Whole genome sequencing provides better diagnostic yield and future value than whole exome sequencing

Mattick, John S; Dinger, Marcel; Schonrock, Nicole; Cowley, Mark

doi:10.5694/mja17.01176

ARTICLE
AUTHORS
REFERENCES

Topics

The integration of genome sequencing with clinical records and data from the internet of things will transform health care

There is a great deal of optimism about the potential of genomics to transform medicine and health care. That optimism is justified. Indeed, it is hard to imagine a future where personal genomic information is not consulted routinely at the point of care. Every one of us is different, with personal genetic idiosyncrasies and risks — of cancer, cardiac arrest, blood clots, emphysema, diabetes, arthritis or toxic reactions to medications, among many others; the list will only continue to grow. Knowledge of individual genetic variation will change medicine from the art of crisis response to the science of health management, with huge benefits, both individually and systemically. It will also create new enterprises at a time of rapid change in the largest and fastest growing industry in the world.

1 Garvan Institute of Medical Research, Sydney, NSW
2 St Vincent's Clinical School, UNSW Sydney, Sydney, NSW
3 Kinghorn Centre of Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW

Correspondence: j.mattick@garvan.org.au

Acknowledgements:

We thank Howard Jacob for his comments on the manuscript. This work was supported by funding from the Kinghorn Foundation, the New South Wales State Government and the National Health and Medical Research Council of Australia.

Competing interests:

The Garvan Institute of Medical Research is the owner of Genome.One, which is clinically accredited (ISO15189) to provide whole human genome sequencing and analysis.

