Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Application of Whole Exome Sequencing to Identify Disease-Causing Variants in Inherited Human Diseases

  • Goh, Gerald (Department of Genetics, Yale University School of Medicine) ;
  • Choi, Murim (Department of Genetics, Yale University School of Medicine)
  • Received : 2012.09.30
  • Accepted : 2012.11.16
  • Published : 2012.12.31
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Abstract

The recent advent of next-generation sequencing technologies has dramatically changed the nature of biomedical research. Human genetics is no exception－it has never been easier to interrogate human patient genomes at the nucleotide level to identify disease-associated variants. To further facilitate the efficiency of this approach, whole exome sequencing (WES) was first developed in 2009. Over the past three years, multiple groups have demonstrated the power of WES through robust disease-associated variant discoveries across a diverse spectrum of human diseases. Here, we review the application of WES to different types of inherited human diseases and discuss analytical challenges and possible solutions, with the aim of providing a practical guide for the effective use of this technology.

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References

  1. 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. Proc Natl Acad Sci U S A 2009;106: 19096-19101. https://doi.org/10.1073/pnas.0910672106
  2. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009;461:272-276. https://doi.org/10.1038/nature08250
  3. Clark MJ, Chen R, Lam HY, Karczewski KJ, Chen R, Euskirchen G, et al. Performance comparison of exome DNA sequencing technologies. Nat Biotechnol 2011;29:908-914. https://doi.org/10.1038/nbt.1975
  4. Bilguvar K, Ozturk AK, Louvi A, Kwan KY, Choi M, Tatli B, et al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 2010;467: 207-210. https://doi.org/10.1038/nature09327
  5. Dixon-Salazar TJ, Silhavy JL, Udpa N, Schroth J, Bielas S, Schaffer AE, et al. Exome sequencing can improve diagnosis and alter patient management. Sci Transl Med 2012;4: 138ra178.
  6. Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, et al. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 2012;488:499-503. https://doi.org/10.1038/nature11280
  7. Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 2012;482: 98-102. https://doi.org/10.1038/nature10814
  8. 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: 471-475. https://doi.org/10.1038/nature11396
  9. Neale BM, Kou Y, Liu L, Ma'ayan A, Samocha KE, Sabo A, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012;485:242-245. https://doi.org/10.1038/nature11011
  10. O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012;485: 246-250. https://doi.org/10.1038/nature10989
  11. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 2012;485:237-241. https://doi.org/10.1038/nature10945
  12. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell 2001;104:545-556. https://doi.org/10.1016/S0092-8674(01)00241-0
  13. Gibson G. Rare and common variants: twenty arguments. Nat Rev Genet 2011;13:135-145.
  14. Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE, Gravel S, et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 2012;337:64-69. https://doi.org/10.1126/science.1219240
  15. Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, et al. Recent segmental duplications in the human genome. Science 2002;297:1003-1007. https://doi.org/10.1126/science.1072047
  16. 1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 2010; 467:1061-1073. https://doi.org/10.1038/nature09534
  17. Krumm N, Sudmant PH, Ko A, O'Roak BJ, Malig M, Coe BP, et al. Copy number variation detection and genotyping from exome sequence data. Genome Res 2012;22:1525-1532. https://doi.org/10.1101/gr.138115.112
  18. Li J, Lupat R, Amarasinghe KC, Thompson ER, Doyle MA, Ryland GL, et al. CONTRA: copy number analysis for targeted resequencing. Bioinformatics 2012;28:1307-1313. https://doi.org/10.1093/bioinformatics/bts146
  19. Hanchard N, Murdock D, Magoulas P, Bainbridge M, Muzny D, Wu Y, et al. Exploring the utility of whole-exome sequencing as a diagnostic tool in a child with atypical episodic muscle weakness. Clin Genet 2012 Aug 17 [Epub]. http://dx.doi.org/10.1111/j.1399-0004.2012.01951.x.

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