Expression of the Down syndrome cell-adhesion molecule (DSCAM) is increased in the brains of patients with several neurological disorders, including Down syndrome and fragile X syndrome (FBhh0000123). DSCAM maps to 21q22.2-q22.3, within or near the originally defined Down syndrome critical region. There is a second similar gene in humans (DSCAML1) and four related genes in flies (Dscam1, Dscam4, Dscam2, Dscam3). Although Dmel\Dscam1 is the best studied, there are genetic reagents available for all four fly genes.
Dmel\Dscam1 is notable for undergoing extensive alternative splicing, theoretically producing over 30,000 protein isoforms; this extreme diversity of isoforms has been shown to be necessary for the process of neuronal self-avoidance during neural development. In contrast, the human DSCAM gene has only a few alternative isoforms.
Transgenic constructs of wild-type human Hsap\DSCAM have been introduced into flies. When expressed using a Dmel\Dscam1 promoter, the human gene partially rescues a Dscam1 loss-of-function phenotype (exhibiting a later stage of lethality); severe abnormalities of brain structure are still observed. Overexpression of Dscam1 results in gut neural abnormalities and reduced the efficiency of food clearance from the larval gut.
Extensive genetic and physical interaction data are available for Dmel\Dscam1; see below and in the gene report for Dscam1. In particular, the protein of Fmr1, the fly ortholog of the gene implicated in fragile X syndrome, has been found to bind to Dscam1 RNA.
[updated Jan. 2023 by FlyBase; FBrf0222196]
Down syndrome is characterized by a particular combination of phenotypic features that includes mental retardation and characteristic facial structure. Individuals with Down syndrome often have specific major congenital malformations such as those of the heart (30-40% in some studies) and of the gastrointestinal tract. 90% of Down syndrome patients have a significant hearing loss (Mazzoni et al., 1994; pubmed:7881226). A number of other diseases are observed at higher frequency among Down syndrome individuals, including leukemia (Robison, 1992; pubmed:1532221) and Alzheimer disease (Wisniewski et al., 1985; pubmed:3158266). [from MIM:190685; 2016.07.19]
DSCAM encodes a cell adhesion molecule that plays a role in neuronal self-avoidance by promoting repulsion between specific neuronal processes of either the same cell or the same subtype of cells. (Gene Cards, DSCAM; 2016.07.25). See Garrett et al., 2012 (pubmed:22912601) for a recent review.
High-scoring ortholog of human genes DSCAM and DSCAML1 (4 Drosophila to 2 human). Dmel\Dscam1 shares 29-30% identity and 46-47% similarity with the human genes.
