Exome sequencing as a tool for Mendelian disease gene discovery

Nature Reviews Genetics

Volumn 12, Issue 11, 2011, Pages 745-755

  Bamshad, Michael J ^a,b   Ng, Sarah B ^b   Bigham, Abigail W ^a,c   Tabor, Holly K ^a,d   Emond, Mary J ^b   Nickerson, Deborah A ^b   Shendure, Jay ^b  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d SEATTLE CHILDREN S RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EXOME; GENE FREQUENCY; GENE IDENTIFICATION; GENE MUTATION; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; HEALTH BEHAVIOR; HERITABILITY; HUMAN; INHERITANCE; MENDELIAN DISORDER; PEDIGREE; PRIORITY JOURNAL; RARE DISEASE; REVIEW;

ALLELES; BASE SEQUENCE; EXOME; GENETIC PREDISPOSITION TO DISEASE; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MOLECULAR SEQUENCE DATA; PEDIGREE; PHENOTYPE; SEQUENCE ANALYSIS, DNA;

EID: 80054746492     PISSN: 14710056     EISSN: 14710064     Source Type: Journal    
DOI: 10.1038/nrg3031     Document Type: Review

References (91)

1. McKusick, V. A. Mendelian Inheritance in Man and its online version, OMIM. Am. J. Hum. Genet. 80, 588-604 (2007). (Pubitemid 46564398)
2. Kaiser, J. Human genetics. Affordable 'exomes' fill gaps in a catalogue of rare diseases. Science 330, 903 (2010).
3. Antonarakis, S. E. & Beckmann, J. S. Mendelian disorders deserve more attention. Nature Rev. Genet. 7, 277-282 (2006).
4. Schork, N. J., Murray, S. S., Frazer, K. A. & Topol, E. J. Common vs. rare allele hypotheses for complex diseases. Curr. Opin. Genet. Dev. 19, 212-219 (2009).
5. Manolio, T. A. et al. Finding the missing heritability of complex diseases. Nature 461, 747-753 (2009).
6. McClellan, J. & King, M. C. Genetic heterogeneity in human disease. Cell 141, 210-217 (2010).
7. Metzker, M. L. Sequencing technologies-the next generation. Nature Rev. Genet. 11, 31-46 (2010).
8. Mamanova, L. et al. Target-enrichment strategies for next-generation sequencing. Nature Methods 7, 111-118 (2010).
9. Biesecker, L. G. Exome sequencing makes medical genomics a reality. Nature Genet. 42, 13-14 (2010).
10. Ng, S. B. et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461, 272-276 (2009).
11. Ng, S. B. et al. Exome sequencing identifies the cause of a Mendelian disorder. Nature Genet. 42, 30-35 (2010).
12. Bilguvar, K. et al. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 467, 207-210 (2010).
13. Stenson, P. D. et al. The Human Gene Mutation Database: providing a comprehensive central mutation database for molecular diagnostics and personalized genomics. Hum. Genomics 4, 69-72 (2009).
14. Kryukov, G. V., Pennacchio, L. A. & Sunyaev, S. R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet. 80, 727-739 (2007). (Pubitemid 46564409)
15. Simpson, M. A. et al. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nature Genet. 43, 303-305 (2011).
16. Krawitz, P. M. et al. Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome. Nature Genet. 42, 827-829 (2010).
17. Tsurusaki, Y. et al. Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing. J. Med. Genet. 48, 606-609 (2011).
18. Liu, Y. et al. Confirmation by exome sequencing of the pathogenic role of NCSTN mutations in acne inversa (hidradenitis suppurativa). J. Invest. Dermatol. 131, 1570-1572 (2011).
19. Yamaguchi, T. et al. Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese. J. Bone Miner. Res. 26, 1655-1661 (2011).
20. Zuchner, S. et al. Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa. Am. J. Hum. Genet. 88, 201-206 (2011).
21. Otto, E. A. et al. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature Genet. 42, 840-850 (2010).
22. Haack, T. B. et al. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nature Genet. 42, 1131-1134 (2010).
23. Ng, S. B. et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nature Genet. 42, 790-793 (2010).
24. Al Badr, W. et al. Exome capture and massively parallel sequencing identifies a novel HPSE2 mutation in a Saudi Arabian child with Ochoa (urofacial) syndrome. J. Pediatr. Urol. 28 Mar 2011 (doi:10.1016/j.jpurol.2011. 02.034).
25. Bolze, A. et al. Whole-exome-sequencing-based discovery of human FADD deficiency. Am. J. Hum. Genet. 87, 873-881 (2010).
26. Caliskan, M. et al. Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13. Hum. Mol. Genet. 20, 1285-1289 (2011).
27. Glazov, E. A. et al. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genet. 7, e1002027 (2011).
