1887
Volume 2012, Issue 1
  • ISSN: 2305-7823
  • E-ISSN:

Abstract

Abstract

Genetics have undoubtedly become an integral part of biomedical science and clinical practice, with important implications in deciphering disease pathogenesis and progression, identifying diagnostic and prognostic markers, as well as designing better targeted treatments. The exponential growth of our understanding of different genetic concepts is paralleled by a growing list of genetic terminology that can easily intimidate the unfamiliar reader. Rendering genetics incomprehensible to the clinician however, defeats the very essence of genetic research: its utilization for combating disease and improving quality of life. Herein we attempt to correct this notion by presenting the basic genetic concepts along with their usefulness in the cardiology clinic. Bringing genetics closer to the clinician will enable its harmonious incorporation into clinical care, thus not only restoring our perception of its simple and elegant nature, but importantly ensuring the maximal benefit for our patients.

Loading

Article metrics loading...

/content/journals/10.5339/gcsp.2012.6
2012-07-04
2019-08-20
Loading full text...

Full text loading...

/deliver/fulltext/gcsp/2012/1/gcsp.2012.6.html?itemId=/content/journals/10.5339/gcsp.2012.6&mimeType=html&fmt=ahah

References

  1. [1]. Watson   JD., and Crick   FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. . Nature . 1953; ;171: : 4356 , 737– 738 .
    [Google Scholar]
  2. [2]. Watson   JD., and Crick   FH. The structure of DNA. . Cold Spring Harb Symp Quant Biol . 1953; ;18: : 123– 131 .
    [Google Scholar]
  3. [3]. Thoma   F., and Koller   T. Influence of histone H1 on chromatin structure. . Cell . 1977; ;12: : 1 , 101– 107 .
    [Google Scholar]
  4. [4]. Franklin   RE., and Gosling   RG. Evidence for 2-chain helix in crystalline structure of sodium deoxyribonucleate. . Nature . 1953; ;172: : 4369 , 156– 157 .
    [Google Scholar]
  5. [5]. Franklin   RE., and Gosling   RG. Molecular configuration in sodium thymonucleate. . Nature . 1953; ;171: : 4356 , 740– 741 .
    [Google Scholar]
  6. [6]. Wilkins   MH   et al.   Helical structure of crystalline deoxypentose nucleic acid. . Nature . 1953; ;172: : 4382 , 759– 762 .
    [Google Scholar]
  7. [7]. Wilkins   MH., , Stokes   AR., and Wilson   HR. Molecular structure of deoxypentose nucleic acids. . Nature . 1953; ;171: : 4356 , 738– 740 .
    [Google Scholar]
  8. [8]. Crick   FH. The Complementary Structure of DNA. . Proc Natl Acad Sci USA . 1954; ;40: : 8 , 756– 758 .
    [Google Scholar]
  9. [9]. Spector   DL. The dynamics of chromosome organization and gene regulation. . Annu Rev Biochem . 2003; ;72: : 573– 608 .
    [Google Scholar]
  10. [10]. Lamond   AI., and Earnshaw   WC. Structure and function in the nucleus. . Science . 1998; ;280: : 5363 , 547– 53 .
    [Google Scholar]
  11. [11]. Antequera   F., and Bird   A. Predicting the total number of human genes. . Nat Genet . 1994; ;8: : 2 , 114.
    [Google Scholar]
  12. [12]. Nowak   R. Mining treasures from ’junk DNA’. . Science . 1994; ;263: : 5147 , 608– 610 .
    [Google Scholar]
  13. [13]. Small   D., , Nelkin   B., and Vogelstein   B. Nonrandom distribution of repeated DNA sequences with respect to supercoiledloops and the nuclear matrix. . Proc Natl Acad Sci U S A . 1982; ;79: : 19 , 5911– 5915 .
    [Google Scholar]
  14. [14]. Tsongalis   GJ   et al.   Partial characterization of nuclear matrix attachment regions from human fibroblastDNA using Alu-polymerase chain reaction. . Cancer Res . 1992; ;52: : 13 , 3807– 3810 .
    [Google Scholar]
  15. [15]. Finishing the euchromatic sequence of the human genome, Nature.2004;431:7011,931–945.
  16. [16]. Pennisi   E. Genomics. DNA study forces rethink of what it means to be a gene. . Science . 2007; ;316: : 5831 , 1556– 1557 .
    [Google Scholar]
