Human Genetics

, Volume 120, Issue 3, pp 301–333 | Cite as

A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3′ UTR variants

Review Article

Abstract

In an attempt both to catalogue 3′ regulatory region (3′ RR)-mediated disease and to improve our understanding of the structure and function of the 3′ RR, we have performed a systematic analysis of disease-associated variants in the 3′ RRs of human protein-coding genes. We have previously analysed the variants that have occurred in two specific domains/motifs of the 3′ untranslated region (3′ UTR) as well as in the 3′ flanking region. Here we have focused upon 83 known variants within the upstream sequence (USS; between the translational termination codon and the upstream core polyadenylation signal sequence) of the 3′ UTR. To place these variants in their proper context, we first performed a comprehensive survey of known cis-regulatory elements within the USS and the mechanisms by which they effect post-transcriptional gene regulation. Although this survey supports the view that RNA regulatory elements function within the context of specific secondary structures, there are no general rules governing how secondary structure might exert its influence. We have therefore addressed this question by systematically evaluating both functional and non-functional (based upon in vitro reporter gene and/or electrophoretic mobility shift assay data) USS variant-containing sequences against known cis-regulatory motifs within the context of predicted RNA secondary structures. This has allowed us not only to establish a reliable and objective means to perform secondary structure prediction but also to identify consistent patterns of secondary structural change that could potentiate the discrimination of functional USS variants from their non-functional counterparts. The resulting rules were then used to infer potential functionality in the case of some of the remaining functionally uncharacterised USS variants, from their predicted secondary structures. This not only led us to identify further patterns of secondary structural change but also several potential novel cis-regulatory motifs within the 3′ UTRs studied.

Supplementary material

439_2006_218_MOESM1_ESM.doc (1.7 mb)
Supplementary material

References

  1. Abelson JF, Kwan KY, O’Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rasin MR, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS IV, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Sestan N, State MW (2005) Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 310:317–320PubMedGoogle Scholar
  2. Adereth Y, Dammai V, Kose N, Li R, Hsu T (2005) RNA-dependent integrin alpha3 protein localization regulated by the Muscleblind-like protein MLP1. Nat Cell Biol 7:1140–1147Google Scholar
  3. Ainger K, Avossa D, Diana AS, Barry C, Barbarese E, Carson JH (1997) Transport and localization elements in myelin basic protein mRNA. J Cell Biol 138:1077–1087PubMedGoogle Scholar
  4. Aissouni Y, Perez C, Calmels B, Benech PD (2002) The cleavage/polyadenylation activity triggered by a U-rich motif sequence is differently required depending on the poly(A) site location at either the first or last 3′-terminal exon of the 2′-5′ oligo(A) synthetase gene. J Biol Chem 277:35808–35814PubMedGoogle Scholar
  5. Allamand V, Richard P, Lescure A, Ledeuil C, Desjardin D, Petit N, Gartioux C, Ferreiro A, Krol A, Pellegrini N, Urtizberea JA, Guicheney P (2006) A single homozygous point mutation in a 3′ untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy. EMBO Rep 7:450–454PubMedGoogle Scholar
  6. Al-Maghrebi M, Brule H, Padkina M, Allen C, Holmes WM, Zehner ZE (2002) The 3′ untranslated region of human vimentin mRNA interacts with protein complexes containing eEF-1gamma and HAX-1. Nucleic Acids Res 30:5017–5028PubMedGoogle Scholar
  7. Apostolou S, Klein JO, Mitsuuchi Y, Shetler JN, Poulikakos PI, Jhanwar SC, Kruger WD, Testa JR (2004) Growth inhibition and induction of apoptosis in mesothelioma cells by selenium and dependence on selenoprotein SEP15 genotype. Oncogene 23:5032–5240PubMedGoogle Scholar
  8. Aranda-Abreu GE, Hernandez ME, Soto A, Manzo J (2005) Possible cis-acting signal that could be involved in the localization of different mRNAs in neuronal axons. Theor Biol Med Model 2:33PubMedGoogle Scholar
  9. Arya SK, Ginsberg CC, Davis-Warren A, D’Costa J (1999) In vitro phenotype of SDF1 gene mutant that delays the onset of human immunodeficiency virus disease in vivo. J Hum Virol 2:133–138PubMedGoogle Scholar
  10. Aston CE, Ralph DA, Lalo DP, Manjeshwar S, Gramling BA, DeFreese DC, West AD, Branam DE, Thompson LF, Craft MA, Mitchell DS, Shimasaki CD, Mulvihill JJ, Jupe ER (2005) Oligogenic combinations associated with breast cancer risk in women under 53 years of age. Hum Genet 116:208–221PubMedGoogle Scholar
  11. Audrezet MP, Chen JM, Le Marechal C, Ruszniewski P, Robaszkiewicz M, Raguenes O, Quere I, Scotet V, Ferec C (2002) Determination of the relative contribution of three genes - the cystic fibrosis transmembrane conductance regulator gene, the cationic trypsinogen gene, and the pancreatic secretory trypsin inhibitor gene-to the etiology of idiopathic chronic pancreatitis. Eur J Hum Genet 10:100–106PubMedGoogle Scholar
  12. Baker M, Gaukrodger N, Mayosi BM, Imrie H, Farrall M, Watkins H, Connell JM, Avery PJ, Keavney B (2005) Association between common polymorphisms of the proopiomelanocortin gene and body fat distribution: a family study. Diabetes 54:2492–2496PubMedGoogle Scholar
  13. Bakheet T, Frevel M, Williams BR, Greer W, Khabar KS (2001) ARED: human AU-rich element-containing mRNA database reveals an unexpectedly diverse functional repertoire of encoded proteins. Nucleic Acids Res 29:246–254PubMedGoogle Scholar
  14. Barreau C, Paillard L, Osborne HB (2006) AU-rich elements and associated factors: are there unifying principles? Nucleic Acids Res 33:7138–7150PubMedGoogle Scholar
  15. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedGoogle Scholar
  16. Basak AN, Ozer A, Kirdar B, Akar N (1993) A novel 13 bp deletion in the 3′ UTR of the beta-globin gene causes beta-thalassemia in a Turkish patient. Hemoglobin 17:551–555PubMedGoogle Scholar
  17. Becker KF, Reich U, Schott C, Hofler H (1995) Single nucleotide polymorphisms in the human E-cadherin gene. Hum Genet 96:739–740PubMedGoogle Scholar
  18. Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, Carraro G, Thiene G, Towbin JA, Danieli GA, Rampazzo A (2005) Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res 65:366–373PubMedGoogle Scholar
  19. Benjafield AV, Katyk K, Morris BJ (2003) Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. Clin Genet 64:433–438PubMedGoogle Scholar
  20. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37:766–770PubMedGoogle Scholar
  21. Berger A, Stierkorb E, Nickenig G (2005) The role of the AUUUUA hexamer for the posttranscriptional regulation of the AT1 receptor mRNA stability. Biochem Biophys Res Commun 330:805–812PubMedGoogle Scholar
  22. Bertram L, Parkinson M, McQueen MB, Mullin K, Hsiao M, Menon R, Moscarillo TJ, Blacker D, Tanzi RE (2005) Further evidence for LBP-1c/CP2/LSF association in Alzheimer’s disease families. J Med Genet 42:857–862PubMedGoogle Scholar
  23. Berry MJ (2005) Insights into the hierarchy of selenium incorporation. Nat Genet 37:1162–1163PubMedGoogle Scholar
