Next-generation sequencing: Impact of exome sequencing in characterizing Mendelian disorders

Journal of Human Genetics

Volumn 57, Issue 10, 2012, Pages 621-632

  Rabbani, Bahareh ^a   Mahdieh, Nejat ^a   Hosomichi, Kazuyoshi ^a   Nakaoka, Hirofumi ^a   Inoue, Ituro ^a  

^a NATIONAL INSTITUTE OF GENETICS   (Japan)

Author keywords

exome sequencing; mendelian disorder; mutation; next generation sequencing; NGS; WES

Indexed keywords

MASP1 PROTEIN; MLL2 PROTEIN; POLR3A PROTEIN; POLR3B PROTEIN; PROTEIN; UNCLASSIFIED DRUG;

AUTOSOMAL INHERITANCE; AUTOSOMAL RECESSIVE DISORDER; DE NOVO MUTATION; DNA HYBRIDIZATION; DNA STRUCTURE; EXOME; GENE EXPRESSION; GENE FUNCTION; GENE IDENTIFICATION; GENE MUTATION; GENE SEQUENCE; GENE TRANSFER; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC DISORDER; GENETIC VARIABILITY; HETEROZYGOSITY; HIGH THROUGHPUT SCREENING; HUMAN; LINKAGE ANALYSIS; MENDELIAN DISORDER; MUTATION RATE; NEXT GENERATION SEQUENCING; RECESSIVE INHERITANCE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; WHOLE EXOME SEQUENCING;

DATABASES, GENETIC; DNA MUTATIONAL ANALYSIS; EXOME; GENETIC ASSOCIATION STUDIES; GENETIC DISEASES, INBORN; GENETIC LINKAGE; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; GENETICS, POPULATION; GENOME, HUMAN; HUMANS; PEDIGREE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84867946004     PISSN: 14345161     EISSN: 1435232X     Source Type: Journal    
DOI: 10.1038/jhg.2012.91     Document Type: Review

References (169)

1. Green, E, D. & Guyer, M. S. Charting a course for genomic medicine from base pairs to bedside. Nature 470, 204-213 (2011
2. Reich, D, E. & Lander, E. S. On the allelic spectrum of human disease. Trends Genet. 17, 502-510 (2001
3. Lander, E S. Initial impact of the sequencing of the human genome. Nature 470, 187-197 (2011
4. Pritchard, J K. Are rare variants responsible for susceptibility to complex diseases? Am. J. Hum. Genet. 69, 124-137 (2001
5. Gorlov, I. P., Gorlova, O. Y., Sunyaev, S. R., Spitz, M. R. & Amos, C. I. Shifting paradigm of association studies: Value of rare single-nucleotide polymorphisms. Am. J. Hum. Genet. 82, 100-112 (2008
6. McKusick, V. A. Mendelian Inheritance in Man and its online version, OMIM. Am. J. Hum. Genet. 80, 588-604 (2007
7. Antonarakis, S. E. & Beckmann, J. S. Mendelian disorders deserve more attention. Nat. Rev. Genet. 7, 277-282 (2006
8. Peltonen, L., Perola, M., Naukkarinen, J & Palotie, A. Lessons from studying monogenic disease for common disease. Hum Mol Genet 15(Spec No 1), R67-R74.
