A Likelihood-Based Framework for Variant Calling and De Novo Mutation Detection in Families

• DOI: 10.1371/journal.pgen.1002944
• Publication Date: 2012-10-04T20:50:45Z
• Authors: Bingshan Li; Wei Chen; Xiaowei Zhan; Fabio Busonero; Serena Sanna; Carlo Sidore; Francesco Cucca; Hyun M. Kang; Gonçalo R. Abecasis
• Keywords: Mendelian inheritance; Sequence (biology)

Family samples, which can be enriched for rare causal variants by focusing on families with multiple extreme individuals and facilitate detection of de novo mutation events, provide an attractive resource next-generation sequencing studies. Here, we describe, implement, evaluate a likelihood-based framework analysis next generation sequence data in family samples. Our is able to identify variant sites accurately assign individual genotypes, handle increasing the sensitivity specificity calling detection. Through simulations show explicit modeling relationships especially useful analyses low-frequency that genotype accuracy increases number sequenced per family. Compared standard approach ignoring relatedness, our methods more variants, have high detecting events. The improvement using over particularly pronounced variants. Furthermore family-aware dramatically reduces Mendelian inconsistencies beneficial family-based analysis. We hope software will continuing efforts genetic factors underlying human diseases.