  24. Bilenoglu O, Basak AN, Russell JE (2002) A 3′ UTR mutation affects beta-globin expression without altering the stability of its fully processed mRNA. Br J Haematol 119:1106–1114PubMedGoogle Scholar
  25. Binder R, Horowitz JA, Basilion JP, Koeller DM, Klausner RD, Harford JB (1994) Evidence that the pathway of transferrin receptor mRNA degradation involves an endonucleolytic cleavage within the 3′ UTR and does not involve poly(A) tail shortening. EMBO J 13:1969–1980PubMedGoogle Scholar
  26. Bonilla C, Boxill LA, Donald SA, Williams T, Sylvester N, Parra EJ, Dios S, Norton HL, Shriver MD, Kittles RA (2005) The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum Genet 116:402–406PubMedGoogle Scholar
  27. Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, Tiret L, Cambien F, Corvol P, Soubrier F (1994) Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 24:63–69PubMedGoogle Scholar
  28. Bowen DG, Walker CM (2005) Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 436:946–952PubMedGoogle Scholar
  29. Brackenridge S, Proudfoot NJ (2000) Recruitment of a basal polyadenylation factor by the upstream sequence element of the human lamin B2 polyadenylation signal. Mol Cell Biol 20:2660–2669PubMedGoogle Scholar
  30. Brackenridge S, Ashe HL, Giacca M, Proudfoot NJ (1997) Transcription and polyadenylation in a short human intergenic region. Nucleic Acids Res 25:2326–2336PubMedGoogle Scholar
  31. Branson R, Potoczna N, Kral JG, Lentes KU, Hoehe MR, Horber FF (2003) Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. New Engl J Med 348:1096–1103PubMedGoogle Scholar
  32. Brown CY, Lagnado CA, Goodall GJ (1996) A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A+U-rich elements. Proc Natl Acad Sci USA 93:13721–13725PubMedGoogle Scholar
  33. Brull DJ, Serrano N, Zito F, Jones L, Montgomery HE, Rumley A, Sharma P, Lowe GD, World MJ, Humphries SE, Hingorani AD (2003) Human CRP gene polymorphism influences CRP levels: implications for the prediction and pathogenesis of coronary heart disease. Arterioscler Thromb Vasc Biol 23:2063–2069PubMedGoogle Scholar
  34. Campa D, Zienolddiny S, Maggini V, Skaug V, Haugen A, Canzian F (2004) Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis 25:229–235PubMedGoogle Scholar
  35. Campbell IG, Allen J, Eccles DM (2003) Prohibitin 3′ untranslated region polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 12:1273–1274PubMedGoogle Scholar
  36. Cappellini MD, Martinez di Montemuros F, Tavazzi D, Fargion S, Pizzuti A, Comino A, Cainelli T, Fiorelli G (2001) Seven novel point mutations in the uroporphyrinogen decarboxylase (UROD) gene in patients with familial porphyria cutanea tarda (f-PCT). Hum Mutat 17:350PubMedGoogle Scholar
  37. Caput D, Beutler B, Hartog K, Thayer R, Brown-Shimer S, Cerami A (1986) Identification of a common nucleotide sequence in the 3′-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci USA 83:1670–1674PubMedGoogle Scholar
  38. Carlton VE, Hu X, Chokkalingam AP, Schrodi SJ, Brandon R, Alexander HC, Chang M, Catanese JJ, Leong DU, Ardlie KG, Kastner DL, Seldin MF, Criswell LA, Gregersen PK, Beasley E, Thomson G, Amos CI, Begovich AB (2005) PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Am J Hum Genet 77:567–581PubMedGoogle Scholar
  39. Casey JL, Hentze MW, Koeller DM, Caughman SW, Rouault TA, Klausner RD, Harford JB (1988) Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation. Science 240:924–928PubMedGoogle Scholar
  40. Casey JL, Koeller DM, Ramin VC, Klausner RD, Harford JB (1989) Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3′ untranslated region of the mRNA. EMBO J 8:3693–3639PubMedGoogle Scholar
  41. Chabanon H, Mickleburgh I, Hesketh J (2004) Zipcodes and postage stamps: mRNA localisation signals and their trans-acting binding proteins. Brief Funct Genomic Proteomic 3:240–256PubMedGoogle Scholar
  42. Chabanon H, Mickleburgh I, Burtle B, Pedder C, Hesketh J (2005) An AU-rich stem–loop structure is a critical feature of the perinuclear localization signal of c-myc mRNA. Biochem J 392:475–483PubMedGoogle Scholar
  43. Charmandari E, Chrousos GP, Ichijo T, Bhattacharyya N, Vottero A, Souvatzoglou E, Kino T (2005) The human glucocorticoid receptor (hGR) beta isoform suppresses the transcriptional activity of hGRalpha by interfering with formation of active coactivator complexes. Mol Endocrinol 19:52–64PubMedGoogle Scholar
  44. Chen CY, Shyu AB (1995) AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci 20:465–470PubMedGoogle Scholar
  45. Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJ, Stoecklin G, Moroni C, Mann M, Karin M (2001) AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107:451–464PubMedGoogle Scholar
  46. Chen JM, Férec C, Cooper DN (2006) A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes I: General principles and overview. Hum Genet [Epub ahead of print]Google Scholar
  47. Christian K, Lang M, Maurel P, Raffalli-Mathieu F (2004) Interaction of heterogeneous nuclear ribonucleoprotein A1 with cytochrome P450 2A6 mRNA: implications for post-transcriptional regulation of the CYP2A6 gene. Mol Pharmacol 65:1405–1414PubMedGoogle Scholar
  48. Comings DE, Wu S, Rostamkhani M, McGue M, Iacono WG, MacMurray JP (2002) Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women. Am J Med Genet 114:527–529PubMedGoogle Scholar
  49. Cox DG, Pontes C, Guino E, Navarro M, Osorio A, Canzian F, Moreno V; Bellvitge Colorectal Cancer Study Group (2004) Polymorphisms in prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) and risk of colorectal cancer. Br J Cancer 91:339–343Google Scholar
  50. Culjkovic B, Topisirovic I, Skrabanek L, Ruiz-Gutierrez M, Borden KL (2005) eIF4E promotes nuclear export of cyclin D1 mRNAs via an element in the 3′UTR. J Cell Biol 169:245–256PubMedGoogle Scholar
  51. Dahlman I, Eaves IA, Kosoy R, Morrison VA, Heward J, Gough SC, Allahabadia A, Franklyn JA, Tuomilehto J, Tuomilehto-Wolf E, Cucca F, Guja C, Ionescu-Tirgoviste C, Stevens H, Carr P, Nutland S, McKinney P, Shield JP, Wang W, Cordell HJ, Walker N, Todd JA, Concannon P (2002) Parameters for reliable results in genetic association studies in common disease. Nat Genet 30:149–150PubMedGoogle Scholar
  52. Dahlman I, Wahrenberg H, Persson L, Arner P (2004) No association of reported functional protein tyrosine phosphatase 1B 3′ UTR gene polymorphism with features of the metabolic syndrome in a Swedish population. J Intern Med 255:694–695PubMedGoogle Scholar
  53. Dammerman M, Sandkuijl LA, Halaas JL, Chung W, Breslow JL (1993) An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3′ untranslated region polymorphisms. Proc Natl Acad Sci USA 90:4562–4566PubMedGoogle Scholar
  54. Deinum J, van Gool JM, Kofflard MJ, ten Cate FJ, Danser AH (2001) Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy. Hypertension 38:1278–1281PubMedGoogle Scholar
  55. Derijk RH, Schaaf MJ, Turner G, Datson NA, Vreugdenhil E, Cidlowski J, de Kloet ER, Emery P, Sternberg EM, Detera-Wadleigh SD (2001) A human glucocorticoid receptor gene variant that increases the stability of the glucocorticoid receptor beta-isoform mRNA is associated with rheumatoid arthritis. J Rheumatol 28:2383–2388PubMedGoogle Scholar
  56. van Dijk EL, Sussenbach JS, Holthuizen PE (1998) Identification of RNA sequences and structures involved in site-specific cleavage of IGF-II mRNAs. RNA 4:1623–1635PubMedGoogle Scholar