1. Mattick JS. The central role of RNA in human development and cognition. FEBS Lett 2011; 585: 1600-1616.
2. Freedman ML, Monteiro AN, Gayther SA, et al. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet 2011; 43: 513-518.
3. Noll AC, Miller NA, Smith LD, et al. Clinical detection of deletion structural variants in whole-genome sequences. NPJ Genom Med 2016; 1: 16026.
4. Mallawaarachchi AC, Hort Y, Cowley MJ, et al. Whole-genome sequencing overcomes pseudogene homology to diagnose autosomal dominant polycystic kidney disease. Eur J Hum Genet 2016; 24: 1584-1590.
5. Hannan AJ. Tandem repeats mediating genetic plasticity in health and disease. Nat Rev Genet 2018; 19: 286-298.
6. Belkadi A, Bolze A, Itan Y, et al. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc Natl Acad Sci USA 2015; 112: 5473-5478.
7. Mercer TR, Gerhardt DJ, Dinger ME, et al. Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 2012; 30: 99-104.
8. Deveson IW, Brunck ME, Blackburn J, et al. Universal alternative splicing of noncoding exons. Cell Syst 2018.
9. Gilissen C, Hehir-Kwa JY, Thung DT, et al. Genome sequencing identifies major causes of severe intellectual disability. Nature 2014; 511: 344-347.
10. Rauch A, Wieczorek D, Graf E, et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 2012; 380: 1674-1682.
11. de Ligt J, Willemsen MH, van Bon BW, et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 2012; 367: 1921-1929.
12. Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013; 369: 1502-1511.
13. Lee H, Deignan JL, Dorrani N, et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 2014; 312: 1880-1887.
14. Yang Y, Muzny DM, Xia F, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 2014; 312: 1870-1879.
15. Hamdan FF, Srour M, Capo-Chichi JM, et al. De novo mutations in moderate or severe intellectual disability. PLoS Genet 2014; 10: e1004772.
16. Srivastava S, Cohen JS, Vernon H, et al. Clinical whole exome sequencing in child neurology practice. Ann Neurol 2014; 76: 473-483.
17. Farwell KD, Shahmirzadi L, El-Khechen D, et al. Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet Med 2015; 17: 578-586.
18. Wright CF, Fitzgerald TW, Jones WD, et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet 2015; 385: 1305-1314.
19. Todd EJ, Yau KS, Ong R, et al. Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth. Orphanet J Rare Dis 2015; 10: 148.
20. Lazaridis KN, Schahl KA, Cousin MA, et al. Outcome of whole exome sequencing for diagnostic odyssey cases of an individualized medicine clinic: The Mayo Clinic Experience. Mayo Clin Proc 2016; 91: 297-307.
21. Parsons DW, Roy A, Yang Y, et al. Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol 2016; 2: 616-624.
22. Posey JE, Rosenfeld JA, James RA, et al. Molecular diagnostic experience of whole-exome sequencing in adult patients. Genet Med 2016; 18: 678-685.
23. Stark Z, Tan TY, Chong B, et al. A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. Genet Med 2016; 18: 1090-1096.
24. Retterer K, Juusola J, Cho MT, et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med 2016; 18: 696-704.
25. Nolan D, Carlson M. Whole exome sequencing in pediatric neurology patients: clinical implications and estimated cost analysis. J Child Neurol 2016; 31: 887-894.
26. Sawyer SL, Hartley T, Dyment DA, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet 2016; 89: 275-284.
27. Kuperberg M, Lev D, Blumkin L, et al. Utility of whole exome sequencing for genetic diagnosis of previously undiagnosed pediatric neurology patients. J Child Neurol 2016; 31: 1534-1539.
28. Monroe GR, Frederix GW, Savelberg SM, et al. Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability. Genet Med 2016; 18: 949-956.
29. Trujillano D, Bertoli-Avella AM, Kumar Kandaswamy K, et al. Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Eur J Hum Genet 2017; 25: 176-182.
30. Harris E, Topf A, Barresi R, et al. Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy. Orphanet J Rare Dis 2017; 12: 151.
31. Vissers L, van Nimwegen KJM, Schieving JH, et al. A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Genet Med 2017; 19: 1055-1063.
32. Evers C, Staufner C, Granzow M, et al. Impact of clinical exomes in neurodevelopmental and neurometabolic disorders. Mol Genet Metab 2017; 121: 297-307.
33. Fu F, Li R, Li Y, et al. Whole exome sequencing as a diagnostic adjunct to clinical testing in a tertiary referral cohort of 3988 fetuses with structural abnormalities. Ultrasound Obstet Gynecol 2018; 51: 493-502.
34. Tan TY, Dillon OJ, Stark Z, et al. Diagnostic impact and cost-effectiveness of whole-exome sequencing for ambulant children with suspected monogenic conditions. JAMA Pediatr 2017; 171: 855-862.
35. Long PA, Evans JM, Olson TM. Diagnostic yield of whole exome sequencing in pediatric dilated cardiomyopathy. J Cardiovasc Dev Dis 2017; 4.
36. Lata S, Marasa M, Li Y, et al. Whole-exome sequencing in adults with chronic kidney disease: a pilot study. Ann Intern Med 2018; 168: 100-109.
37. Cordoba M, Rodriguez-Quiroga SA, Vega PA, et al. Whole exome sequencing in neurogenetic odysseys: an effective, cost- and time-saving diagnostic approach. PLoS ONE 2018; 13: e0191228.
38. Soden SE, Saunders CJ, Willig LK, et al. Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med 2014; 6: 265ra168.
39. Yuen RK, Thiruvahindrapuram B, Merico D, et al. Whole-genome sequencing of quartet families with autism spectrum disorder. Nat Med 2015; 21: 185-191.
40. Willig LK, Petrikin JE, Smith LD, et al. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet Respir Med 2015; 3: 377-387.
41. Ellingford JM, Barton S, Bhaskar S, et al. Whole genome sequencing increases molecular diagnostic yield compared with current diagnostic testing for inherited retinal disease. Ophthalmology 2016; 123: 1143-1150.
42. Bick D, Fraser PC, Gutzeit MF, et al. Successful application of whole genome sequencing in a medical genetics clinic. J Pediatr Genet 2017; 6: 61-76.
43. Lionel AC, Costain G, Monfared N, et al. Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med 2018; 20: 435-443.
44. Cirino AL, Lakdawala NK, McDonough B, et al. A comparison of whole genome sequencing to multigene panel testing in hypertrophic cardiomyopathy patients. Circ Cardiovasc Genet 2017; 10: e001768.

Online responses are no longer available. Please refer to our instructions for authors page for more information.

Whole genome sequencing provides better diagnostic yield and future value than whole exome sequencing

Topics

Author

Comment

Do you have any competing interests to declare? *