Using NextGen sequencing to identify the molecular basis for genetic disease: an evolutionary perspective

In this review, I consider how genetic diseases are related to the evolution of humans and the importance of understanding the results from NextGen sequencing projects in this context. Genome wide association studies (GWAS) were predicated on the assumption that genetic disease was caused by many small effect variations found in large numbers of individuals. However, NextGen sequencing has demonstrated that many disease-causing mutations have a large effect and occur only within restricted populations, families or even individuals. The frequency with which specific types of mutations occur, their effect size and their distribution within the human population is currently an area of active research in genetics. A greater appreciation of human evolutionary history will allow us to design more informative studies to address these questions and properly interpret their results.