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preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 10

Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data

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Technological advances have dramatically reduced the cost of sequencing the human genome. Tools for analyzing such data across families including annotation of clinically important variants and aggregation of variants for personalizing drug prescriptions have been developed but few are publically available. Here we describe such tools then demonstrate their application in several distinct data sets. In particular, we use the tools to define the genetic basis of a new congenital arrhythmia syndrome.

Vyšlo v časopise: Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005496
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005496

Souhrn

Technological advances have dramatically reduced the cost of sequencing the human genome. Tools for analyzing such data across families including annotation of clinically important variants and aggregation of variants for personalizing drug prescriptions have been developed but few are publically available. Here we describe such tools then demonstrate their application in several distinct data sets. In particular, we use the tools to define the genetic basis of a new congenital arrhythmia syndrome.

Zdroje

1. Mardis ER. The $1,000 genome, the $100,000 analysis? Genome medicine. 2010;2(11):84. Epub 2010/12/01. doi: gm205 [pii] doi: 10.1186/gm205 21114804; PubMed Central PMCID: PMC3016626.

2. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nature genetics. 2010;42(9):790–3. Epub 2010/08/17. doi: ng.646 [pii] doi: 10.1038/ng.646 20711175; PubMed Central PMCID: PMC2930028.

3. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, et al. Exome sequencing identifies the cause of a mendelian disorder. Nature genetics. 2010;42(1):30–5. Epub 2009/11/17. doi: ng.499 [pii] doi: 10.1038/ng.499 19915526; PubMed Central PMCID: PMC2847889.

4. Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. The New England journal of medicine. 2010;362(13):1181–91. Epub 2010/03/12. doi: 10.1056/NEJMoa0908094 20220177.

5. Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11(10):685–96. Epub 2010/09/18. doi: 10.1038/nrg2841 20847746.

6. Holm H, Gudbjartsson DF, Sulem P, Masson G, Helgadottir HT, Zanon C, et al. A rare variant in MYH6 is associated with high risk of sick sinus syndrome. Nature genetics. 2011. Epub 2011/03/08. doi: ng.781 [pii] doi: 10.1038/ng.781 21378987.

7. Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N, Sigurdsson A, et al. Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nature genetics. 2014. doi: 10.1038/ng.2882 24464100.

8. Flannick J, Thorleifsson G, Beer NL, Jacobs SB, Grarup N, Burtt NP, et al. Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nature genetics. 2014;46(4):357–63. doi: 10.1038/ng.2915 24584071; PubMed Central PMCID: PMC4051628.

9. Consortium STD, Estrada K, Aukrust I, Bjorkhaug L, Burtt NP, Mercader JM, et al. Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA: the journal of the American Medical Association. 2014;311(22):2305–14. doi: 10.1001/jama.2014.6511 24915262.

10. Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, et al. Making a definitive diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011;13(3):255–62. Epub 2010/12/22. doi: 10.1097/GIM.0b013e3182088158 21173700.

11. Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(45):19096–101. Epub 2009/10/29. doi: 0910672106 [pii] doi: 10.1073/pnas.0910672106 19861545; PubMed Central PMCID: PMC2768590.

12. Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA: the journal of the American Medical Association. 2014;312(18):1880–7. doi: 10.1001/jama.2014.14604 25326637; PubMed Central PMCID: PMC4278636.

13. Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA: the journal of the American Medical Association. 2014;312(18):1870–9. doi: 10.1001/jama.2014.14601 25326635; PubMed Central PMCID: PMC4326249.

14. Cooper DN, Ball EV, Krawczak M. The human gene mutation database. Nucleic acids research. 1998;26(1):285–7. Epub 1998/02/21. doi: gkb003 [pii]. 9399854; PubMed Central PMCID: PMC147254.

