- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
The human gene CHD8 has been identified as a susceptibility locus for the development of autism spectrum disorder (ASD); see FBhh0001275. CDH8 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, kis, for which for which a variety of genetic reagents have been generated, including classical loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis.
Dmel\kis is also orthologous to other members of the gene family: CHD6, CHD7, and CHD9. CHD7 has been associated with syndromic autism in the context of CHARGE syndrome (FBhh0000115); a subset of individuals with this syndrome develop autistic phenotypes. None of the human genes orthologous to kis has been introduced into flies.
Homozygous loss-of-function alleles of Dmel\kis are lethal in the embryonic or larval stages; animals heterozygous for loss-of-function mutations do not exhibit detectable phenotypes. This model uses animals heterozygous for a loss-of-function mutation of kis 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 kis 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 CHD7 and CHD8 as high confidence (score 1). The CHD7 gene is associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism; CHD7 is associated with CHARGE syndrome. [2020.11.01]
CHD8 encodes a member of the chromodomain-helicase-DNA binding protein family, which is characterized by a SNF2-like domain and two chromatin organization modifier domain; members of this family have been shown to function in several processes that include transcriptional regulation, epigenetic remodeling, promotion of cell proliferation, and regulation of RNA synthesis. [Gene Cards, CHD8; 2020.11.03]
Many to one: 4 human genes to 1 Drosophila gene; the human genes are CHD6, CHD7, CHD8, and CHD9.
Moderate-scoring ortholog of human CHD6, CHD7, CHD8, and CHD9 (1 Drosophila to 4 human). Dmel\kis shares 28-30% identity and 38-42% similarity with the human genes.