No abstract

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli.

The APC gene was investigated in 31 unrelated polyposis coli families by SSCP analysis and the protein truncation test. Twenty-three germline mutations were identified which gave rise to a variety of different phenotypes. Some of these mutations have already been described; however we report six previously unpublished mutations. Typical disease symptoms were observed in families who harboured mutations between exon 4 (codon 169) and codon 1393 of exon 15. Mutations beyond codon 1403 were associated with more varied phenotype with respect to the development of extracolonic symptoms. In this report we provide support for the notion that there appears to be a correlation between the location of an APC mutation (beyond codon 1403) and extracolonic manifestations of familial adenomatous polyposis. (J Med Genet 1996;33:274-280)

In linkage analysis and gene mapping in general, typing error and/or errors in specifying pedigree relationships between individuals typically lead to an upwards bias in recombination fraction estimates and to a loss of power for detecting linkage. [Ott J: Analysis of Human Genetic Linkage. Baltimore, Johns Hopkins University Press, 1991]. The presence of nonpaternity is the most common source of error of misspecification of pedigree relationships between individuals that can have a negative impact on pedigree analysis. We have developed estimates of underlying nonpaternity probabilities based on observed Mendelian inconsistencies. The methods were applied to a sample of 1,607 children and their parents. Genetic marker data were investigated to test for exclusions due to nonpaternity. Among the 1,607 children, 11 or 0.68% exclusions were found. When a constant nonpaternity rate was assumed for each child, its maximum likelihood estimate turned out to be 0.78% with asymptotic 95% confidence limits of 0.41% and 1.35%. When varying nonpaternity rates were assumed, its mean was estimated as 0.83% with asymptotic 95% confidence limits of 0.32% and 1.33%.