Distinguishing neutral from deleterious mutations in growing populations

Greg B Ewing,Jeffrey D Jensen

doi:10.3389/fgene.2014.00007

Abstract

Distinguishing neutral from deleterious mutations in growing populations

Highlights

The identification of disease causing rare variants is becoming possible with the advent of generation sequencing (Nejentsev et al, 2009; Calvo et al, 2010; Johansen et al, 2010)
An intuitive understanding of the underlying dynamics of the evolution of rare variants can be gained by considering the coalescent trees that are likely under models of population growth
Population growth results in trees where coalescent events are rare in the recent past and tend toward a more star like topology (Wakeley, 2009), owing to the relationship between population size and rate of coalescence

Summary

Introduction

The identification of disease causing rare variants is becoming possible with the advent of generation sequencing (Nejentsev et al, 2009; Calvo et al, 2010; Johansen et al, 2010). The recent rapid population expansion of humans is expected to give rise to an excess of rare variants both neutral and deleterious (Keinan and Clark, 2012) and is expected to make the detection of these rare disease causing variants more difficult. Kim and Schuster (2013) first infer the demographic history of the population, finding support for a model of population structure and expansion, as supported by previous studies (Gutenkunst et al, 2009; Gravel et al, 2011) but, with a lower growth rate.

Results

Conclusion