Chromodomain-helicase-DNA-binding protein 7 is an ATP-dependent 'chromatin' or 'nucleosome' remodeling factor [5] that in humans is encoded by the CHD7 gene. [6] [7]
CHD7 is an ATP-dependent chromatin remodeler homologous to the Drosophila trithorax-group protein Kismet. [8] Mutations in CHD7 are associated with CHARGE syndrome. [9] This protein belongs to a larger group of ATP-dependent chromatin remodeling complexes, the CHD subfamily.
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Abnormal |
| Recessive lethal study | Abnormal |
| Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Abnormal [10] |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal [11] |
| Body temperature | Normal |
| Eye morphology | Abnormal [12] |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Micronucleus test | Normal |
| Heart weight | Normal |
| Brain histopathology | Abnormal |
| Salmonella infection | Normal [13] |
| Citrobacter infection | Normal [14] |
| All tests and analysis from [15] [16] |
Model organisms have been used in the study of CHD7 function. A conditional knockout mouse line, called Chd7tm2a(EUCOMM)Wtsi [17] [18] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. [19] [20] [21]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [15] [22] Twenty four tests were carried out on mutant mice and five significant abnormalities were observed. [15] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice. Male heterozygotes displayed abnormal pelvic elevation in a modified SHIRPA test and have a high incidence of Bergmeister's papilla in both eyes. When the brains of heterozygous animals were studied, an absence of corpus callosum was observed. [15]
Mutations in this gene have been associated with the CHARGE syndrome.
CHARGE syndrome is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart defects, atresia of the nasal choanae, restricted growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness. These features are no longer used in making a diagnosis of CHARGE syndrome, but the name remains. About two thirds of cases are due to a CHD7 mutation. CHARGE syndrome occurs only in 0.1–1.2 per 10,000 live births; as of 2009, it was the leading cause of congenital deafblindness in the US.
T-box transcription factor TBX1 also known as T-box protein 1 and testis-specific T-box protein is a protein that in humans is encoded by the TBX1 gene. Genes in the T-box family are transcription factors that play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, proteins made by this gene family bind to specific areas of DNA called T-box binding element (TBE) to control the expression of target genes.
Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins. Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement.
Unconventional myosin-Va is a motor protein in charge of the intracellular transport of vesicles, organelles and protein complexes along the actin filaments. In humans it is coded for by the MYO5A gene.
6-phosphofructokinase, liver type (PFKL) is an enzyme that in humans is encoded by the PFKL gene on chromosome 21. This gene encodes the liver (L) subunit of an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene. SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. In humans, SMC3 is present in all cohesin complexes whereas there are multiple paralogs for the other subunits.
Centromere protein J is a protein that in humans is encoded by the CENPJ gene. It is also known as centrosomal P4.1-associated protein (CPAP). During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein.
Tyrosine-protein kinase, or Bromodomain adjacent to zinc finger domain, 1B (BAZ1B) is an enzyme that in humans is encoded by the BAZ1B gene.
Whirlin is a protein that in humans is encoded by the DFNB31 gene.
NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial is an enzyme that in humans is encoded by the NDUFS3 gene on chromosome 11. This gene encodes one of the iron-sulfur protein (IP) components of mitochondrial NADH:ubiquinone oxidoreductase. Mutations in this gene are associated with Leigh syndrome resulting from mitochondrial complex I deficiency.
Ubiquitin-associated protein 1 is a protein that in humans is encoded by the UBAP1 gene.
AT-rich interactive domain-containing protein 2 (ARID2) is a protein that in humans is encoded by the ARID2 gene.
Non-imprinted in Prader-Willi/Angelman syndrome region protein 1 is a protein that in humans is encoded by the NIPA1 gene. This gene encodes a potential transmembrane protein which functions either as a receptor or transporter molecule, possibly as a magnesium transporter. This protein is thought to play a role in nervous system development and maintenance. Alternative splice variants have been described, but their biological nature has not been determined. Mutations in this gene have been associated with the human genetic disease autosomal dominant spastic paraplegia 6.
Elongation factor G 1, mitochondrial is a protein that in humans is encoded by the GFM1 gene. It is an EF-G homolog.
Putative Polycomb group protein ASXL1 is a protein that in humans is encoded by the ASXL1 gene.
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 is a protein that in humans is encoded by the SMARCAL1 gene.
1-acylglycerol-3-phosphate O-acyltransferase ABHD5, also known as comparative gene identification-58 (CGI-58), is an enzyme that in humans is encoded by the ABHD5 gene.
Meckel syndrome, type 1 also known as MKS1 is a protein that in humans is encoded by the MKS1 gene.
SLX4 is a protein involved in DNA repair, where it has important roles in the final steps of homologous recombination. Mutations in the gene are associated with the disease Fanconi anemia.
Glutaredoxin domain-containing cysteine-rich protein 1 is a protein that in humans is encoded by the GRXCR1 gene.
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