Lamb, J, Barnby,G., Bonora,E., Sykes,N., Bacchelli,E., Blasi,F., Maestrini,E., Broxholme,J.,
Tzenova,J., Weeks,D., Bailey,A.J., Monaco,A.P
J. Med. Genet. 2005;42(2):132-137.
BACKGROUND AND METHODS: Autism is a severe neurodevelopmental disorder, which has
a complex genetic predisposition. The ratio of males to females affected by autism
is approximately 4:1, suggesting that sex specific factors are involved in its development.
We reported previously the results of a genomewide screen for autism susceptibility
loci in 83 affected sibling pairs (ASP), and follow up analysis in 152 ASP. Here,
we report analysis of an expanded sample of 219 ASP, using sex and parent of origin
linkage modelling at loci on chromosomes 2, 7, 9, 15, and 16. RESULTS: The results
suggest that linkage to chromosomes 7q and 16p is contributed largely by the male-male
ASP (MLS = 2.55 v 0.12, and MLS = 2.48 v 0.00, for the 145 male-male and 74 male-female/female-female
ASP on chromosomes 7 and 16 respectively). Conversely linkage to chromosome 15q appears
to be attributable to the male-female/female-female ASP (MLS = 2.62 v 0.00, for non-male
and male-male ASP respectively). On chromosomes 2 and 9, all ASP contribute to linkage.
These data, supported by permutation, suggest a possible sex limited effect of susceptibility
loci on chromosomes 7, 15, and 16. Parent of origin linkage modelling indicates two
distinct regions of paternal and maternal identity by descent sharing on chromosome
7 (paternal MLS = 1.46 at approximately 112 cM, and maternal MLS = 1.83 at approximately
135 cM; corresponding maternal and paternal MLS = 0.53 and 0.28 respectively), and
maternal specific sharing on chromosome 9 (maternal MLS = 1.99 at approximately 30
cM; paternal MLS = 0.02). CONCLUSION: These data support the possibility of two discrete
loci underlying linkage of autism to chromosome 7, and implicate possible parent of
origin specific effects in the aetiology of autism