  17. [17]. Crick   FH. On protein synthesis. . Symp Soc Exp Biol . 1958; ;12: : 138– 163 .
    [Google Scholar]
  18. [18]. Crick   F. Central dogma of molecular biology. . Nature . 1970; ;227: : 5258 , 561– 563 .
    [Google Scholar]
  19. [19]. Kollmar   R., and Farnham   PJ. Site-specific initiation of transcription by RNA polymerase II. . Proc Soc Exp BiolMed . 1993; ;203: : 2 , 127– 139 .
    [Google Scholar]
  20. [20]. Balvay   L., , Libri   D., and Fiszman   MY. Pre-mRNA secondary structure and the regulation of splicing. . Bioessays . 1993; ;15: : 3 , 165– 169 .
    [Google Scholar]
  21. [21]. Gorlach   M., , Burd   CG., and Dreyfuss   G. The mRNA poly(A)-binding protein: localization, abundance, and RNA-bindingspecificity. . Exp Cell Res . 1994; ;211: : 2 , 400– 407 .
    [Google Scholar]
  22. [22]. Munroe   D., and Jacobson   A. Tales of poly(A): a review. . Gene . 1990; ;91: : 2 , 151– 158 .
    [Google Scholar]
  23. [23]. Varani   G. A cap for all occasions. . Structure . 1997; ;5: : 7 , 855– 858 .
    [Google Scholar]
  24. [24]. Staley   JP., and Guthrie   C. Mechanical devices of the spliceosome: motors, clocks, springs, and things. . Cell . 1998; ;92: : 3 , 315– 326 .
    [Google Scholar]
  25. [25]. Gebauer   F., and Hentze   MW. Molecular mechanisms of translational control. . Nat Rev Mol Cell Biol . 2004; ;5: : 10 , 827– 835 .
    [Google Scholar]
  26. [26]. McCarthy   MI   et al.   Genome-wide association studies for complex traits: consensus, uncertainty andchallenges. . Nat Rev Genet . 2008; ;9: : 5 , 356– 369 .
    [Google Scholar]
  27. [27]. Arvanitis   DA   et al.   The Ser96Ala variant in histidine-rich calcium-binding protein is associated withlife-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy. . EurHeart J . 2008; ;29: : 20 , 2514– 2525 .
    [Google Scholar]
  28. [28]. Sachidanandam   R   et al.   A map of human genome sequence variation containing 1.42 million single nucleotidepolymorphisms. . Nature . 6822; ; 409 , 928– 933 .
    [Google Scholar]
  29. [29]. International HapMap Consortium   . A second generation human haplotype map of over 3.1 million SNPs. . Nature . 2007Oct 18; ;449: : 7164 , 851– 861 .
    [Google Scholar]
  30. [30]. Weber   JL   et al.   Human diallelic insertion/deletion polymorphisms. . Am J Hum Genet . 2002 Oct; ;71: : 4 , 854– 862 .
    [Google Scholar]
  31. [31]. Mills   RE   et al.   An initial map of insertion and deletion (INDEL) variation in the human genome. . Genome Res . 2006 Sep; ;16: : 9 , 1182– 1190 .
    [Google Scholar]
  32. [32]. Hastings   PJ   et al.   Mechanisms of change in gene copy number. . Nat Rev Genet . 2009; ;10: : 8 , 551– 564 .
    [Google Scholar]
  33. [33]. Olivotto   I   et al.   Developmental origins of hypertrophic cardiomyopathy phenotypes: a unifyinghypothesis. . Nat Rev Cardiol . 2009; ;6: : 4 , 317– 321 .
    [Google Scholar]
  34. [34]. Shephard   R., and Semsarian   C. Role of animal models in HCM research. . J Cardiovasc Transl Res . 2009; ;2: : 4 , 471– 482 .
    [Google Scholar]
  35. [35]. Vignier   N   et al.   Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cardiacmyosin-binding protein C mutant levels in cardiomyopathic mice. . Circ Res . 2009; ;105: : 3 , 239– 248 .
    [Google Scholar]
  36. [36]. Nishi   H   et al.   Possible gene dose effect of a mutant cardiac beta-myosin heavy chain gene on theclinical expression of familial hypertrophic cardiomyopathy. . Biochem Biophys ResCommun . 1994; ;200: : 1 , 549– 556 .
    [Google Scholar]
  37. [37]. Nanni   L   et al.   Hypertrophic cardiomyopathy: two homozygous cases with “typical” hypertrophiccardiomyopathy and three new mutations in cases with progression to dilatedcardiomyopathy. . Biochem Biophys Res Commun . 2003; ;309: : 2 , 391– 398 .
    [Google Scholar]
  38. [38]. Frey   N., , Luedde   M., and Katus   HA. Mechanisms of disease: hypertrophic cardiomyopathy. . Nat Rev Cardiol . 9: : 2 , 91– 100 .
    [Google Scholar]
