title: Rare de novo and transmitted copy-number variation in autistic spectrum disorders.
abstract: To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited "ultrarare" duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
authors.forename: Michael
authors.initials: M
authors.lastname: Ronemus
authors.forename: Boris
authors.initials: B
authors.lastname: Yamrom
authors.forename: Yoon-ha
authors.initials: YH
authors.lastname: Lee
authors.forename: Anthony
authors.initials: A
authors.lastname: Leotta
authors.forename: Jude
authors.initials: J
authors.lastname: Kendall
authors.forename: Steven
authors.initials: S
authors.lastname: Marks
authors.forename: B
authors.initials: B
authors.lastname: Lakshmi
authors.forename: Deepa
authors.initials: D
authors.lastname: Pai
authors.forename: Kenny
authors.initials: K
authors.lastname: Ye
authors.forename: Andreas
authors.initials: A
authors.lastname: Buja
authors.forename: Abba
authors.initials: A
authors.lastname: Krieger
authors.forename: Seungtai
authors.initials: S
authors.lastname: Yoon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Troge
authors.forename: Linda
authors.initials: L
authors.lastname: Rodgers
authors.forename: Ivan
authors.initials: I
authors.lastname: Iossifov
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
mesh_terms: D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics*; D030561:Databases, Nucleic Acid / Q000706:statistics & numerical data; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D015233:Models, Statistical; D018377:Neurotransmitter Agents / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D011336:Probability; D035781:Siblings
chemical_list: D018377:Neurotransmitter Agents