Genetic Analysis of Multiply-Affected Families of Insulin-Dependent Diabetes Mellitus (IDDM) Probands

Abstract

The present study combines segregation and linkage information on 30 families ascertained through a proband and a first degree relative affected with insulin-dependent diabetes mellitus (IDDM). An autosomal dominant model with incomplete penetrance was much more likely to fit the family data than a recessive model, whether or not linkage to HLA was assumed. The lod scores for linkage to HLA were 2.46 at Θ_M = Θ_F = 0.00 for dominant and 1.45 at Θ_M = Θ_F = 0.22 for a recessive model. The results are discussed in light of heterogeneity in likelihoods and lod scores when the families are grouped by familial types, which indicate that the increase in likelihood of a dominant hypothesis can be attributed to the parent-child families and not the sib-sib families.

HFE C282Y and H63D in adults with malignancies in a community medical oncology practice

“…In some studies, presumed hemochromatosis heterozygotes were ascertained only by self-reported kinship to a putative hemochromatosis homozygote in questionnaire surveys [53]. In family-based studies in which HFE mutation or other DNA-based testing is not used, non-paternity is an additional source of error (1.0 – 1.4% non-paternity in American Caucasians) [54,55]. …”

Population genetic analyses of insulin dependent diabetes mellitus using HLA allele frequencies

“…Another methodology to determine mode of inheritance is linkage analysis in IDDM families. We have done linkage analysis on a set of 30 multiply affected IDDM families (Murphy et al 1983). These results, while they support the finding that susceptibility to IDDM is HLA-linked, were also inadequate to determine an exact mode of inheritance.…”