9. Holley, R. W. The nucleotide sequence of a nucleic acid. Sci. Am. 214, 30-39 (1966
10. Sanger, F., Nicklen, S. & Coulson, A. R. DNA sequencing with chain-terminating inhibitors. Proc. Natl Acad. Sci. USA 74, 5463-5467 (1977
11. Maxam, A. M. & Gilbert, W. A new method for sequencing DNA. Proc. Natl Acad. Sci. USA 74, 560-564 (1977
12. Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M. et al. Exome sequencing identifies the cause of a mendelian disorder. Nat. Genet. 42, 30-35 (2010
13. Lindhurst, M. J., Sapp, J. C., Teer, J. K., Johnston, J. J., Finn, E. M., Peters, K. et al. A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N. Engl. J. Med. 365, 611-619 (2011
14. Riordan, J R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z. et al. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science 245, 1066-1073 (1989
15. Gusella, J F., Wexler, N. S., Conneally, P. M., Naylor, S. L., Anderson, M. A., Tanzi, R. E. et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306, 234-238 (1983
16. Lander, E, S. & Botstein, D. Homozygosity mapping: A way to map human recessive traits with the DNA of inbred children. Science 236, 1567-1570 (1987
17. Pomares, E., Riera, M., Permanyer, J., Mendez, P., Castro-Navarro, J., Andres- Gutierrez, A. et al. Comprehensive SNP-chip for retinitis pigmentosa-leber congenital amaurosis diagnosis: New mutations and detection of mutational founder effects. Eur. J. Hum. Genet. 18, 118-124 (2010
18. Vissers, L. E., de Ligt, J., Gilissen, C., Janssen, I., Steehouwer, M., de Vries, P. et al. A de novo paradigm for mental retardation. Nat. Genet. 42, 1109-1112 (2010
19. Cooper, D. N., Chen, J. M., Ball, E. V., Howells, K., Mort, M., Phillips, A. D. et al. Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics. Hum. Mutat. 31, 631-655 (2011
20. Botstein, D. & Risch, N. Discovering genotypes underlying human phenotypes: Past successes for mendelian disease, future approaches for complex disease. Nat. Genet. 33(Suppl), 228-237 (2003
21. Majewski, J., Schwartzentruber, J., Lalonde, E., Montpetit, A. & Jabado, N. What can exome sequencing do for you? J. Med. Genet. 48, 580-589 (2011
22. Hodges, E., Xuan, Z., Balija, V., Kramer, M., Molla, M. N., Smith, S. W. et al. Genomewide in situ exon capture for selective resequencing. Nat. Genet. 39, 1522-1527 (2007
23. Gnirke, A., Melnikov, A., Maguire, J., Rogov, P., LeProust, E. M., Brockman, W. et al. Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing. Nat. Biotechnol. 27, 182-189 (2009
24. Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754-1760 (2009
25. Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078-2079 (2009
26. McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A. et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297-1303 (2010
27. Robinson, J. T., Thorvaldsdottir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24-26 (2011
28. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010
29. Kumar, P., Henikoff, S. & Ng, P. C. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat. Protoc. 4, 1073-1081 (2009
30. Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P. et al. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248-249 (2010
31. Yandell, M., Huff, C., Hu, H., Singleton, M., Moore, B., Xing, J., Jorde, L. B. et al. A probabilistic disease-gene finder for personal genomes. Genome Res. 21, 1529-1542 (2011
32. Sauna, Z. E. & Kimchi-Sarfaty, C. Understanding the contribution of synonymous mutations to human disease. Nat. Rev. Genet. 12, 683-691 (2011
33. Bamshad,M. J., Ng, S. B., Bigham, A.W., Tabor, H. K., Emond,M. J., Nickerson, D. A. et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat. Rev. Genet. 12, 745-755 (2011
34. Sherry, S. T., Ward, M. H., Kholodov, M., Baker, J., Phan, L., Smigielski, E. M. et al. dbSNP: The NCBI database of genetic variation. Nucleic Acids Res. 29, 308-311 (2001
35. Consortium, G. P. A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010
36. Altshuler, D. M., Gibbs, R. A., Peltonen, L., Dermitzakis, E., Schaffner, S. F., Yu, F. et al. Integrating common and rare genetic variation in diverse human populations. Nature 467, 52-58 (2010
