A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development.

Molecular Psychiatry
Else EisingSimon E Fisher

Abstract

Genetic investigations of people with impaired development of spoken language provide windows into key aspects of human biology. Over 15 years after FOXP2 was identified, most speech and language impairments remain unexplained at the molecular level. We sequenced whole genomes of nineteen unrelated individuals diagnosed with childhood apraxia of speech, a rare disorder enriched for causative mutations of large effect. Where DNA was available from unaffected parents, we discovered de novo mutations, implicating genes, including CHD3, SETD1A and WDR5. In other probands, we identified novel loss-of-function variants affecting KAT6A, SETBP1, ZFHX4, TNRC6B and MKL2, regulatory genes with links to neurodevelopment. Several of the new candidates interact with each other or with known speech-related genes. Moreover, they show significant clustering within a single co-expression module of genes highly expressed during early human brain development. This study highlights gene regulatory pathways in the developing brain that may contribute to acquisition of proficient speech.

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Citations

Oct 9, 2018·Journal of Paediatrics and Child Health·Angela T Morgan, Richard Webster
Feb 24, 2019·Brain : a Journal of Neurology·Frédérique J LiégeoisAngela T Morgan
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Apr 17, 2019·Clinical Linguistics & Phonetics·Lawrence D ShribergHeather L Mabie
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Mar 3, 2020·International Journal of Speech-language Pathology·Åsa MogrenAnita McAllister
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Methods Mentioned

BETA
PCR
exome sequencing

Software Mentioned

DAVID
seq2
BIC
BreakDancer
WGCNA package
Picard
SAMtools
Burrows Aligner ( BWA )
Polyphen
Genome Analysis Toolkit Software ( GATK

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