Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 22 December 2006:
Vol. 314. no. 5807, pp. 1930 - 1933
DOI: 10.1126/science.1131262
Prev | Table of Contents | Next

Reports

Human Catechol-O-Methyltransferase Haplotypes Modulate Protein Expression by Altering mRNA Secondary Structure

A. G. Nackley,1 S. A. Shabalina,2 I. E. Tchivileva,1 K. Satterfield,1 O. Korchynskyi,3 S. S. Makarov,4 W. Maixner,1 L. Diatchenko1*

Catechol-O-methyltransferase (COMT) is a key regulator of pain perception, cognitive function, and affective mood. Three common haplotypes of the human COMT gene, divergent in two synonymous and one nonsynonymous position, code for differences in COMT enzymatic activity and are associated with pain sensitivity. Haplotypes divergent in synonymous changes exhibited the largest difference in COMT enzymatic activity, due to a reduced amount of translated protein. The major COMT haplotypes varied with respect to messenger RNA local stem-loop structures, such that the most stable structure was associated with the lowest protein levels and enzymatic activity. Site-directed mutagenesis that eliminated the stable structure restored the amount of translated protein. These data highlight the functional significance of synonymous variations and suggest the importance of haplotypes over single-nucleotide polymorphisms for analysis of genetic variations.

1 Center for Neurosensory Disorders, University of North Carolina, Chapel Hill, NC 27599, USA.
2 National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD 20894, USA.
3 Thurston Arthritis Center, University of North Carolina, Chapel Hill, NC 27599, USA.
4 Attagene, Inc., 7030 Kit Creek Road, Research Triangle Park, NC 27560, USA.

* To whom correspondence should be addressed. E-mail: lbdiatch{at}email.unc.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Effects of Catechol-O-Methyltransferase on Normal Variation in the Cognitive Function of Children.
J. H. Barnett, J. Heron, D. Goldman, P. B. Jones, and K. Xu (2009)
Am J Psychiatry 166, 909-916
   Abstract »    Full Text »    PDF »
Complex Renal Traits: Role of Adrenergic Genetic Polymorphism.
M. M. Fung and D. T. O'Connor (2009)
J. Am. Soc. Nephrol. 20, 1172-1174
   Full Text »    PDF »
Coding-Sequence Determinants of Gene Expression in Escherichia coli.
G. Kudla, A. W. Murray, D. Tollervey, and J. B. Plotkin (2009)
Science 324, 255-258
   Abstract »    Full Text »    PDF »
Gene Mutations in Esophageal Mucosa of Chagas Disease Patients.
F. DA SILVA MANOEL-CAETANO, A. F.P. SILVEIRA, and A. E. SILVA (2009)
Anticancer Res 29, 1243-1247
   Abstract »    Full Text »    PDF »
Determination of Genetic Predisposition to Patent Ductus Arteriosus in Preterm Infants.
J. M. Dagle, N. T. Lepp, M. E. Cooper, K. L. Schaa, K. J.P. Kelsey, K. L. Orr, D. Caprau, C. R. Zimmerman, K. M. Steffen, K. J. Johnson, et al. (2009)
Pediatrics 123, 1116-1123
   Abstract »    Full Text »    PDF »
Investigating Protein-Coding Sequence Evolution with Probabilistic Codon Substitution Models.
M. Anisimova and C. Kosiol (2009)
Mol. Biol. Evol. 26, 255-271
   Abstract »    Full Text »    PDF »
ABL single nucleotide polymorphisms may masquerade as BCR-ABL mutations associated with resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia.
T. Ernst, J. Hoffmann, P. Erben, B. Hanfstein, A. Leitner, R. Hehlmann, A. Hochhaus, and M. C. Muller (2008)
Haematologica 93, 1389-1393
   Abstract »    Full Text »    PDF »
Genetic Dissection of the Role of Catechol-O-Methyltransferase in Cognition and Stress Reactivity in Mice.
F. Papaleo, J. N. Crawley, J. Song, B. K. Lipska, J. Pickel, D. R. Weinberger, and J. Chen (2008)
J. Neurosci. 28, 8709-8723
   Abstract »    Full Text »    PDF »
Breast Cancer Risk Reduction and Membrane-Bound Catechol O-Methyltransferase Genetic Polymorphisms.
Y. Ji, J. Olson, J. Zhang, M. Hildebrandt, L. Wang, J. Ingle, Z. Fredericksen, T. Sellers, W. Miller, J. M. Dixon, et al. (2008)
Cancer Res. 68, 5997-6005
   Abstract »    Full Text »    PDF »
Phosphodiesterase 11A (PDE11A) and Genetic Predisposition to Adrenocortical Tumors.
R. Libe, A. Fratticci, J. Coste, F. Tissier, A. Horvath, B. Ragazzon, F. Rene-Corail, L. Groussin, X. Bertagna, M. L. Raffin-Sanson, et al. (2008)
Clin. Cancer Res. 14, 4016-4024
   Abstract »    Full Text »    PDF »
Restricted expression of the human DAZ protein in premeiotic germ cells.
W. J. Huang, Y.-W. Lin, K.-N. Hsiao, K. S. Eilber, E. C. Salido, and P. H. Yen (2008)
Hum. Reprod. 23, 1280-1289
   Abstract »    Full Text »    PDF »
Exploring the genetic susceptibility of chronic widespread pain: the tender points in genetic association studies.
K. L. Limer, B. I. Nicholl, W. Thomson, and J. McBeth (2008)
Rheumatology 47, 572-577
   Abstract »    Full Text »    PDF »
A network of dopaminergic gene variations implicated as risk factors for schizophrenia.
M. E. Talkowski, G. Kirov, M. Bamne, L. Georgieva, G. Torres, H. Mansour, K. V. Chowdari, V. Milanova, J. Wood, L. McClain, et al. (2008)
Hum. Mol. Genet. 17, 747-758
   Abstract »    Full Text »    PDF »
Association of Polymorphisms in Odorant-Binding Protein Genes With Variation in Olfactory Response to Benzaldehyde in Drosophila.
P. Wang, R. F. Lyman, S. A. Shabalina, T. F. C. Mackay, and R. R. H. Anholt (2007)
Genetics 177, 1655-1665
   Abstract »    Full Text »    PDF »
Congenic Interval Mapping of RNO10 Reveals a Complex Cluster of Closely-Linked Genetic Determinants of Blood Pressure.
Y. Saad, S. Yerga-Woolwine, J. Saikumar, P. Farms, E. Manickavasagam, E. J. Toland, and B. Joe (2007)
Hypertension 50, 891-898
   Abstract »    Full Text »    PDF »
Silent Polymorphisms Speak: How They Affect Pharmacogenomics and the Treatment of Cancer.
Z. E. Sauna, C. Kimchi-Sarfaty, S. V. Ambudkar, and M. M. Gottesman (2007)
Cancer Res. 67, 9609-9612
   Abstract »    Full Text »    PDF »
Organismal complexity, cell differentiation and gene expression: human over mouse.
A. E. Vinogradov and O. V. Anatskaya (2007)
Nucleic Acids Res. 35, 6350-6356
   Abstract »    Full Text »    PDF »
.
J. Ross (2007)
Cancer Epidemiol. Biomarkers Prev. 16, 857-858
   Full Text »    PDF »
Is COMT a Susceptibility Gene for Schizophrenia?.
H. J. Williams, M. J. Owen, and M. C. O'Donovan (2007)
Schizophr Bull 33, 635-641
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)