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

This paper presents various aspects of Pedigree Analysis through a review of a study of a Newfoundland genetic isolate. This study has evolved over a number of years and involved many researchers. The population came to attention due to a greatly enhanced incidence of a variety of lymphoreticular malignancies. Genetic analysis shows clearly that there are (at least) two groups of traits. Whereas the distribution of the leukaemia and lymphosarcoma cases show no clear genealogical pattern, the existence of a single recessive allele causing susceptibility to Hodgkin's disease and immunodeficiency in an isolated New-foundland population can be inferred. There appears to be no heterozygote penetrance, but in the period up to 1974 homozygote penetrance was high and perhaps complete. More important, the ancestral paths of the allele can be inferred. Many ancestral individuals are obligatory carriers, and most others have either probability >95% or <5% of having carried the allele. More recently, methods were developed and applied in order to investigate linkage of this locus to conventional blood group and serum protein marker loci. Although no linkages were found, some observed associations were clarified, and some definite non-linkages established.