Complex Segregation Analysis with Pointers

Lalouel, Jean-Marc; Morton, N.E.

doi:10.1159/000153231

Cited by 322 publications

(156 citation statements)

References 9 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…Segregation analysis was performed using the software Pointer (Lalouel and Morton, 1981). Pointer assumes the mixed model of inheritance, that is, segregation is explained by a major gene, a polygenic background and unmeasured environmental exposures.…”

Section: Discussionmentioning

confidence: 99%

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Heimdal

Olsson²,

Tretli³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Clustering of testicular cancer cases in families is well known, although the aetiology is not. We present the results of a segregation analysis performed with the algorithm Pointer on familial data on 978 Scandinavian patients with testicular cancer. The segregation analysis favoured the involvement of major gene effects over models incorporating solely polygenic effects in testicular cancer aetiology. Overall, a recessive model best fits the family observations with an estimated gene frequency of 3.8% and a lifetime risk for homozygous men of developing the disease of 43%. This implies that 7.6% of men in the general population will be carriers of the mutant allele and that 0.1% would be homozygote and are, therefore, at high risk of developing the cancer. The testicular cancer incidence has changed greatly during the last generation. Also, the lethality of the disease has changed because of the introduction of new therapy. As failure to take account of such time trends might lead to inappropriate evidence for a recessive model, the analyses were repeated under different assumptions. The analyses favoured a recessive model of inheritance under all assumptions tested. However, the assumptions underlying the analyses are complex and, as this is the first segregation analysis of testicular cancer, the results must be interpreted cautiously.

show abstract

Section: Discussionmentioning

confidence: 99%

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Heimdal

Olsson²,

Tretli³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Extended pedigrees were decomposed before the analysis into nuclear families with the inclusion of pointers, who are affected relatives through whom the nuclear family was ascertained. 27 Pointers were coded as defined in Morton et al 28 The different combinations of parental phenotypes and selection criteria of the resulting nuclear families are shown in Table 2.…”

Section: Family Datamentioning

confidence: 99%

Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis

et al. 2000

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic relapsing disorder affecting the gastro-intestinal tract and is subdivided into two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although the aetiology of IBD is unknown, a strong genetic susceptibility is suggested and different candidate regions have been identified for both CD and UC. The IBD1 region on chromosome 16 has been confirmed to be important for susceptibility to CD, whereas conflicting evidence has been obtained for UC. We performed a combined linkage and segregation analysis in the identified IBD1 region on a sample of 82 extended families with IBD using a parametric method implemented in the computer program COMDS. This approach allows simultaneous evaluation of linkage while estimating the mode of inheritance and to include severity of the trait to characterise the CD and UC phenotypes. Our results are consistent with the presence of a major gene in the IBD1 region close to D16S408 involved in both UC and CD. Furthermore, our data support evidence that a single mutation in the gene leads more frequently to UC, whereas inheritance of two mutant alleles results in the more severe CD. In our study the IBD1 locus was found to have a major role in IBD predisposition in the Italian population.

show abstract

“…Segregation analysis was carried out under a mixed model using the computer program POINTER (Lalouel and Morton, 1981). The mixed model assumes an underlying scale of genetic liability to which a major locus, polygenes and environmental factors operate.…”

Section: Segregation Analysismentioning

confidence: 99%

“…We have examined the familial occurrence of ovarian cancer among a Finnish population by conducting a complex segregation analysis (Lalouel and Morton, 1981) on an unselected sample of Finnish ovarian cancer patients. We have had the advantage of using data obtained from population registries and the Finnish Cancer Registry; therefore, the data used is completely verified from genealogical registries and medical records.…”

mentioning

confidence: 99%

Segregation analysis of epithelial ovarian cancer in Finland

Auranen

Iselius²

1998

Br J Cancer

View full text Add to dashboard Cite

Summary Epithelial ovarian cancer is known to aggregate in families. The dominantly inherited ovarian cancer predisposing genes, BRCA 1, BRCA2 and genes involved in the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently been identified. However, in the majority of families with more than one case of ovarian cancer, dominant inheritance cannot be recognized. We investigated familial clustering of epithelial ovarian cancer in a population-based sample of 663 Finnish ovarian cancer patients. A segregation analysis with the POINTER software was conducted on the 937 nuclear families from these 663 pedigrees. The major gene model was favoured, and the sporadic and multifactorial models were strongly rejected. In the studied population, the best fitting model was a recessive mode of inheritance, and 8% of ovarian cancer patients were estimated to be homozygous for the deleterious genotype. This evidence for recessively inherited ovarian cancer predisposition should be interpreted cautiously, as the analysis is subject to certain errors, which are discussed in the article. Results of this analysis, however, strongly emphasize the role of genetic factors in all familial aggregation of epithelial ovarian cancer.

show abstract

Complex Segregation Analysis with Pointers

Cited by 322 publications

References 9 publications

A segregation analysis of testicular cancer based on Norwegian and Swedish families

A segregation analysis of testicular cancer based on Norwegian and Swedish families

Combined segregation and linkage analysis of inflammatory bowel disease in the IBD1 region using severity to characterise Crohn's disease and ulcerative colitis

Segregation analysis of epithelial ovarian cancer in Finland

Contact Info

Product

Resources

About