37. Musunuru, K., Pirruccello, J. P., Do, R., Peloso, G. M., Guiducci, C., Sougnez, C. et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N. Engl. J. Med. 363, 2220-2227 (2010
38. Pierce, S. B., Walsh, T., Chisholm, K. M., Lee, M. K., Thornton, A. M., Fiumara, A. et al. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault syndrome. Am. J. Hum. Genet. 87, 282-288 (2010
39. Ng, S. B., Bigham, A. W., Buckingham, K. J., Hannibal, M. C., McMillin, M. J., Gildersleeve, H. I. et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat. Genet. 42, 790-793 (2010
40. Pelak, K., Shianna, K. V., Ge, D., Maia, J. M., Zhu, M., Smith, J. P. et al. The characterization of twenty sequenced human genomes. PLoS Genet 6, e1001111 (2010
41. Zangen, D., Kaufman, Y., Zeligson, S., Perlberg, S., Fridman, H., Kanaan, M. et al. XX ovarian dysgenesis is caused by a PSMC3IP/HOP2 mutation that abolishes coactivation of estrogen-driven transcription. Am. J. Hum. Genet. 89, 572-579 (2011
42. Pierson, T. M., Adams, D., Bonn, F., Martinelli, P., Cherukuri, P. F., Teer, J. K. et al. Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. PLoS Genet 7, e1002325 (2011
43. Puente, X. S., Quesada, V., Osorio, F. G., Cabanillas, R., Cadinanos, J., Fraile, J. M. et al. Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am. J. Hum. Genet. 88, 650-656 (2011
44. Wang, J. L., Yang, X., Xia, K., Hu, Z. M., Weng, L., Jin, X. et al. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain 133(Part 12), 3510-3518 (2010
45. Sun, Y., Almomani, R., Aten, E., Celli, J., van der Heijden, J., Venselaar, H. et al. Terminal osseous dysplasia is caused by a single recurrent mutation in the FLNA gene. Am. J. Hum. Genet. 87, 146-153 (2010
46. Robinson, P. N., Krawitz, P. & Mundlos, S. Strategies for exome and genome sequence data analysis in disease-gene discovery projects. Clin. Genet. 80, 127-132 (2011
47. Sirmaci, A., Walsh, T., Akay, H., Spiliopoulos, M., Sakalar, Y. B., Hasanefendioglu- Bayrak, 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
48. Depienne, C., Bouteiller, D., Meneret, A., Billot, S., Groppa, S., Klebe, S. et al. RAD51 haploinsufficiency causes congenital mirror movements in humans. Am. J. Hum. Genet. 90, 301-307 (2012
49. Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A. et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat. Genet. 44, 200-205 (2011
50. Abou Jamra, R., Philippe, O., Raas-Rothschild, A., Eck, S. H., Graf, E., Buchert, R. et al. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am. J. Hum. Genet. 88, 788-795 (2011
51. Tsurusaki, Y., Kosho, T., Hatasaki, K., Narumi, Y., Wakui, K., Fukushima, Y. et al. Exome sequencing in a family with an X-linked lethal malformationsyndrome: Clinical consequences of hemizygous truncating OFD1 mutations in male patients. Clin. Genet, doi:10.1111/j.1399-0004.2012.01885.x (2012
52. Gilissen, C., Hoischen, A., Brunner, H. G. & Veltman, J. A. Disease gene identification strategies for exome sequencing. Eur. J. Hum. Genet. 20, 490-497 (2011
53. Hoischen, A., van Bon, B. W., Gilissen, C., Arts, P., van Lier, B., Steehouwer, M. et al. De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. Nat. Genet. 42, 483-485 (2010
54. Saitsu, H., Osaka, H., Sasaki, M., Takanashi, J., Hamada, K., Yamashita, A. et al. Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. Am. J. Hum. Genet. 89, 644-651 (2011
55. Gilissen, C., Arts, H. H., Hoischen, A., Spruijt, L., Mans, D. A., Arts, P. et al. Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome. Am. J. Hum. Genet. 87, 418-423 (2010
56. Roach, J. C., Glusman, G., Smit, A. F., Huff, C. D., Hubley, R., Shannon, P. T. et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328, 636-639 (2010
57. Lynch, M. Rate molecular spectrum, and consequences of human mutation. Proc. Natl Acad. Sci. USA 107, 961-968 (2010
58. Gilissen, C., Hoischen, A., Brunner, H. G. & Veltman, J. A. Unlocking Mendelian disease using exome sequencing. Genome Biol. 12, 228 (2011
59. O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S. et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat. Genet. 43, 585-589 (2011
60. Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J. et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485, 237-241 (2012
61. Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J. et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74, 285-299 (2012
62. Koboldt, D. C., Ding, L., Mardis, E. R. & Wilson, R. K. Challenges of sequencing human genomes. Brief Bioinform. 11, 484-498 (2010
63. Eid, J., Fehr, A., Gray, J., Luong, K., Lyle, J., Otto, G. et al. Real-time DNA sequencing from single polymerase molecules. Science 323, 133-138 (2009
64. Branton, D., Deamer, D. W., Marziali, A., Bayley, H., Benner, S. A., Butler, T. et al. The potential and challenges of nanopore sequencing. Nat. Biotechnol. 26, 1146-1153 (2008
65. Watson, J. D. & Crick, F. H. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171, 737-738 (1953
66. Botstein, D., White, R. L., Skolnick, M. & Davis, R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32, 314-331 (1980
67. Mullis, K., Faloona, F., Scharf, S., Saiki, R., Horn, G. & Erlich, H. Specific enzymatic amplification of DNA in vitro: The polymerase chain reaction. Cold Spring Harb. Symp. Quant. Biol. 51, 263-273 (1986
68. Smith, L. M., Sanders, J. Z., Kaiser, R. J., Hughes, P., Dodd, C., Connell, C. R. et al. Fluorescence detection in automated DNA sequence analysis. Nature 321, 674-679 (1986
69. Royer-Pokora, B., Kunkel, L. M., Monaco, A. P., Goff, S. C., Newburger, P. E., Baehner, R. L. et al. Cloning the gene for an inherited human disorder - chronic granulomatous disease - on the basis of its chromosomal location. Nature 322, 32-38 (1986
70. Cohen, D., Chumakov, I. & Weissenbach, J. A first-generation physical map of the human genome. Nature 366, 698-701 (1993
71. Fleischmann, R. D., Adams, M. D., White, O., Clayton, R. A., Kirkness, E. F., Kerlavage, A. R. et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269, 496-512 (1995
72. Dunham, I., Shimizu, N., Roe, B. A., Chissoe, S., Hunt, A. R., Collins, J. E. et al. The DNA sequence of human chromosome 22. Nature 402, 489-495 (1999
73. Adams, M. D., Celniker, S. E., Holt, R. A., Evans, C. A., Gocayne, J. D., Amanatides, P. G. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185-2195 (2000
74. Myers, E. W., Sutton, G. G., Smith, H. O., Adams, M. D. & Venter, J. C. On the sequencing and assembly of the human genome. Proc. Natl Acad. Sci. USA 99, 4145-4146 (2002
75. Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G. et al. The sequence of the human genome. Science 291, 1304-1351 (2001
76. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J. et al. Initial sequencing and analysis of the human genome. Nature 409, 860-921 (2001
77. Margulies, M., Egholm, M., Altman, W. E., Attiya, S., Bader, J. S., Bemben, L. A. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376-380 (2005
78. Wheeler, D. A., Srinivasan, M., Egholm, M., Shen, Y., Chen, L., McGuire, A. et al. The complete genome of an individual by massively parallel DNA sequencing. Nature 452, 872-876 (2008
79. Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C. et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461, 272-276 (2009
80. Bolze, A., Byun, M., McDonald, D., Morgan, N. V., Abhyankar, A., Premkumar, L. et al. Whole-exome-sequencing-based discovery of human FADD deficiency. Am. J. Hum. Genet. 87, 873-881 (2010
81. Walsh, T., Shahin, H., Elkan-Miller, T., Lee, M. K., Thornton, A. M., Roeb, W. 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
82. Haack, T. B., Danhauser, K., Haberberger, B., Hoser, J., Strecker, V., Boehm, D. et al. Exome sequencing identifies ACAD9 mutations as a cause of complex I deficiency. Nat. Genet. 42, 1131-1134 (2010
83. Krawitz, P. M., Schweiger, M. R., Rodelsperger, C., Marcelis, C., Kolsch, U., Meisel, C. et al. Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome. Nat. Genet. 42, 827-829 (2010
84. Bilguvar, K., Ozturk, A. K., Louvi, A., Kwan, K. Y., Choi, M., Tatli, B. et al. Wholeexome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature 467, 207-210 (2010
