Determining Probability of Rare Variants: Design Implications for Family-Based Sequencing Studies

• Activity Number: 631
• Type: Invited
• Date/Time: Thursday, August 2, 2012 : 10:30 AM to 12:20 PM
• Sponsor: ENAR
• Author(s): Wenyi Wang*+ and Gang Peng
• Companies: MD Anderson Cancer Center and MD Anderson Cancer Center
• Keywords: Mendelian model ; rare variants ; DNA sequencing ; inherited diseases

Abstract

It is still challenging to find rare variants in order to better understand the genetic basis of human disease. Family-based sequencing studies have been performed, in search for functionally important genes. A high false discovery rate in calling rare variants precludes comprehensive downstream functional analyses. To improve accuracy, recent studies have used linkage information among relatives. Ongoing sequencing studies include data on extended family members. We developed FamSeqPro, which evaluates the probability of variants in family-based sequencing data, given raw measurements from all family members, at a single base level. Using FamSeqPro, we performed simulation studies to identify cost-effective designs for finding inherited genetic mutations in families with diseases of interest. We illustrate the performance of FamSeqPro in real data: whole-genome sequencing of a family trio.