Lack of evidence for an association between WNT2 and RELN polymorphisms and autism.
Autism is a pervasive neurodevelopmental disorder characterized by deficits in language development and social interaction, as well as stereotypical, repetitive behaviors. The etiology of autism is largely unknown. Family and twin studies have provided compelling evidence for a strong genetic component in most idiopathic cases. Several recent candidate gene studies have suggested that alleles of WNT2 and the reelin gene (RELN), two genes involved in distinct aspects of neurodevelopment, confer greater susceptibility to autism. We screened WNT2 for DNA polymorphisms by sequencing all exons and adjacent intronic regions in 24 autistic patients, and identified not only the WNT2 variants reported previously (two common single-nucleotide polymorphisms (SNPs) in the 5' upstream region and the 3' untranslated region (UTR), respectively), but also two new SNPs in its 3' UTR. We genotyped all four WNT2 polymorphisms and a polymorphic trinucleotide repeat in the 5' UTR of RELN in 107 families with multiple autistic children, and evaluated evidence for association between these variants and autism by the transmission disequilibrium test (TDT). Our results revealed no deviation from the null hypothesis of no association. Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism.
Li
Jun
J
Department of Genetics M344, Stanford University School of Medicine, Stanford, CA 94305-5120, USA.
Nguyen
Loan
L
Gleason
Christopher
C
Lotspeich
Linda
L
Spiker
Donna
D
Risch
Neil
N
Myers
Richard M
RM
D020121:5' Untranslated Regions / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D035781:Siblings; D018911:Trinucleotide Repeats / Q000235:genetics*; D051153:Wnt Proteins; D051154:Wnt2 Protein
D020121:5' Untranslated Regions; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D000091042:Reelin Protein; C495244:WNT2 protein, human; D051153:Wnt Proteins; D051154:Wnt2 Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases