Quantifying the contribution of recessive coding variation to developmental disorders
Martin HC., Jones WD., McIntyre R., Sanchez-Andrade G., Sanderson M., Stephenson JD., Jones CP., Handsaker J., Gallone G., Bruntraeger M., McRae JF., Prigmore E., Short P., Niemi M., Kaplanis J., Radford EJ., Akawi N., Balasubramanian M., Dean J., Horton R., Hulbert A., Johnson DS., Johnson K., Kumar D., Lynch SA., Mehta SG., Morton J., Parker MJ., Splitt M., Turnpenny PD., Vasudevan PC., Wright M., Bassett A., Gerety SS., Wright CF., FitzPatrick DR., Firth HV., Hurles ME., Barrett JC.
Genetic architecture of developmental disorders The genetics of developmental disorders (DDs) is complex. Martin et al. wanted to determine the degree of recessive inheritance of DDs in protein-coding genes. They examined the exomes of more than 6000 families in populations with high and low proportions of consanguineous marriages. They found that 3.6% of DDs in individuals of European ancestry involved recessive coding disorders, less than a tenth of the levels previously estimated. Furthermore, among South Asians with high parental relatedness, rather than most of the disorders arising from inherited variants, fewer than half had a recessive coding diagnosis. Science , this issue p. 1161