  39. [39]. Kelly   M., and Semsarian   C. Multiple mutations in genetic cardiovascular disease: a marker of disease severity?. . Circ Cardiovasc Genet . 2009; ;2: : 2 , 182– 190 .
    [Google Scholar]
  40. [40]. Girolami   F   et al.   Clinical features and outcome of hypertrophic cardiomyopathy associated with triplesarcomere protein gene mutations. . J Am Coll Cardiol . 2010; ;55: : 14 , 1444– 1453 .
    [Google Scholar]
  41. [41]. Ingles   J   et al.   Compound and double mutations in patients with hypertrophic cardiomyopathy:implications for genetic testing and counselling. . J Med Genet . 2005; ;42: : 10 , e59.
    [Google Scholar]
  42. [42]. Richard   P   et al.   Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations,and implications for a molecular diagnosis strategy. . Circulation . 2003; ;107: : 17 , 2227– 2232 .
    [Google Scholar]
  43. [43]. Van Driest   SL   et al.   Myosin binding protein C mutations and compound heterozygosity in hypertrophiccardiomyopathy. . J Am Coll Cardiol . 2004; ;44: : 9 , 1903– 1910 .
    [Google Scholar]
  44. [44]. Lekanne Deprez   RH   et al.   Two cases of severe neonatal hypertrophic cardiomyopathy caused by compoundheterozygous mutations in the MYBPC3 gene. . J Med Genet . 2006; ;43: : 10 , 829– 832 .
    [Google Scholar]
  45. [45]. Tester   DJ   et al.   Compendium of cardiac channel mutations in 541 consecutive unrelated patientsreferred for long QT syndrome genetic testing. . Heart Rhythm . 2005; ;2: : 5 , 507– 517 .
    [Google Scholar]
  46. [46]. Roger   VL   et al.   Executive summary: heart disease and stroke statistics–2012 update: a report fromthe American Heart Association. . Circulation . 2012; ;125: : 1 , 188– 197 .
    [Google Scholar]
  47. [47]. Roger   VL   et al.   Heart disease and stroke statistics–2012 update: a report from the American HeartAssociation. . Circulation . 2012; ;125: : 1 , e2– e220 .
    [Google Scholar]
  48. [48]. Maron   BJ   et al.   American College of Cardiology/European Society of Cardiology Clinical ExpertConsensus Document on Hypertrophic Cardiomyopathy. A report of the AmericanCollege of Cardiology Foundation Task Force on Clinical Expert ConsensusDocuments and the European Society of Cardiology Committee for PracticeGuidelines. . Eur Heart J . 2003; ;24: : 21 , 1965– 1991 .
    [Google Scholar]
  49. [49]. Ackerman   MJ   et al.   HRS/EHRA expert consensus statement on the state of genetic testing for thechannelopathies and cardiomyopathies: this document was developed as a partnershipbetween the Heart Rhythm Society (HRS) and the European Heart RhythmAssociation (EHRA). . Europace . 13: : 8 , 1077– 1109 .
    [Google Scholar]
  50. [50]. Ackerman   MJ   et al.   HRS/EHRA expert consensus statement on the state of genetic testing for thechannelopathies and cardiomyopathies this document was developed as a partnershipbetween the Heart Rhythm Society (HRS) and the European Heart RhythmAssociation (EHRA). . Heart Rhythm . 8: : 8 , 1308– 1339 .
    [Google Scholar]
  51. [51]. Priori   SG   et al.   Clinical and molecular characterization of patients with catecholaminergicpolymorphic ventricular tachycardia. . Circulation . 2002; ;106: : 1 , 69– 74 .
    [Google Scholar]
  52. [52]. Thierfelder   L   et al.   Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophiccardiomyopathy: a disease of the sarcomere. . Cell . 1994; ;77: : 5 , 701– 712 .
    [Google Scholar]
  53. [53]. Kathiresan   S., and Srivastava   D. Genetics of human cardiovascular disease. . Cell . 148: : 6 , 1242– 1257 .
    [Google Scholar]
  54. [54]. Charron   P   et al.   Genetic counselling and testing in cardiomyopathies: a position statement of theEuropean Society of Cardiology Working Group on Myocardial and PericardialDiseases. . Eur Heart J . 31: : 22 , 2715– 2726 .
    [Google Scholar]
  55. [55]. Skrzynia   C., , Demo   EM., and Baxter   SM. Genetic counseling and testing for hypertrophic cardiomyopathy: an adultperspective. . J Cardiovasc Transl Res . 2009; ;2: : 4 , 493– 499 .
