Causal impact of Mobile Elements (MEs) on neurodevelopmental disorders

Sammy Hansali, Anthony Wong, Anbo Zhou, Xiaolong Cao, Vaidhyanathan Mahaganapathy, Marco Azaro, Christine Gwin, Sherri Wilson, Steven Buyske, Christopher W. Bartlett, Judy F. Flax, Linda M. Brzustowicz, and Jinchuan Xing

Mobile Elements (MEs) are stretches of DNA sequences that selectively insert themselves into specific regions of the genome, often disrupting normal RNA splicing and gene expression. Transposition of MEs into conserved regions of the genome can have catastrophic effects on cell behavior, and leads to the downstream development of mendelian disease and hereditary cancers. We are interested in discovering the causal relationship of ME activity and onset of complex, polygenic neurodevelopmental disorders like Autism Spectrum Disorder (ASD). To do so, we analyzed the whole genome sequences, pedigrees, and phenotypic information of 272 individuals, from a total of 73 families, comprising the New Jersey Language and Autism Study cohort. From our analysis, 52 genes contain MEs that are likely to disrupt the gene function and segregate with the disorder phenotype. 30 of those genes are highly likely to be important for neurodevelopmental disorder onset, according to our criteria. This work is accompanied by more projects tackling the question of "What drives onset of neurodevelopmental disorders, on the genetic level?" by looking at other polygenic genetic variants such as Copy Number Variants and microRNAs in the same cohort. We hope that these works will provide scientists with potential drug targets in the future, and help increase the body of knowledge around these disorders.