Identification of Novel Gene Variants for Autism Spectrum Disorders in the Lebanese Population Using Whole-Exome Sequencing

Abstract

In our previous study, in which array CGH was used on 19 Lebanese ASD subjects and their parents, we identified rare copy number variants (CNVs) in 14 subjects. The five remaining subjects did not show any CNVs related to autism spectrum disorders (ASD). In the present complementary study, we applied whole-exome sequencing (WES), which allows the identification of rare genetic variations such as single nucleotide variations and small insertions/deletions, to the five negative CNV subjects. After stringent filtering of initial data on the five families, three novel genes potentially related to neurodevelopment were identified, including a de novo mutation in the MIS18BP1 gene. In addition, genes already known to be related to ASD contained sequence variations. Our findings outline the potential involvement of the novel de novo mutation in the MIS18BP1 gene in the genetic etiology and pathophysiology of ASD and highlights the genetic complexity of these disorders. Further studies with larger cohorts of subjects are needed to confirm these observations, and functional analyses need to be performed to understand the precise pathophysiology in these cases.

Structural variation and eQTL analysis in two experimental populations of chickens divergently selected for feather-pecking behavior

“…Although genome-wide significance was closely missed for these associations, we strongly believe that the AWM approach by Reverter and Fortes [ 37 ] led to the discovery of a high-confidence set of variants for this complex trait. Among these putative ETV1 targets are CSF2RB , which has been associated with major depression and schizophrenia [ 60 ], and MIS18BP1 , a gene implicated in the autism spectrum [ 61 ]. Furthermore, an ETV1 antibody coimmunoprecipitated the GABAA receptor α6 (GABAARα6) promoter region in mice [ 57 ], and ETV1 is a regulator of gene expression in CD4 and CD8 T cells [ 62 ].…”

Structural variation and eQTL analysis in two experimental populations of chickens divergently selected for feather pecking behavior

“…According to the Human Protein Atlas ETV1 expression is specific to salivary glands and the brain, specifically the cerebellum and thalamus (https://www.proteinatlas.org/ENSG00000006468-ETV1; accessed August 2022) ETV1 is associated with the differential expression of 23 genes between HFP and LFP and ETV1 binding sites are enriched in proximity to these genes (Figure 3). Among these putative ETV1 targets are CSF2RB , which has been associated with major depression and schizophrenia [47], and MIS18BP1 , a gene implicated in autism spectrum [48]. Furthermore, ETV1 antibody coimmunoprecipitated the GABAA receptor α6 (GABAARα6) promoter region in mice [44] and is a regulator of gene expression in CD4 and CD8 T cells [49].…”