85. Caliskan, M., Chong, J. X., Uricchio, L., Anderson, R., Chen, P., Sougnez, C. 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
86. Zuchner, S., Dallman, J., Wen, R., Beecham, G., Naj, A., Farooq, A. et al. Wholeexome sequencing links a variant in DHDDS to retinitis pigmentosa. Am. J. Hum. Genet. 88, 201-206 (2011
87. Becker, J., Semler, O., Gilissen, C., Li, Y., Bolz, H. J., Giunta, C. et al. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomalrecessive osteogenesis imperfecta. Am. J. Hum. Genet. 88, 362-371 (2011
88. Glazov, E. A., Zankl, A., Donskoi, M., Kenna, T. J., Thomas, G. P., Clark, G. R. 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
89. Sloan, J. L., Johnston, J. J., Manoli, I., Chandler, R. J., Krause, C., Carrillo-Carrasco, N. et al. Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. Nat. Genet. 43, 883-886 (2011
90. O'Sullivan, J., Bitu, C. C., Daly, S. B., Urquhart, J. E., Barron, M. J., Bhaskar, S. S. et al. Whole-exome sequencing identifies FAM20A mutations as a cause of amelogenesis imperfecta and gingival hyperplasia syndrome. Am. J. Hum. Genet. 88, 616-620 (2011
91. Vissers, L. E., Lausch, E., Unger, S., Campos-Xavier, A. B., Gilissen, C., Rossi, A. et al. Chondrodysplasia and abnormal joint development associated with mutations in IMPAD1, encoding the Golgi-resident nucleotide phosphatase, gPAPP. Am. J. Hum. Genet. 88, 608-615 (2011
92. Gotz, A., Tyynismaa, H., Euro, L., Ellonen, P., Hyotylainen, T., Ojala, T. et al. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am. J. Hum. Genet. 88, 635-642 (2011
93. Tariq, M., Belmont, J. W., Lalani, S., Smolarek, T. & Ware, S. M. SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing. Genome Biol. 12, R91 (2011
94. Snape, K., Hanks, S., Ruark, E., Barros-Nunez, P., Elliott, A., Murray, A. et al. Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat. Genet. 43, 527-529 (2011
95. Theis, J. L., Sharpe, K. M., Matsumoto, M. E., Chai, H. S., Nair, A. A., Theis, J. D. et al. Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy. Circ. Cardiovasc. Genet. 4, 585-594 (2011
96. Takata, A., Kato, M., Nakamura, M., Yoshikawa, T., Kanba, S., Sano, A. et al. Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia. Genome Biol. 12, R92 (2011
97. Aldahmesh, M. A., Khan, A. O., Mohamed, J. Y., Alkuraya, H., Ahmed, H., Bobis, S. et al. Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. J. Med. Genet. 48, 597-601 (2011
98. Doi, H., Yoshida, K., Yasuda, T., Fukuda, M., Fukuda, Y., Morita, H. et al. Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomalrecessive spinocerebellar ataxia with psychomotor retardation. Am. J. Hum. Genet. 89, 320-327 (2011
99. Shaheen, R., Faqeih, E., Sunker, A., Morsy, H., Al-Sheddi, T., Shamseldin, H. E. et al. Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome. Am. J. Hum. Genet. 89, 328-333 (2011
100. Sanna-Cherchi, S., Burgess, K. E., Nees, S. N., Caridi, G., Weng, P. L., Dagnino, M. et al. Exome sequencing identified MYO1E and NEIL1 as candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome. Kidney Int. 80, 389-396 (2011
101. Barak, T., Kwan, K. Y., Louvi, A., Demirbilek, V., Saygi, S., Tuysuz, B. et al. Recessive LAMC3 mutations cause malformations of occipital cortical development. Nat. Genet. 43, 590-594 (2011
102. Galmiche, L., Serre, V., Beinat, M., Assouline, Z., Lebre, A. S., Chretien, D. et al. Exome sequencing identifies MRPL3 mutation in mitochondrial cardiomyopathy. Hum. Mutat. 32, 1225-1231 (2011
103. Ozgul, R. K., Siemiatkowska, A. M., Yucel, D., Myers, C. A., Collin, R. W., Zonneveld, M. N. et al. Exome sequencing and cis-regulatory mapping identify mutations in MAK, a gene encoding a regulator of ciliary length, as a cause of retinitis pigmentosa. Am. J. Hum. Genet. 89, 253-264 (2011
104. Hanson, D., Murray, P. G., O'Sullivan, J., Urquhart, J., Daly, S., Bhaskar, S. S. et al. Exome sequencing identifies CCDC8 mutations in 3-M syndrome, suggesting that CCDC8 contributes in a pathway with CUL7 and OBSL1 to control human growth. Am. J. Hum. Genet. 89, 148-153 (2011
105. Kalay, E., Yigit, G., Aslan, Y., Brown, K. E., Pohl, E., Bicknell, L. S. et al. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat. Genet. 43, 23-26 (2010