15. Yu W, Yesupriya A, Wulf A, Hindorff LA, Dowling N, Khoury MJ, et al. GWAS Integrator: a bioinformatics tool to explore human genetic associations reported in published genome-wide association studies. Eur J Hum Genet. 2011. Epub 2011/05/26. doi: 10.1038/ejhg.2011.91 21610748.

16. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(23):9362–7. Epub 2009/05/29. doi: 10.1073/pnas.0903103106 19474294; PubMed Central PMCID: PMC2687147.

17. Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nature genetics. 2014;46(3):310–5. doi: 10.1038/ng.2892 24487276; PubMed Central PMCID: PMC3992975.

18. Ashley EA, Butte AJ, Wheeler MT, Chen R, Klein TE, Dewey FE, et al. Clinical assessment incorporating a personal genome. Lancet. 2010;375(9725):1525–35. Epub 2010/05/04. doi: S0140-6736(10)60452-7 [pii] doi: 10.1016/S0140-6736(10)60452-7 20435227; PubMed Central PMCID: PMC2937184.

19. Dewey FE, Chen R, Cordero SP, Ormond KE, Caleshu C, Karczewski KJ, et al. Phased whole-genome genetic risk in a family quartet using a major allele reference sequence. PLoS genetics. 2011;7(9):e1002280. doi: 10.1371/journal.pgen.1002280 21935354; PubMed Central PMCID: PMC3174201.

20. Pruitt KD, Tatusova T, Maglott DR. NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic acids research. 2007;35(Database issue):D61–5. Epub 2006/11/30. doi: gkl842 [pii] doi: 10.1093/nar/gkl842 17130148; PubMed Central PMCID: PMC1716718.

21. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic acids research. 2010;38(16):e164. doi: 10.1093/nar/gkq603 20601685; PubMed Central PMCID: PMC2938201.

22. Dewey FE, Perez MV, Wheeler MT, Watt C, Spin J, Langfelder P, et al. Gene coexpression network topology of cardiac development, hypertrophy, and failure. Circulation Cardiovascular genetics. 2011;4(1):26–35. doi: 10.1161/CIRCGENETICS.110.941757 21127201; PubMed Central PMCID: PMC3324316.

23. Dong J, Horvath S. Understanding network concepts in modules. BMC systems biology. 2007;1 : 24. doi: 10.1186/1752-0509-1-24 17547772; PubMed Central PMCID: PMC3238286.

24. Yip AM, Horvath S. Gene network interconnectedness and the generalized topological overlap measure. BMC bioinformatics. 2007;8 : 22. doi: 10.1186/1471-2105-8-22 17250769; PubMed Central PMCID: PMC1797055.

25. Langfelder P, Zhang B, Horvath S. Defining clusters from a hierarchical cluster tree: the Dynamic Tree Cut package for R. Bioinformatics. 2008;24(5):719–20. doi: 10.1093/bioinformatics/btm563 18024473.

26. Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P, Magnusson G, et al. Rate of de novo mutations and the importance of father's age to disease risk. Nature. 2012;488(7412):471–5. doi: 10.1038/nature11396 22914163; PubMed Central PMCID: PMC3548427.

27. Roach JC, Glusman G, Smit AF, Huff CD, Hubley R, Shannon PT, et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science. 2010;328(5978):636–9. doi: 10.1126/science.1186802 20220176; PubMed Central PMCID: PMC3037280.

28. Wall JD, Tang LF, Zerbe B, Kvale MN, Kwok PY, Schaefer C, et al. Estimating genotype error rates from high-coverage next-generation sequence data. Genome research. 2014;24(11):1734–9. doi: 10.1101/gr.168393.113 25304867; PubMed Central PMCID: PMC4216915.

29. Roach JC, Glusman G, Hubley R, Montsaroff SZ, Holloway AK, Mauldin DE, et al. Chromosomal haplotypes by genetic phasing of human families. American journal of human genetics. 2011;89(3):382–97. doi: 10.1016/j.ajhg.2011.07.023 21855840; PubMed Central PMCID: PMC3169815.

30. Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clinical pharmacology and therapeutics. 2012;92(4):414–7. doi: 10.1038/clpt.2012.96 22992668.

31. Riggs ER, Wain KE, Riethmaier D, Savage M, Smith-Packard B, Kaminsky EB, et al. Towards a Universal Clinical Genomics Database: The 2012 International Standards for Cytogenomic Arrays (ISCA) Consortium Meeting. Human mutation. 2013. Epub 2013/03/07. doi: 10.1002/humu.22306 23463607.

32. Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, et al. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Science translational medicine. 2011;3(65):65ra4. Epub 2011/01/14. doi: 10.1126/scitranslmed.3001756 21228398.

33. Berg JS, Adams M, Nassar N, Bizon C, Lee K, Schmitt CP, et al. An informatics approach to analyzing the incidentalome. Genetics in medicine: official journal of the American College of Medical Genetics. 2013;15(1):36–44. Epub 2012/09/22. doi: 10.1038/gim.2012.112 22995991; PubMed Central PMCID: PMC3538953.

34. Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65. Epub 2012/11/07. doi: 10.1038/nature11632 23128226; PubMed Central PMCID: PMC3498066.

35. Liu X, Jian X, Boerwinkle E. dbNSFP: a lightweight database of human nonsynonymous SNPs and their functional predictions. Hum Mutat. 2011;32(8):894–9. Epub 2011/04/27. doi: 10.1002/humu.21517 21520341; PubMed Central PMCID: PMC3145015.

36. Gonzalez-Perez A, Lopez-Bigas N. Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. American journal of human genetics. 2011;88(4):440–9. Epub 2011/04/05. doi: 10.1016/j.ajhg.2011.03.004 21457909; PubMed Central PMCID: PMC3071923.

37. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nature reviews Genetics. 2011;12(11):745–55. Epub 2011/09/29. doi: 10.1038/nrg3031 21946919.

38. Miller CL, Anderson DR, Kundu RK, Raiesdana A, Nurnberg ST, Diaz R, et al. Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus. PLoS genetics. 2013;9(7):e1003652. doi: 10.1371/journal.pgen.1003652 23874238; PubMed Central PMCID: PMC3715442.

39. Vissers LE, de Ligt J, Gilissen C, Janssen I, Steehouwer M, de Vries P, et al. A de novo paradigm for mental retardation. Nature genetics. 2010;42(12):1109–12. doi: 10.1038/ng.712 21076407.

40. O'Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature genetics. 2011;43(6):585–9. doi: 10.1038/ng.835 21572417; PubMed Central PMCID: PMC3115696.

41. Wu G, Ai T, Kim JJ, Mohapatra B, Xi Y, Li Z, et al. alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circulation Arrhythmia and electrophysiology. 2008;1(3):193–201. doi: 10.1161/CIRCEP.108.769224 19684871; PubMed Central PMCID: PMC2726717.

42. Ueda K, Valdivia C, Medeiros-Domingo A, Tester DJ, Vatta M, Farrugia G, et al. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(27):9355–60. doi: 10.1073/pnas.0801294105 18591664; PubMed Central PMCID: PMC2442127.

43. Cheng J, Van Norstrand DW, Medeiros-Domingo A, Valdivia C, Tan BH, Ye B, et al. Alpha1-syntrophin mutations identified in sudden infant death syndrome cause an increase in late cardiac sodium current. Circulation Arrhythmia and electrophysiology. 2009;2(6):667–76. doi: 10.1161/CIRCEP.109.891440 20009079; PubMed Central PMCID: PMC2810855.

44. Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA, Chaib H, et al. Clinical interpretation and implications of whole-genome sequencing. JAMA: the journal of the American Medical Association. 2014;311(10):1035–45. doi: 10.1001/jama.2014.1717 24618965; PubMed Central PMCID: PMC4119063.

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