Autism genetics: strategies, challenges, and opportunities.
Although genes have long been appreciated to play a critical role in determining the risk for pervasive developmental disorders, the specific transcripts contributing to autism spectrum disorders (ASD) have been quite difficult to characterize. However, recent findings are now providing the first insights into the molecular mechanisms underlying these syndromes and have begun to shed light on the allelic architecture of ASD. In this article, we address what is known about the relative contributions of various types of genetic variation to ASD, consider the obstacles facing gene discovery in this complex disorder, and evaluate the common methodologies employed to address these issues, including linkage, molecular and array-based cytogenetics, and association strategies. We review the current literature, highlighting recent findings implicating both rare mutations and common genetic polymorphisms in the etiology of autism. Finally, we describe key advances in genomic technologies that are transforming all areas of human genetics and consider both the opportunities and challenges for autism research posed by these rapid changes.
Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Brian J
BJ
O'Roak
Matthew W
MW
State
D000483:Alleles; D001321:Autistic Disorder / Q000175:diagnosis / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D036281:Genetic Research; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008126:Lod Score; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D012307:Risk Factors; D012931:Social Environment; D018709:Statistics, Nonparametric
C403049:CNTNAP2 protein, human; D005819:Genetic Markers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins