Skip to main content

Advertisement

SpringerLink
Log in

Characterization of SNPs in the dopamine-β-hydroxylase gene providing new insights into its structure-function relationship

  • Original Article
  • Published:
neurogenetics Aims and scope Submit manuscript

Abstract

Dopamine-β-hydroxylase (DBH, EC 1.14.17.1), an oxido-reductase that catalyses the conversion of dopamine to norepinephrine, is largely expressed in sympathetic neurons and adrenal medulla. Several regulatory and structural variants in DBH associated with various neuropsychiatric, cardiovascular diseases and a few that may determine enzyme activity have also been identified. Due to paucity of studies on functional characterization of DBH variants, its structure-function relationship is poorly understood. The purpose of the study was to characterize five non-synonymous (ns) variants that were prioritized either based on previous association studies or Sorting Tolerant From Intolerant (SIFT) algorithm. The DBH ORF with wild type (WT) and site-directed mutagenized variants were transfected into HEK293 cells to generate transient and stable lines expressing these variant enzymes. Activity was determined by UPLC-PDA and corresponding quantity by MRMHR on a TripleTOF 5600 MS respectively of spent media from stable cell lines. Homospecific activity computed for the WT and variant proteins showed a marginal decrease in A318S, W544S and R549C variants. In transient cell lines, differential secretion was observed in the case of L317P, W544S and R549C. Secretory defect in L317P was confirmed by localization in ER. R549C exhibited both decreased homospecific activity and differential secretion. Of note, all the variants were seen to be destabilizing based on in silico folding analysis and molecular dynamics (MD) simulation, lending support to our experimental observations. These novel genotype-phenotype correlations in this gene of considerable pharmacological relevance have implications for dopamine-related disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Botstein D, Risch N (2003) Discovering genotypes underlying human phenotypes: past successes for Mendelian disease, future approaches for complex disease. Nat Genet 33(Suppl):228–237. doi:10.1038/ng1090

    Article  CAS  PubMed  Google Scholar 

  2. Pritchard JK, Cox NJ (2002) The allelic architecture of human disease genes: common disease-common variant...or not? Hum Mol Genet 11(20):2417–2423

    Article  CAS  PubMed  Google Scholar 

  3. Reich DE, Lander ES (2001) On the allelic spectrum of human disease. Trends Genet 17(9):502–510

    Article  CAS  PubMed  Google Scholar 

  4. Bodmer W, Bonilla C (2008) Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 40(6):695–701. doi:10.1038/ng.f.136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pritchard JK (2001) Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet 69(1):124–137. doi:10.1086/321272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cirulli ET, Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet 11(6):415–425. doi:10.1038/nrg2779

    Article  CAS  PubMed  Google Scholar 

  7. Mardis ER (2008) The impact of next-generation sequencing technology on genetics. Trends Genet 24(3):133–141. doi:10.1016/j.tig.2007.12.007

    Article  CAS  PubMed  Google Scholar 

  8. Schmitt MW, Kennedy SR, Salk JJ, Fox EJ, Hiatt JB, Loeb LA (2012) Detection of ultra-rare mutations by next-generation sequencing. Proc Natl Acad Sci U S A 109(36):14508–14513. doi:10.1073/pnas.1208715109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34(2):154–156. doi:10.1038/ng1161

    Article  CAS  PubMed  Google Scholar 

  10. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M (2003) The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A 100(3):928–933. doi:10.1073/pnas.0335507100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH (2005) Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37(2):161–165. doi:10.1038/ng1509

    Article  CAS  PubMed  Google Scholar 

  12. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354(12):1264–1272. doi:10.1056/NEJMoa054013

    Article  CAS  PubMed  Google Scholar 

  13. Au N, Rettie AE (2008) Pharmacogenomics of 4-hydroxycoumarin anticoagulants. Drug Metab Rev 40(2):355–375. doi:10.1080/03602530801952187

    Article  CAS  PubMed  Google Scholar 

  14. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R (2008) SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med 359(8):789–799. doi:10.1056/NEJMoa0801936

    Article  CAS  PubMed  Google Scholar 

  15. Sanderson S, Emery J, Higgins J (2005) CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. Genet Med 7(2):97–104. doi:10.1097/01.GIM.0000153664.65759.CF

