Computational Molecular Biology 2016, Vol.6, No.2, 1-9
1
Research Article Open Access
Whole transcriptome cerebral cortex gene analysis in Alzheimer’s diseases
S. Pooja
1,2
, Anitha P. Muttagi
1
, Seema J. Patel
1
, H. Gurumurthy
1
, Prashantha C. Nagaraja
1
1 GM Institute of Technology, Department of Biotechnology, Davanagere, India
2 Division of Bioinformatics, Scientific Bio-Minds, Bangalore, India
Corresponding author Email
Computational Molecular Biology, 2016, Vol.6, No.2 doi
Received: 25 Dec., 2015
Accepted: 21 Mar., 2016
Published: 29 Mar., 2016
Copyright © 2016
Pooja et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article
:
Pooja S., Muttagi A.P., Patel S.J., Gurumurthy H., and Prashantha C.N., 2016, Whole transcriptome cerebral cortex gene analysis in Alzheimer’s diseases,
Computational Molecular Biology, 6(2): 1-9 (doi
Abstract
Neurodegenerative disorder such as Alzheimer's is most common form of memory loss observed on aging population. The
genetic factors are strongly influenced by risk of accumulation of β-amyloid protein, apolipoprotein (APOE4), intracellular
neurofibrillary tangles of hyperphosphorylated tau proteins that form plaques in the extracellular region of brain. There is no clear
method to diagnosis Alzheimer’s disease in the earliest stages, but there are few treatments available to reduce the symptoms but
there is no clear cure for the disease. A Genetic markers, inflammatory markers and blood based protein markers that could predict
onset on disease prognosis. There is a need to identify markers from the entire genome that influenced by interlink with gene-gene,
gene-protein and gene-environment interactions. Different transcriptional factors such as amyloid precursor protein gene (Aβ) and
the presenilin 1 and 2 genes are major risk for Alzheimer’s disease. Using computational techniques to identify susceptible genetic
factors from functional genomics and proteomics to understand transcriptional coregulation and transcription factor binding sites
which potentially contribute to Alzheimer’s disease.
Keywords
Alzheimer’s disease, Transcriptional analysis, Microarray, Biostatistics
1 Introduction
Alzheimer’s disease (AD) is a neurological disorder causing dementia and memory loss in the Aging people
(Breteler, 1992). The protocatalytic characteristic of beta amyloid precursor protein (APP) and apolipoprotein
ApoE has familial mutations that associated regulation of familial and sporadic AD (Christensen et al., 2004). The
research evidences that helps to predict 40-42 amino-acid peptides generates multiple proteolytic cleavage of the
APP that triggers numerous pathophysiological changes that toxic oligomers of APP, the overall function is remain
unknown (Zheng and Koo, 2011). The genetic variants encoding an alanine-to-threonine substitution at residue
673 (A673T) that confers mutations in AD (Jonsson et al., 2012). The mutations in presenilin1 (PSEN1) and
presenilin 2 (PSEN2) enzymes involved in transcriptional regulation to synthesize protein that may processing of
APP to develop familial AD (Cruts et al., 1998; Hardy et al., 2001; Kauwe et al., 2007). More recently, PSEN1
mutations have also been identified in some sporadic cases of late onset AD (Cruchaga et al., 2012). There are so
many number of gene mutations in AD itself have also been identified many of these mutation clusters at or near
the β or γ proteolytic sites, favoring either the overproduction of total amyloid-β (Aβ) (Citron et al., 1992; Di Fede
et al., 2009, Zhou et al., 2011) or an increased ratio of the pro-aggregating Aβ1-42 species relative to Aβ1-40 (De
Jonghe et al., 2001; Kwok et al., 2000; Scheuner et al., 1996; Suzuki et al., 1994). In other instances, mutations
within the Aβ peptide promote an increased propensity for aggregation (Nilsberth et al., 2001; Tomiyama et al.,
2008). Together, these genetic findings provide strong support for the amyloid hypothesis of AD, which postulates
that an imbalance in the production and clearance of Aβ initiates a cascade of amyloid accumulation,
neurotoxicity and neurodegeneration (Ertekin-Taner, 2008). Although it is clear that expression levels of AD genes
are important in AD etiology, much remains unknown about their specific regulation (Theuns and Van
Broeckhoven, 2000).
The Apolipoprotein E (ApoE) is a major cholesterol carrier in the blood-brain barrier (Liu et al., 2013; Herz and
Chen, 2006). ApoE is primarily produced by astrocytes and its function is to deliver lipids to neurons through the
