title: Presence of large deletions in kindreds with autism.
abstract: Autism is caused, in part, by inheritance of multiple interacting susceptibility alleles. To identify these inherited factors, linkage analysis of multiplex families is being performed on a sample of 105 families with two or more affected sibs. Segregation patterns of short tandem repeat polymorphic markers from four chromosomes revealed null alleles at four marker sites in 12 families that were the result of deletions ranging in size from 5 to >260 kb. In one family, a deletion at marker D7S630 was complex, with two segments deleted (37 kb and 18 kb) and two retained (2,836 bp and 38 bp). Three families had deletions at D7S517, with each family having a different deletion (96 kb, 183 kb, and >69 kb). Another three families had deletions at D8S264, again with each family having a different deletion, ranging in size from <5.9 kb to >260 kb. At a fourth marker, D8S272, a 192-kb deletion was found in five families. Unrelated subjects and additional families without autism were screened for deletions at these four sites. Families screened included 40 families from Centre d'Etude du Polymorphisme Humaine and 28 families affected with learning disabilities. Unrelated samples were 299 elderly control subjects, 121 younger control subjects, and 248 subjects with Alzheimer disease. The deletion allele at D8S272 was found in all populations screened. For the other three sites, no additional deletions were identified in any of the groups without autism. Thus, these deletions appear to be specific to autism kindreds and are potential autism-susceptibility alleles. An alternative hypothesis is that autism-susceptibility alleles elsewhere cause the deletions detected here, possibly by inducing errors during meiosis.
authors.affiliation: Geriatrics Research Education and Clinical Center, Puget Sound Veterans Affairs Medical Center, University of Washington, Seattle 98108, USA.
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dawson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Munson
authors.forename: Ian
authors.initials: I
authors.lastname: D'Souza
authors.forename: Julie
authors.initials: J
authors.lastname: Osterling
authors.forename: Annette
authors.initials: A
authors.lastname: Estes
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Leutenegger
authors.forename: Pamela
authors.initials: P
authors.lastname: Flodman
authors.forename: Moyra
authors.initials: M
authors.lastname: Smith
authors.forename: Wendy H
authors.initials: WH
authors.lastname: Raskind
authors.forename: M Anne
authors.initials: MA
authors.lastname: Spence
authors.forename: William
authors.initials: W
authors.lastname: McMahon
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Wijsman
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001321:Autistic Disorder / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion; D020080:Tandem Repeat Sequences
chemical_list: D005819:Genetic Markers; D004247:DNA