Hierarchical Modeling of Linkage Disequilibrum: Genetic Structure and Spatial Relations
AUTOR(ES)
Conti, David V.
FONTE
The American Society of Human Genetics
RESUMO
Linkage disequilibrium (LD) mapping offers much promise for the positional cloning of disease-causing genes. However, conventional estimates of LD may fluctuate substantially across contiguous genomic regions, because of population-specific phenomena such as mutation, genetic drift, population structure, and variations in allele frequencies. This fluctuation makes it difficult to interpret patterns of LD and distinguish where a causal gene is located. To address this issue, we propose hierarchical modeling of LD (HLD) for fine-scale mapping. This approach incorporates information on haplotype block structure and chromosomal spatial relations to refine the pattern of LD, increasing the ability to localize disease genes. Here, we present a framework for HLD, a simulation study assessing the performance of HLD under various scenarios, and an application of HLD to existing data. This work demonstrates that hierarchical modeling of linkage disequilibrium is a valuable and flexible approach for fine-scale mapping.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=379228Documentos Relacionados
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