28. Walsh, T. et al. Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. Am. J. Hum. Genet. 87, 90-94 (2010).
29. Johnston, J. J. et al. Massively parallel sequencing of exons on the X chromosome identifies RBM10 as the gene that causes a syndromic form of cleft palate. Am. J. Hum. Genet. 86, 743-748 (2010).
30. Norton, N. et al. Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. Am. J. Hum. Genet. 88, 273-282 (2011).
31. Musunuru, K. et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N. Engl. J. Med. 363, 2220-2227 (2010).
32. Johnson, J. O. et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68, 857-864 (2010).
33. Wang, J. L. et al. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 133, 3510-3518 (2010).
34. Gilissen, C. et al. Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome. Am. J. Hum. Genet. 87, 418-423 (2010).
35. Lalonde, E. et al. Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing. Hum. Mutat. 31, 918-923 (2010).
36. Sirmaci, A. et al. MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes. Am. J. Hum. Genet. 87, 679-686 (2010).
37. Hoischen, A. et al. De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. Nature Genet. 42, 483-485 (2010).
38. Kalay, E. et al. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nature Genet. 43, 23-26 (2011).
39. Hubisz, M. J., Pollard, K. S. & Siepel, A. PHAST and RPHAST: phylogenetic analysis with space/time models. Brief. Bioinf. 12, 41-51 (2011).
40. Cooper, G. M. et al. Single-nucleotide evolutionary constraint scores highlight disease-causing mutations. Nature Methods 7, 250-251 (2010).
41. Kumar, P. H. & S. Ng, P. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nature Protoc. 4, 1073-1081 (2009).
42. Adzhubei, I. A. et al. A method and server for predicting damaging missense mutations. Nature Methods 7, 248-249 (2010).
43. Stone, E. A. & Sidow, A. Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity. Genome Res. 15, 978-986 (2005). (Pubitemid 40994218)
44. Nachman, M. W. & Crowell, S. L. Estimate of the mutation rate per nucleotide in humans. Genetics 156, 297-304 (2000).
45. Vissers, L. E. et al. A de novo paradigm for mental retardation. Nature Genet. 42, 1109-1112 (2010).
46. Girard, S. L. et al. Increased exonic de novo mutation rate in individuals with schizophrenia. Nature Genet. 43, 860-863 (2011).
47. O'Roak, B. J. et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature Genet. 43, 585-589 (2011).
48. Blakemore, A. I. & Froguel, P. Investigation of Mendelian forms of obesity holds out the prospect of personalized medicine. Ann. N.Y. Acad. Sci. 1214, 180-189 (2010).
49. Dietz, H. C. New therapeutic approaches to Mendelian disorders. N. Engl. J. Med. 363, 852-863 (2010).
50. St. Hilaire, C. et al. NT5E mutations and arterial calcifications. N. Engl. J. Med. 364, 432-42 (2011).
51. Choi, M. et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc. Natl Acad. Sci. USA 106, 19096-19101 (2009).
52. Worthey, E. A. et al. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet. Med. 13, 255-262 (2011).
53. Bonnefond, A. et al. Molecular diagnosis of neonatal diabetes mellitus using next-generation sequencing of the whole exome. PLoS ONE 5, e13630 (2010).
54. Montenegro, G. et al. Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Ann. Neurol. 69, 464-470 (2011).
55. Chiu, R. W. et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc. Natl Acad. Sci. USA 105, 20458-20463 (2008).
56. Chiu, R. W. & Lo, Y. M. Non-invasive prenatal diagnosis by fetal nucleic acid analysis in maternal plasma: the coming of age. Semin. Fetal Neonatal Med. 16, 88-93 (2011).
57. Bell, C. J. et al. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci. Transl. Med. 3, 654 (2011).
58. Ashley, E. A. et al. Clinical assessment incorporating a personal genome. Lancet 375, 1525-1535 (2010).
59. Kingsmore, S. F. & Saunders, C. J. Deep sequencing of patient genomes for disease diagnosis: when will it become routine? Sci. Transl. Med. 3, 8723 (2011).
60. Scriver, C. R. The PAH gene, phenylketonuria, and a paradigm shift. Hum. Mutat. 28, 831-845 (2007). (Pubitemid 47579933)
61. Ormond, K. E. et al. Challenges in the clinical application of whole-genome sequencing. Lancet 375, 1749-1751 (2010).