  57. van Dijk EL, Sussenbach JS, Holthuizen PE (2000) Distinct RNA structural domains cooperate to maintain a specific cleavage site in the 3′-UTR of IGF-II mRNAs. J Mol Biol 300:449–467PubMedGoogle Scholar
  58. Di Paola R, Frittitta L, Miscio G, Bozzali M, Baratta R, Centra M, Spampinato D, Santagati MG, Ercolino T, Cisternino C, Soccio T, Mastroianno S, Tassi V, Almgren P, Pizzuti A, Vigneri R, Trischitta V (2002) A variation in 3′ UTR of hPTP1B increases specific gene expression and associates with insulin resistance. Am J Hum Genet 70:806–812PubMedGoogle Scholar
  59. Dixon DA, Balch GC, Kedersha N, Anderson P, Zimmerman GA, Beauchamp RD, Prescott SM (2003) Regulation of cyclooxygenase-2 expression by the translational silencer TIA-1. J Exp Med 198:475–481PubMedGoogle Scholar
  60. Doi K, Noiri E, Nakao A, Fujita T, Kobayashi S, Tokunaga K (2006) Functional polymorphisms in the vascular endothelial growth factor gene are associated with development of end-stage renal disease in males. J Am Soc Nephrol 17:823–830PubMedGoogle Scholar
  61. Echwald SM, Bach H, Vestergaard H, Richelsen B, Kristensen K, Drivsholm T, Borch-Johnsen K, Hansen T, Pedersen O (2002) A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro. Diabetes 51:1–6PubMedGoogle Scholar
  62. Espel E (2005) The role of the AU-rich elements of mRNAs in controlling translation. Semin Cell Dev Biol 16:59–67PubMedGoogle Scholar
  63. Fang Y, van Meurs JB, d’Alesio A, Jhamai M, Zhao H, Rivadeneira F, Hofman A, van Leeuwen JP, Jehan F, Pols HA, Uitterlinden AG (2005) Promoter and 3′-untranslated-region haplotypes in the vitamin D receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am J Hum Genet 77:807–823PubMedGoogle Scholar
  64. Fialcowitz EJ, Brewer BY, Keenan BP, Wilson GM (2005) A hairpin-like structure within an AU-rich mRNA-destabilizing element regulates trans-factor binding selectivity and mRNA decay kinetics. J Biol Chem 280:22406–22417PubMedGoogle Scholar
  65. Fitze G, Schierz M, Kuhlisch E, Schreiber M, Ziegler A, Roesner D, Schackert HK (2003) Novel intronic polymorphisms in the RET proto-oncogene and their association with Hirschsprung disease. Hum Mutat 22:177PubMedGoogle Scholar
  66. Florez JC, Agapakis CM, Burtt NP, Sun M, Almgren P, Rastam L, Tuomi T, Gaudet D, Hudson TJ, Daly MJ, Ardlie KG, Hirschhorn JN, Groop L, Altshuler D (2005) Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 People. Diabetes 54:1884–1891PubMedGoogle Scholar
  67. Fritz DT, Jiang S, Xu J, Rogers MB (2006) A polymorphism in a conserved post-transcriptional regulatory motif alters BMP2 RNA protein interactions. Mol Endocrinol [Epub ahead of print]Google Scholar
  68. Gardier S, Vincent M, Lantelme P, Rial MO, Bricca G, Milon H (2004) A1166C polymorphism of angiotensin II type 1 receptor, blood pressure and arterial stiffness in hypertension. J Hypertens 22:2135–2142PubMedGoogle Scholar
  69. Garner C, Best S, Menzel S, Rooks H, Spector TD, Thein SL (2005) Two candidate genes for low platelet count identified in an Asian Indian kindred by genome-wide linkage analysis: glycoprotein IX and thrombopoietin. Eur J Hum Genet 14:101–108Google Scholar
  70. Gaukrodger N, Mayosi BM, Imrie H, Avery P, Baker M, Connell JM, Watkins H, Farrall M, Keavney B (2005) A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families. J Med Genet 42:474–478PubMedGoogle Scholar
  71. Gaunt TR, Cooper JA, Miller GJ, Day IN, O’Dell SD (2001) Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males. Hum Mol Genet 10:1491–1501PubMedGoogle Scholar
  72. Gladyshev VN, Jeang KT, Wootton JC, Hatfield DL (1998) A new human selenium-containing protein. Purification, characterization, and cDNA sequence. J Biol Chem 273:8910–8915PubMedGoogle Scholar
  73. Glisovic T, Ben-David Y, Lang MA, Raffalli-Mathieu F (2003) Interplay between hnRNP A1 and a cis-acting element in the 3′ UTR of CYP2A5 mRNA is central for high expression of the gene. FEBS Lett 535:147–152PubMedGoogle Scholar
  74. Gomes MV, Soares MR, Pasqualim-Neto A, Marcondes CR, Lobo RB, Ramos ES (2005) Association between birth weight, body mass index and IGF2/ApaI polymorphism. Growth Horm IGF Res 15:360–362PubMedGoogle Scholar
  75. Graziano F, Kawakami K, Watanabe G, Ruzzo A, Humar B, Santini D, Catalano V, Ficarelli R, Merriman T, Panunzi S, Testa E, Cascinu S, Bearzi I, Tonini G, Magnani M (2004) Association of thymidylate synthase polymorphisms with gastric cancer susceptibility. Int J Cancer 112:1010–1014PubMedGoogle Scholar
  76. Gu D, O’Dell SD, Chen XH, Miller GJ, Day IN (2002) Evidence of multiple causal sites affecting weight in the IGF2-INS-TH region of human chromosome 11. Hum Genet 110:173–181PubMedGoogle Scholar
  77. Gu J, Liang D, Wang Y, Lu C, Wu X (2005) Effects of N-acetyl transferase 1 and 2 polymorphisms on bladder cancer risk in Caucasians. Mutat Res 581:97–104PubMedGoogle Scholar
  78. Hall-Pogar T, Zhang H, Tian B, Lutz CS (2005) Alternative polyadenylation of cyclooxygenase-2. Nucleic Acids Res 33:2565–2579PubMedGoogle Scholar
  79. Han J, Brown T, Beutler B (1990) Endotoxin-responsive sequences control cachectin/tumor necrosis factor biosynthesis at the translational level. J Exp Med 171:465–475PubMedGoogle Scholar
  80. Han SW, Kim GW, Seo JS, Kim SJ, Sa KH, Park JY, Lee J, Kim SY, Goronzy JJ, Weyand CM, Kang YM (2004) VEGF gene polymorphisms and susceptibility to rheumatoid arthritis. Rheumatology 43:1173–1177PubMedGoogle Scholar
  81. Hashizume K, Mashima Y, Fumayama T, Ohtake Y, Kimura I, Yoshida K, Ishikawa K, Yasuda N, Fujimaki T, Asaoka R, Koga T, Kanamoto T, Fukuchi T, Miyaki K; Glaucoma Gene Research Group (2005) Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population. Invest Ophthalmol Vis Sci 46:1993–2001PubMedGoogle Scholar
  82. Heinimann K, Thompson A, Locher A, Furlanetto T, Bader E, Wolf A, Meier R, Walter K, Bauerfeind P, Marra G, Muller H, Foernzler D, Dobbie Z (2001) Nontruncating APC germ-line mutations and mismatch repair deficiency play a minor role in APC mutation-negative polyposis. Cancer Res 61:7616–7622PubMedGoogle Scholar
  83. Holcik M, Liebhaber SA (1997) Four highly stable eukaryotic mRNAs assemble 3′ untranslated region RNA-protein complexes sharing cis and trans components. Proc Natl Acad Sci USA 94:2410–2414PubMedGoogle Scholar
  84. Hong LE, Wonodi I, Avila MT, Buchanan RW, McMahon RP, Mitchell BD, Stine OC, Carpenter WT Jr, Thaker GK (2005) Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia. Am J Med Genet B Neuropsychiatr Genet 136:8–11Google Scholar
  85. Houldsworth A, Metzner M, Rossol S, Shaw S, Kaminski E, Demaine AG, Cramp ME (2005) Polymorphisms in the IL-12B gene and outcome of HCV infection. J Interferon Cytokine Res 25:271–276PubMedGoogle Scholar
  86. Hu YJ, Korotkov KV, Mehta R, Hatfield DL, Rotimi CN, Luke A, Prewitt TE, Cooper RS, Stock W, Vokes EE, Dolan ME, Gladyshev VN, Diamond AM (2001) Distribution and functional consequences of nucleotide polymorphisms in the 3′-untranslated region of the human Sep15 gene. Cancer Res 61:2307–2310PubMedGoogle Scholar
  87. Hu J, Lutz CS, Wilusz J, Tian B (2005) Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation. RNA 11:1485–1493PubMedGoogle Scholar
  88. Huang JL, Gao PS, Mathias RA, Yao TC, Chen LC, Kuo ML, Hsu SC, Plunkett B, Togias A, Barnes KC, Stellato C, Beaty TH, Huang SK (2004) Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability. Hum Mol Genet 13:2691–2697PubMedGoogle Scholar
