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 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 and regions of exclusion were established. RESULTS: The entire X chromosome could be excluded for a lambda xs value of 4. The ability to exclude an X-linked gene decreased with smaller lambda 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 lambda 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 (lambda xs < 4) could not be excluded, in particular, a gene of small effect located between DXS453 and DXS1001.
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 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 and regions of exclusion were established. RESULTS: The entire X chromosome could be excluded for a lambda xs value of 4. The ability to exclude an X-linked gene decreased with smaller lambda 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 lambda 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 (lambda xs < 4) could not be excluded, in particular, a gene of small effect located between DXS453 and DXS1001.
Authors: N Risch; D Spiker; L Lotspeich; N Nouri; D Hinds; J Hallmayer; L Kalaydjieva; P McCague; S Dimiceli; T Pitts; L Nguyen; J Yang; C Harper; D Thorpe; S Vermeer; H Young; J Hebert; A Lin; J Ferguson; C Chiotti; S Wiese-Slater; T Rogers; B Salmon; P Nicholas; P B Petersen; C Pingree; W McMahon; D L Wong; L L Cavalli-Sforza; H C Kraemer; R M Myers Journal: Am J Hum Genet Date: 1999-08 Impact factor: 11.025
Authors: Joachim Hallmayer; Emma J Glasson; Carol Bower; Beverly Petterson; Lisa Croen; Judith Grether; Neil Risch Journal: Am J Hum Genet Date: 2002-09-12 Impact factor: 11.025
Authors: Thomas H Wassink; Veronica J Vieland; Val C Sheffield; Christopher W Bartlett; Rhinda Goedken; Deborah Childress; Joseph Piven Journal: Psychiatr Genet Date: 2008-04 Impact factor: 2.458