62. Tong, M. Y., Cassa, C. A. & Kohane, I. S. Automated validation of genetic variants from large databases: ensuring that variant references refer to the same genomic locations. Bioinformatics 27, 891-893 (2011).
63. Kohonen-Corish, M. R. et al. How to catch all those mutations-the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010. Hum. Mutat. 31, 1374-1381 (2010).
64. Roach, J. C. et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328, 636-639 (2010).
65. Beskow, L. M. & Burke, W. Offering individual genetic research results: context matters. Sci. Transl. Med. 2, 3820 (2010).
66. Richards, C. S. et al. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet. Med. 10, 294-300 (2008). (Pubitemid 351544132)
67. Fabsitz, R. R. et al. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circ. Cardiovasc. Genet. 3, 574-580 (2011).
68. Caulfield, T. et al. Research ethics recommendations for whole-genome research: consensus statement. PLoS Biol. 6, e73 (2008).
69. Wolf, S. M. et al. Managing incidental findings in human subjects research: analysis and recommendations. J. Law Med. Ethics 36, 219-248 (2008).
70. Ravitsky, V. & Wilfond, B. S. Disclosing individual genetic results to research participants. Am. J. Bioeth. 6, 8-17 (2006). (Pubitemid 44691474)
71. Green, E. D. & Guyer, M. S. Charting a course for genomic medicine from base pairs to bedside. Nature 470, 204-213 (2011).
72. Dahl, F. et al. Multigene amplification and massively parallel sequencing for cancer mutation discovery. Proc. Natl Acad. Sci. USA 104, 9387-9392 (2007). (Pubitemid 47185789)
73. Fredriksson, S. et al. Multiplex amplification of all coding sequences within 10 cancer genes by Gene-Collector. Nucleic Acids Res. 35, e47 (2007).
74. Gnirke, A. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nature Biotech. 27, 182-189 (2009).
75. Okou, D. T. et al. Microarray-based genomic selection for high-throughput resequencing. Nature Methods 4, 907-909 (2007). (Pubitemid 350042376)
76. Porreca, G. J. et al. Multiplex amplification of large sets of human exons. Nature Methods 4, 931-936 (2007). (Pubitemid 350042382)
77. Albert, T. J. et al. Direct selection of human genomic loci by microarray hybridization. Nature Methods 4, 903-905 (2007). (Pubitemid 350042375)
78. Turner, E. H., Lee, C., Ng, S. B., Nickerson, D. A. & Shendure, J. Massively parallel exon capture and library-free resequencing across 16 genomes. Nature Methods 6, 315-316 (2009).
79. Turner, E. H., Ng, S. B., Nickerson, D. A. & Shendure, J. Methods for genomic partitioning. Annu. Rev. Genomics Hum. Genet. 10, 263-284 (2009).
80. Nielsen, R., Paul, J. S., Albrechtsen, A. & Song, Y. S. Genotype and SNP calling from next-generation sequencing data. Nature Rev. Genet. 12, 443-451 (2011).
81. Alkan, C., Coe, B. P. & Eichler, E. E. Genome structural variation discovery and genotyping. Nature Rev. Genet. 12, 363-376 (2011).
82. Adey, A. et al. Rapid, low-input, low-bias construction of shotgun fragment libraries by high-density in vitro transposition. Genome Biol. 11, R119 (2010).
83. Cirulli, E. T. & Goldstein, D. B. Uncovering the roles of rare variants in common disease through whole-genome sequencing. Nature Rev. Genet. 11, 415-425 (2010).
84. Lanktree, M. B., Hegele, R. A., Schork, N. J. & Spence, J. D. Extremes of unexplained variation as a phenotype: an efficient approach for genome-wide association studies of cardiovascular disease. Circ. Cardiovasc. Genet. 3, 215-221 (2010).
85. Cohen, J. C. et al. Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science 305, 869-872 (2004). (Pubitemid 39038422)
86. Li, B. & Leal, S. M. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am. J. Hum. Genet. 83, 311-321 (2008).
87. Morris, A. P. & Zeggini, E. An evaluation of statistical approaches to rare variant analysis in genetic association studies. Genet. Epidemiol. 34, 188-193 (2010).
88. Price, A. L. et al. Pooled association tests for rare variants in exon-resequencing studies. Am. J. Hum. Genet. 86, 832-838 (2010).
89. Madsen, B. E. & Browning, S. R. A groupwise association test for rare mutations using a weighted sum statistic. PLoS Genet. 5, e1000384 (2009).
90. Bansal, V., Libiger, O., Torkamani, A. & Schork, N. J. Statistical analysis strategies for association studies involving rare variants. Nature Rev. Genet. 11, 773-785 (2010).
91. DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genet. 43, 491-498 (2011).