  89. Ioannidis JP, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, Buchbinder SP, Coutinho RA, Eugen-Olsen J, Gallart T, Katzenstein TL, Kostrikis LG, Kuipers H, Louie LG, Mallal SA, Margolick JB, Martinez OP, Meyer L, Michael NL, Operskalski E, Pantaleo G, Rizzardi GP, Schuitemaker H, Sheppard HW, Stewart GJ, Theodorou ID, Ullum H, Vicenzi E, Vlahov D, Wilkinson D, Workman C, Zagury JF, O’Brien TR; International Meta-Analysis of HIV Host Genetics (2001) Effects of CCR5-Delta32, CCR2–64I, and SDF-1 3’A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med 135:782–795Google Scholar
  90. Jaeger S, Barends S, Giege R, Eriani G, Martin F (2005) Expression of metazoan replication-dependent histone genes. Biochimie 87:827–834PubMedGoogle Scholar
  91. Jankovic L, Dimovski AJ, Kollia P, Karageorga M, Loukopoulos D, Huisman TH (1991) A C→G mutation at nt position 6 3′ to the terminating codon may be the cause of a silent beta-thalassemia. Int J Hematol 54:289–293PubMedGoogle Scholar
  92. Jeong BH, Kim NH, Choi EK, Lee C, Song YH, Kim JI, Carp RI, Kim YS (2005) Polymorphism at 3′ UTR +28 of the prion-like protein gene is associated with sporadic Creutzfeldt-Jakob disease. Eur J Hum Genet 13:1094–1097PubMedGoogle Scholar
  93. Jones A, Dhamrait SS, Payne JR, Hawe E, Li P, Toor IS, Luong L, Wootton PT, Miller GJ, Humphries SE, Montgomery HE (2003) Genetic variants of angiotensin II receptors and cardiovascular risk in hypertension. Hypertension 42:500–506PubMedGoogle Scholar
  94. Jonsson UB, Bystrom J, Stalenheim G, Venge P (2006) A (G->C) transversion in the 3′ UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP. J Leukoc Biol 79:846–851 Google Scholar
  95. Jupe ER, Liu XT, Kiehlbauch JL, McClung JK, Dell’Orco RT (1996) The 3′ untranslated region of prohibitin and cellular immortalization. Exp Cell Res 224:128–135PubMedGoogle Scholar
  96. Jupe ER, Badgett AA, Neas BR, Craft MA, Mitchell DS, Resta R, Mulvihill JJ, Aston CE, Thompson LF (2001) Single nucleotide polymorphism in prohibitin 3′ untranslated region and breast-cancer susceptibility. Lancet 357:1588–1589PubMedGoogle Scholar
  97. Kanetsky PA, Swoyer J, Panossian S, Holmes R, Guerry D, Rebbeck TR (2002) A polymorphism in the agouti signaling protein gene is associated with human pigmentation. Am J Hum Genet 70:770–775PubMedGoogle Scholar
  98. Katz LA, Schultz RE, Semina EV, Torfs CP, Krahn KN, Murray JC (2004) Mutations in PITX2 may contribute to cases of omphalocele and VATER-like syndromes. Am J Med Genet A 130:277–283Google Scholar
  99. Kaufmann I, Martin G, Friedlein A, Langen H, Keller W (2004) Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBO J 23:616–626PubMedGoogle Scholar
  100. Khabar KS (2005) The AU-rich transcriptome: more than interferons and cytokines, and its role in disease. J Interferon Cytokine Res 25:1–10PubMedGoogle Scholar
  101. Khabar KS, Bakheet T, Williams BR (2005) AU-rich transient response transcripts in the human genome: expressed sequence tag clustering and gene discovery approach. Genomics 85:165–175PubMedGoogle Scholar
  102. Kiledjian M, Wang X, Liebhaber SA (1995) Identification of two KH domain proteins in the alpha-globin mRNP stability complex. EMBO J 14:4357–4364PubMedGoogle Scholar
  103. Kimura R, Nishioka T, Ishida T (2003) The SDF1-G801A polymorphism is not associated with SDF1 gene expression in Epstein-Barr virus-transformed lymphoblastoid cells. Genes Immun 4:356–361PubMedGoogle Scholar
  104. Kimura R, Nishioka T, Soemantri A, Ishida T (2005) Allele-specific transcript quantification detects haplotypic variation in the levels of the SDF-1 transcripts. Hum Mol Genet 14:1579–1585PubMedGoogle Scholar
  105. Kleiman FE, Ramirez AO, Dodelson de Kremer R, Gravel RA, Argarana CE (1998) A frequent TG deletion near the polyadenylation signal of the human HEXB gene: occurrence of an irregular DNA structure and conserved nucleotide sequence motif in the 3′ untranslated region. Hum Mutat 12:320–329PubMedGoogle Scholar
  106. Klein B, Weirich G, Brauch H (2001) DHPLC-based germline mutation screening in the analysis of the VHL tumor suppressor gene: usefulness and limitations. Hum Genet 108:376–384PubMedGoogle Scholar
  107. Klenerman P, Hill A (2005) T cells and viral persistence: lessons from diverse infections. Nat Immunol 6:873–879PubMedGoogle Scholar
  108. Knowles JW, Erickson LM, Guy VK, Sigel CS, Wilder JC, Maeda N (2003) Common variations in noncoding regions of the human natriuretic peptide receptor A gene have quantitative effects. Hum Genet 112:62–70PubMedGoogle Scholar
  109. Koeller DM, Casey JL, Hentze MW, Gerhardt EM, Chan LN, Klausner RD, Harford JB (1989) A cytosolic protein binds to structural elements within the iron regulatory region of the transferrin receptor mRNA. Proc Natl Acad Sci USA 86:3574–3578PubMedGoogle Scholar
  110. Koeller DM, Horowitz JA, Casey JL, Klausner RD, Harford JB (1991) Translation and the stability of mRNAs encoding the transferrin receptor and c-fos. Proc Natl Acad Sci USA 88:7778–7782PubMedGoogle Scholar
  111. Korotkov KV, Novoselov SV, Hatfield DL, Gladyshev VN (2002) Mammalian selenoprotein in which selenocysteine (Sec) incorporation is supported by a new form of Sec insertion sequence element. Mol Cell Biol 22:1402–1411PubMedGoogle Scholar
  112. Kovacs A, Green F, Hansson LO, Lundman P, Samnegard A, Boquist S, Ericsson CG, Watkins H, Hamsten A, Tornvall P (2005) A novel common single nucleotide polymorphism in the promoter region of the C-reactive protein gene associated with the plasma concentration of C-reactive protein. Atherosclerosis 178:193–198PubMedGoogle Scholar
  113. Krippl P, Langsenlehner U, Renner W, Yazdani-Biuki B, Wolf G, Wascher TC, Paulweber B, Haas J, Samonigg H (2003) A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. Int J Cancer 106:468–471PubMedGoogle Scholar
  114. Kruys V, Marinx O, Shaw G, Deschamps J, Huez G (1989) Translational blockade imposed by cytokine-derived UA-rich sequences. Science 245:852–855PubMedGoogle Scholar
  115. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443PubMedGoogle Scholar
  116. Kumar R, Smeds J, Berggren P, Straume O, Rozell BL, Akslen LA, Hemminki K (2001) A single nucleotide polymorphism in the 3′untranslated region of the CDKN2A gene is common in sporadic primary melanomas but mutations in the CDKN2B, CDKN2C, CDK4 and p53 genes are rare. Int J Cancer 95:388–393PubMedGoogle Scholar
  117. Kumaraswamy E, Malykh A, Korotkov KV, Kozyavkin S, Hu Y, Kwon SY, Moustafa ME, Carlson BA, Berry MJ, Lee BJ, Hatfield DL, Diamond AM, Gladyshev VN (2000) Structure-expression relationships of the 15-kDa selenoprotein gene. Possible role of the protein in cancer etiology. J Biol Chem 275:35540–35547PubMedGoogle Scholar
  118. Lambert JC, Goumidi L, Vrieze FW, Frigard B, Harris JM, Cummings A, Coates J, Pasquier F, Cottel D, Gaillac M, St Clair D, Mann DM, Hardy J, Lendon CL, Amouyel P, Chartier-Harlin MC (2000) The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer’s disease. Hum Mol Genet 9:2275–2280PubMedGoogle Scholar
  119. Legendre M, Gautheret D (2003) Sequence determinants in human polyadenylation site selection. BMC Genomics 4:7PubMedGoogle Scholar
  120. Leroy-Matheron C, Duchemin J, Levent M, Gouault-Heilmann M (1999) Genetic modulation of plasma protein S levels by two frequent dimorphisms in the PROS1 gene. Thromb Haemost 82:1088–1092PubMedGoogle Scholar
