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 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.
Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory of Developmental and Molecular Neurobiology, Stanford University, Calif, USA.
J
J
Hallmayer
J M
JM
Hebert
D
D
Spiker
L
L
Lotspeich
W M
WM
McMahon
P B
PB
Petersen
P
P
Nicholas
C
C
Pingree
A A
AA
Lin
L L
LL
Cavalli-Sforza
N
N
Risch
R D
RD
Ciaranello
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics*; D002874:Chromosome Mapping; D005190:Family; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D016017:Odds Ratio; D014960:X Chromosome / Q000235:genetics*
D005819:Genetic Markers