cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2013-6-24-28cardiovascular-96Research ArticleМНЕНИЕ ПО ПРОБЛЕМЕOPINION ON A PROBLEMПРИМЕНЕНИЕ МЕТОДА СЕКВЕНИРОВАНИЯ ЭКЗОМОВ ДЛЯ ДИАГНОСТИКИ ПРЕДРАСПОЛОЖЕННОСТИ К КОМПЛЕКСНЫМ ЗАБОЛЕВАНИЯМ В ПРОФИЛАКТИЧЕСКОЙ МЕДИЦИНЕEXOME SEQUENCING AND THE DIAGNOSTICS OF COMPLEX DISEASE PREDISPOSITION IN PREVENTIVE MEDICINEЩербаковаН. В.ShcherbakovaN. V.

лаборант исследователь лаборатории молекулярной генетики

МешковА. Н.MeshkovA. N.

руководитель лаборатории

Тел.: 8 (901) 512–12–71 

tel.: 8 (901) 512–12–71 

meshkov@lipidclinic.ruБойцовС. А.BoytsovS. A.

директор, руководитель отдела клинической кардиологии и молекулярной генетики

ФГБУ “Государственный научно-исследовательский центр профилактической медицины” Минздрава России, МоскваState Research Centre for Preventive Medicine, Moscow2013201220131262428Copyright © Щербакова Н.В., Мешков А.Н., Бойцов С.А., 20132013Щербакова Н.В., Мешков А.Н., Бойцов С.А.Shcherbakova N.V., Meshkov A.N., Boytsov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/96

Развитие профилактической медицины в XXI веке, по-видимому, невозможно без использования индивидуальных генетических данных пациента. Генодиагностика в настоящий момент служит золотым стандартом в диагностике моногенных заболеваний. В последние годы активно изучаются генетические факторы, влияющие на развитие комплексных (мультифакториальных) заболеваний, таких как ишемическая болезнь сердца, гипертоническая болезнь и т.д. Данный обзор посвящен анализу возможности выявления новых генетических факторов наследственности комплексных заболеваний, полученных при секвенировании экзомов пациентов. 

The further development of preventive medicine in the 21st century may be impossible without the assessment of individual patients’ genetic data. At present, genetic methods are the gold standard in the diagnostics of monogenic diseases. Recently, genetic factors linked to complex (multifactorial) diseases, such as coronary heart disease and arterial hypertension, have been actively explored. This review focuses on the possible identification of new genetic factors of complex disease heritability, using the exome sequencing approach. 