  121. Liao Z, Liu H, Swisher SG, Wang L, Wu TT, Correa AM, Roth JA, Cox JD, Komaki R, Ajani JA, Wei Q (2006) Polymorphism at the 3′-UTR of the thymidylate synthase gene: A potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys 64:700–708 PubMedGoogle Scholar
  122. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773PubMedGoogle Scholar
  123. Lin HJ, Tsai FJ, Hung P, Chen WC, Chen HY, Fan SS, Tsai SW (2006) Association of E-cadherin gene 3′-UTR C/T polymorphism with primary open angle glaucoma. Ophthalmic Res 38:44–48PubMedGoogle Scholar
  124. Lopez de Silanes I, Zhan M, Lal A, Yang X, Gorospe M (2004) Identification of a target RNA motif for RNA-binding protein HuR. Proc Natl Acad Sci USA 101:2987–2992Google Scholar
  125. Lopez de Silanes I, Galban S, Martindale JL, Yang X, Mazan-Mamczarz K, Indig FE, Falco G, Zhan M, Gorospe M (2005) Identification and functional outcome of mRNAs associated with RNA-binding protein TIA-1. Mol Cell Biol 25:9520–9531Google Scholar
  126. Lu JW, Gao CM, Wu JZ, Cao HX, Tajima K, Feng JF (2006) Polymorphism in the 3′-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy. J Hum Genet 51:155–160 PubMedGoogle Scholar
  127. Luedecking-Zimmer E, DeKosky ST, Nebes R, Kamboh MI (2003) Association of the 3′ UTR transcription factor LBP-1c/CP2/LSF polymorphism with late-onset Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 117:114–117Google Scholar
  128. Mandola MV, Stoehlmacher J, Zhang W, Groshen S, Yu MC, Iqbal S, Lenz HJ, Ladner RD (2004) A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 14:319–327PubMedGoogle Scholar
  129. Mango R, Clementi F, Borgiani P, Forleo GB, Federici M, Contino G, Giardina E, Garza L, Fahdi IE, Lauro R, Mehta JL, Novelli G, Romeo F (2003) Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction. J Med Genet 40:933–936PubMedGoogle Scholar
  130. Mango R, Biocca S, del Vecchio F, Clementi F, Sangiuolo F, Amati F, Filareto A, Grelli S, Spitalieri P, Filesi I, Favalli C, Lauro R, Mehta JL, Romeo F, Novelli G (2005) In vivo and in vitro studies support that a new splicing isoform of OLR1 gene is protective against acute myocardial infarction. Circ Res 97:152–158PubMedGoogle Scholar
  131. Manjeshwar S, Branam DE, Lerner MR, Brackett DJ, Jupe ER (2003) Tumor suppression by the prohibitin gene 3′untranslated region RNA in human breast cancer. Cancer Res 63:5251–5256PubMedGoogle Scholar
  132. Maragoudaki E, Vrettou C, Kanavakis E, Traeger-Synodinos J, Metaxotou-Mavrommati A, Kattamis C (1998) Molecular, haematological and clinical studies of a silent beta-gene C→G mutation at 6 bp 3′ to the termination codon (+1480 C→G) in twelve Greek families. Br J Haematol 103:45–51PubMedGoogle Scholar
  133. Mata J, Marguerat S, Bahler J (2005) Post-transcriptional control of gene expression: a genome-wide perspective. Trends Biochem Sci 30:506–514PubMedGoogle Scholar
  134. Mathews DH, Sabina J, Zuker M, Turner DH (1999) Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288:911–940PubMedGoogle Scholar
  135. Medina P, Navarro S, Estelles A, Vaya A, Woodhams B, Mira Y, Villa P, Migaud-Fressart M, Ferrando F, Aznar J, Bertina RM, Espana F (2004) Contribution of polymorphisms in the endothelial protein C receptor gene to soluble endothelial protein C receptor and circulating activated protein C levels, and thrombotic risk. Thromb Haemost 91:905–911PubMedGoogle Scholar
  136. Medina P, Navarro S, Estelles A, Vaya A, Bertina RM, Espana F (2005) Influence of the 4600A/G and 4678G/C polymorphisms in the endothelial protein C receptor (EPCR) gene on the risk of venous thromboembolism in carriers of factor V Leiden. Thromb Haemost 94:389–394PubMedGoogle Scholar
  137. Meehan HA, Connell GJ (2001) The hairpin loop but not the bulged C of the iron responsive element is essential for high affinity binding to iron regulatory protein-1. J Biol Chem 276:14791–14796PubMedGoogle Scholar
  138. Meinsma D, Holthuizen PE, Van den Brande JL, Sussenbach JS (1991) Specific endonucleolytic cleavage of IGF-II mRNAs. Biochem Biophys Res Commun 179:1509–1516PubMedGoogle Scholar
  139. Meinsma D, Scheper W, Holthuizen PE, Van den Brande JL, Sussenbach JS (1992) Site-specific cleavage of IGF-II mRNAs requires sequence elements from two distinct regions of the IGF-II gene. Nucleic Acids Res 20:5003–5009PubMedGoogle Scholar
  140. Merkel M, Heeren J (2005) Give me A5 for lipoprotein hydrolysis!. J Clin Invest 115:2694–2696PubMedGoogle Scholar
  141. Meyer IM, Miklos I (2005) Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs. Nucleic Acids Res 33:6338–6348PubMedGoogle Scholar
  142. Meyre D, Bouatia-Naji N, Tounian A, Samson C, Lecoeur C, Vatin V, Ghoussaini M, Wachter C, Hercberg S, Charpentier G, Patsch W, Pattou F, Charles MA, Tounian P, Clement K, Jouret B, Weill J, Maddux BA, Goldfine ID, Walley A, Boutin P, Dina C, Froguel P (2005) Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet 37:863–867PubMedGoogle Scholar
  143. Mickleburgh I, Burtle B, Nury D, Chabanon H, Chrzanowska-Lightowlers Z, Hesketh JE (2004) Isolation and identification of a protein binding to the localization element of metallothionein-1 mRNA. Biochem Soc Trans 32:705–706PubMedGoogle Scholar
  144. Mickleburgh I, Burtle B, Hollas H, Campbell G, Chrzanowska-Lightowlers Z, Vedeler A, Hesketh J (2005) Annexin A2 binds to the localization signal in the 3′ untranslated region of c-myc mRNA. FEBS J 272:413–421PubMedGoogle Scholar
  145. Mignone F, Gissi C, Liuni S, Pesole G (2002) Untranslated regions of mRNAs. Genome Biol 3:reviews0004.1–0004.10Google Scholar
  146. Miwa Y, Takiuchi S, Kamide K, Yoshii M, Horio T, Tanaka C, Banno M, Miyata T, Sasaguri T, Kawano Y (2004) Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients. Biochem Biophys Res Commun 322:428–433PubMedGoogle Scholar
  147. Morahan G, Huang D, Ymer SI, Cancilla MR, Stephen K, Dabadghao P, Werther G, Tait BD, Harrison LC, Colman PG (2001) Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 27:218–221PubMedGoogle Scholar
  148. Moreira A, Wollerton M, Monks J, Proudfoot NJ (1995) Upstream sequence elements enhance poly(A) site efficiency of the C2 complement gene and are phylogenetically conserved. EMBO J 14:3809–3819PubMedGoogle Scholar
  149. Moreira A, Takagaki Y, Brackenridge S, Wollerton M, Manley JL, Proudfoot NJ (1998) The upstream sequence element of the C2 complement poly(A) signal activates mRNA 3′ end formation by two distinct mechanisms. Genes Dev 12:2522–2534PubMedGoogle Scholar
  150. Mori Y, Imaizumi K, Katayama T, Yoneda T, Tohyama M (2000) Two cis-acting elements in the 3′ untranslated region of alpha-CaMKII regulate its dendritic targeting. Nat Neurosci 3:1079–1084PubMedGoogle Scholar
  151. Morohashi K, Takada T, Omori K, Suzuki E, Gejyo F (2003) Vascular endothelial growth factor gene polymorphisms in Japanese patients with sarcoidosis. Chest 123:1520–1526PubMedGoogle Scholar
  152. Mousses S, Ozcelik H, Lee PD, Malkin D, Bull SB, Andrulis IL (1995) Two variants of the CIP1/WAF1 gene occur together and are associated with human cancer. Hum Mol Genet 4:1089–1092PubMedGoogle Scholar
  153. Muhl A, Moslinger D, Item CB, Stockler-Ipsiroglu S (2001) Molecular characterisation of 34 patients with biotinidase deficiency ascertained by newborn screening and family investigation. Eur J Hum Genet 9:237–243PubMedGoogle Scholar
  154. Mueller T, Mas-Marques A, Sarrazin C, Wiese M, Halangk J, Witt H, Ahlenstiel G, Spengler U, Goebel U, Wiedenmann B, Schreier E, Berg T (2004) Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment-induced recovery from hepatitis C virus infection. J Hepatol 41:652–658PubMedGoogle Scholar