106. Bjursell, M. K., Blom, H. J., Cayuela, J. A., Engvall, M. L., Lesko, N., Balasubramaniam, S. et al. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am. J. Hum. Genet. 89, 507-515 (2011
107. Bredrup, C., Saunier, S., Oud, M. M., Fiskerstrand, T., Hoischen, A., Brackman, D. et al. Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19. Am. J. Hum. Genet. 89, 634-643 (2011
108. Aldahmesh, M. A., Mohamed, J. Y., Alkuraya, H. S., Verma, I. C., Puri, R. D., Alaiya, A. A. et al. Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am. J. Hum. Genet. 89, 745-750 (2011
109. Dauber, A., Nguyen, T. T., Sochett, E., Cole, D. E., Horst, R., Abrams, S. A. et al. Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J. Clin. Endocrinol. Metab. 97, E268-E274 (2011
110. Logan, C. V., Lucke, B., Pottinger, C., Abdelhamed, Z. A., Parry, D. A., Szymanska, K. et al. Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Nat. Genet. 43, 1189-1192 (2011
111. Albers, C. A., Cvejic, A., Favier, R., Bouwmans, E. E., Alessi, M. C., Bertone, P. et al. Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nat. Genet. 43, 735-737 (2011
112. de Greef, J. C., Wang, J., Balog, J., den Dunnen, J. T., Frants, R. R., Straasheijm, K. R. et al. Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am. J. Hum. Genet. 88, 796 (2011
113. Sergouniotis, P. I., Davidson, A. E., Mackay, D. S., Li, Z., Yang, X., Plagnol, V. et al. Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis. Am. J. Hum. Genet. 89, 183-190 (2011
114. Erlich, Y., Edvardson, S., Hodges, E., Zenvirt, S., Thekkat, P., Shaag, A. et al. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 21, 658-664 (2011
115. Clayton-Smith, J., O'Sullivan, J., Daly, S., Bhaskar, S., Day, R., Anderson, B. et al. Whole-exome-sequencing identifies mutations in histone acetyltransferase gene KAT6B in individuals with the Say-Barber-Biesecker variant of Ohdo syndrome. Am. J. Hum. Genet. 89, 675-681 (2011
116. Chen, W. J., Lin, Y., Xiong, Z. Q., Wei, W., Ni, W., Tan, G. H. et al. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia. Nat. Genet. 43, 1252-1255 (2011
117. Simpson, M. A., Irving, M. D., Asilmaz, E., Gray, M. J., Dafou, D., Elmslie, F. V. et al. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat. Genet. 43, 303-305 (2011
118. Isidor, B., Lindenbaum, P., Pichon, O., Bezieau, S., Dina, C., Jacquemont, S. et al. Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat. Genet. 43, 306-308 (2011
119. Hoischen, A., van Bon, B. W., Rodriguez-Santiago, B., Gilissen, C., Vissers, L. E., de Vries, P. et al. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Nat. Genet. 43, 729-731 (2011
120. Boyden, E. D., Campos-Xavier, A. B., Kalamajski, S., Cameron, T. L., Suarez, P., Tanackovich, G. et al. Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity. Am. J. Hum. Genet. 89, 767-772 (2011
121. Min, B. J., Kim, N., Chung, T., Kim, O. H., Nishimura, G., Chung, C. Y. et al. Wholeexome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type. Am. J. Hum. Genet. 89, 760-766 (2011
122. Noskova, L., Stranecky, V., Hartmannova, H., Pristoupilova, A., Baresova, V., Ivanek, R. et al. Mutations in DNAJC5, encoding cysteine-string protein alpha, cause autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. Am. J. Hum. Genet. 89, 241-252 (2011
123. Sirmaci, A., Spiliopoulos, M., Brancati, F., Powell, E., Duman, D., Abrams, A. et al. Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia. Am. J. Hum. Genet. 89, 289-294 (2011
124. Dickinson, R. E., Griffin, H., Bigley, V., Reynard, L. N., Hussain, R., Haniffa, M. et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 118, 2656-2658 (2011
125. Zimprich, A., Benet-Pages, A., Struhal, W., Graf, E., Eck, S. H., Offman, M. N. et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am. J. Hum. Genet. 89, 168-175 (2011
126. Vilarino-Guell, C., Wider, C., Ross, O. A., Dachsel, J. C., Kachergus, J. M., Lincoln, S. J. et al. VPS35 mutations in Parkinson disease. Am. J. Hum. Genet. 89, 162-167 (2011
