Next Generation Sequencing in Autism Spectrum Disorder

Yin, Jiani C.; Oleson, David; Schaaf, Christian P.

doi:10.21926/obm.genet.1801014

Cited by 3 publications

(2 citation statements)

References 88 publications

(101 reference statements)

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“… 49 In this study, researchers were able to identify two families from the National Institute of Mental Health repository and whole-exome sequence analyses of family members. 76 SCN9A was chosen as one of the candidate genes based on the abundance of variants. One variant, Na v 1.7 C1143F , was validated and it was determined that there were changes in recovery of fast inactivation of the current.…”

Section: The Autism Spectrum Disorder Risk Gene Scn9a and Pain Comorbiditiesmentioning

confidence: 99%

A mini-review: Bridging the gap between autism spectrum disorder and pain comorbidities

Brown

Singh

2020

Canadian Journal of Pain

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Background Pain is a complex neurobiological response with a multitude of causes; however, patients with autism spectrum disorder (ASD) often report chronic pain with no known etiology. Recent research has been aimed toward identifying the causal mechanisms of pain in mouse and human models of ASD. In recent years, efforts have been made to better document and explore secondary phenotypes observed in ASD patients in the clinic. As new sequencing studies have become more powered with larger cohorts within ASD, specific genes and their variants are often left uncharacterized or validated. In this review we highlight ASD risk genes often presented with pain comorbidities. Aims This mini-review bridges the gap between two fields of literature, neurodevelopmental disorders and pain research. We discuss the importance of the genetic landscape of ASD and its links to pain phenotypes. Results Among the numerous genes implicated in ASD, few have been implicated with varying severities of pain comorbidity. Mutations in these genes, such as SCN9A, SHANK3 , and CNTNAP2 , lead to altered neuronal function that produce different responses to pain, shown in both mouse and human models. Conclusion There is a necessity to use new technologies to advance the current understanding of ASD risk genes and their contributions to pain. Secondly, there is a need to power future ASD risk genes associated with pain with their own cohort, because a better understanding is needed of this subpopulation.

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Section: The Autism Spectrum Disorder Risk Gene Scn9a and Pain Comorbiditiesmentioning

confidence: 99%

A mini-review: Bridging the gap between autism spectrum disorder and pain comorbidities

Brown

Singh

2020

Canadian Journal of Pain

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“…Next generation sequencing has proven to be a powerful way to identify variants in many neurological disorders [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. To explore the genetic predisposition to a regressive form of autism, we performed targeted exon capturing and the sequencing of candidate genes.…”

Section: Introductionmentioning

confidence: 99%

Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression

Yin

Chun

Zavadenko

et al. 2020

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Approximately 30% of individuals with autism spectrum disorder (ASD) experience developmental regression, the etiology of which remains largely unknown. We performed a complete literature search and identified 47 genes that had been implicated in such cases. We sequenced these genes in a preselected cohort of 134 individuals with regressive autism. In total, 16 variants in 12 genes with evidence supportive of pathogenicity were identified. They were classified as variants of uncertain significance based on ACMG standards and guidelines. Among these were recurring variants in GRIN2A and PLXNB2, variants in genes that were linked to syndromic forms of ASD (GRIN2A, MECP2, CDKL5, SCN1A,PCDH19, UBE3A, and SLC9A6), and variants in the form of oligogenic heterozygosity (EHMT1, SLC9A6, and MFSD8).

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Drosophila melanogaster Peroxisome Biogenesis Factor 7plays a role in embryonic development

Pridie

2019

Preprint

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Running title: Drosophila melanogaster Pex7Abstract Peroxisomes are organelles responsible for aspects of lipid metabolism and management of reactive oxygen species. Peroxisome Biogenesis Factor (Peroxin, Pex) genes encode proteins essential to peroxisome biogenesis or function. In yeast and mammals, PEROXIN7 acts as a cytosolic receptor protein that targets a subset of enzymes for peroxisome matrix import.Proteins targeted by PEROXIN7 contain a peroxisome targeting sequence 2 (PTS2) motif. The PTS2 was not found in the D. melanogaster homologs of proteins that are PEROXIN7 targets in yeast or mammals, however comparative genomics suggest a Pex7 homolog is present in the D.melanogaster genome. Herein we report novel, tissue-specific patterns for transcription and translation of Pex7 in the D. melanogaster embryo that appear to be strongest in presumptive neuronal lineages. We also show that targeted somatic Pex7 knockout in neural precursors via targeted somatic CRISPR knockout affected survival of mutant embryos. Pex7 over-expression via Gal4-UAS also reduced adult survival but was not deleterious at the embryo stage. Notably, targeted somatic rescue of Pex7 in the neural precursors of Pex7 homozygous mutants also impaired embryo survival. We conclude that D. melanogaster has tissue-specific developmental requirements of Pex7 expression. This may be related to the requirement for peroxisomemediated lipid synthesis in cells of the central nervous system. Baron et al., 2016). Together, these data suggest that D. melanogaster Pex7 function is required for normal development of a specific subset of cells, likely of neuronal lineage. Materials and Methods Drosophila stocks, embryo collection and viability assays

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Next Generation Sequencing in Autism Spectrum Disorder

Cited by 3 publications

References 88 publications

A mini-review: Bridging the gap between autism spectrum disorder and pain comorbidities

A mini-review: Bridging the gap between autism spectrum disorder and pain comorbidities

Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression

Drosophila melanogaster Peroxisome Biogenesis Factor 7plays a role in embryonic development

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