профилактическая медицинагенетическая диагностикасеквенирование экзомакомплексные или мультифакториальные заболеванияpreventive medicinegenetic diagnosticsexome sequencingcomplex or multifactorial diseasesReferencesBamshad MJ, Ng SB, Bigham AW, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011; 12 (11): 745–55.Bamshad MJ, Ng SB, Bigham AW, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011; 12 (11): 745–55.Marenberg ME, RischN, Berkman LF, et al. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994; 330 (15): 1041–6.Marenberg ME, RischN, Berkman LF, et al. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994; 330 (15): 1041–6.Mayer B, Erdmann J and Schunkert H. Genetics and heritability of coronary artery disease and myocardial infarction. Clin Res Cardiol. 2007; 96 (1): 1–7.Mayer B, Erdmann J and Schunkert H. Genetics and heritability of coronary artery disease and myocardial infarction. Clin Res Cardiol. 2007; 96 (1): 1–7.Marian AJ. The enigma of genetics etiology of atherosclerosis in the post￾GWAS era. Curr Atheroscler Rep. 2012; 14 (4): 295–9.Marian AJ. The enigma of genetics etiology of atherosclerosis in the post￾GWAS era. Curr Atheroscler Rep. 2012; 14 (4): 295–9.Morris AP, Voight BF, Teslovich TM, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012; 44 (9): 981–90.Morris AP, Voight BF, Teslovich TM, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012; 44 (9): 981–90.Schunkert H, Konig IR, Kathiresan S, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011; 43 (4): 333–8.Schunkert H, Konig IR, Kathiresan S, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011; 43 (4): 333–8.The International HapMap Consortium. A haplotype map of the human genome. Nature. 2005; 437 (7063): 1299–320.The International HapMap Consortium. A haplotype map of the human genome. Nature. 2005; 437 (7063): 1299–320.Abecasis GR, Altshuler D, Auton A, et al. A map of human genome variation from population-scale sequencing. Nature. 2010; 467 (7319): 1061–73.Abecasis GR, Altshuler D, Auton A, et al. A map of human genome variation from population-scale sequencing. Nature. 2010; 467 (7319): 1061–73.Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466 (7307): 707–13.Teslovich TM, Musunuru K, Smith AV, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466 (7307): 707–13.Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008; 322 (5903): 881–8.Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008; 322 (5903): 881–8.Do R, Kathiresan S, Abecasis GR. Exome sequencing and complex disease: practical aspects of rare variant association studies. Hum Mol Genet. 2012; 21 (R1): R1–9.Do R, Kathiresan S, Abecasis GR. Exome sequencing and complex disease: practical aspects of rare variant association studies. Hum Mol Genet. 2012; 21 (R1): R1–9.Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005; 308 (5720): 385–9.Klein RJ, Zeiss C, Chew EY, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005; 308 (5720): 385–9.Huang Y, Paxton WA, Wolinsky SM, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996; 2 (11): 1240–3.Huang Y, Paxton WA, Wolinsky SM, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996; 2 (11): 1240–3.Wagner MJ, Rare-variant genome-wide association studies: a new frontier in genetic analysis of complex traits. Pharmacogenomics. 2013; 14 (4): 413–24.Wagner MJ, Rare-variant genome-wide association studies: a new frontier in genetic analysis of complex traits. Pharmacogenomics. 2013; 14 (4): 413–24.Maher B. Personal genomes: The case of the missing heritability. Nature 2008; 456 (7218): 18–21.Maher B. Personal genomes: The case of the missing heritability. Nature 2008; 456 (7218): 18–21.Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet, 2011; 13 (2): 135–45.Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet, 2011; 13 (2): 135–45.Bhattacharjee S, Wang Z, CiampaJ, et al. Using principal components of genetic variation for robust and powerful detection of gene-gene interactions in case-control and case-only studies. Am J Hum Genet. 2010; 86 (3): 331–42.Bhattacharjee S, Wang Z, CiampaJ, et al. Using principal components of genetic variation for robust and powerful detection of gene-gene interactions in case-control and case-only studies. Am J Hum Genet. 2010; 86 (3): 331–42.Cirulli ET and GoldsteinDB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010; 11 (6): 415–25.Cirulli ET and GoldsteinDB. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nat Rev Genet. 2010; 11 (6): 415–25.Feldman MW and LewontinRC. The heritability hang-up. Science. 1975; 190 (4220): 1163–8.Feldman MW and LewontinRC. The heritability hang-up. Science. 1975; 190 (4220): 1163–8.Eichler EE, FlintJ, GibsonG, et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010; 11 (6): 446–50.Eichler EE, FlintJ, GibsonG, et al. Missing heritability and strategies for finding the underlying causes of complex disease. Nat Rev Genet. 2010; 11 (6): 446–50.Visscher PM, Hill WG, Wray NR. Heritability in the genomics era — concepts and misconceptions. Nat Rev Genet. 2008; 9 (4): 255–66.Visscher PM, Hill WG, Wray NR. Heritability in the genomics era — concepts and misconceptions. Nat Rev Genet. 2008; 9 (4): 255–66.Pritchard JK. Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet. 2001; 69 (1): 124–37.Pritchard JK. Are rare variants responsible for susceptibility to complex diseases? Am J Hum Genet. 2001; 69 (1): 124–37.Mackay TF. The genetic architecture of quantitative traits. Annu Rev Genet. 2001; 35: 303–39.Mackay TF. The genetic architecture of quantitative traits. Annu Rev Genet. 2001; 35: 303–39.Mackay TF, Stone EA and AyrolesJF. The genetics of quantitative traits: challenges and prospects. Nat Rev Genet. 2009; 10 (8): 565–77.Mackay TF, Stone EA and AyrolesJF. The genetics of quantitative traits: challenges and prospects. Nat Rev Genet. 2009; 10 (8): 565–77.Jablonka E, Raz G. Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol. 2009; 84 (2): 131–76.Jablonka E, Raz G. Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol. 2009; 84 (2): 131–76.Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007; 447 (7143): 433–40.Feinberg AP. Phenotypic plasticity and the epigenetics of human disease. Nature. 2007; 447 (7143): 433–40.Speliotes EK, WillerCJ, BerndtSI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010; 42 (11): 937–48.Speliotes EK, WillerCJ, BerndtSI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010; 42 (11): 937–48.Park JH, WacholderS, GailMH, et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat Genet. 2010; 42 (7): 570–5.Park JH, WacholderS, GailMH, et al. Estimation of effect size distribution from genome-wide association studies and implications for future discoveries. Nat Genet. 2010; 42 (7): 570–5.Gibson G. Hints of hidden heritability in GWAS. Nat Genet. 2010; 42 (7): 558–60.Gibson G. Hints of hidden heritability in GWAS. Nat Genet. 2010; 42 (7): 558–60.Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet. 2008; 40 (6): 695–701.Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet. 2008; 40 (6): 695–701.Dickson SP, WangK, KrantzI, et al. Rare variants create synthetic genome￾wide associations. PLoS Biol. 2010; 8 (1): e1000294.Dickson SP, WangK, KrantzI, et al. Rare variants create synthetic genome￾wide associations. PLoS Biol. 2010; 8 (1): e1000294.Tomlinson I, Webb E, Carvajal-CarmonaL, et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007; 39 (8): 984–8.Tomlinson I, Webb E, Carvajal-CarmonaL, et al. A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet. 2007; 39 (8): 984–8.Prokunina-Olsson L, Hall JL. No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue. Mol Cancer. 2009; 8: 96.Prokunina-Olsson L, Hall JL. No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue. Mol Cancer. 2009; 8: 96.Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996; 273 (5283): 1856–62.Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996; 273 (5283): 1856–62.

The authors declare that there are no conflicts of interest present.