Journal Article


Louise Gallagher
Michael Gill
Sean Ennis
Andrew J Green
Bronagh O'hici
Marice Mullarkey
Adam Dunlop
Paula Carthy
James S Sutcliffe
Richard J L Anney
and 2 others



pedigree chromosomes human pair 2 chromosome mapping polymorphism single nucleotide integrin alpha4 humans microsatellite repeats karyotyping female alleles genetic predisposition to disease genetics autistic disorder haplotypes mutation male

Fine mapping and association studies in a candidate region for autism on chromosome 2q31-q32. (2008)

Abstract Autism (OMIM %209850) is a neurodevelopmental disorder with a strong genetic component. We previously reported a de novo rearrangement of chromosome 2q31 in a patient with autism [Gallagher et al. (2003); J Autism Dev Disord 33(1):105-108]. Further cytogenetic analysis revealed this to be a 46,XY, t(9;2)(q31.1;q32.2q31.3) translocation. Association mapping with microsatellite and SNP markers of this translocated region on 2q revealed association with markers in Integrin alpha-4 (ITGA4; GeneID 3676). ITGA4 was tested for association in a sample of 179 trio-based families. SNP markers in exons 16 and 17 showed evidence of association. Mutation screening revealed a G to A synonymous variation in the last nucleotide of exon 16 (rs12690517), significantly associated with autism in the Irish sample (OR = 1.6; P = 0.04). The location of this SNP at a putative splice donor site may affect the splicing of the ITGA4 protein. Haplotype analysis showed significant overtransmission of haplotypes surrounding this marker. These markers were investigated in two additional samples, 102 families from Vanderbilt University (VT) (n = 102), and AGRE (n = 267). A non-significant trend towards overtransmission of the associated allele of rs12690517 in the Irish sample (OR = 1.2; P = 0.067) and haplotypes at the 3' end of ITGA4 was observed in the AGRE sample. The VT sample showed association with markers and haplotypes across the gene, but no association with the rs12690517 marker or its surrounding haplotypes. The combined sample showed evidence of association with rs12690517 (OR = 1.3; P = 0.008) and surrounding haplotypes. The findings indicate some evidence for the role of ITGA4 as candidate gene for autism.
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Full list of authors on original publication

Louise Gallagher, Michael Gill, Sean Ennis, Andrew J Green, Bronagh O'hici, Marice Mullarkey, Adam Dunlop, Paula Carthy, James S Sutcliffe, Richard J L Anney and 2 others

Experts in our system

Louise Gallagher
Trinity College Dublin
Total Publications: 61
Michael Gill
Trinity College Dublin
Total Publications: 294
Sean Ennis
University College Dublin
Total Publications: 52
Andrew Green
University College Dublin
Total Publications: 25
Richard Anney
Trinity College Dublin
Total Publications: 40