Genetic studies of autistic disorder and chromosome 7

Genome-wide scans have suggested that a locus on 7q is involved in the etio logy of autistic disorder (AD). We have identified II AD family in which th ree sibs inherited from their mother a paracentric inversion in the chromos ome 7 candidate region (inv(7)(q22-q31.2)). Clinically, the two male sibs h ave AD, while the female sib has expressive language disorder. The mother c arries the inversion, but does not express AD. Haplotype data on the family suggest that the chromosomal origin of the inversion was from the children 's maternal grandfather. Based on these data, we have genotyped 76 multiple x (greater than or equal to 2 AD affected/family) families for markers in t his region of 7q. Two-point linkage analysis yielded a maximum heterogeneit y lod score of 1.47 and maximum lod score (MLS) of 1.03 at D7S495. Multipoi nt MLS and NPL analyses resulted in peak scores of 1.77 at D7S2527 and 2.01 at D7S640. Examination of affected sibpairs revealed significant paternal (P = 0.007), but not maternal (P = 0.75), identity-by-descent sharing at D7 S640. Significant linkage disequilibrium was detected with paternal (P = 0. 02), but not maternal (P = 0.15), transmissions at D7S1824 in multiplex and singleton families. There was also evidence for an increase in recombinati on in the region (D7S1817 to D7S1824) in the AD families versus non-AD fami lies (P = 0.03, sex-averaged; and P = 0.01, sex-specific). These results pr ovide further evidence for the presence of an AD locus on chromosome 7q, as well as provide evidence suggesting that this locus may be paternally expr essed. (C) 1999 Academic Press.