Abstract The melanocortin-4 receptor (MC4R) was cloned in 1993 by degenerate PCR;
however, its function was unknown. Subsequent studies suggest that the MC4R might be …

There has been growing debate over the nature of the genetic contribution to individual
susceptibility to common complex diseases such as diabetes, osteoporosis, and cancer. The …

INTRODUCTION Loss-of-function mutations in one gene copy can lead to reduced amounts
of protein and, consequently, human disease, a condition termed haploinsufficiency. It is …

We propose in this paper a unified approach for testing the association between rare
variants and phenotypes in sequencing association studies. This approach maximizes …

Genetic studies have revealed thousands of loci predisposing to hundreds of human
diseases and traits, revealing important biological pathways and defining novel therapeutic …

Each human carries a large number of deleterious mutations. Together, these mutations
make a significant contribution to human disease. Identification of deleterious mutations …

Rare genetic variants contribute to complex disease risk; however, the abundance of rare
variants in human populations remains unknown. We explored this spectrum of variation by …

Although whole-genome association studies using tagSNPs are a powerful approach for
detecting common variants, they are underpowered for detecting associations with rare …

Exome association studies to date have generally been underpowered to systematically
evaluate the phenotypic impact of very rare coding variants. We leveraged extensive …

Deep sequencing will soon generate comprehensive sequence information in large disease
samples. Although the power to detect association with an individual rare variant is limited …