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Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene
Author(s) -
Wassink Thomas H.,
Piven Joseph,
Vieland Veronica J.,
Jenkins Laura,
Frantz Rebecca,
Bartlett Christopher W.,
Goedken Rhinda,
Childress Deb,
Spence M. Anne,
Smith Moyra,
Sheffield Val C.
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30180
Subject(s) - genetics , biology , heritability of autism , autism , candidate gene , genetic linkage , linkage disequilibrium , transmission disequilibrium test , breakpoint , exon , gene , chromosome , haplotype , allele , phenotype , medicine , psychiatry
Autism is a highly heritable neurodevelopmental syndrome with a complex genetic etiology for which no disease genes have yet been definitively identified. We ascertained three subjects with autism spectrum disorders and chromosome 2q37.3 terminal deletions, and refined the deletion breakpoint regions using polymorphism mapping and fluorescence in situ hybridization (FISH) probes. We then genotyped polymorphic markers downstream from the breakpoint region in a sample of autism affected sibling pair families. Both the chromosomal breakpoints and linkage analyses focused our attention on the gene centaurin gamma‐2 ( CENTG2 ), an attractive candidate gene based also on its function and pattern of expression. We therefore assessed CENTG2 for its involvement in autism by (1) screening its exons for variants in 199 autistic and 160 non‐autistic individuals, and (2) genotyping and assessing intra‐genic polymorphisms for linkage and linkage disequilibrium (LD). The exon screen revealed a Ser → Gly substitution in one proband, an Arg → Gly substitution in another, and a number of additional variants unique to the autism families. No unique variants were found in the control subjects. The genotyping produced strong evidence for linkage from two intronic polymorphisms, with a maximum two‐point HLOD value of 3.96 and a posterior probability of linkage (PPL) of 51%. These results were contradicted, however, by substantially weaker evidence for linkage from multi‐point analyses and by no evidence of LD. We conclude, therefore, that 2q37.3 continues to be a region of interest for autism susceptibility, and that CENTG2 is an intriguing candidate gene that merits further scrutiny for its role in autism. © 2005 Wiley‐Liss, Inc.