title: Phenotypic homogeneity provides increased support for linkage on chromosome 2 in autistic disorder.
abstract: Autistic disorder (AutD) is a neurodevelopmental disorder characterized by significant disturbances in social, communicative, and behavioral functioning. A two-stage genomic screen analysis of 99 families with AutD revealed suggestive evidence for linkage to chromosome 2q (D2S116 nonparametric sib-pair LOD score [MLS] 1.12 at 198 cM). In addition, analysis of linkage disequilibrium for D2S116 showed an allele-specific P value of <.01. Recently, linkage to the same region of 2q was reported in an independent genome screen. This evidence for linkage increased when analysis was restricted to the subset of patients with AutD who had delayed onset (>36 mo) of phrase speech (PSD). We similarly classified our data set of 82 sib pairs with AutD, identifying 45 families with AutD and PSD. Analysis of this PSD subset increased our support for linkage to 2q (MLS 2.86 and HLOD 2.12 for marker D2S116). These data support evidence for a gene on chromosome 2 contributing to risk of AutD, and they suggest that phenotypic homogeneity increases the power to find susceptibility genes for AutD.
authors.affiliation: Center for Human Genetics, CARL Building, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shao
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Raiford
authors.forename: Chantelle M
authors.initials: CM
authors.lastname: Wolpert
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Cope
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Ravan
authors.forename: Allison A
authors.initials: AA
authors.lastname: Ashley-Koch
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Abramson
authors.forename: Harry H
authors.initials: HH
authors.lastname: Wright
authors.forename: Robert G
authors.initials: RG
authors.lastname: DeLong
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
mesh_terms: D017668:Age of Onset; D000465:Algorithms; D001321:Autistic Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008957:Models, Genetic; D010641:Phenotype; D013064:Speech Disorders / Q000235:genetics