Congenital heart defects occur at a high frequency in individuals with Down syndrome; this phenotype correlates with the distal portion of the originally defined critical region. Several of the genes included in this interval are known to be expressed in the heart; 6 of these candidate genes were assessed in Drosophila (FBrf0216615). Each was expressed alone and in all possible pairwise combinations and tested for effects on rhythmicity or heart failure following stress. DSCAM and COL6A2 were identified as the most strongly interacting pair of genes when overexpressed in the Drosophila heart, affecting viability and dramatically disrupting several indices of heart function.
For the 6 genes assessed, either a transgenic copy of the human gene was used (including for Hsap\COL6A2), or a UAS construct for the orthologous fly gene, or the orthologous gene from mouse (in the case of DSCAM, Mmus\Dscam was used).
[updated July 2016 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]
COL6A2 encodes one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues (Gene Cards, COL6A2; 2016.07.27).
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.
Most ortholog prediction algorithms do not identify a gene orthologous to human COL6A2 in Drosophila.
