A new resource to mine recessive disease genes

July 29, 2016

Joseph Gleeson and colleagues have generated a publically accessible whole-exome variome from 1,111 unrelated individuals within the Greater Middle East Variome Consortium.

Autism Research Initiative (SFARI)

Box plot comparing F values for Africa, Europe, East Asia, and various GME regions. Africa, Europe, and East Asia have lower F values; GME regions show higher spread and larger median values. X-axis: regions, Y-axis: F values. — Consanguinity in the GME population: Distributions of the inbreeding coefficient (F) for GME and 1000 Genomes Project populations. The GME populations are subdivided into six different GME subregions. The 1000 Genomes Project populations are subdivided into African, European and East Asian regions. GME populations (purple) show elevated F values, consistent with increased rates of consanguineous marriage. Abbreviations: NWA, northwest Africa; NEA, northeast Africa; AP, Arabian Peninsula; SD, Syrian Desert; TP, Turkish Peninsula; PP, Persia and Pakistan. Image from Scott E.M. et al. (2016).

The Greater Middle East (GME) population is known to show an elevated burden of recessive Mendelian disease, due to the tradition of consanguinity that is practiced in a number of countries in this region. To better understand the extent of rare genetic variation in this population, SFARI Investigator Joseph Gleeson and his colleagues in the GME Variome Consortium generated a whole-exome variome from 1,111 unrelated individuals from GME regions. The researchers performed a number of initial characterizations of the dataset, including a pilot study of recessive hereditary spastic paraplegia, to illustrate its application. The GME variome is a publicly accessible resource and its use in future sequencing projects is expected to aid in the identification of causative recessive genes linked to diseases of all classes, including autism spectrum disorder.