirm previous effort to identify type 2 diabetes susceptibility genes in a Northern Chinese population by conducting a new genome scan with both an increased number of type 2 diabetes families and a new set of microsatellite markers within the previously localized regions.


METHODS
A genome scan method was applied. After multiplexed PCR, electrophoreses, genescan and genotyping analysis, we obtained size information for all loci, and then a further study was done by both parametric and non-parametric linkage analysis to investigate the P values and Z values of these loci.


RESULTS
We surveyed 34 microsatellite markers which distributed within 5 regions along chromosome 1, and a total of 12,000 genotypes were screened. Evidence of linkage with diabetes was identified for 8 of the 34 loci. All P values of the 8 loci were lower than 0.05, and the highest Z value was 2.17. A very interesting finding is that all 5 markers at the p- terminal 1p36.3-1p36.23 region, spanning a long range of 16.9 cM, were identified to have a low P value of less than 0.05, which suggests that this region may contain multiple susceptibility genes. Regions 4 and 5 also confirmed the previous findings, and we narrowed these two regions to a 2.7 cM and 2.5 cM regions, respectively.


CONCLUSIONS
We further confirmed the results gained in the previous genome-wide scan using an increased number of NIDDM families and a new set of microsatellite markers lying within the initially localized regions. The fact that all 5 loci at the p- terminal region displayed a low P value of less than 0.05 suggests that more than 1 susceptibility gene may reside in this region.
Du
W
W
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Sun
H
H
Wang
H
H
Qiang
B
B
Shen
Y
Y
Yao
Z
Z
Gu
J
J
Xiong
M
M
Huang
W
W
Chen
Z
Z
Zuo
J
J
Hua
X
X
Gao
W
W
Sun
Q
Q
Fang
F
F
D002878:Chromosomes, Human, Pair 1; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats