Individual-Specific Liability Groups in Genetic Linkage, with Applications to Kindreds with Li-Fraumeni Syndrome
AUTOR(ES)
Shete, Sanjay
FONTE
The American Society of Human Genetics
RESUMO
In this report, we present a simple and powerful way to incorporate individual-specific liability classes into linkage analysis. The proposed method is applicable to both quantitative and qualitative traits. In linkage studies, we may have information about different covariates. Incorporation of these covariates along with the estimates of residual familial effects, age-at-onset effects, and susceptibility in the definition of liability classes can increase the power to detect genetic linkage. In this study, we show how one can form individual-specific liability classes and use these classes in standard linkage-analysis programs, such as the widely used LINKAGE package, to perform more powerful genetic linkage analysis. Our simulation study shows that this approach yields higher LOD scores and more-accurate estimates of the recombination fraction in the families showing linkage. The proposed method is also applied to kindreds collected, at the M. D. Anderson Cancer Center, through probands with childhood soft-tissue sarcoma. Confirmed germ-line mutations in the p53 tumor-suppressor gene have been identified in these families. Application of our method to these families yielded significantly higher LOD scores and more-accurate recombination fractions than did analysis that did not account for individual-specific covariate information.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=384961Documentos Relacionados
- Two families with the Li-Fraumeni cancer family syndrome
- Medical genetics: advances in brief: p53 germline mutations in Li-Fraumeni syndrome
- Spontaneous in vitro immortalization of breast epithelial cells from a patient with Li-Fraumeni syndrome.
- Modificadores de penetrância de mutações germinativas no gene TP53 em famílias brasileiras com diagnóstico clínico da síndrome de Li-Fraumeni e Li-Fraumeni like: impacto dos polimorfismos intragênicos do TP53 e de genes
- Heterogeneity in Li-Fraumeni families: p53 mutation analysis and immunohistochemical staining.