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Transcript of 6.IJAEST-Vol-No-7-Issue-No-2-Association-of-GSTO1-and-GSTO2-in-Late-Onset-Alzheimer’s-diseaseA-Bioinformatics-approach-217-221...
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Association of GSTO1 and GSTO2 in Late Onset
Alzheimers disease:A Bioinformatics approach
M.Naga Jyothi,Dept. Computer Science and Engineering,P.V.P Siddhartha Institute of Technology,
Vijayawada,India,[email protected]
Dr. K.Nageswara Rao,Professor & Head,Dept. Computer Science and Engineering,
P.V.P Siddhartha Institute of Technologyrganization,
Vijayawada,India,
Dr. V.Srinivasa Rao, Dr. K.Srinivas,Professor & Head, Professor
Dept. Computer Science and Engineering, Dept. Computer Science and Engineering,V.R Siddhartha Engineering College, V.R Siddhartha Engineering College,Vijayawada, India. Vijayawada, India.
[email protected] [email protected]
Abstract Late-onset Alzheimers disease (AD) is a
complex and multifactorial form of Alzheimer's disease
with the possible involvement of several genes. Research is
still going on to find out the major genes that cause this
complicated Late Onset Alzheimers disease. Yet only a
small proportion of the genetic contribution to Alzheimers
disease can be explained. In the present study, role of
genes that are suspected to cause Late Onset Alzheimers
is analyzed through multiple sequence alignment method
using Clustalw2 tool and a phylogram is constructed. This
sequence alignment method used, protein sequences of
disease causing genes. Our study showed that GSTO1,
GSTO2 proteins are found to be closely related and play a
typical role amongst all Late Onset Alzheimers disease
proteins. Proteins LRP1 and VLDLR are also found to be
closely related next to GSTO1 and GSTO2.
Analyzing disease causing genes through this
bioinformatics approach would help in finding genes that
are most likely involved in causing disease.Indepth study
of such genes may find a solution to prevent late Onset
Alzheimers disease.
Keywords: Dementia, Late Onset Alzheimers disease, Proteinsequence, Phylogram, Clustalw2
I. INTRODUCTIONAlzheimers disease (AD) is a progressive
neurogenerative disorder that occurs predominantly in later
life. It is the commonest cause of dementia and represents the
fourth largest cause of death in developed world [1].
Alzheimers disease is a genetically complex disease [2].Since
the 1990s, the genetics of Alzheimer disease (AD) has been an
active area of research. In the early 1990s, segregation analysis
studies suggested a complex model possibly involved in
polygenes and environmental factors emerged for Late Onset
Alzheimers disease (LOAD) [3, 4]. However, identified genes
explain only a small proportion of familial Alzheimers disease
and leave an important gap in late-onset forms, which are those
most closely resembling sporadic disease. [2].
II. MATERIALS AND METHODS:We have collected 46 genes that are supposed to be
the cause for LOAD through literature survey of various
papers related to Alzheimers [5, 6, 7, 8, and 9] and from
www.genecards.org.The corresponding protein sequences in
M.Naga Jyothi*, et al. / (IJAEST) INTERNATIONAL JOURNAL OF ADVANCED ENGINEERING SCIENCES AND TECHNOLOGIES
Vol No. 7, Issue No. 2, 217 - 221
ISSN: 2230-7818 @ 2011 http://www.ijaest.iserp.org. All rights Reserved. Page 49
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FASTA format are obtained from UniProt (Universal Protein
Resource) site, www.uniprot.org. These sequences are given
to EMBL-EBIs ClustalW2 tool for multiple sequence
alignment. ClustalW2 is a general purpose multiple sequence
alignment program for DNA or proteins. It calculates the best
match for the selected sequences, and lines them up so that the
identities, similarities and differences can be seen.Clustalw2
tool can be found at
http://www.ebi.ac.uk/Tools/msa/clustalw2/. Table 1 showing
the genes/proteins that have been involved in the present
study, which are supposed to cause Late Onset Alzheimers
disease(LOAD).
