M.Naga Jyothi*, et al. / (IJAEST) INTERNATIONAL JOURNAL OF ADVANCED ENGINEERING SCIENCES AND TECHNOLOGIES Vol No. 7, Issue No.

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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, mjyothi.mtech@gmail.com Dept. Computer Science and Engineering, P.V.P Siddhartha Institute of Technologyrganization, Vijayawada,India, drknrao@ieee.org Professor Dept. Computer Science and Engineering, V.R Siddhartha Engineering College, Vijayawada, India. vrdrks@gmail.com

Dr. K.Nageswara Rao, Professor & Head,

Dr. V.Srinivasa Rao,

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 complicated Late Onset Alzheimers disease. Yet only a disease can be explained. In the present study, role of

still going on to find out the major genes that cause this small proportion of the genetic contribution to Alzheimers

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I. Alzheimers II.

Keywords: Dementia, Late Onset Alzheimers disease, Protein sequence, Phylogram, Clustalw2

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INTRODUCTION (AD) disease

Professor & Head, Dept. Computer Science and Engineering, V.R Siddhartha Engineering College, Vijayawada, India. drvsrao9@gmail.com

Dr. K.Srinivas,

is

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]. MATERIALS AND METHODS:

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.

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genes that are suspected to cause Late Onset Alzheimers

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

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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) 317 2039 449 593 639 364 976 2146 248 2214

Tissue Type

Protein name

1 2 3 4 5 6 7 8 9 10

APOE-e4 CR1 CLU BIN1 CD2AP CD33 EPHA1 ABCA7 MS4A6A sortilinrelated receptor 1 [SORL1]

P02649 P17927 P10909 O00499 Q9Y5K6 P20138 P21709 Q8IZY2 Q9H2W1 Q92673

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Brain P12821 1306 1613 Lung, Heart O75581 Q9UQC2 676 O95992 P42898 P04156 P02656 Q92542 P02787 P01375 P03372 Q9UMX0 Q00059 P00749 P14735 272 656 253 99 709 698 233 595 589 246 431 1019 Cytoplasm

11 12

13

14 15 16 17 18 19 20 21 22 23 24 25

angiotensinconverting enzyme [ACE] low-density lipoprotein receptor-related protein 6 [LRP6] GRB-2associated binding protein [GAB2] cholesterol 25-hydroxylase [CH25H] MTHFR PRNP APOC NCSTN TF tumor necrosis factor alpha (TNF) ESR1 UBQLN1 TFAM PLAU IDE

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Monocytic/myeloi d lineage cells. Membrane Brain kidney, Cytoplasm,Cell membrane Cell membrane Liver Membrane Liver Cell membrane Nucleus Brain Mitochondrion

Brain Splenic follicular dendritic cells. Plasma. Brain

APOE-e4 CR1 CLU BIN1 CD2AP CD33 EPHA1 ABCA7 MS4A6A SORL1

ACE LRP6

GAB2

CH25H MTHFR PRNP APOC NCSTN TRFE TNFA ESR1 UBQL1 TFAM UROK IDE

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26 27 28 29 30 31 32 33 34 35 36

38

P78417

241

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Q13126 283 156 873 250 423 652 602 P42771 P98155 P06340 P01011 Heart Q13492 P06276

39 40 41 42 43 44

Glutathione S-transferase omega2 (GSTO2) 5_-metylthioadenosine phosphorylase (MTAP) cyclin-dependent kinase inhibitor (CDKN2A) lipoprotein receptor (VLDLR) human leukocyte antigen (HLA): HLA-DOA

Q9H4Y5

243

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45 46 III. DISCUSSION AND RESULTS
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alpha-1-antichymotrypsin (ACT or SERPINA3) PICALM BCHEK

TABLE 1: Genes/Proteins that have been cause to Late Onset Alzheimers disease (LOAD)

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

Multiple 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.

