Genetic Studies of Autistic Disorder and Chromosome 7

doi:10.1006/geno.1999.5968

Genomics

Volume 61, Issue 3, 1 November 1999, Pages 227-236

https://doi.org/10.1006/geno.1999.5968 Get rights and content

Abstract

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.

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¹: To whom correspondence should be addressed at Department of Medicine, Center for Human Genetics, CARL Building, Box 3445, Duke University Medical Center, Durham, NC 27710. Telephone: (919) 684-2063. Fax: (919) 684-2275. E-mail: [email protected].

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Regular ArticleGenetic Studies of Autistic Disorder and Chromosome 7

Abstract

Am. J. Hum. Genet.

Genomics

Am. J. Hum. Genet.

Am. J. Hum. Genet.

Int. Rev. Neurobiol.

Am. J. Hum. Genet.

Genomics

Curr. Biol.

J. Am. Acad. Dermatol.

Cell

Autism as a strongly genetic disorder: Evidence from a British twin study

Psychol. Med.

Genomic screen for autistic disorder

Am. J. Hum. Genet. (Suppl.)

A case-control family history study of autism

J. Child Psychol. Psychiatry

Paracentric inversions in man

Clin Genet

Genetic imprinting in the mouse: Implications for gene regulation

J. Inherit. Metab. Dis.

Autism or atypical autism in maternally but not paternally derived proximal 15q duplication

Am. J. Hum. Genet.

A genetic linkage map of the mouse: Current applications and future prospects

Science

Familial aggregation in autism: Evidence against X-linkage as a major genetic etiology

Am. J. Hum. Genet. (Suppl.)

A cytogenetic survey of men being investigated for subfertility

J. Reprod. Fertil.

Increased frequencies of sister chromatid exchanges at common fragile sites (1)(q42) and (19)(q13)

Hum. Genet.

Localization of a gene implicated in a severe speech and language disorder

Nat. Genet.

Cytogenetic and molecular analysis of inv dup(15) chromosomes observed in two patients with autistic disorder and mental retardation

Am. J. Med. Genet.

Etiology of autism: Genetic influences

Pediatrics

Chromosomal disorders and autism

J. Autism Dev. Disord.

Induction of sister chromatid exchanges at common fragile sites

Am. J. Hum. Genet.

Chromosome breakage and recombination at fragile sites

Am. J. Hum. Genet.

Genomic imprinting: Review and relevance to human diseases

Am. J. Hum. Genet.

Male-to-male transmission in extended pedigrees with multiple cases of autism

Am. J. Med. Genet.

Affected-sib-pair interval mapping and exclusion for complex genetic traits—sampling considerations

Genet Epidemiol.

What are the polymorphonuclear projections in trisomy 13?

Am. J. Hum. Genet. (Suppl.)

Regular Article
Genetic Studies of Autistic Disorder and Chromosome 7