Autism genetics – an overview

Abstract

Autism spectrum disorder (ASD) is a highly heritable, clinically diverse group of neurodevelopmental disorders. Its genetic heterogeneity is remarkable, with more than 800 ASD predisposition genes identified to date. They are involved in various biological processes, including chromatin remodeling and gene transcription regulation, cell growth and proliferation, ubiquitination, and neuronal-specific processes, such as synaptic organization and activity, dendritic morphology, and axonogenesis. This review aims to discuss basic autism genetics, explicate ways to investigate ASD in model systems, highlight some key genes and their molecular pathways, and introduce novel theories of ASD pathogenesis, such as imbalance of excitatory and inhibitory brain activity, oligogenic heterozygosity, and the female protective model. © 2016 John Wiley & Sons, Ltd.

In case you missed it: The Prenatal Diagnosis editors bring you the most significant advances of 2017

“…The recurrence rate is ~23% for a male child and ~8% for a female child after 1 affected sibling. This rises considerably after 2 affected siblings: ~47% for a male child and 20% for a female child …”

“…Due to the rapid pace of research in neurodevelopment, Prenatal Diagnosis dedicated its January 2017 special topic issue to prenatal testing for neuropsychiatric conditions. In this issue, Yin and Schaaf provided an excellent overview of the complex genetics and clinical presentation of ASD . The genetic heterogeneity in autism makes genetic counseling very difficult.…”

“…Variants in genes associated with the following biological processes are thought to play a role in the etiology of ASD: chromatin remodeling ( MECP2, CHD8, EHMT1, ANKRD1 ), transcription ( FOXP1, TBR1, RAI1 ), RNA binding and regulation ( FMR1 ), protein ubiquitination ( UBE3A, MAGEL2, USP7 ), cell growth and proliferation ( TSC1 and TSC2, PTEN, NF1, CDKL5, SYNGAP1, DYRK1A, MET ), synaptic organization and activity ( SHANK2, SHANK3 ), transmembrane protein activity (neurexins and neuroligins), and cell adhesion. With chromosome microarray analyses, deletions or duplications as small as 5 kb have been instrumental in identifying specific areas of the germ line that are susceptible to ASD . These include 1q21.1 deletion, 3q29 deletion, 15q, 16p11.2, and 22q13.3.…”

“…In this issue, Yin and Schaaf provided an excellent overview of the complex genetics and clinical presentation of ASD. 19 The genetic heterogeneity in autism makes genetic counseling very difficult. The recurrence rate is~23% for a male child and~8% for a female child after 1 affected sibling.…”

“…This rises considerably after 2 affected siblings:~47% for a male child and 20% for a female child. 19 There are over 800 genes that predispose to autism. Whole exome sequencing alone has led to the identification of more than 150 new candidate genes.…”