Parental imprinting effect at the INS-IGF2 diabetes susceptibility locus.
Although association of insulin-dependent diabetes mellitus with a haplotype at a locus encompassing the genes for insulin and the insulin-like growth factor II has been well established, two major studies disagree as to whether linkage to this locus is confined to paternally inherited alleles, or is present in alleles transmitted from either parental sex. Towards resolving this discrepancy, we examined parent-of-origin specific association rather than linkage, using the haplotype relative risk method in a mixed Caucasian population. We find that the haplotype relative risk (HRR) conferred by paternal chromosomes was much higher (5.1, p < 0.01) than the corresponding maternal value (2.3, p = 0.07), which narrowly failed to reach statistical significance. Thus, although we cannot exclude an effect of the maternal allele, such an effect appears to be considerably weaker. We review evidence that parental imprinting is genotype-dependent, which may explain the different degrees to which the paternal effect is seen in different populations.
Polychronakos
C
C
Montreal Children's Hospital Research Institute, Department of Pediatrics, McGill University, Québec, Canada.
Kukuvitis
A
A
Giannoukakis
N
N
Colle
E
E
D000328:Adult; D000483:Alleles; D002648:Child; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D005819:Genetic Markers; D007328:Insulin; D007335:Insulin-Like Growth Factor II