AUTISM AND THE X-CHROMOSOME - MULTIPOINT SIB-PAIR ANALYSIS

Background: Genetic factors undoubtedly play a major etiologic role in autism, but how it is inherited remains unanswered. The increased inc idence in males suggests possible involvement of the X chromosome. Met hods: Using data from 38 multiplex families with autism (2 or more aut istic siblings), we performed a multipoint sib-pair linkage analysis b etween autism and 35 microsatellite markers located on the X chromosom e. The model included a single parameter, the risk ratio lambda(XS) (i e, ratio of risk to siblings compared with the population prevalence), owing to an X-linked gene. Different lambda(XS) values were assumed a nd regions of exclusion were established. Results: The entire X chromo some could be excluded for a lambda(XS) value of 4. The ability to exc lude an X-linked gene decreased with smaller lambda(XS) values, and so me positive evidence was obtained with smaller values. A maximum lod s core of 1.24 was obtained at locus DXS424 with a lambda(XS) value of 1 .5. Conclusions: We were able to exclude any moderate to strong gene e ffect causing autism on the X chromosome. Smaller gene effects (lambda (XS)<4) could not be excluded, in particular, a gene of small effect l ocated between DXS453 and DXS1001.