Abstract
Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian—South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.
Highlights
Autism spectrum disorders (ASD) are a range of complex neurodevelopmental conditions characterized by dysfunctions in mental development [1]
Most ASD studies highlight a strong genetic heterogeneity where both de novo germline and rare inherited variants are distributed across numerous genes yet, interconnected in similar
The findings of Retinoic Acid Response Elements (RAREs) sequences in the promoter regions, in humans as in mice, made us consider that RA receptors (RARs) family might regulate FOXN1 and ALDH1A3 genes
Summary
Autism spectrum disorders (ASD) are a range of complex neurodevelopmental conditions characterized by dysfunctions in mental development [1]. It has been hypothesized that ASD are a group of continuous disorders instead of a single discrete disorder [2], explaining why ASD patient symptomatology is so variable. Prevalence of ASD has increased worldwide [3], in Colombia there are no official reports regarding its prevalence. Whole Exome Sequencing in Colombian ASD Trios
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