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PMID: 16848976 Published · ppublish English Journal Article Review

From DNA to RNA to disease and back: the 'central dogma' of regulatory disease variation.

Human genomics ·Vol. 2 ·No. 6 ·2006-06-00 ·Pages 383-90

Stranger BE, Dermitzakis ET

Abstract

Much of the focus of human disease genetics is directed towards identifying nucleotide variants that contribute to disease phenotypes. This is a complex problem, often involving contributions from multiple loci and their interactions, as well as effects due to environmental factors. Although some diseases with a genetic basis are caused by nucleotide changes that alter an amino acid sequence, in other cases, disease risk is associated with altered gene regulation. This paper focuses on how studies of gene expression variation might complement disease studies and provide crucial links between genotype and phenotype.

MeSH Terms
DNA/genetics Disease Gene Expression Regulation/genetics Genetic Variation/genetics Genome, Human/genetics Humans RNA/genetics
Chemicals
RNA DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Stranger Barbara E
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. bes@sanger.ac.uk
Dermitzakis Emmanouil T
References (55)
55 references, click to expand
  1. Genetics of susceptibility to human infectious disease.
    Nat Rev Genet. 2001 Dec;2(12):967-77 PMID: 11733749
  2. Genome-wide associations of gene expression variation in humans.
    PLoS Genet. 2005 Dec;1(6):e78 PMID: 16362079
  3. Allelic variation in human gene expression.
    Science. 2002 Aug 16;297(5584):1143 PMID: 12183620
  4. Gene expression phenotype in heterozygous carriers of ataxia telangiectasia.
    Am J Hum Genet. 2002 Oct;71(4):791-800 PMID: 12226795
  5. Variation in gene expression within and among natural populations.
    Nat Genet. 2002 Oct;32(2):261-6 PMID: 12219088
  6. Detection of regulatory variation in mouse genes.
    Nat Genet. 2002 Nov;32(3):432-7 PMID: 12410233
  7. Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.
    Nat Genet. 2002 Dec;32(4):650-4 PMID: 12426569
  8. Population stratification and spurious allelic association.
    Lancet. 2003 Feb 15;361(9357):598-604 PMID: 12598158
  9. Genetics of gene expression surveyed in maize, mouse and man.
    Nature. 2003 Mar 20;422(6929):297-302 PMID: 12646919
  10. The endophenotype concept in psychiatry: etymology and strategic intentions.
    Am J Psychiatry. 2003 Apr;160(4):636-45 PMID: 12668349
  11. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease.
    Nature. 2003 May 29;423(6939):506-11 PMID: 12724780
  12. The ENCODE (ENCyclopedia Of DNA Elements) Project.
    Science. 2004 Oct 22;306(5696):636-40 PMID: 15499007
  13. Genetic inheritance of gene expression in human cell lines.
    Am J Hum Genet. 2004 Dec;75(6):1094-105 PMID: 15514893
  14. Molecular basis and PCR-DNA typing of the Fya/fyb blood group polymorphism.
    Hum Genet. 1995 Apr;95(4):407-10 PMID: 7705836
  15. Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus.
    Nat Genet. 1995 Mar;9(3):284-92 PMID: 7773291
  16. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression.
    J Biol Chem. 1996 May 31;271(22):13055-60 PMID: 8662692
  17. Permutation tests for multiple loci affecting a quantitative character.
    Genetics. 1996 Jan;142(1):285-94 PMID: 8770605
  18. The future of genetic studies of complex human diseases.
    Science. 1996 Sep 13;273(5281):1516-7 PMID: 8801636
  19. A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants.
    J Virol. 1999 Dec;73(12):10264-71 PMID: 10559343
  20. Association mapping in structured populations.
    Am J Hum Genet. 2000 Jul;67(1):170-81 PMID: 10827107
  21. Regional and strain-specific gene expression mapping in the adult mouse brain.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11038-43 PMID: 11005875
  22. Transferrin polymorphism influences iron status in blacks.
    Clin Chem. 2000 Oct;46(10):1535-9 PMID: 11017929
  23. Human disease genes.
    Nature. 2001 Feb 15;409(6822):853-5 PMID: 11237009
  24. Variation is the spice of life.
    Nat Genet. 2001 Mar;27(3):234-6 PMID: 11242096
  25. The role of linkage studies for common diseases.
    Curr Opin Genet Dev. 2001 Jun;11(3):264-7 PMID: 11377961
  26. Statistical significance for genomewide studies.
    Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5 PMID: 12883005
