TY - JOUR
T1 - Evidence for increased recombination near the human insulin gene
T2 - Implication for disease association studies
AU - Chakravarti, A.
AU - Elbein, S. C.
AU - Permutt, M. A.
PY - 1986
Y1 - 1986
N2 - Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5' FP), all at the insulin locus, have been studied in U.S. Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5' FP only. The data suggest that ~1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population associations between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect associations. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes.
AB - Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5' FP), all at the insulin locus, have been studied in U.S. Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5' FP only. The data suggest that ~1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population associations between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect associations. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes.
UR - http://www.scopus.com/inward/record.url?scp=0022501681&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022501681&partnerID=8YFLogxK
U2 - 10.1073/pnas.83.4.1045
DO - 10.1073/pnas.83.4.1045
M3 - Article
C2 - 3006026
AN - SCOPUS:0022501681
SN - 0027-8424
VL - 83
SP - 1045
EP - 1049
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -