A GWAS study investigating alcohol consumption in humans found an association with variants in the AUTS2 gene. AUTS2 is a component of a Polycomb group PRC1-like complex; in contrast to the canonical role of PRC1 in the maintenance of gene repression, PRC1-AUTS2 activates transcription. The AUTS2 gene has been implicated as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability (MIM:615834), and developmental delay. There is a single low-scoring ortholog in Drosophila, tay, for which classical loss-of-function alleles, RNAi targeting constructs, alleles caused by insertional mutagenesis have been generated.
The human Hsap\AUTS2 has been introduced into flies, but has not been characterized in the context of this disease model.
Amorphic alleles of Dmel\tay, when homozygous, are lethal. Adults carrying partial loss-of-function insertion mutations exhibit reduced alcohol sensitivity; pan-neuronal down-regulation of tay effected by RNAi also results in reduced alcohol sensitivity. Genetic and physical interactions of Dmel\tay have been described; see below and in the tay gene report.
[updated Oct. 2018 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
The AUTS2 gene has been implicated in neurodevelopment and as a candidate gene for numerous neurological disorders, including autism spectrum disorders, intellectual disability, and developmental delay. [Gene Cards, AUTS2; 2018.10.23]
AUTS2 encodes a component of a Polycomb group (PcG) multiprotein PRC1-like complex; it is described as a transcriptional activator and regulator. [Gene Cards, AUTS2; 2018.10.23]
In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. [from MIM:607270; 2018.10.23]
One to one: 1 human to 1 Drosophila.
Low-scoring ortholog of human AUTS2 (1 Drosophila to 1 human); Dmel\tay shares 22% identity and 32% similarity with the human gene.
