Autism spectrum disorder ASD) is a lifelong psychiatric condition that affects about 1 in 88 children. It has a strong genetic basis, but with a high degree of heterogeneity -- although ~10% ASD cases have an identifiable genetic syndrome, each syndrome and its underlying genetic cause only account for ~1% or less of the ASD cases. Recent genetic studies have identified more genetic causes from rare mutations, but they currently can only explain ~20% of the cases. It is possible that some of the clinically relevant mutations may reside in the genomic regions where current technologies fall short of detection. One such example is the trinucleotide repeat TNR) sequences.
Fragile X syndrome is one of the leading known genetic causes of ASD, which is mostly caused by an expansion of TNRs beyond 200 times at the regulatory region of the fragile X mental retardation 1 FMR1) gene. TNR expansion causes loss of the gene function and disrupts the early brain development of the patients. TNR expansion in other known ASD-risk genes, such as AFF2 and DMPK, has also been found in individuals with ASD, suggesting that it may be an important risk factor for ASD. However, a large-scale screening of TNR expansion in human genome has not been carried out. Using a combination of bioinformatics analysis and high-throughput sample screening strategy, I propose a systematic search of novel TNR expansion in ASD. This project should provide a complement to the findings generated by the existing variant detection technologies, such as next-generation sequencing. A screening of novel TNR expansion may thus improve the diagnostic yield for ASD.