  27. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors.
    Nat Genet. 2003 Sep;35(1):57-64 PMID: 12897782
  28. Applications of a rat multiple tissue gene expression data set.
    Genome Res. 2004 Apr;14(4):742-9 PMID: 15060018
  29. Genetic analysis of genome-wide variation in human gene expression.
    Nature. 2004 Aug 12;430(7001):743-7 PMID: 15269782
  30. The 5A/6A polymorphism in the promoter of the stromelysin-1 (MMP-3) gene predicts progression of angiographically determined coronary artery disease in men in the LOCAT gemfibrozil study. Lopid Coronary Angiography Trial.
    Atherosclerosis. 1998 Jul;139(1):49-56 PMID: 9699891
  31. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS).
    Lancet. 1998 Sep 12;352(9131):866-70 PMID: 9742978
  32. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria.
    Nat Genet. 1999 Jun;22(2):145-50 PMID: 10369255
  33. Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus.
    Nat Genet. 2005 Jan;37(1):67-72 PMID: 15568023
  34. Genetic structure, self-identified race/ethnicity, and confounding in case-control association studies.
    Am J Hum Genet. 2005 Feb;76(2):268-75 PMID: 15625622
  35. The landscape of genetic complexity across 5,700 gene expression traits in yeast.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1572-7 PMID: 15659551
  36. Genome-wide association studies for common diseases and complex traits.
    Nat Rev Genet. 2005 Feb;6(2):95-108 PMID: 15716906
  37. Polymorphisms in the promoter region of catalase gene and essential hypertension.
    Dis Markers. 2005;21(1):3-7 PMID: 15735318
  38. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk.
    Nature. 2005 Apr 14;434(7035):857-63 PMID: 15829955
  39. Complement factor H polymorphism in age-related macular degeneration.
    Science. 2005 Apr 15;308(5720):385-9 PMID: 15761122
  40. A variant in the CD209 promoter is associated with severity of dengue disease.
    Nat Genet. 2005 May;37(5):507-13 PMID: 15838506
  41. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities.
    Nat Genet. 2005 May;37(5):478-85 PMID: 15838509
  42. Cis-acting expression quantitative trait loci in mice.
    Genome Res. 2005 May;15(5):681-91 PMID: 15837804
  43. Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels.
    Am J Hum Genet. 2005 Jul;77(1):64-77 PMID: 15897982
  44. The genetics of regulatory variation in the human genome.
    Hum Genomics. 2005 Jun;2(2):126-31 PMID: 16004727
  45. A variable number of tandem repeats polymorphism in an E2F-1 binding element in the 5' flanking region of SMYD3 is a risk factor for human cancers.
    Nat Genet. 2005 Oct;37(10):1104-7 PMID: 16155568
  46. Mapping determinants of human gene expression by regional and genome-wide association.
    Nature. 2005 Oct 27;437(7063):1365-9 PMID: 16251966
  47. Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans.
    BMC Med Genet. 2005 Oct 17;6:37 PMID: 16229747
  48. A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis.
    Int J Immunogenet. 2005 Dec;32(6):401-5 PMID: 16313306
  49. GSK3B polymorphisms alter transcription and splicing in Parkinson's disease.
    Ann Neurol. 2005 Dec;58(6):829-39 PMID: 16315267
  50. Evaluation of the RET regulatory landscape reveals the biological relevance of a HSCR-implicated enhancer.
    Hum Mol Genet. 2005 Dec 15;14(24):3837-45 PMID: 16269442
  51. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer.
    Hum Mol Genet. 2006 Jan 1;15(1):1-10 PMID: 16306136
  52. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density.
    BMC Genet. 2005;6:55 PMID: 16309561
  53. Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer.
    Breast Cancer Res Treat. 2006 Jan;95(1):65-72 PMID: 16267613
  54. A common genetic variant is associated with adult and childhood obesity.
    Science. 2006 Apr 14;312(5771):279-83 PMID: 16614226
  55. Genetic dissection of transcriptional regulation in budding yeast.
    Science. 2002 Apr 26;296(5568):752-5 PMID: 11923494
Article Info
Journal
Human genomics
Abbr.
Hum Genomics
ISSN
1479-7364
DOI
10.1186/1479-7364-2-6-383
Email
bes@sanger.ac.uk
Published
2006-06-00
Pages
383-90
Language
English
Region
England
NLM ID
101202210
PMCID
PMC3525162
Subset
IM
External Links
PubMed source DOI: 10.1186/1479-7364-2-6-383 PMC Full Text View journal details
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