In Silico Study of Alzheimer Disease Associated Genes and Comparative Transcriptome RNA Seq Analysis

Abstract

x newlineABSTRACT newlineAlzheimer disease (AD) is a progressive, neurodegenerative disorder with no cure. Even after newline110 years of discovery of the disease poorly understood AD etiology poses a grave challenge newlineto researchers. Numerous sporadic studies have been carried out but a holistic work newlineconsidering all genes associated with AD have not been carried out. There exists a dire need newlineof a combinatorial study comprising Alzheimer associated genes (ADA) for enhanced newlineunderstanding of AD. Various factors have been associated with AD like obesity and sex. newlineEtiology of AD is different in male and female and female brain is more susceptible to AD newlinebut underlying molecular mechanism is unknown. This gender biasness of disease is wellknown newlinebut unexplained. Functional and sequence based clustering of ADA genes revealed newlinethat they have diversified function supporting multifactorial nature of AD. Further expression newlineanalysis of AD transcriptome was correlated to ADA and their clustering output. Explicitly, newlineGonadotropin releasing hormone receptor pathway was found to be most significantly newlineassociated with AD. Significant no. of obesity genes was found to be common in AD newlinemajority of which on pathway analysis clustered into signalling pathways. Sex associated newlinegenes (X, Y, Mitochondria encoded and sex-biased genes) along with ADA and obesity newlinegenes were studied on AD transcriptome for their expression. Significant no. genes from all newlinethe three classes were found to be differentially expressed (DE) which indicates their newlineassociation with AD. Almost all DE genes were in correlation with their molecular function newlinebased enrichment analysis and can be further explored for their therapeutic potential. For e.g. newlineMT-T1 gene, up-regulated in all AD samples, can be considered as potential drug target since newlinereduction in oxidative stress may have therapeutic effect in AD. Significant no. of nonprotein newlinecoding genes was also found to be DE in AD. This is the first study focussing Y newlinechromosome transcriptome in context to the AD disease. Majority of the genes were downregulated newlinethereby conforming lower transcriptional activity in Alzheimer brain. Repressed newlineactivity of Y chromosome genes in AD samples justify it s importance and probably explains newlinesusceptibility of females in AD. Some Tc factor encoding genes and their target genes were newlinefound to have significant role in AD. These results justify current approach and warrants to newlineexplore the role of all DGE genes in AD through further experimentation. It is an attempt to newlineexplore the association of AD with obesity, sex and gender in order to have broad newlineunderstanding of AD and has proposed different therapeutic targets and pathways. newlineKeywords: Alzheimer, gene, transcriptome, obesity, sex newline