6.ijaest-vol-no-7-issue-no-2-association-of-gsto1-and-gsto2-in-late-onset-alzheimer’s-diseasea-bioinformatics-approach-217-221...

8/6/2019 6.IJAEST-Vol-No-7-Issue-No-2-Association-of-GSTO1-and-GSTO2-in-Late-Onset-Alzheimers-diseaseA-Bioinformatics-ap

http:///reader/full/6ijaest-vol-no-7-issue-no-2-association-of-gsto1-and-gsto2-in-late-onset-alzheimers-diseasea-bioin 1/5

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,

[email protected]

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



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


Vol No. 7, Issue No. 2, 217 - 221

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/



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


Vol No. 7, Issue No. 2, 217 - 221

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

6.ijaest-vol-no-7-issue-no-2-association-of-gsto1-and-gsto2-in-late-onset-alzheimer’s-diseasea-bioinformatics-approach-217-221...

Documents