  155. Mummidi S, Ahuja SS, Gonzalez E, Anderson SA, Santiago EN, Stephan KT, Craig FE, O’Connell P, Tryon V, Clark RA, Dolan MJ, Ahuja SK (1998) Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression. Nat Med 4:786–793PubMedGoogle Scholar
  156. Munro TP, Magee RJ, Kidd GJ, Carson JH, Barbarese E, Smith LM, Smith R (1999) Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking. J Biol Chem 274:34389–34395PubMedGoogle Scholar
  157. Nakata K, Ujike H, Sakai A, Takaki M, Imamura T, Tanaka Y, Kuroda S (2003) The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia. Biol Psychiatry 53:571–576PubMedGoogle Scholar
  158. Natalizio BJ, Muniz LC, Arhin GK, Wilusz J, Lutz CS (2002) Upstream elements present in the 3′-untranslated region of collagen genes influence the processing efficiency of overlapping polyadenylation signals. J Biol Chem 277:42733–42740PubMedGoogle Scholar
  159. Nicaud V, Poirier O, Behague I, Herrmann SM, Mallet C, Troesch A, Bouyer J, Evans A, Luc G, Ruidavets JB, Arveiler D, Bingham A, Tiret L, Cambien F (1999) Polymorphisms of the endothelin-A and -B receptor genes in relation to blood pressure and myocardial infarction: the Etude Cas-Témoins sur l’Infarctus du Myocarde (ECTIM) Study. Am J Hypertens 12:304–310PubMedGoogle Scholar
  160. Niino M, Kikuchi S, Fukazawa T, Yabe I, Tashiro K (2003) Genetic polymorphisms of osteopontin in association with multiple sclerosis in Japanese patients. J Neuroimmunol 136:125–129PubMedGoogle Scholar
  161. Nury D, Chabanon H, Levadoux-Martin M, Hesketh J (2005) An eleven nucleotide section of the 3′-untranslated region is required for perinuclear localization of rat metallothionein-1 mRNA. Biochem J 387:419–428PubMedGoogle Scholar
  162. Oakley RH, Sar M, Cidlowski JA (1996) The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function. J Biol Chem 271:9550–9559PubMedGoogle Scholar
  163. O’Dell SD, Miller GJ, Cooper JA, Hindmarsh PC, Pringle PJ, Ford H, Humphries SE, Day IN (1997) Apa l polymorphism in insulin-like growth factor II (IGF2) gene and weight in middle-aged males. Int J Obes Relat Metab Disord 21:822–825PubMedGoogle Scholar
  164. Ono K, Mannami T, Baba S, Tomoike H, Suga S, Iwai N (2002) A single-nucleotide polymorphism in C-type natriuretic peptide gene may be associated with hypertension. Hypertens Res 25:727–730PubMedGoogle Scholar
  165. de Pagter-Holthuizen P, Jansen M, van der Kammen RA, van Schaik FM, Sussenbach JS (1988) Differential expression of the human insulin-like growth factor II gene. Characterization of the IGF-II mRNAs and an mRNA encoding a putative IGF-II-associated protein. Biochim Biophys Acta 950:282–295PubMedGoogle Scholar
  166. Panza F, D’Introno A, Colacicco AM, Capurso C, Basile AM, Torres F, Capurso A, Solfrizzi V (2004) LBP-1c/CP2/LSF gene polymorphism and risk of sporadic Alzheimer’s disease. J Neurol Neurosurg Psychiatr 75:166–168PubMedGoogle Scholar
  167. Peeters RP, van Toor H, Klootwijk W, de Rijke YB, Kuiper GG, Uitterlinden AG, Visser TJ (2003) Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab 88:2880–2888PubMedGoogle Scholar
  168. Peeters RP, van den Beld AW, van Toor H, Uitterlinden AG, Janssen JA, Lamberts SW, Visser TJ (2005) A polymorphism in type I deiodinase is associated with circulating free insulin-like growth factor I levels and body composition in humans. J Clin Endocrinol Metab 90:256–263PubMedGoogle Scholar
  169. Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173PubMedGoogle Scholar
  170. Pennacchio LA, Olivier M, Hubacek JA, Krauss RM, Rubin EM, Cohen JC (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038PubMedGoogle Scholar
  171. Peyvandi F, Garagiola I, Palla R, Marziliano N, Mannucci PM (2005) Role of the 2 adenine (g.11293_11294insAA) insertion polymorphism in the 3′ untranslated region of the factor VII (FVII) gene: molecular characterization of a patient with severe FVII deficiency. Hum Mutat 26:455–461PubMedGoogle Scholar
  172. Piecyk M, Wax S, Beck AR, Kedersha N, Gupta M, Maritim B, Chen S, Gueydan C, Kruys V, Streuli M, Anderson P (2000) TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha. EMBO J 19:4154–4163PubMedGoogle Scholar
  173. Pillai RS (2005) MicroRNA function: multiple mechanisms for a tiny RNA? RNA 11:1753–1761PubMedGoogle Scholar
  174. Pitzalis MV, Sarzani R, Dessi-Fulgheri P, Iacoviello M, Forleo C, Lucarelli K, Pietrucci F, Salvi F, Sorrentino S, Romito R, Guida P, Rappelli A, Rizzon P (2003) Allelic variants of natriuretic peptide receptor genes are associated with family history of hypertension and cardiovascular phenotype. J Hypertens 21:1491–1496PubMedGoogle Scholar
  175. Preuss CV, Wood TC, Szumlanski CL, Raftogianis RB, Otterness DM, Girard B, Scott MC, Weinshilboum RM (1998) Human histamine N-methyltransferase pharmacogenetics: common genetic polymorphisms that alter activity. Mol Pharmacol 53:708–717PubMedGoogle Scholar
  176. Puga I, Lainez B, Fernandez-Real JM, Buxade M, Broch M, Vendrell J, Espel E (2005) A polymorphism in the 3′ untranslated region of the gene for tumor necrosis factor receptor 2 modulates reporter gene expression. Endocrinology 146:2210–2220PubMedGoogle Scholar
  177. Putland RA, Sassinis TA, Harvey JS, Diamond P, Coles LS, Brown CY, Goodall GJ (2002) RNA destabilization by the granulocyte colony-stimulating factor stem–loop destabilizing element involves a single stem–loop that promotes deadenylation. Mol Cell Biol 22:1664–1673PubMedGoogle Scholar
  178. Qian X, Shu A, Qin W, Xing Q, Gao J, Yang J, Feng G, He L (2004) A novel insertion mutation in the FOXL2 gene is detected in a big Chinese family with blepharophimosis-ptosis-epicanthus inversus. Mutat Res 554:19–22PubMedGoogle Scholar
  179. van Rij RP, Broersen S, Goudsmit J, Coutinho RA, Schuitemaker H (1998) The role of a stromal cell-derived factor-1 chemokine gene variant in the clinical course of HIV-1 infection. AIDS 12:F85-F90PubMedGoogle Scholar
  180. Reddy KK, Oitomen FM, Patel GP, Bag J (2005) Perinuclear localization of slow troponin C m RNA in muscle cells is controlled by a cis-element located at its 3′ untranslated region. RNA 11:294–307PubMedGoogle Scholar
  181. Robins H, Li Y, Padgett RW (2005) Incorporating structure to predict microRNA targets. Proc Natl Acad Sci USA 102:4006–4009PubMedGoogle Scholar
  182. Ross J (1995) mRNA stability in mammalian cells. Microbiol Rev 59:423–450PubMedGoogle Scholar
  183. Ross AF, Oleynikov Y, Kislauskis EH, Taneja KL, Singer RH (1997) Characterization of a beta-actin mRNA zipcode-binding protein. Mol Cell Biol 17:2158–2165PubMedGoogle Scholar
  184. Roth SM, Schrager MA, Metter EJ, Riechman SE, Fleg JL, Hurley BF, Ferrell RE (2002) IGF2 genotype and obesity in men and women across the adult age span. Int J Obes Relat Metab Disord 26:585–587PubMedGoogle Scholar
  185. Rousseau D, Kaspar R, Rosenwald I, Gehrke L, Sonenberg N (1996) Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E. Proc Natl Acad Sci USA 93:1065–1070PubMedGoogle Scholar
  186. Ruggiero T, Olivero M, Follenzi A, Naldini L, Calogero R, Di Renzo MF (2003) Deletion in a (T)8 microsatellite abrogates expression regulation by 3′-UTR. Nucleic Acids Res 31:6561–6569PubMedGoogle Scholar
  187. Russell AI, Cunninghame Graham DS, Shepherd C, Roberton CA, Whittaker J, Meeks J, Powell RJ, Isenberg DA, Walport MJ, Vyse TJ (2004) Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum Mol Genet 13:137–147PubMedGoogle Scholar