    [Google Scholar]
  56. [56]. Bos   JM., , Towbin   JA., and Ackerman   MJ. Diagnostic, prognostic, and therapeutic implications of genetic testing forhypertrophic cardiomyopathy. . J Am Coll Cardiol . 2009; ;54: : 3 , 201– 211 .
    [Google Scholar]
  57. [57]. Girolami   F   et al.   A molecular screening strategy based on beta-myosin heavy chain, cardiacmyosin binding protein C and troponin T genes in Italian patients withhypertrophic cardiomyopathy. . J Cardiovasc Med (Hagerstown) . 2006; ;7: : 8 , 601– 607 .
    [Google Scholar]
  58. [58]. Demo   EM., , Skrzynia   C., and Baxter   S. Genetic counseling and testing for hypertrophic cardiomyopathy: the pediatricperspective. . J Cardiovasc Transl Res . 2009; ;2: : 4 , 500– 507 .
    [Google Scholar]
  59. [59]. Morita   H   et al.   Shared genetic causes of cardiac hypertrophy in children and adults. . N Engl J Med . 2008; ;358: : 18 , 1899– 1908 .
    [Google Scholar]
  60. [60]. Hershberger   RE   et al.   Genetic evaluation of cardiomyopathy–a Heart Failure Society of America practiceguideline. . J Card Fail . 2009; ;15: : 2 , 83– 97 .
    [Google Scholar]
  61. [61]. Semsarian   C. Guidelines for the diagnosis and management of hypertrophic cardiomyopathy. . Heart Lung Circ . 2007; ;16: : 1 , 16– 18 .
    [Google Scholar]
  62. [62]. Cowan   J   et al.   Genetic testing and genetic counseling in cardiovascular genetic medicine: overviewand preliminary recommendations. . Congest Heart Fail . 2008; ;14: : 2 , 97– 105 .
    [Google Scholar]
  63. [63]. Hershberger   RE. Cardiovascular genetic medicine: evolving concepts, rationale, and implementation. . JCardiovasc Transl Res . 2008; ;1: : 2 , 137– 143 .
    [Google Scholar]
  64. [64]. Olivotto   I., , Kassem   HS., and Girolami   F. Genetic testing for hypertrophic cardiomyopathy: ongoing voyage from explorationto clinical exploitation. . Cardiogenetics . 2011; ; e5-8.
    [Google Scholar]
  65. [65]. Wordsworth   S   et al.   DNA testing for hypertrophic cardiomyopathy: a cost-effectiveness model. . Eur HeartJ . 2010; ;31: : 8 , 926– 935 .
    [Google Scholar]
  66. [66]. Vidal   M., , Cusick   ME., and Barabasi   AL. Interactome networks and human disease. . Cell . 2011; ;144: : 6 , 986– 998 .
    [Google Scholar]
  67. [67]. Hall   JL   et al.   Molecular signature of recovery following combination left ventricular assist device(LVAD) support and pharmacologic therapy. . Eur Heart J . 2007; ;28: : 5 , 613– 627 .
    [Google Scholar]
  68. [68]. Birks   EJ   et al.   Gene profiling changes in cytoskeletal proteins during clinical recovery afterleft ventricular-assist device support. . Circulation . 2005; ;112: : 9 Suppl , I57– I64 .
    [Google Scholar]
  69. [69]. Pham   MX   et al.   Gene-expression profiling for rejection surveillance after cardiac transplantation. . NEngl J Med . 2010; ;362: : 20 , 1890– 1900 .
    [Google Scholar]
  70. [70]. Movassagh   M   et al.   Distinct epigenomic features in end-stage failing human hearts. . Circulation . 2011; ;124: : 22 , 2411– 2422 .
    [Google Scholar]
  71. [71]. D’Alessandra   Y   et al.   Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. . Eur Heart J . 2010; ;31: : 22 , 2765– 2773 .
    [Google Scholar]
  72. [72]. Willner   D   et al.   Metagenomic detection of phage-encoded platelet-binding factors in thehuman oral cavity. . Proc Natl Acad Sci U S A . 2011; ;108: : Suppl 1 , 4547– 4553 .
    [Google Scholar]
  73. [73]. Li   S   et al.   Signature microRNA expression profile of essential hypertension and its novellink to human cytomegalovirus infection. . Circulation . 2011; ;124: : 2 , 175– 184 .
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.5339/gcsp.2012.6
Loading
/content/journals/10.5339/gcsp.2012.6
Loading

Data & Media loading...

Supplementary File 1

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error