    Article  CAS  PubMed  Google Scholar 

  16. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R, Chaudhari U, Kastelein JJ (2015) Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1489–1499. doi:10.1056/NEJMoa1501031

    Article  CAS  PubMed  Google Scholar 

  17. Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA (2015) Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 372(16):1500–1509. doi:10.1056/NEJMoa1500858

    Article  CAS  PubMed  Google Scholar 

  18. Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, Kim KS, Kim CH, Malison RT, Gelernter J, Cubells JF (2001) A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 68(2):515–522. doi:10.1086/318198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kopeckova M, Paclt I, Goetz P (2006) Polymorphisms and low plasma activity of dopamine-beta-hydroxylase in ADHD children. Neuro Endocrinol Lett 27(6):748–754

    CAS  PubMed  Google Scholar 

  20. Kopeckova M, Paclt I, Goetz P (2006) Polymorphisms of dopamine-beta-hydroxylase in ADHD children. Folia Biol (Praha) 52(6):194–201

    CAS  Google Scholar 

  21. Ates O, Celikel FC, Taycan SE, Sezer S, Karakus N (2013) Association between 1603C>T polymorphism of DBH gene and bipolar disorder in a Turkish population. Gene 519(2):356–359. doi:10.1016/j.gene.2013.01.031

    Article  CAS  PubMed  Google Scholar 

  22. Fernandez F, Lea RA, Colson NJ, Bellis C, Quinlan S, Griffiths LR (2006) Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with aura. J Neurol Sci 251(1–2):118–123. doi:10.1016/j.jns.2006.09.013

    Article  CAS  PubMed  Google Scholar 

  23. Fernandez F, Colson N, Quinlan S, MacMillan J, Lea RA, Griffiths LR (2009) Association between migraine and a functional polymorphism at the dopamine beta-hydroxylase locus. Neurogenetics 10(3):199–208. doi:10.1007/s10048-009-0176-2

    Article  CAS  PubMed  Google Scholar 

  24. Gotoh F, Kanda T, Sakai F, Yamamoto M, Takeoka T (1976) Serum dopamine-beta-hydroxylase activity in migraine. Arch Neurol 33(9):656–657

    Article  CAS  PubMed  Google Scholar 

  25. O'Connor DT, Cervenka JH, Stone RA, Levine GL, Parmer RJ, Franco-Bourland RE, Madrazo I, Langlais PJ, Robertson D, Biaggioni I (1994) Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson’s disease and congenital dopamine beta-hydroxylase deficiency. Clin Sci (Lond) 86(2):149–158

    Article  Google Scholar 

  26. Miyata S, Nagata H, Yamao S, Nakamura S, Kameyama M (1984) Dopamine-beta-hydroxylase activities in serum and cerebrospinal fluid of aged and demented patients. J Neurol Sci 63(3):403–409

    Article  CAS  PubMed  Google Scholar 

  27. Lipcsey A (1981) The dopamine theory of schizophrenia: reduced serum dopamine beta hydroxylase activity in paranoid schizophrenia. Orv Hetil 122(8):483

    CAS  PubMed  Google Scholar 

  28. Schanberg SM, Stone RA, Kirshner N, Gunnells JC, Robinson RR (1974) Plasma dopamine beta-hydroxylase: a possible aid in the study and evaluation of hypertension. Science 183(4124):523–525

    Article  CAS  PubMed  Google Scholar 

  29. Yashima O, Ozawa M, Sato M, Suzuki K, Kimura T (1974) The role of serum dopamine-beta-hydroxylase in essential hypertension. Jpn Circ J 38(12):1085–1088

    Article  CAS  PubMed  Google Scholar 

  30. Williams HJ, Bray N, Murphy KC, Cardno AG, Jones LA, Owen MJ (1999) No evidence for allelic association between schizophrenia and a functional variant of the human dopamine beta-hydroxylase gene (DBH). Am J Med Genet 88(5):557–559. doi:10.1002/(SICI)1096-8628(19991015)88:5<557::AID-AJMG22>3.0.CO;2-F

