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In the June 7 online issue of PLoS Genetics , they report that several hundred genes within almost 800 brainsamples of patients with Alzheimer's disease or other disorders hadaltered expression levels that did not result fromneurodegeneration. Many of those variants were likely the cause. "We now understand that disease likely develops from genevariants that have modest effects on gene expression, and which arealso found in healthy people. But some of the variants -- elevatingexpression of some genes, reducing levels of others -- combine toproduce a perfect storm that leads to dysfunction," says leadinvestigator Nilufer Ertekin-Taner, M.D., Ph.D., a Mayo Clinicneurologist and neuroscientist. "If we can identify the genes linked to a disease that are tooactive or too dormant, we might be able to define new drug targetsand therapies," she says. "That could be the case forboth neurodegenerative disease as well as disease in general." Dr. Ertekin-Taner says no other lab has performed the extent ofbrain gene expression study conducted at Mayo Clinic's Floridacampus. "The novelty, and the usefulness, of our study is thesheer number of brain samples that we looked at and the way inwhich we analyzed them. These results demonstrate the significantcontribution of genetic factors that alter brain gene expressionand increase risk of disease," she says. This form of data analysis measures gene expression levels byquantifying the amount of RNA produced in tissue and scans thegenome of patients to identify genetic variants that associate withthese levels. Mayo researchers measured the level of 24,526 transcripts(messenger RNA) for 18,401 genes using cerebellar autopsy tissuefrom 197 Alzheimer's disease patients and from 177 patients withother forms of neurodegeneration. The researchers then validatedthe results by examining the temporal cortex from 202 Alzheimer'sdisease patients and from 197 with other pathologies. Thedifference between these samples is that while the temporal cortexis affected by Alzheimer's disease, the cerebellum is relativelyspared. From these analyses, the researchers identified more than 2,000markers of altered expression in both groups of patients that werecommon between the cerebellum and temporal cortex. Some of thesemarkers also influenced risk of human diseases, suggesting theircontribution to development of neurodegenerative and other diseasesregardless of their location in the brain. They identified novel expression "hits" for genetic riskmarkers of diseases that included progressive supranuclear palsy,Parkinson's disease, and Paget's disease, and confirmed other knownassociations for lupus, ulcerative colitis, and type 1 diabetes. "Altered expression of brain genes can be linked to a numberof diseases that affect the entire body," Dr. Ertekin-Tanersays. They then compared their eGWAS to GWAS data on Alzheimer's disease,conducted by the federally funded Alzheimer's Disease GeneticsConsortium, to test whether some of the risk genes alreadyidentified promote disease through altered expression. "We found that a number of genes already linked to Alzheimer'sdisease do, in fact, have altered gene expression, but we alsodiscovered that many of the variants in what we call the gray zoneof the GWAS -- genes whose contribution to Alzheimer's disease wasuncertain -- were also influencing brain expression levels,"Dr. Ertekin-Taner says. "That offers us new candidate riskgenes to explore. "This is a powerful approach to understanding disease,"she says. "It can find new genes that contribute to risk, aswell as new genetic pathways, and can also help us understand thefunction for a large number of genes and other molecular regulatorsin the genome that are implicated in very important diseases." The study was funded in part by National Institutes of Healthgrants and the Mayo Alzheimer's Disease Research Center. Thecomplete results are being made available to the scientificcommunity. Study co-authors include Fanggeng Zou, Ph.D., High Seng Chai,Curtis Younkin, Mariet Allen, Steven Younkin, M.D., Ph.D., andMinerva Carrasquillo, Ph.D., who also provided genotypes for theMayo Alzheimer's disease GWAS; Dennis Dickson, M.D., Julia Crook,Ph.D., Shane Pankratz, Ph.D., Neill Graff-Radford, M.D., and RonaldPetersen, M.D., Ph.D. I am an expert from pvcsmartcard.com, while we provides the quality product, such as Plastic Barcode Cards Manufacturer , China PVC Gift Card, RFID Smart Card,and more.
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