Genetic studies of autistic disorder and chromosome 7.

Journal Article (Journal Article)

Genome-wide scans have suggested that a locus on 7q is involved in the etiology of autistic disorder (AD). We have identified an AD family in which three sibs inherited from their mother a paracentric inversion in the chromosome 7 candidate region (inv(7)(q22-q31.2)). Clinically, the two male sibs have AD, while the female sib has expressive language disorder. The mother carries 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 multiplex (>/=2 AD affecteds/family) families for markers in this region of 7q. Two-point linkage analysis yielded a maximum heterogeneity lod score of 1.47 and maximum lod score (MLS) of 1.03 at D7S495. Multipoint 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 D7S640. 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 recombination in the region (D7S1817 to D7S1824) in the AD families versus non-AD families (P = 0.03, sex-averaged; and P = 0.01, sex-specific). These results provide further evidence for the presence of an AD locus on chromosome 7q, as well as provide evidence suggesting that this locus may be paternally expressed.

Full Text

Duke Authors

Cited Authors

  • Ashley-Koch, A; Wolpert, CM; Menold, MM; Zaeem, L; Basu, S; Donnelly, SL; Ravan, SA; Powell, CM; Qumsiyeh, MB; Aylsworth, AS; Vance, JM; Gilbert, JR; Wright, HH; Abramson, RK; DeLong, GR; Cuccaro, ML; Pericak-Vance, MA

Published Date

  • November 1, 1999

Published In

Volume / Issue

  • 61 / 3

Start / End Page

  • 227 - 236

PubMed ID

  • 10552924

International Standard Serial Number (ISSN)

  • 0888-7543

Digital Object Identifier (DOI)

  • 10.1006/geno.1999.5968


  • eng

Conference Location

  • United States