    Article  CAS  PubMed  Google Scholar 

  31. Yamamoto K, Cubells JF, Gelernter J, Benkelfat C, Lalonde P, Bloom D, Lal S, Labelle A, Turecki G, Rouleau GA, Joober R (2003) Dopamine beta-hydroxylase (DBH) gene and schizophrenia phenotypic variability: a genetic association study. Am J Med Genet B Neuropsychiatr Genet 117B(1):33–38. doi:10.1002/ajmg.b.10011

    Article  PubMed  Google Scholar 

  32. Puzynski S, Bidzinski A, Mrozek S, Zaluska M (1983) Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness. II. Erythrocyte catechol-O-methyltransferase activity in endogenous depression. Acta Psychiatr Scand 67(2):96–100

    Article  CAS  PubMed  Google Scholar 

  33. Sofuoglu S, Dogan P, Kose K, Esel E, Basturk M, Oguz H, Gonul AS (1995) Changes in platelet monoamine oxidase and plasma dopamine-beta-hydroxylase activities in lithium-treated bipolar patients. Psychiatry Res 59(1–2):165–170

    Article  CAS  PubMed  Google Scholar 

  34. Strandman E, Wetterberg L, Perris C, Ross SB (1978) Serum dopamine-beta-hydroxylase in affective disorders. Neuropsychobiology 4(4):248–255

    Article  CAS  PubMed  Google Scholar 

  35. Tang YL, Epstein MP, Anderson GM, Zabetian CP, Cubells JF (2007) Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans. Eur J Hum Genet 15(8):878–883. doi:10.1038/sj.ejhg.5201838

    Article  CAS  PubMed  Google Scholar 

  36. Tang Y, Buxbaum SG, Waldman I, Anderson GM, Zabetian CP, Kohnke MD, Cubells JF (2006) A single nucleotide polymorphism at DBH, possibly associated with attention-deficit/hyperactivity disorder, associates with lower plasma dopamine beta-hydroxylase activity and is in linkage disequilibrium with two putative functional single nucleotide polymorphisms. Biol Psychiatry 60(10):1034–1038. doi:10.1016/j.biopsych.2006.02.017

    Article  CAS  PubMed  Google Scholar 

  37. Tang Y, Anderson GM, Zabetian CP, Kohnke MD, Cubells JF (2005) Haplotype-controlled analysis of the association of a non-synonymous single nucleotide polymorphism at DBH (+ 1603C --> T) with plasma dopamine beta-hydroxylase activity. Am J Med Genet B Neuropsychiatr Genet 139B(1):88–90. doi:10.1002/ajmg.b.30220

    Article  CAS  PubMed  Google Scholar 

  38. Ishii A, Kobayashi K, Kiuchi K, Nagatsu T (1991) Expression of two forms of human dopamine-beta-hydroxylase in COS cells. Neurosci Lett 125(1):25–28

    Article  CAS  PubMed  Google Scholar 

  39. Li B, Tsing S, Kosaka AH, Nguyen B, Osen EG, Bach C, Chan H, Barnett J (1996) Expression of human dopamine beta-hydroxylase in Drosophila Schneider 2 cells. Biochem J 313(Pt 1):57–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kim CH, Leung A, Huh YH, Yang E, Kim DJ, Leblanc P, Ryu H, Kim K, Kim DW, Garland EM, Raj SR, Biaggioni I, Robertson D, Kim KS (2011) Norepinephrine deficiency is caused by combined abnormal mRNA processing and defective protein trafficking of dopamine beta-hydroxylase. J Biol Chem 286(11):9196–9204. doi:10.1074/jbc.M110.192351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Musacchio JM, Goldstein M, Anagnoste B, Poch G, Kopin IJ (1966) Inhibition of dopamine-beta-hydroxylase by disulfiram in vivo. J Pharmacol Exp Ther 152(1):56–61

    CAS  PubMed  Google Scholar 

  42. Stanley WC, Li B, Bonhaus DW, Johnson LG, Lee K, Porter S, Walker K, Martinez G, Eglen RM, Whiting RL, Hegde SS (1997) Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase. Br J Pharmacol 121(8):1803–1809. doi:10.1038/sj.bjp.0701315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Beliaev A, Learmonth DA, Soares-da-Silva P (2006) Synthesis and biological evaluation of novel, peripherally selective chromanyl imidazolethione-based inhibitors of dopamine beta-hydroxylase. J Med Chem 49(3):1191–1197. doi:10.1021/jm051051f

