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November 1996

Austism and the X Chromosome: Multipoint sib-Pair Analysis

Author Affiliations

From the Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory of Developmental and Molecular Neurobiology, and the Autism Genetics Program (Drs Hallmayer, Spiker, Lotspeich, and Ciaranello and Ms Hebert), and the Department of Genetics (Ms lin and Drs Cavalli-Sforza and Risch), Standord University, Stanford, Calif; and the Department of Psychiatry, University of Utah (Dr McMahon), and Children's Behavior Therapy Unit (Dr Petersen, Mr Nicholas, and Ms Pingree), Salt Lae City. Dr Hallmayer is now affiliated with Graylands Hospital, University of Western Australia, Perth.
Dr Ciaranello died on December 15, 1994.

Arch Gen Psychiatry. 1996;53(11):980-983. doi:10.1001/archpsyc.1996.01830110021003

Background:  Genetic factors undoubtedly play a major etiologic role in autism, but how it is inherited remains unanswered. The increased incidence in males suggests possible involvement of the X chromosome.

Methods:  Using data from 38 multiplex families with autism (2 or more autistic siblings), we performed a multipoint sib-pair linkage analysis between autism and 35 microsatellite markers located on the X chromosome. The model included a single parameter, the risk ratio λXS(ie, ratio of risk to siblings compared with the population prevalence), owing to an X-linked gene. Different λXSvalues were assumed and regions of exclusion were established.

Results:  The entire X chromosome could be excluded for a λXS value of 4. The ability to exclude an X-linked gene decreased with smaller λXS values, and some positive evidence was obtained with smaller values. A maximum lod score of 1.24 was obtained at locus DXS424 with a λXS value of 1.5.

Conclusions:  We were able to exclude any moderate to strong gene effect causing autism on the X chromosome. Smaller gene effects (λXS<4) could not be excluded, in particular, a gene of small effect located between DXS453 and DXS1001.

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