S.No. Gene Name Ac. No. Length
(Amino
acids)
Tissue Type Protein name
1 APOE-e4 P02649 317 Brain APOE-e4
2 CR1 P17927 2039 Splenic folliculardendritic cells.
CR1
3 CLU P10909 449 Plasma. CLU
4 BIN1 O00499 593 Brain BIN1
5 CD2AP Q9Y5K6 639 CD2AP
6 CD33 P20138 364 Monocytic/myeloid lineage cells.
CD33
7 EPHA1 P21709 976 Membrane EPHA18 ABCA7 Q8IZY2 2146 Brain ABCA7
9 MS4A6A Q9H2W1 248 MS4A6A
10 sortilinrelatedreceptor 1 [SORL1]
Q92673 2214 Brain SORL1
11 angiotensin-converting enzyme [ACE]
P12821 1306 Lung, kidney,Heart
ACE
12 low-densitylipoprotein receptor-relatedprotein 6[LRP6]
O75581 1613 LRP6
13 GRB-2associated bindingprotein[GAB2]
Q9UQC2 676 Cytoplasm,Cellmembrane
GAB2
14 cholesterol 25-hydroxylase[CH25H]
O95992 272 CH25H
15 MTHFR P42898 656 MTHFR
16 PRNP P04156 253 Cell membrane PRNP
17 APOC P02656 99 Liver APOC
18 NCSTN Q92542 709 Membrane NCSTN19 TF P02787 698 Liver TRFE
20 tumor necrosis factor alpha (TNF) P01375 233 Cell membrane TNFA
21 ESR1 P03372 595 Nucleus ESR1
22 UBQLN1 Q9UMX0 589 Brain UBQL1
23 TFAM Q00059 246 Mitochondrion TFAM
24 PLAU P00749 431 UROK
25 IDE P14735 1019 Cytoplasm IDE
M.Naga Jyothi*, et al. / (IJAEST) INTERNATIONAL JOURNAL OF ADVANCED ENGINEERING SCIENCES AND TECHNOLOGIES
Vol No. 7, Issue No. 2, 217 - 221
ISSN: 2230-7818 @ 2011 http://www.ijaest.iserp.org. All rights Reserved. Page 50
http://www.uniprot.org/http://www.uniprot.org/http://www.uniprot.org/http://www.ebi.ac.uk/Tools/msa/clustalw2/http://www.ebi.ac.uk/Tools/msa/clustalw2/http://www.uniprot.org/uniprot/P17927http://www.uniprot.org/uniprot/P10909http://www.uniprot.org/uniprot/P20138http://www.uniprot.org/locations/SL-0162http://www.uniprot.org/uniprot/Q8IZY2http://www.uniprot.org/uniprot/P12821http://www.uniprot.org/uniprot/O75581http://www.uniprot.org/uniprot/Q9UQC2http://www.uniprot.org/locations/SL-0086http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/uniprot/P42898http://www.uniprot.org/uniprot/P04156http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/uniprot/Q92542http://www.uniprot.org/locations/SL-0162http://www.uniprot.org/uniprot/P02787http://www.uniprot.org/uniprot/P01375http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/uniprot/P03372http://www.uniprot.org/locations/SL-0191http://www.uniprot.org/uniprot/Q9UMX0http://www.uniprot.org/uniprot/Q00059http://www.uniprot.org/locations/SL-0173http://www.uniprot.org/uniprot/P00749http://www.uniprot.org/uniprot/P14735http://www.uniprot.org/locations/SL-0086http://www.uniprot.org/locations/SL-0086http://www.uniprot.org/uniprot/P14735http://www.uniprot.org/uniprot/P00749http://www.uniprot.org/locations/SL-0173http://www.uniprot.org/uniprot/Q00059http://www.uniprot.org/uniprot/Q9UMX0http://www.uniprot.org/locations/SL-0191http://www.uniprot.org/uniprot/P03372http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/uniprot/P01375http://www.uniprot.org/uniprot/P02787http://www.uniprot.org/locations/SL-0162http://www.uniprot.org/uniprot/Q92542http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/uniprot/P04156http://www.uniprot.org/uniprot/P42898http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/locations/SL-0039http://www.uniprot.org/locations/SL-0086http://www.uniprot.org/uniprot/Q9UQC2http://www.uniprot.org/uniprot/O75581http://www.uniprot.org/uniprot/P12821http://www.uniprot.org/uniprot/Q8IZY2http://www.uniprot.org/locations/SL-0162http://www.uniprot.org/uniprot/P20138http://www.uniprot.org/uniprot/P10909http://www.uniprot.org/uniprot/P17927http://www.ebi.ac.uk/Tools/msa/clustalw2/http://www.uniprot.org/ -