    Article  CAS  PubMed  Google Scholar 

  44. Goldstein M, Anagnoste B, Lauber E, McKeregham MR (1964) Inhibition of dopamine-beta-hydroxylase by disulfiram. Life Sci 3:763–767

    Article  CAS  Google Scholar 

  45. Hegde SS, Friday KF (1998) Dopamine-beta-hydroxylase inhibition: a novel sympatho-modulatory approach for the treatment of congestive heart failure. Curr Pharm Des 4(6):469–479

    CAS  PubMed  Google Scholar 

  46. Stanley WC, Lee K, Johnson LG, Whiting RL, Eglen RM, Hegde SS (1998) Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor. J Cardiovasc Pharmacol 31(6):963–970

    Article  CAS  PubMed  Google Scholar 

  47. Cubells JF, Zabetian CP (2004) Human genetics of plasma dopamine beta-hydroxylase activity: applications to research in psychiatry and neurology. Psychopharmacology 174(4):463–476. doi:10.1007/s00213-004-1840-8

    Article  CAS  PubMed  Google Scholar 

  48. Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4(7):1073–1081. doi:10.1038/nprot.2009.86

    Article  CAS  PubMed  Google Scholar 

  49. Sternberg SR (1983) Biomedical image processing. Computer 16(1):22–34. doi:10.1109/mc.1983.1654163

    Article  Google Scholar 

  50. Ferreira T, Rasband WS (2012) “ImageJ User Guide—IJ 146”, https://imagej.nih.gov/ij/docs/guide

  51. Nagatsu T, Udenfriend S (1972) Photometric assay of dopamine-β-hydroxylase activity in human blood. Clin Chem 18(9):980–983

    CAS  PubMed  Google Scholar 

  52. Feilchenfeld NB, Richter HW, Waddell WH (1982) A time-resolved assay of dopamine beta-hydroxylase activity utilizing high-pressure liquid chromatography. Anal Biochem 122(1):124–128

    Article  CAS  PubMed  Google Scholar 

  53. Gundry RL, White MY, Murray CI, Kane LA, Fu Q, Stanley BA, Van Eyk JE (2009) Preparation of proteins and peptides for mass spectrometry analysis in a bottom-up proteomics workflow. Curr Protoc Mol Biol chapter 10:Unit10 25. doi:10.1002/0471142727.mb1025s88

  54. Vendelboe TV, Harris P, Zhao Y, Walter TS, Harlos K, El Omari K, Christensen HEM (2016) The crystal structure of human dopamine Î2-hydroxylase at 2.9 Ã… resolution. Science Adv 2(4). doi:10.1126/sciadv.1500980

  55. Van Durme J, Delgado J, Stricher F, Serrano L, Schymkowitz J, Rousseau F (2011) A graphical interface for the FoldX forcefield. Bioinformatics 27(12):1711–1712. doi:10.1093/bioinformatics/btr254

    Article  PubMed  Google Scholar 

  56. Krieger E, Vriend G (2002) Models@Home: distributed computing in bioinformatics using a screensaver based approach. Bioinformatics 18(2):315–318

    Article  CAS  PubMed  Google Scholar 

  57. Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, Lindahl E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 2:19–25. doi:10.1016/j.softx.2015.06.001

    Article  Google Scholar 

  58. Schuler LD, Daura X, van Gunsteren WF (2001) An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J Comput Chem 22(11):1205–1218. doi:10.1002/jcc.1078

    Article  CAS  Google Scholar 

  59. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18(12):1463–1472. doi:10.1002/(sici)1096-987x(199709)18:12<1463::aid-jcc4>3.0.co;2-h

    Article  CAS  Google Scholar 

  60. Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103(19):8577–8593. doi:10.1063/1.470117

    Article  CAS  Google Scholar 

  61. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC (2005) GROMACS: fast, flexible, and free. J Comput Chem 26(16):1701–1718. doi:10.1002/jcc.20291

