hrprod Archives - Gen9 Genetics

The genome of any individual contains about 4 to 5 million genetic variants that differ from the reference, and understanding how these variants give rise to trait diversity and disease susceptibility is a central goal of human genetics (Auton et al. ., 2015). A vast majority (96% -99%) of an individual's variants are common, although at the population level, the vast majority of variants are rare (Montgomery et al., 2011, Nelson et al., 2012, Tennessen et al. al., 2012, UK10K Consortium et al., 2015). Variants common in the human population generally contribute small additive effects towards complex traits, as negative selection has eliminated deleterious large-effect alleles (Altshuler et al., 2008). However, population expansion around 10,000 years ago left humans with a host of rare variations, and most of the traits of Mendelian disease are caused by rare alleles with large effect sizes (Keinan and Clark , 2012). Due to their scarcity in an individual's genome, rare variants that play an important role in complex traits are likely to have large functional effects (Bomba et al., 2017), and traditional computational or population genome methods cannot. reliably estimate its contribution (Uricchio et al., 2016).