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26 CALHM1 Q8IU99 346 Brain CAHM1
27 GAPDH P04406 335 G3P
28 PSEN1 P49768 467 Brain PSN1
29 cystatin C (CST3) P01034 146 Brain CYTC
30 alpha-2-macroglobulin(A2M) P01023 1474 A2MG31 complement component 1, r
subcomponent (C1R)P00736 705 C1R
32 OLR1 P78380 273 Brain OLR133 LRP1 Q07954 4544 Brain LRP1
34 transcription factor LBP-1c/CP2/LSF (TFCP2)
Q12800 502 Brain TFCP2
35 choline acyltransferase(CHAT)
P28329 748 CLAT
36 vesicular acetylcholinetransporter(SLC18A3)
Q16572 532 Membrane VACHT
37 catenin alpha 3(CTNNA3)
Q9UI47 895 Brain CTNNA3
38 Glutathione S-transferase omega-1 (GSTO1)
P78417 241 Brain GSTO1
39 Glutathione S-transferase omega-2 (GSTO2)
Q9H4Y5 243 Liver GSTO2
40 5_-metylthioadenosinephosphorylase (MTAP)
Q13126 283 MTAP
41 cyclin-dependent kinase inhibitor(CDKN2A)
P42771 156 CD2A1
42 lipoprotein receptor (VLDLR) P98155 873 Heart VLDLR
43 human leukocyte antigen (HLA):HLA-DOA
P06340 250
44 alpha-1-antichymotrypsin (ACTor SERPINA3)
P01011 423 Plasma, Brain AACT
45 PICALM Q13492 652 PICAL
46 BCHEK P06276 602 CHLE
TABLE 1: Genes/Proteins that have been cause to Late Onset Alzheimers disease (LOAD)
III. DISCUSSION AND RESULTSMultiple sequence alignment is performed to the 46
LOAD causing proteins by submitting corresponding protein
FASTA to Clustalw2 tool. Result of alignment is obtained in
the form of phylogram (Fig1).The phylogram displays the
sequential relationship of proteins along with the scores, that
represent the distance between protein sequences.
Phylogram showed that Glutathione S-transferase
omega-1 (GSTO1) and Glutathione S-transferase omega-2
(GSTO2) has minimum scores of 0.17684 and 0.18001. Low
density lipoprotein receptor-related protein 1 (LRP1) and
Very-Low-Density-Lipoprotein Receptor (VLDLR) have the
lowest scores next to GSTO1 and GSTO2.From the study it is
observed that GSTO1 and GSTO2 may play a significant role
in Late Onset Alzheimers disease. Also LRP1 and VLDLR
M.Naga Jyothi*, et al. / (IJAEST) INTERNATIONAL JOURNAL OF ADVANCED ENGINEERING SCIENCES AND TECHNOLOGIES
Vol No. 7, Issue No. 2, 217 - 221
ISSN: 2230-7818 @ 2011 http://www.ijaest.iserp.org. All rights Reserved. Page 51
http://www.uniprot.org/uniprot/Q8IU99http://www.uniprot.org/uniprot/P04406http://www.uniprot.org/uniprot/P49768http://www.uniprot.org/uniprot/P01034http://www.uniprot.org/uniprot/P01023http://www.uniprot.org/uniprot/P00736http://www.uniprot.org/uniprot/P78380http://www.uniprot.org/uniprot/Q07954http://www.uniprot.org/uniprot/Q12800http://www.uniprot.org/uniprot/Q16572http://www.uniprot.org/uniprot/Q9UI47http://www.uniprot.org/uniprot/P78417http://www.uniprot.org/uniprot/Q9H4Y5http://www.uniprot.org/uniprot/Q13126http://www.uniprot.org/uniprot/P98155http://www.uniprot.org/uniprot/P06340http://www.uniprot.org/uniprot/P06340http://www.uniprot.org/uniprot/P98155http://www.uniprot.org/uniprot/Q13126http://www.uniprot.org/uniprot/Q9H4Y5http://www.uniprot.org/uniprot/P78417http://www.uniprot.org/uniprot/Q9UI47http://www.uniprot.org/uniprot/Q16572http://www.uniprot.org/uniprot/Q12800http://www.uniprot.org/uniprot/Q07954http://www.uniprot.org/uniprot/P78380http://www.uniprot.org/uniprot/P00736http://www.uniprot.org/uniprot/P01023http://www.uniprot.org/uniprot/P01034http://www.uniprot.org/uniprot/P49768http://www.uniprot.org/uniprot/P04406http://www.uniprot.org/uniprot/Q8IU99 -
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