Initially identified in an analysis of two genome-wide association studies (FBrf0223922), the human genes ITGAM and ITGA9 are proposed as candidate susceptibility loci for Alzheimer disease. ITGAM and ITGA9 are alpha integrin subunits, for which there are multiple low-scoring orthologous genes in flies. For the fly gene assayed, scb, classical amorphic and hypomorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. ITGAM has also been identified as a susceptibility locus for Systemic lupus erythematous (MIM:609939).
The ITGAM and ITGA9 genes have not been introduced into flies.
The fly ortholog scb 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 scb was observed to enhance the phenotype associated with tau toxicity. Animals homozygous for amorphic alleles of Dmel\scb are lethal. Physical and genetic interactions of Dmel\scb have been characterized; see below and in the gene report for scb.
[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]
Loci identified as showing significant association with susceptibility to Alzheimer disease in an analysis of two genome-wide association studies (GWAS).
ITGAM and ITGA9 are alpha integrin sub-units; there are multiple alpha integrin genes in human. Integrins are heterodimeric integral membrane proteins and are required for various adhesive interactions. [from GeneCards, ITGAM, ITGA9; 2016.06.01]
Many to many: there are multiple low-scoring orthologous genes (alpha integrin sub-units) in flies.
Many to many: there are multiple low-scoring orthologous genes (alpha integrin sub-units) in flies.
Many to many: there are multiple low-scoring orthologous genes (alpha integrin sub-units) in humans. Dmel\scb shares 24% identity and 40% similarity with the human gene ITGA9; it shares 20% identity and 34% similarity with the human gene ITGAM.
