Identification of autism susceptibility candidates on 7q

Autism is a progressive developmental disorder characterized by deficits in language and social communication, as well as stereotyped patterns of behavior. Peak LOD scores from several genomic screening efforts (IMGSAC, 1998; Bass et al., 1998; Philippe et al., 1999) indicate the presence of an autism susceptibility locus within human Chromosome 7 (7q31-q35). We have identified a family (Duke Family 7543) in which AD affection status is found to segregate with a paracentric inversion, Inv(7)(q22q31.2), located within the area of peak linkage (Ashley-Koch et al., 1999). Utilizing 19 BACs for FISH and 11 probes for pulse field analysis, we have localized the distal breakpoint of this inversion to 300 kb of NIH YAC contig 0. The availability of fully sequenced BACs have allowed us to utilize web-based exon prediction software (GENSCAN, GRAIL, FGENE) to search for novel genes in our breakpoint region. BLAST analysis of 20 predicted exons, followed by primer development and PCR amplification of fetal and adult brain cDNA libraries, have yielded the discovery of three novel transcripts. Extension and Northern analysis, respectively, will be utilized to determine the transcript size and expression patterns of these genes, aiding in the determination of their status as autism susceptibility candidates.

Duke Scholars

Author Allison Elizabeth Ashley-Koch Medicine, Nephrology