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FB2026_01
,
released March 12, 2026
The human gene CHD2 has been identified as a susceptibility locus for the development of autism spectrum disorder (ASD). CDH2 is a member of a gene family of DNA helicases that act as chromatin remodeling factors and contribute to regulation of transcription. This model uses the single orthologous gene in Drosophila, Chd1, for which for which a variety of genetic reagents have been generated, including RNAi targeting constructs, alleles caused by insertional mutagenesis and imprecise excision, and over-expression constructs.
Dmel\Chd1 is also orthologous to a second member of the gene family, CHD1. Human CHD1 may also be associated with ASD; the available evidence is described as 'suggestive' in SFARI Gene (see below). CHD2 is implicated in a severe form of childhood-onset epilepsy (MIM:615369); CHD1 is implicated in a neurodevelopmental disorder, Pilarowski-Bjornsson syndrome (MIM:617682). Neither CHD2 nor CHD1 has been introduced into flies.
Homozygous loss-of-function alleles of Dmel\Chd1 are lethal in the embryonic stage; animals heterozygous for loss-of-function mutations do not exhibit detectable phenotypes. This model uses animals heterozygous for a loss-of-function mutation of Chd1 and also heterozygous for a mutation in a second Drosophila gene orthologous to a human gene associated with ASD susceptibility, Rim (see FBhh0001277). This genetic combination exhibits second site non-complementation: assayed in the larval neuromuscular junction, failure of presynaptic homeostatic plasticity (PHP) is observed. During testing of deficiencies for candidate genes that impact PHP using the same assumption of second site non-complementation, several deficiencies plus a heterozygous loss-of-function mutation of Chd1 exhibit failure of presynaptic homeostatic plasticity.
The PHP phenotypes of different double heterozygous mutation combinations have been used to isolate and characterize genetic modifiers.
[updated Nov. 2020 by FlyBase; FBrf0222196]
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996, pubmed:8655659; Risch et al., 1999, pubmed:10417292). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (MIM:608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008; pubmed:18698615). [from MIM:209850; 2017.03.18]
The SFARI Gene autism database (https://gene.sfari.org) rates the gene-autism association for CHD2 as high confidence (score 1); some reported cases are syndromic. The SFARI Gene autism database rates the gene-autism association for CHD1 as 'suggestive evidence, syndromic' (score 3S). [2020.11.01]
The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [Gene Cards, CHD2; 2020.11.03]
Many to one: 2 human genes to 2 Drosophila gene; the human genes are CHD1 and CHD2.
High-scoring ortholog of human CHD1 and CHD2 (1 Drosophila to 2 human). Dmel\Chd1 shares 45% identity and 59-60% similarity with the human genes.