  188. Sachchithananthan M, Stasinopoulos SJ, Wilusz J, Medcalf RL (2005) The relationship between the prothrombin upstream sequence element and the G20210A polymorphism: the influence of a competitive environment for mRNA 3′-end formation. Nucleic Acids Res 33:1010–1020PubMedGoogle Scholar
  189. Sakano S, Berggren P, Kumar R, Steineck G, Adolfsson J, Onelov E, Hemminki K, Larsson P (2003) Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene. Int J Cancer 104:98–103PubMedGoogle Scholar
  190. Santana da Silva LC, Carvalho TS, da Silva FB, Morari L, Fachel AA, Pires R, Refosco LF, Desnick RJ, Giugliani R, Saraiva Pereira ML (2003) Molecular characterization of phenylketonuria in South Brazil. Mol Genet Metab 79:17–24PubMedGoogle Scholar
  191. Schaaf MJ, Cidlowski JA (2002) AUUUA motifs in the 3′UTR of human glucocorticoid receptor alpha and beta mRNA destabilize mRNA and decrease receptor protein expression. Steroids 67:627–636PubMedGoogle Scholar
  192. Scheper W, Meinsma D, Holthuizen PE, Sussenbach JS (1995) Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs. Mol Cell Biol 15:235–245PubMedGoogle Scholar
  193. Schrager MA, Roth SM, Ferrell RE, Metter EJ, Russek-Cohen E, Lynch NA, Lindle RS, Hurley BF (2004) Insulin-like growth factor-2 genotype, fat-free mass, and muscle performance across the adult life span. J Appl Physiol 97:2176–2183PubMedGoogle Scholar
  194. Seegers D, Zwiers A, Strober W, Pena AS, Bouma G (2002) A TaqI polymorphism in the 3′UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun 3:419–423PubMedGoogle Scholar
  195. Sgourou A, Papachatzopoulou A, Psiouri L, Antoniou M, Zoumbos N, Gibbs R, Athanassiadou A (2002) The beta-globin C→G mutation at 6 bp 3′ to the termination codon causes beta-thalassaemia by decreasing the mRNA level. Br J Haematol 118:671–676PubMedGoogle Scholar
  196. Shao Y, Ismail-Beigi F (2004) Control of Na+-K+-ATPase beta 1-subunit expression: role of 3′-untranslated region. Am J Physiol Cell Physiol 286:C580-C585PubMedGoogle Scholar
  197. Sharma P, Hingorani A, Jia H, Hopper R, Brown MJ (1999) Quantitative association between a newly identified molecular variant in the endothelin-2 gene and human essential hypertension. J Hypertens 17:1281–1287PubMedGoogle Scholar
  198. Shav-Tal Y, Singer RH (2005) RNA localization. J Cell Sci 118:4077–4081PubMedGoogle Scholar
  199. Shaw G, Kamen R (1986) A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46:659–667PubMedGoogle Scholar
  200. Shi J, Tian J, Pritchard A, Lendon C, Lambert JC, Iwatsubo T, Mann DM (2006) A 3′-UTR polymorphism in the oxidized LDL receptor 1 gene increases Abeta(40) load as cerebral amyloid angiopathy in Alzheimer’s disease. Acta Neuropathol 111:15–20PubMedGoogle Scholar
  201. Shiffman D, Ellis SG, Rowland CM, Malloy MJ, Luke MM, Iakoubova OA, Pullinger CR, Cassano J, Aouizerat BE, Fenwick RG, Reitz RE, Catanese JJ, Leong DU, Zellner C, Sninsky JJ, Topol EJ, Devlin JJ, Kane JP (2005) Identification of four gene variants associated with myocardial infarction. Am J Hum Genet 77:596–605PubMedGoogle Scholar
  202. Small KM, Mialet-Perez J, Seman CA, Theiss CT, Brown KM, Liggett SB (2004) Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects. Proc Natl Acad Sci USA 101:13020–13025PubMedGoogle Scholar
  203. Spencer-Jones NJ, Wang X, Snieder H, Spector TD, Carter ND, O’dell SD (2005) Protein tyrosine phosphatase-1B gene PTPN1: selection of tagging single nucleotide polymorphisms and association with body fat, insulin sensitivity, and the metabolic syndrome in a normal female population. Diabetes 54:3296–3304PubMedGoogle Scholar
  204. Spurdle AB, Hopper JL, Chen X, McCredie MR, Giles GG, Newman B, Chenevix-Trench G (2002) Prohibitin 3′ untranslated region polymorphism and breast cancer risk in Australian women. Lancet 360:925–926PubMedGoogle Scholar
  205. Spurdle AB, Purdie DM, Chen X, Chenevix-Trench G (2003) The prohibitin 3′ untranslated region polymorphism is not associated with risk of ovarian cancer. Gynecol Oncol 90:145–149PubMedGoogle Scholar
  206. Stanilova S, Miteva L (2005) TaqI polymorphism in 3′UTR of the IL-12B and association with IL-12p40 production from human PBMC. Genes Immun 6:364–366PubMedGoogle Scholar
  207. Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN (2003) Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat 21:577–581PubMedGoogle Scholar
  208. Stoeckle MY (1992) Removal of a 3′ non-coding sequence is an initial step in degradation of gro alpha mRNA and is regulated by interleukin-1. Nucleic Acids Res 20:1123–1127PubMedGoogle Scholar
  209. Stoecklin G, Lu M, Rattenbacher B, Moroni C (2003) A constitutive decay element promotes tumor necrosis factor alpha mRNA degradation via an AU-rich element-independent pathway. Mol Cell Biol 23:3506–3515PubMedGoogle Scholar
  210. Styrkarsdottir U, Cazier JB, Kong A, Rolfsson O, Larsen H, Bjarnadottir E, Johannsdottir VD, Sigurdardottir MS, Bagger Y, Christiansen C, Reynisdottir I, Grant SF, Jonasson K, Frigge ML, Gulcher JR, Sigurdsson G, Stefansson K (2003) Linkage of osteoporosis to chromosome 20p12 and association to BMP2. PLoS Biol 1:E69PubMedGoogle Scholar
  211. Suviolahti E, Ridderstrale M, Almgren P, Klannemark M, Melander O, Carlsson E, Carlsson M, Hedenbro J, Orho-Melander M (2003) Pro-opiomelanocortin gene is associated with serum leptin levels in lean but not in obese individuals. Int J Obes Relat Metab Disord 27:1204–1211PubMedGoogle Scholar
  212. Tadokoro K, Fujii H, Inoue T, Yamada M (1991) Polymerase chain reaction (PCR) for detection of ApaI polymorphism at the insulin like growth factor II gene (IGF2). Nucleic Acids Res 19:6967PubMedGoogle Scholar
  213. Talmud PJ, Palmen J, Putt W, Lins L, Humphries SE (2005) Determination of the functionality of common APOA5 polymorphisms. J Biol Chem 280:28215–28220PubMedGoogle Scholar
  214. Tamminen M, Kakko S, Kesaniemi YA, Savolainen MJ (1996) A polymorphic site in the 3′ untranslated region of the cholesteryl ester transfer protein (CETP) gene is associated with low CETP activity. Atherosclerosis 124:237–247PubMedGoogle Scholar
  215. Tan MS, Chang SY, Chang DM, Tsai JC, Lee YJ (2003) Association of resistin gene 3′-untranslated region +62G→A polymorphism with type 2 diabetes and hypertension in a Chinese population. J Clin Endocrinol Metab 88:1258–1263PubMedGoogle Scholar
  216. Taylor AE, Yip A, Brayne C, Easton D, Evans JG, Xuereb J, Cairns N, Esiri MM, Rubinsztein DC (2001) Genetic association of an LBP-1c/CP2/LSF gene polymorphism with late onset Alzheimer’s disease. J Med Genet 38:232–233PubMedGoogle Scholar
  217. Trabetti E, Biscuola M, Cavallari U, Malerba G, Girelli D, Olivieri O, Martinelli N, Corrocher R, Pignatti PF (2006) On the association of the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction or coronary artery disease. Eur J Hum Genet 14:127–130PubMedGoogle Scholar
  218. Tran H, Schilling M, Wirbelauer C, Hess D, Nagamine Y (2004) Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH protein RHAU. Mol Cell 13:101–111PubMedGoogle Scholar
  219. Tsai FJ, Wu HC, Chen HY, Lu HF, Hsu CD, Chen WC (2003) Association of E-cadherin gene 3′-UTR C/T polymorphism with calcium oxalate stone disease. Urol Int 70:278–281PubMedGoogle Scholar
  220. Ulrich CM, Bigler J, Velicer CM, Greene EA, Farin FM, Potter JD (2000) Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiol Biomarkers Prev 9:1381–1385PubMedGoogle Scholar