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Brain Liver Plasma, Brain

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CALHM1 GAPDH PSEN1 cystatin C (CST3) alpha-2-macroglobulin(A2M) complement component 1, r subcomponent (C1R) OLR1 LRP1 transcription factor LBP1c/CP2/LSF (TFCP2) choline acyltransferase (CHAT) vesicular acetylcholine transporter (SLC18A3) catenin alpha 3 (CTNNA3) Glutathione S-transferase omega1 (GSTO1)

Q8IU99 P04406 P49768 P01034 P01023 P00736 P78380 Q07954 Q12800 P28329 Q16572

346 335 467 146 1474 705 273 4544 502 748 532

Brain Brain Brain

CAHM1 G3P PSN1 CYTC A2MG C1R OLR1 LRP1 TFCP2 CLAT

Brain Brain Brain

Membrane

VACHT CTNNA3 GSTO1

Q9UI47

895

Brain

GSTO2 MTAP CD2A1 VLDLR

AACT PICAL CHLE

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seem

to have important role next to GSTO1 and

for GSTO1 and a second transcribed member of the GST omega class, GSTO2 [10].

GSTO2.Allelic association studies for age-at-onset effects in AD and PD revealed that a signicant association was found

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IV. CONCLUSION
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Fig1:Phylogram showing sequential relationship of Late Onset Alzheimers disease(LOAD) causing proteins. conducting more detailed studies and experiments on these genes by considering this observation as a hypothesis will help in simplifying this complicated LOAD.

From the present study, an observation was made that GSTO1, GSTO2, LRP1 and VLDLR are having a significant impact in causing Late Onset Alzheimers disease. However,

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REFERENCES

1.Clark RF, Goate AM. Molecular genetics of Alzheimer's disease. ArchNeurol. 1993,Nov;50(11):11641172. [PubMed] 2. Adriano Jimenez-Escrig et al. multigenerational A pedigree of late-onset Alzheimers disease implies new genetic causes. Brain (2005), 128, 17071715. 3. Farrer LA et al. Segregation analysis reveals evidence of a major gene for Alzheimer disease. Am J Hum Genet 1991, 48:1026-1033. 4. Rao VS et al. Multiple etiologies for Alzheimer disease are revealed by segregation analysis. Am J Hum Genet 1994, 55:991-1000. 5 M.Ilyas Kamboh,Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. Molecular Genetics of Late-Onset Alzheimers Disease. 6. Joseph H. Lee et a.l., Analyses of the National Institute on Aging.: Late-Onset Alzheimers Disease Family Study Implication of Additional Loci for the National Institute on Aging Late-Onset Alzheimers Disease Family Study Group Alzheimers disease: Genes, Proteins, and 7. Selkoe DJ, Therapy. Physiol Rev. 2001 Apr; 81(2).

include Data Mining and Bioinformatics. She is a member of CSI. Dr. K. Nageswara Rao received Ph.D. degree and in Computer degree Science in and Engineering from Andhra University M.Tech Computer Science and Engineering from the Andhra University. Currently, he is a Professor and Head at P.V.P Siddhartha Institute of Technology, Vijayawada, India.

T
PhD in Engineering Security. Security.

Dr. V. Srinivasa Rao has received Computer from Science and Berhampur

University, India and M.Tech degree in Computer Science and Technology

9. S.P McIlroy et a.,. Butyrylcholinesterase K variant is genetically associated with late onset Alzheimers disease in Northern Ireland. 10. Yi-Ju Li et al. Glutathione S-transferase omega-1 modies age-at-onset of Alzheimer disease and Parkinson disease. Human Molecular Genetics, 2003, Vol. 12, No. 24 32593267,DOI: 10.1093/hmg/dd M. Naga Jyothi is pursuing M.Tech in

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P.V.P Siddhartha Her Institute Technology. research
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8. Peggy Vaughn. .Studies find possible new genetic risk factors for Alzheimers disease.NIH-funded genome-wide association study is largest ever conducted in Alzheimers research. April 4, 2011.

Computer science and Engineering from of interests

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from Andhra University. He is working as a Professor Engineering, V.R Siddhartha Engineering College,

and Head in the department of Computer Science and Vijayawada, Andhra Pradesh, India. His research interest includes Data mining, Bioinformatics and Network

Dr. K. Srinivas has received PhD in Computer Science and Engineering from Acharya Nagarjuna University, Guntur, and Andhra Pradesh, India. and M.Tech (CSE) from JNTU Kakinada. Currently he is working as a Professor in the department of Computer Science and engineering, V.R Siddhartha Engineering College, Vijayawada, Andhra Pradesh, India. His research interest includes Data mining, Bioinformatics and Network

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