    Article  Google Scholar 

  62. Balasco N, Esposito L, De Simone A, Vitagliano L (2013) Role of loops connecting secondary structure elements in the stabilization of proteins isolated from thermophilic organisms. Protein Sci 22(7):1016–1023. doi:10.1002/pro.2279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mustapic M, Maihofer AX, Mahata M, Chen Y, Baker DG, O'Connor DT, Nievergelt CM (2014) The catecholamine biosynthetic enzyme dopamine beta-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter. Hum Mol Genet 23(23):6375–6384. doi:10.1093/hmg/ddu332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Sternberg DE, VanKammen DP, Lerner P, Bunney WE (1982) Schizophrenia: dopamine beta-hydroxylase activity and treatment response. Science 216(4553):1423–1425

    Article  CAS  PubMed  Google Scholar 

  65. Sternberg DE, van Kammen DP, Lerner P, Ballenger JC, Marder SR, Post RM, Bunney WE Jr (1983) CSF dopamine beta-hydroxylase in schizophrenia. Arch Gen Psychiatry 40(7):743–747

    Article  CAS  PubMed  Google Scholar 

  66. Gerber SA, Rush J, Stemman O, Kirschner MW, Gygi SP (2003) Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci U S A 100(12):6940–6945. doi:10.1073/pnas.0832254100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kettenbach AN, Rush J, Gerber SA (2011) Absolute quantification of protein and post-translational modification abundance with stable isotope-labeled synthetic peptides. Nat Protoc 6(2):175–186. doi:10.1038/nprot.2010.196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kapoor A, Shandilya M, Kundu S (2011) Structural insight of dopamine beta-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms. PLoS One 6(10):e26509. doi:10.1371/journal.pone.0026509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

HEK293 and PC-12 cells were kindly provided by Prof R. N. K. Bamezai at Jawaharlal Nehru University (JNU), New Delhi, and Dr. Pushkar Sharma at National Institute of Immunology (NII), New Delhi, respectively on request. This work was supported by Department of Biotechnology, Government of India, New Delhi (Grant# BT/01/COE/07UDSC) to BKT and SK; Junior and senior research fellowship (Grant # DBT-JRF/07-08/264) from Dept. of Biotechnology, Govt. of India, New Delhi, to TJP; UGC research fellowship in sciences for meritorious students, Dept. of Genetics, University of Delhi South campus, New Delhi, to TJP. The dimeric crystal structure of DBH was kindly provided by Prof. Hans E.M.Christensen, Department of Chemistry, Technical University of Denmark. We gratefully acknowledge M/s Waters (India) Private limited for technical assistance with DBH activity assays; SCIEX, Gurgaon, for providing access to their MS platform; Dr. Dipankar Malakar at SCIEX, Gurgaon, for MS analysis for quantitation of DBH using MRMHR; Central Instrumentation Facility (CIF), University of Delhi South Campus for UPLC, confocal microscopy and sequencing facilities rendered throughout this work; infrastructure support provided by the University Grants Commission (UGC), New Delhi, through Special Assistance Programme and Department of Science and Technology, New Delhi, through FIST and DU-DST PURSE programmes to the Department of Genetics, University of Delhi, South Campus.

Contributors

Prof. B.K Thelma and Dr. Toyanji Joseph Punchaichira formulated and designed the study. Experimental work and the first draft of the manuscript were done by Dr. Toyanji Joseph Punchaichira. Mr. Anirban Mukhopadhyay and Mr. Sanjay Kumar Dey contributed towards the molecular dynamics simulation. Prof. B.K Thelma and Prof. Suman Kundu were instrumental in finalizing the manuscript.

Author information

Authors and Affiliations

  1. Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India

    Toyanji Joseph Punchaichira, Anirban Mukhopadhyay & B. K. Thelma

  2. Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India

    Sanjay Kumar Dey & Suman Kundu

Authors
  1. Toyanji Joseph Punchaichira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanjay Kumar Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anirban Mukhopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suman Kundu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. K. Thelma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. K. Thelma.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Punchaichira, T.J., Dey, S.K., Mukhopadhyay, A. et al. Characterization of SNPs in the dopamine-β-hydroxylase gene providing new insights into its structure-function relationship. Neurogenetics 18, 155–168 (2017). https://doi.org/10.1007/s10048-017-0519-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10048-017-0519-3

Keywords

Search

Navigation