  221. Valdes AM, Hart DJ, Jones KA, Surdulescu G, Swarbrick P, Doyle DV, Schafer AJ, Spector TD (2004) Association study of candidate genes for the prevalence and progression of knee osteoarthritis. Arthritis Rheum 50:2497–2507PubMedGoogle Scholar
  222. Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20:515–524PubMedGoogle Scholar
  223. Vasilopoulos Y, Cork MJ, Murphy R, Williams HC, Robinson DA, Duff GW, Ward SJ, Tazi-Ahnini R (2004) Genetic association between an AACC insertion in the 3′UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis. J Invest Dermatol 123:62–66PubMedGoogle Scholar
  224. Vielhaber E, Jacobson DP, Ketterling RP, Liu JZ, Sommer SS (1993) A mutation in the 3′ untranslated region of the factor IX gene in four families with hemophilia B. Hum Mol Genet 2:1309–1310PubMedGoogle Scholar
  225. Villette S, Kyle JA, Brown KM, Pickard K, Milne JS, Nicol F, Arthur JR, Hesketh JE (2002) A novel single nucleotide polymorphism in the 3′ untranslated region of human glutathione peroxidase 4 influences lipoxygenase metabolism. Blood Cells Mol Dis 29:174–178PubMedGoogle Scholar
  226. Waggoner SA, Liebhaber SA (2003) Regulation of alpha-globin mRNA stability. Exp Biol Med 228:387–395Google Scholar
  227. Walczak R, Westhof E, Carbon P, Krol A (1996) A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs. RNA 2:367–379PubMedGoogle Scholar
  228. Walczak R, Carbon P, Krol A (1998) An essential non-Watson-Crick base pair motif in 3′UTR to mediate selenoprotein translation. RNA 4:74–84PubMedGoogle Scholar
  229. Wang Z, Kiledjian M (2000) Identification of an erythroid-enriched endoribonuclease activity involved in specific mRNA cleavage. EMBO J 19:295–305PubMedGoogle Scholar
  230. Wang WY, Zee RY, Morris BJ (1997) Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Clin Genet 51:31–34PubMedCrossRefGoogle Scholar
  231. Wang Z, Day N, Trifillis P, Kiledjian M (1999) An mRNA stability complex functions with poly(A)-binding protein to stabilize mRNA in vitro. Mol Cell Biol 19:4552–4560PubMedGoogle Scholar
  232. Wang J, Pitarque M, Ingelman-Sundberg M (2006) 3′-UTR polymorphism in the human CYP2A6 gene affects mRNA stability and enzyme expression. Biochem Biophys Res Commun 340:491–497PubMedGoogle Scholar
  233. Webb KE, Martin JF, Hamsten A, Eriksson P, Iacoviello L, Gattone M, Donati MB, Di Castelnuovo A, Erusalimsky J, Humphries SE (2001) Polymorphisms in the thrombopoietin gene are associated with risk of myocardial infarction at a young age. Atherosclerosis 154:703–711PubMedGoogle Scholar
  234. Weiss IM, Liebhaber SA (1994) Erythroid cell-specific determinants of alpha-globin mRNA stability. Mol Cell Biol 14:8123–8132PubMedGoogle Scholar
  235. Weiss IM, Liebhaber SA (1995) Erythroid cell-specific mRNA stability elements in the alpha 2-globin 3′ nontranslated region. Mol Cell Biol 15:2457–2465PubMedGoogle Scholar
  236. Windsor L, Morahan G, Huang D, McCann V, Jones T, James I, Christiansen FT, Price P (2004) Alleles of the IL12B 3′UTR associate with late onset of type 1 diabetes. Hum Immunol 65:1432–1436PubMedGoogle Scholar
  237. Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, Dean M, Honjo T, Tashiro K, Yabe D, Buchbinder S, Vittinghoff E, Goedert JJ, O’Brien TR, Jacobson LP, Detels R, Donfield S, Willoughby A, Gomperts E, Vlahov D, Phair J, ALIVE Study, Hemophilia Growth, Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), O’Brien SJ (1998) Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. Science 279:389–393PubMedGoogle Scholar
  238. Wolford JK, Hanson RL, Kobes S, Bogardus C, Prochazka M (2001) Analysis of linkage disequilibrium between polymorphisms in the KCNJ9 gene with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab 73:97–103PubMedGoogle Scholar
  239. Wolford JK, Colligan PB, Gruber JD, Bogardus C (2003) Variants in the interleukin 6 receptor gene are associated with obesity in Pima Indians. Mol Genet Metab 80:338–343PubMedGoogle Scholar
  240. Wu HC, Lai MT, Wu CI, Chen HY, Wan L, Tsai FJ, Chen WC (2005) E-cadherin gene 3′-UTR C/T polymorphism is associated with prostate cancer. Urol Int 75:350–353PubMedGoogle Scholar
  241. Xia J, Scherer SW, Cohen PT, Majer M, Xi T, Norman RA, Knowler WC, Bogardus C, Prochazka M (1998) A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes. Diabetes 47:1519–1524PubMedGoogle Scholar
  242. Xia J, Bogardus C, Prochazka M (1999) A type 2 diabetes-associated polymorphic ARE motif affecting expression of PPP1R3 is involved in RNA-protein interactions. Mol Genet Metab 68:48–55PubMedGoogle Scholar
  243. Xiang K, Cox NJ, Bell GI (1988) ApaI and SstI RFLPs at the insulin-like growth factor II (IGF2) locus on chromosome 11. Nucleic Acids Res 16:3599PubMedGoogle Scholar
  244. Yang MS, Yu L, Guo TW, Zhu SM, Liu HJ, Shi YY, Gu NF, Feng GY, He L (2004) Evidence for association between single nucleotide polymorphisms in T complex protein 1 gene and schizophrenia in the Chinese Han population. J Med Genet 41:e63PubMedGoogle Scholar
  245. Yilmaz V, Yentur SP, Saruhan-Direskeneli G (2005) IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 30:188–194PubMedGoogle Scholar
  246. Yin LM, Zhu WF, Wei L, Xu XY, Sun DG, Wang YB, Fan WM, Yu M, Tian XL, Wang QX, Gao Y, Zhuang H (2004) Association of interleukin-12 p40 gene 3′-untranslated region polymorphism and outcome of HCV infection. World J Gastroenterol 10:2330–2333PubMedGoogle Scholar
  247. Yu J, Russell JE (2001) Structural and functional analysis of an mRNP complex that mediates the high stability of human beta-globin mRNA. Mol Cell Biol 21:5879–5888PubMedGoogle Scholar
  248. Zehner ZE, Shepherd RK, Gabryszuk J, Fu TF, Al-Ali M, Holmes WM (1997) RNA-protein interactions within the 3′ untranslated region of vimentin mRNA. Nucleic Acids Res 25:3362–3370PubMedGoogle Scholar
  249. Zhang H, Jia Y, Cooper JJ, Hale T, Zhang Z, Elbein SC (2004) Common variants in glutamine:fructose-6-phosphate amidotransferase 2 (GFPT2) gene are associated with type 2 diabetes, diabetic nephropathy, and increased GFPT2 mRNA levels. J Clin Endocrinol Metab 89:748–755PubMedGoogle Scholar
  250. Zhang Z, Xu Y, Zhou J, Wang X, Wang L, Hu X, Guo J, Wei Q, Shen H (2005) Polymorphisms of thymidylate synthase in the 5′- and 3′-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis. Carcinogenesis 26:1764–1769PubMedGoogle Scholar
  251. Zhao J, Hyman L, Moore C (1999) Formation of mRNA 3′ ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis. Microbiol Mol Biol Rev 63:405–445PubMedGoogle Scholar
  252. Zhao Y, Samal E, Srivastava D (2005) Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436:214–220PubMedGoogle Scholar
  253. Zhou XL, Eriksson U, Werelius B, Kressner U, Sun XF, Lindblom A (2004) Definition of candidate low risk APC alleles in a Swedish population. Int J Cancer 110:550–555PubMedGoogle Scholar
  254. Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Jian-Min Chen
    • 1
    • 2
    • 3
  • Claude Férec
    • 1
    • 2
    • 3
    • 4
  • David N. Cooper
    • 5
  1. 1.INSERM, U613BrestFrance
  2. 2.Etablissement Français du Sang – BretagneBrestFrance
  3. 3.Faculté de Médecine de Brest et des Sciences de la SantéUniversité de Bretagne OccidentaleBrestFrance
  4. 4.Laboratoire de Génétique Moléculaire et d’HistocompatibilitéCHRU Brest, Hôpital MorvanBrestFrance
  5. 5.Institute of Medical GeneticsCardiff UniversityCardiffUK

Personalised recommendations