127. Klein, C. J., Botuyan, M. V., Wu, Y., Ward, C. J., Nicholson, G. A., Hammans, S. et al. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat. Genet. 43, 595-600 (2011
128. Norton, N., Li, D., Rieder, M. J., Siegfried, J. D., Rampersaud, E., Zuchner, S. 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
129. Shi, Y., Li, Y., Zhang, D., Zhang, H., Lu, F., Liu, X. et al. Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet. 7, e1002084 (2011
130. Bowne, S. J., Humphries, M. M., Sullivan, L. S., Kenna, P. F., Tam, L. C., Kiang, A. S. et al. A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement. Eur. J. Hum. Genet. 19, 1074-1081 (2011
131. Weedon, M. N., Hastings, R., Caswell, R., Xie, W., Paszkiewicz, K., Antoniadi, T. et al. Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am. J. Hum. Genet. 89, 308-312 (2011
132. Zhou, C., Zang, D., Jin, Y., Wu, H., Liu, Z., Du, J. et al. Mutation in ribosomal protein L21 underlies hereditary hypotrichosis simplex. Hum. Mutat. 32, 710-714 (2011
133. Le Goff, C., Mahaut, C., Wang, L. W., Allali, S., Abhyankar, A., Jensen, S. et al. Mutations in the TGFbeta binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am. J. Hum. Genet. 89, 7-14 (2011
134. Le Goff, C., Mahaut, C., Abhyankar, A., Le Goff, W., Serre, V., Afenjar, A. et al. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat. Genet. 44, 85-88 (2011
135. Tsurusaki, Y., Osaka, H., Hamanoue, H., Shimbo, H., Tsuji, M., Doi, H. et al. Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing. J. Med. Genet. 48, 606-609 (2011
136. Shamseldin, H. E., Faden, M. A., Alashram, W. & Alkuraya, F. S. Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation. J. Med. Genet. 49, 16-20 (2012
137. Khan, K., Logan, C. V., McKibbin, M., Sheridan, E., Elcioglu, N. H., Yenice, O. et al. Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects. Hum. Mol. Genet. 21, 776-783 (2012
138. Zhang, Z., Xia, W., He, J., Ke, Y., Yue, H., Wang, C. et al. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am. J. Hum. Genet. 90, 125-132 (2012
139. Mitchell, K., O'Sullivan, J., Missero, C., Blair, E., Richardson, R., Anderson, B. et al. Exome sequence identifies RIPK4 as the bartsocas - Papas syndrome locus. Am. J. Hum. Genet. 90, 69-75 (2012
140. Walne, A., Dokal, A., Plagnol, V., Beswick, R., Kirwan, M., de la Fuente, J. et al. Exome sequencing identifies MPL as a causative gene in familial aplastic anemia. Haematologica 97, 524-528 (2012
141. Cabral, R. M., Kurban, M., Wajid, M., Shimomura, Y., Petukhova, L. & Christiano, A. M. Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome. Genomics 99, 202-208 (2012
142. Mayr, J. A., Haack, T. B., Graf, E., Zimmermann, F. A., Wieland, T., Haberberger, B. et al. Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome. Am. J. Hum. Genet. 90, 314-320 (2012
143. Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R. et al. Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 482, 98-102 (2012
144. Gibson, W. T., Hood, R. L., Zhan, S. H., Bulman, D. E., Fejes, A. P., Moore, R. et al. Mutations in EZH2 cause Weaver syndrome. Am. J. Hum. Genet. 90, 110-118 (2012
145. Simpson,M. A., Deshpande, C., Dafou, D., Vissers, L. E.,Woollard, W. J.,Holder, S. E. et al. De Novo mutations of the gene encoding the histone acetyltransferase KAT6B cause genitopatellar syndrome. Am. J. Hum. Genet. 90, 290-294 (2012
146. Campeau, P. M., Kim, J. C., Lu, J. T., Schwartzentruber, J. A., Abdul-Rahman, O. A., Schlaubitz, S. et al. Mutations in KAT6B, encoding a histone acetyltransferase, cause genitopatellar syndrome. Am. J. Hum. Genet. 90, 282-289 (2012
147. Bochukova, E., Schoenmakers, N., Agostini, M., Schoenmakers, E., Rajanayagam, O., Keogh, J. M. et al. A mutation in the thyroid hormone receptor alpha gene. N. Engl. J. Med. 366, 243-249 (2012
148. Hood, R. L., Lines, M. A., Nikkel, S. M., Schwartzentruber, J., Beaulieu, C., Nowaczyk, M. J. et al. Mutations in SRCAP, Encoding SNF2-Related CREBBP Activator Protein, Cause Floating-Harbor Syndrome. Am. J. Hum. Genet. 90, 308- (2012
149. Montenegro, G., Rebelo, A. P., Connell, J., Allison, R., Babalini, C., D'Aloia, M. et al. Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. J. Clin. Invest. 122, 538-544 (2012
