Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders

PloS One
Oscar A Moreno-RamosMaría Claudia Lattig

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 seq...Continue Reading

References

May 30, 2001·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·F M Benes, S Berretta
Oct 29, 2002·Journal of Lipid Research·James E Balmer, Rune Blomhoff
May 14, 2003·Archives of General Psychiatry·John N Constantino, Richard D Todd
Jun 26, 2003·Nucleic Acids Research·Luca CartegniAdrian R Krainer
Nov 11, 2003·Genes, Brain, and Behavior·J L R Rubenstein, M M Merzenich
Mar 1, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Wen-Lin LiaoFu-Chin Liu
Aug 6, 2005·The Journal of Steroid Biochemistry and Molecular Biology·J E Balmer, R Blomhoff
Jul 11, 2006·Human Molecular Genetics·Philip J SmithAdrian R Krainer
Jan 24, 2007·Cancer Immunology, Immunotherapy : CII·Mark A SuckowMartin Tenniswood
Apr 17, 2008·Nature Reviews. Genetics·Brett S Abrahams, Daniel H Geschwind
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Nov 3, 2009·Cell·Julie A SiegenthalerSamuel J Pleasure
Mar 24, 2010·Molecular Psychiatry·J A S VorstmanR A Ophoff
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Sep 25, 2010·Journal of the Neurological Sciences·Stefania AmorosiClaudio Pignata
Jan 15, 2011·Genome Biology·Shaun MahonyDavid K Gifford
Feb 5, 2011·Social Psychiatry and Psychiatric Epidemiology·Charles M Zaroff, Soo Y Uhm
Sep 13, 2011·Brain, Behavior, and Immunity·Charity OnorePaul Ashwood
Nov 3, 2011·Journal of Affective Disorders·C S PereaM C Lattig
Feb 10, 2012·Development·Muriel Rhinn, Pascal Dollé
May 1, 2012·Neuron·Ivan IossifovMichael Wigler
Oct 12, 2012·PloS One·Yongwook ChoiAgnes P Chan
Dec 25, 2012·Neuron·Joseph D BuxbaumUNKNOWN Autism Sequencing Consortium
Jan 25, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mark R MizeeArie Reijerkerk

❮ Previous
Next ❯

Citations

Sep 14, 2016·Frontiers in Neuroscience·Antonio Benítez-BurracoElliot Murphy
Dec 28, 2016·Molecular Immunology·Sheikh F AhmadAdel R A Abd-Allah
Jun 20, 2017·Nature Neuroscience·Madeleine R GeishekerEvan E Eichler
Jan 1, 2015·Journal of Experimental Neuroscience·Ana Maria OlivaresNeena B Haider
Nov 21, 2019·Aging·Sabah NisarMohammad Haris
Dec 3, 2016·Nucleic Acids Research·Tychele N TurnerEvan E Eichler
Jun 17, 2019·Journal of Neurodevelopmental Disorders·Santosh KumarChengji J Zhou
May 30, 2020·Cellular and Molecular Neurobiology·Juliana BaranovaRicardo G Correa
Jan 25, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Ioan Ovidiu SirbuAlexander Radu Moise
Oct 3, 2017·Cell·Tychele N TurnerEvan E Eichler
Jul 10, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Júlio Santos-TerraCarmem Gottfried
Oct 3, 2021·Nature·Mikihito ShibataNenad Sestan

❮ Previous
Next ❯

Methods Mentioned

BETA
ChIP
exome sequencing
immunoprecipitation
PCR

Software Mentioned

GATK
HaplotypeCaller walker Genome Analysis Toolkit ( GATK
Patser
- Toolkit
PicardTools
SilVA
PolyPhen
SIFT
PROVEAN
FASTX

Related Concepts

Related Feeds

Bipolar Disorder

Bipolar disorder is characterized by manic and/or depressive episodes and associated with uncommon shifts in mood, activity levels, and energy. Discover the latest research this illness here.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here

Autism: Treatment Targets

The absence of effective treatments for autism are due to the high clinical and genetic heterogeneity between affected individuals, restricted knowledge of the underlying pathophysiological mechanisms, and the lack of reliable diagnostic biomarkers. Identification of more homogenous biological subgroups is therefore essential for the development of novel treatments based on the molecular mechanisms underpinning autism and autism spectrum disorders. Find the latest research on autism treatment targets here.

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.