Although the approach of genome-wide association studies (GWAS) has emerged as a powerful tool for identifying genes with common variants influencing diseases, they can help explain only a small fraction of the overall disease heritability and it was hypothesized that some of the missing heritability can be explained by rare variants with larger effect sizes.Testing this hypothesis, however, has been hampered by technological limitations.Recent advances in next-generation sequencing (NGS) technology now provide the potential to detect all single nucleotide polymorphisms (SNPs) including rare ones in a genomic region.