Pedigree analysis of Hodgkin's disease in a Newfoundland genealogy

Abstract

An extensive Newfoundland genealogy shows a large number of cases of lymphoreticular malignancies. A recessive pattern of inheritance had been previously suggested, but no quantitative investigation of the hypothesis was made. Here we have investigated a variety of aspects of the descent structure of the pedigree and shown that for only a subset of the traits can the inference be upheld. For Hodgkin's disease (HD) and generalized immunodeficiency (ID) there is clear evidence for a recessive HD/ID susceptibility allele. The remainder do not follow this pattern, show no evidence of a single-locus effect and little of any genetic effect. The ancestry of the HD/ID cases was therefore investigated in detail, and likelihoods computed on the pedigree. These confirmed the recessive nature of the trait, as also did the risk analysis which quite clearly identified the paths of descent taken by the allele. The determination of these paths is a prerequisite for any linkage analysis which might further confirm the single-locus nature of the trait.

A simple method to approximate gene content in large pedigree populations: application to the myostatin gene in dual-purpose Belgian Blue cattle

“…Exact genotype probabilities are marginal probabilities obtained by summing over all possible genotype configurations which are consistent with observations, weighting the configurations by their probability of occurrence as calculated under the assumed genetic model. On a small pedigree exact genotype probabilities can be calculated using one of the graphical models and reverse or simultaneous peeling (Thompson, 1981). The problem considered in the simulation study was too complex for exact calculation, therefore only approximate methods were applied.…”

Segregation of Malignant Hematological Disease in Families with Malignant Lymphoma

“…Sex-concordance, viz. surplus of male-male and female-female pairs vs. male-female pairs in siblings with CLL [45], and the lack of "any genetic effect" in lymphoreticular malignancies associated familial, endemic HL [19] may be interpreted as signs of distortion.…”

“…Genomic imprinting with maternal down regulation, viz. "imprinting of paternal susceptibility" has previously been attributed to CLL-susceptibility as a possible mechanism in the transmission of CLL via feto-maternal microchimerism [20], but very few genealogical publications on the segregation of malignant hematological disease are available for comparison [for review see [19][20][21]. Sex-concordance, viz.…”

Inference of a gene and its paths of descent: The Newfoundland example

“…Information from the complete trait distribution in the current population cannot be full and exact1 incorporated, puted over the complete genealogy. However, an approximation can be obtained by considering independently offspring of members of the core genealo (Thompson, 1981 Reprinted from Thompson (1981). [More recent work has necessitated minor modifications to this genealogy (see Thompson, 1986); these changes do not alter inferences.]…”