Exome sequencing studies have identified hundreds of mutated genes that may underlie autism spectrum disorders, like Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS), but accurately re-sequencing those candidate genes in large groups of people to look for causative mutations is expensive. Now, Brian O'Roak and colleagues have modified a method for targeting and sequencing multiple genes in large groups of people, known as a molecular inversion probe, to create a new, low-cost technique. The researchers used their method to sequence 44 genes in 2,446 individuals affected by various autism spectrum disorders and identified 27 random mutations in 16 different genes. Specifically, O'Roak and the other researchers say that recurrent mutations in six genes -- CHD8, DYRK1A, GRIN2B, TBR1, PTEN, and TBL1XR1 -- likely contribute to one percent of sporadically-arising autism spectrum disorders. Their results reinforces the fact that de novo mutations in multiple genes underlie autism spectrum disorders, and their economical technique can be applied to any disorder for which random, disruptive mutations are suspected to contribute to risk.
Article #22: "Multiplex Targeted Sequencing Identifies Recurrently Mutated Genes in Autism Spectrum Disorders," by B.J. O’Roak; L. Vives; W. Fu; J.D. Egertson; I.B. Stanaway; I.G. Phelps; G. Carvill; A. Kumar; C. Lee; K. Ankenman; J. Munson; J.B. Hiatt; E.H. Turner; R. Levy; D.R. O’Day; N. Krumm; B.P. Coe; B.K. Martin; E. Borenstein; D.A. Nickerson; H.C. Mefford; D. Doherty; J.M. Akey; R. Bernier; E.E. Eichler; J. Shendure at University of Washington School of Medicine in Seattle, WA; I.G. Phelps; G. Carvill; H.C. Mefford; D. Doherty at Seattle Children’s Hospital in Seattle, WA; E. Borenstein at Santa Fe Institute in Santa Fe, NM; E.E. Eichler at Howard Hughes Medical Institute in Seattle, WA.