This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, rare mutations of the CHD7 gene have been identified with CHARGE syndrome (Vissers et al., 2004), and a rare mutation in the CHD7 gene has been identified in an individual with ASD (ORoak et al., 2012).
Molecular Function
This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.
The deletion of Chd7 causes inner year problems in the mouse model and mutations in this gene have been found in some patients with the CHARGE syndrome.
References
Type
Title
Author, Year
Primary
Otitis media in a new mouse model for CHARGE syndrome with a deletion in the Chd7 gene.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mice designated as OME ( otitis media and eye defects) mice, as hearing deficits were observed in these mice in the Jackson Laboratory- these mice harbor a spontaneous mutation, transmitted in an autosomal dominant manner, located somewhere in the Chd7 gene- the exact location is not known. Exon 1 and 4 are spliced together leading to the deletion of exon 2 and 3.
Allele Type: NA
Strain of Origin: Genetic Background: BALB/cByJ
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of critical exons located between positions 8784907 and 8786002 (Chromosome 4 ) of the Chd7 gene using Nestin-cre, in neuronal, glial and other cell types in the central and peripheral nervous system
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6N
Genetic Background: C57BL/6N* C57BL/6J
ES Cell Line: JM8
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 3 of the Chd7 using Math1-cre, specifically from cerebellar granule cell lineage, starting around E14.5
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6N
Genetic Background: C57BL/6N* C57BL/6J
ES Cell Line: JM8
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Atoh1 (math1) enhancer driven cre transgenic line to conditionally trigger knockout of the chd7 gene selectively in the granule cell lineage at the time of specification in the rhombic lip15. chd7fl/fl mice were obtained from eucomm, and the neomycin selection cassette was removed by crossing with flp deleter mice. jq2-atoh1 promoter fragment was ligated to the bacteriophage p1 cre recombinase cdna and injected into mouse embryo pro-nuclei to generate two transgenic mouse lines that carried the atoh1-cre.
Allele Type: Conditional loss of function
Strain of Origin: Genetic Background: not specified
ES Cell Line: not specified
Mutant ES Cell Line: Model Source: 34588434; 23827709; 16145671; 11502254
Description: Chd7 hets have middle and inner ear abnormalities- otitis media, as well has eye defects (keratoconjunctivitis sicca). increased effusion by inflammatory cells in the middle ear and eustachian canal, thickened epithelia, dilated periostem were observed . increase in goblet cells in the middle ear and eustachian canal. reduced ciliary density in the eustachian tube was also seen.
Exp Paradigm: Ear samples were decalcified and embedded in paraffin. sections were cut and stained with hematoxylin/eosin. the middle an dinner ears were assessed for pathological problems, like middle ear effusion, inflammatory cell infiltration, tissue debris and tissue proliferation, number of cilia.
Description: The mean abr thresholds for chd7 hets in each age group were significantly higher than those of wild type mice at all frequencies tested. the dpoae tests show that the hets have amplitudes below zero at very frequency tested. tympanometry measurement showed lower compliance values in hets.
Exp Paradigm: A computer aided evoked potential system was used to measure mouse abr thresholds and dpoae amplitudes.
Description: Craniofacial abnormalities are observed. larger skull height/ skull length , larger nose bone length/ skull length, greater eustachian tube angle was seen in the chd7 hets.
Exp Paradigm: NA
Description: Cerebellar size is disproportionately reduced with hypoplasia of the cerebellar lobules and vermis in chd7 cko mice (only two cko mice survived and were analyzed at p21)
Exp Paradigm: NA
Description: Chd7 cko mice have smaller and irregular cerebellar folia, with vermis folia iv-v, and ix extended towards lateral hemispheres
Exp Paradigm: NA
Description: Chd7 mrna is not detectable by e12.5 in the brain and at birth there is complete lack of chd7 protein in the brain of mutant mice
Exp Paradigm: NA
Description: Male chd7 gcp specific ko mice have reduced motor coordination and shorter latency to fall off on the rotarod compared to sex, age-matched wt controls
Exp Paradigm: NA
Description: Chd7 gcp specific ko leads to reduced proliferation of gcps in vermis lobules i-viii detected by brdu incorporation, authors note there was no change in brdu staining in the hemispheres
Exp Paradigm: NA
Description: Impaired differentiation of purkinje cell progenitors and mislocalization are evident in the vermis and hemispheres by e18.5
Exp Paradigm: NA
Description: Increased apoptosis of gcps is observed in the hemispheres of chd7 gcp specific cko mice , authors note that increase in apoptosis did not reach significance in the vermis
Exp Paradigm: NA
Chromatin modification: histone modification: open chromatin1
Decreased
Description: Dna accessibility, determined by dnase sequencing is found ot be reduced significantly in the gcps from chd7 gcp specific knockouts, specifically regulatory elements around the reln locus are reduced to some extent
Exp Paradigm: NA
Dnase i hypersensitive sites sequencing (dnase-seq)
Description: Chd7 knockout using math1-cre results in loss of chd7 protein from the cerebellar hemispheres starting e14.5, through postnatal stages, as expected
Exp Paradigm: In situ hybridization (ish)
Description: Several regions of dna have increased as well as decreased dna accessibility, compared to wt, in gcps from p7 chd7 gcp specific knockout mice, determined using an assay that finds transposase-accessible chromatin with high-throughput sequencing
Exp Paradigm: NA
Assay for transposase-accessible chromatin with high-throughput sequencing (atac-seq)
Description: Chd7 knockout using math1-cre results in loss of chd7 protein from the cerebellar hemispheres starting e14.5, through postnatal stages, as expected
Exp Paradigm: Immunohistochemistry
Description: Downregulation of several genes was observed, notably reln, in the granule cell precursors isolated from chd7 gcp specific knockout mice
Exp Paradigm: NA
Description: Cerebellar microgyria, eight folds were detected along the mediolateral axis of the anterior cerebellar vermis with 100% penetrance; anteriorâ??posterior foliation of the cerebellar vermis was significantly reduced; mediolateral length of the cerebellum was significantly increased; anteriorâ??posterior and dorsoventral lengths were significantly decreased
Description: Chd7-occupied 22,515 genomic sites in analysis of anterior cerebellum of wt mice and chd7 chip signal was reduced in conditional chd7 knockout mice
Description: Higher ratio of vertical to horizontal divisions in the anteriorâ??posterior plane compared to the mediolateral plane in control mice; ratio of vertical to horizontal divisions was reduced in the anteriorâ??posterior plane and increased in the mediolateral plane
Description: Onset of aberrant folding, marked by the emergence of a single sulcus at the mediolateral midpoint of the anterior cerebellar vermis; by p3.5, two symmetric microgyri had developed around the initial midline sulcus; by p4, four distinct microgyri had emerged
Exp Paradigm: nano CT
Chromatin modification: histone modification: open chromatin1
decreased
Description: Concordant reduction in accessibility and the expression of topologically associated genes
Exp Paradigm: log2 fold-change of RNA signal for genes proximal to CHD7-bound sites with significant changes in accessibility in the CHD7 cKO
Description: Correlation of genomic interaction frequency with enhancer accessibility and h3k27ac levels
Exp Paradigm: in situ chromosome conformation capture with high-throughput sequencing (Hi-C)
Description: Depletion of chd7 significantly reduced chromatin accessibility at chd7-bound sites relative to non-bound regulatory elements; 83% of chd7-bound active enhancers exhibited decreased chromatin accessibility upon chd7 depletion
Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq)
Description: Chd7 depletion in granule cell precursors in the anterior and central cerebellar vermis upon conditional knockout of chd7 using the math1-cre line
