Austism and the X Chromosome: Multipoint sib-Pair Analysis
1996
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 λ XS (ie, ratio of risk to siblings compared with the population prevalence), owing to an X-linked gene. Different λ XS values were assumed and regions of exclusion were established. Results: The entire X chromosome could be excluded for a λ XS value of 4. The ability to exclude an X-linked gene decreased with smaller λ XS values, and some positive evidence was obtained with smaller values. A maximum lod score of 1.24 was obtained at locus DXS424 with a λ XS 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 (λ XS DXS453 and DXS1001 .
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