Initially identified in an analysis of two genome-wide association studies (FBrf0223922), the human gene MAST4 is proposed as a candidate susceptibility locus for Alzheimer disease. MAST4 is a microtubule-associated serine/threonine protein kinase. There is a single fly ortholog, dop, for which classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\dop is also orthologous to the human genes MAST1, MAST3 and MAST2.
The MAST4 gene has not been introduced into flies.
The fly ortholog, dop, was tested for genetic interaction with a transgenically introduced mutational variant of the human tau gene (Hsap\MAPT); RNAi-mediated reduction in the expression of dop was observed to enhance the phenotype associated with tau toxicity. Animals homozygous for amorphic alleles of Dmel\dop are lethal. Genetic interactions of Dmel\dop have been characterized; see the gene report for dop.
[updated June 2016 by FlyBase; FBrf0222196]
Alzheimer disease (AD) is the most common form of progressive dementia in the elderly. [from MIM:104300; 2016.01.08]
Memory loss is the most common sign of Alzheimer disease. As the disorder progresses, some people with AD experience personality and behavioral changes; other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. Total care is usually required during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease. [from Genetics Home Reference, Alzheimer disease; 2016.01.08]
Locus identified as showing significant association with susceptibility to Alzheimer disease in an analysis of two genome-wide association studies (GWAS).
MAST4 is a microtubule-associated serine/threonine protein kinase. [from GeneCards, MAST4; 2016.06.01]
Many to one: 4 human to 1 Drosophila; the fly gene dop is orthologous to MAST4, MAST1, MAST3 and MAST2 in human.
High-scoring ortholog of human genes MAST4, MAST1, MAST3 and MAST2 (1 Drosophila to 4 human). Dmel\dop shares 33-38% identity and 45-50% similarity with the human genes.
