Genome-wide scan for loci of Asperger syndrome

Abstract

Asperger syndrome (AS), characterised by inadequate social interaction, lack of empathy and a dependence of routines and rituals, is classified as belonging to the autism spectrum disorders (DSM-IV and ICD-10). Although the prevalence of AS has been estimated to range from 0.3 up to 48.4 per 10 000, the phenotype still remains relatively unrecognised by clinicians. Several reports, including the original description by Hans Asperger (1944), have suggested that AS has a strong genetic component. Here, we have performed a genome-wide scan on Finnish families ascertained for AS with a strictly defined phenotype. In the initial scan, Z max 41.5 was observed on nine chromosomal regions, 1q21-22, 3p14-24, 3q25-27, 4p14, 4q32, 6p25, 6q16, 13q31-33 and 18p11. In the fine mapping stage, the highest two-point LOD scores were observed on chromosomes 1q21-22 (D1S484, Z max dom ¼3.58), 3p14-24 (D3S2432, Z max dom ¼2.50) and 13q31-33 (D13S793, Z max dom ¼1.59). The loci on 1q21-22 and 3p14-24 overlap with previously published autism susceptibility loci, and the loci on 1q21-22 and 13q31-33 overlap with the reported schizophrenia susceptibility loci. The present study is the first genome-wide screen in AS and therefore replication data sets are needed to evaluate further the significance of the AS-loci identified here.

The genetics of autistic disorders and its clinical relevance: a review of the literature

“…Several research groups have performed full genome screens in AD. 40,[119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137] Research groups, study design and main findings of linkage studies that reported positive results are summarized in Table 1 for genome-wide linkage and association studies with a qualitative AD phenotype, and in Table 2 for linkage studies with either a quantitative phenotype, a specific qualitative endophenotype, or other specific linkage models. 122,123,127,130,[138][139][140][141][142][143][144][145][146][147][148] From Table 1, it can be seen that linkage has been found in at least two independent studies in regions 2q, 3q25-27, 3p25, 6q14-21, 7q31-36 and 17q11-21.…”

“…120,125,131,132 A recent heterogeneity-based genome search metaanalysis 150 again supported region 7q22-q32, which reached genomewide significance in studies on strictly defined autism, and revealed two loci of suggestive significance (10p12-q11.1;17p11.2-q12) in studies on AD and the BAP. Nine linkage studies 119,120,123,126,[131][132][133]136,151 were included in this meta-analysis. Between-scan heterogeneity was low for the locus on 7q, but high for the loci on 10p 12-q11.1 and 17p11.…”

The ups and downs of Wnt signaling in prevalent neurological disorders

“…Third, twin and family studies have provided compelling evidence for a strong genetic component among autistic individuals (Folstein et al, 2003;Hu-Lince et al, 2005;Vorstman et al, 2006). Multiple genome-wide screens have found evidence for linkage to autism in several chromosomes, including chromosomes 2, 6, 7, 15, 17, 20 and X (International Molecular Genetic Study of Autism Consortium (IMGSAC), 1998, 2001); Barrett et al, 1999;Philippe et al, 1999;Risch et al, 1999;Collaborative Linkage Study of Autism, 2001;Buxbaum et al, 2001;Ylisaukko-oja et al, 2004;Hu-Lince et al, 2005). Likewise, analysis of reported cytogenetic abnormalities (i.e.…”

A heterogeneity-based genome search meta-analysis for autism-spectrum disorders

“…A number of such scans has been published in the last decade 9,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and many of them have been recently updated, expanded, or elaborated in twostage designs in an effort to generate additional information for specific promising chromosomal regions. Despite some overlap in the findings of these scans, typically each scan has shown little or no evidence for strong linkage signals and the results are generally difficult to interpret.…”