|
|
|
|
Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism
|
|
|
|
|
|
|
|
نویسنده
|
chahrour m.h. ,yu t.w. ,lim e.t. ,ataman b. ,coulter m.e. ,hill r.s. ,stevens c.r. ,schubert c.r. ,greenberg m.e. ,gabriel s.b. ,walsh c.a.
|
|
منبع
|
plos genetics - 2012 - دوره : 8 - شماره : 4
|
|
چکیده
|
Although autism has a clear genetic component,the high genetic heterogeneity of the disorder has been a challenge for the identification of causative genes. we used homozygosity analysis to identify probands from nonconsanguineous families that showed evidence of distant shared ancestry,suggesting potentially recessive mutations. whole-exome sequencing of 16 probands revealed validated homozygous,potentially pathogenic recessive mutations that segregated perfectly with disease in 4/16 families. the candidate genes (ube3b,cltcl1,nckap5l,znf18) encode proteins involved in proteolysis,gtpase-mediated signaling,cytoskeletal organization,and other pathways. furthermore,neuronal depolarization regulated the transcription of these genes,suggesting potential activity-dependent roles in neurons. we present a multidimensional strategy for filtering whole-exome sequence data to find candidate recessive mutations in autism,which may have broader applicability to other complex,heterogeneous disorders. © 2012 chahrour et al.
|
|
|
|
|
آدرس
|
division of genetics,department of medicine,children's hospital boston,boston,ma,united states,manton center for orphan disease research,children's hospital boston,boston,ma,united states,howard hughes medical institute,children's hospital boston,boston,ma,united states,department of pediatrics,harvard medical school,boston,ma,united states,program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma, United States, division of genetics,department of medicine,children's hospital boston,boston,ma,united states,manton center for orphan disease research,children's hospital boston,boston,ma,united states,howard hughes medical institute,children's hospital boston,boston,ma,united states,department of pediatrics,harvard medical school,boston,ma,united states,program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma,united states,department of neurology,harvard medical school,boston,ma, United States, program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma,united states,biological and biomedical sciences program,harvard university,boston,ma,united states,analytic and translational genetics unit,massachusetts general hospital,boston,ma, United States, department of neurobiology,harvard medical school,boston,ma, United States, division of genetics,department of medicine,children's hospital boston,boston,ma, United States, division of genetics,department of medicine,children's hospital boston,boston,ma,united states,manton center for orphan disease research,children's hospital boston,boston,ma,united states,howard hughes medical institute,children's hospital boston,boston,ma, United States, program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma, United States, division of genetics,department of medicine,children's hospital boston,boston,ma,united states,manton center for orphan disease research,children's hospital boston,boston,ma,united states,howard hughes medical institute,children's hospital boston,boston,ma,united states,department of pediatrics,harvard medical school,boston,ma,united states,program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma, United States, department of neurobiology,harvard medical school,boston,ma, United States, program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma, United States, division of genetics,department of medicine,children's hospital boston,boston,ma,united states,manton center for orphan disease research,children's hospital boston,boston,ma,united states,howard hughes medical institute,children's hospital boston,boston,ma,united states,department of pediatrics,harvard medical school,boston,ma,united states,program in medical and population genetics,broad institute of massachusetts institute of technology and harvard university,cambridge,ma,united states,department of neurology,harvard medical school,boston,ma, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|