150. Ostergaard, P., Simpson,M. A., Mendola, A., Vasudevan, P., Connell, F. C., van Impel, A. et al. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am. J. Hum. Genet. 90, 356-362 (2012
151. Jones, M. A., Ng, B. G., Bhide, S., Chin, E., Rhodenizer, D., He, P. et al. DDOST mutations identified by whole-exome sequencing are implicated in congenital disorders of glycosylation. Am. J. Hum. Genet. 90, 363-368 (2012
152. Lines, M. A.,Huang, L., Schwartzentruber, J., Douglas, S. L., Lynch, D. C., Beaulieu, C. et al. Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly. Am. J. Hum. Genet. 90, 369-377 (2012
153. Harms, M. B., Sommerville, R. B., Allred, P., Bell, S., Ma, D., Cooper, P. et al. Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy. Ann. Neurol. 71, 407-416 (2012
154. Audo, I., Bujakowska, K., Orhan, E., Poloschek, C. M., Defoort-Dhellemmes, S., Drumare, I. et al. Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness. Am. J. Hum. Genet. 90, 321-330 (2012
155. Hussain, M. S., Baig, S. M., Neumann, S., Nurnberg, G., Farooq, M., Ahmad, I. et al. A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function. Am. J. Hum. Genet. 90, 871-878 (2012
156. Kirwan, M., Walne, A. J., Plagnol, V., Velangi, M., Ho, A., Hossain, U. et al. Exome sequencing identifies autosomal-dominant SRP72 mutations associated with familial aplasia and myelodysplasia. Am. J. Hum. Genet. 90, 888-892 (2012
157. Lee, H., Graham, Jr. J. M., Rimoin, D. L., Lachman, R. S., Krejci, P., Tompson, S. W. et al. Exome sequencing identifies PDE4D mutations in acrodysostosis. Am. J. Hum. Genet. 90, 746-751 (2012
158. Lin, Z., Chen, Q., Lee, M., Cao, X., Zhang, J., Ma, D. et al. Exome sequencing reveals mutations in TRPV3 as a cause of Olmsted syndrome. Am. J. Hum. Genet. 90, 558-564 (2012
159. Fiskerstrand, T., Arshad, N., Haukanes, B. I., Tronstad, R. R., Pham, K. D., Johansson, S. et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. N. Engl. J. Med. 366, 1586-1595 (2012
160. Bernier, F. P., Caluseriu, O., Ng, S., Schwartzentruber, J., Buckingham, K. J., Innes, A. M. et al. Haploinsufficiency of SF3B4, a component of the pre-mrna spliceosomal complex, causes Nager syndrome. Am. J. Hum. Genet. 90, 925-933 (2012
161. Spiegel, R., Pines, O., Ta-Shma, A., Burak, E., Shaag, A., Halvardson, J. et al. Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. Am. J. Hum. Genet. 90, 518-523 (2012
162. Zankl, A., Duncan, E. L., Leo, P. J., Clark, G. R., Glazov, E. A., Addor, M. C. et al. Multicentric carpotarsal osteolysis is caused by mutations clustering in the amino-terminal transcriptional activation domain of MAFB. Am. J. Hum. Genet. 90, 494-501 (2012
163. Tsurusaki, Y., Okamoto, N., Ohashi, H., Kosho, T., Imai, Y., Hibi-Ko, Y. et al. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat. Genet. 44, 376-378 (2012
164. Srour, M., Schwartzentruber, J., Hamdan, F. F., Ospina, L. H., Patry, L., Labuda, D. et al. Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population. Am. J. Hum. Genet. 90, 693-700 (2012
165. Polvi, A., Linnankivi, T., Kivela, T., Herva, R., Keating, J. P., Makitie, O. et al. Mutations in CTC1, encoding the CTS telomere maintenance complex component 1, cause cerebroretinal microangiopathy with calcifications and cysts. Am. J. Hum. Genet. 90, 540-549 (2012
166. Schossig, A., Wolf, N. I., Fischer, C., Fischer, M., Stocker, G., Pabinger, S. et al. Mutations in ROGDI cause Kohlschutter-Tonz syndrome. Am. J. Hum. Genet. 90, 701-707 (2012
167. Santen, G. W., Aten, E., Sun, Y., Almomani, R., Gilissen, C., Nielsen, M. et al. Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin- Siris syndrome. Nat. Genet. 44, 379-380 (2012
168. Nakazawa, Y., Sasaki, K., Mitsutake, N., Matsuse, M., Shimada, M., Nardo, T. et al. Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair. Nat. Genet. 44, 586-592 (2012
169. Austin, E. D., Ma, L., Leduc, C., Berman Rosenzweig, E., Borczuk, A., Phillips, J. A. et al. Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. Circ. Cardiovasc. Genet. 44, 586-592 (2012)