search for




 

Exome Sequencing in Mendelian Disorders
J Genet Med 2010;7:119-124
Published online December 31, 2010;  https://doi.org/10.5734/JGM.2010.7.2.119
© 2010 Korean Society of Medical Genetics.

Jong-Keuk Lee

Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Abstract
More than 7,000 rare Mendelian diseases have been reported, but less than half of all rare monogenic disorders has been discovered. In addition, the majority of mutations that are known to cause Mendelian disorders are located in protein-coding regions. Therefore, exome sequencing is an efficient strategy to selectively sequence the coding regions of the human genome to identify novel genes associated with rare genetic disorders. The "exome" represents all of the exons in the human genome, constituting about 1.5% of the human genome. Exome sequencing is carried out by targeted capture and intense parallel sequencing. After the first report of successful exome sequencing for the identification of causal genes and mutations in Freeman Sheldon syndrome, exome sequencing has become a standard approach to identify genes in rare Mendelian disorders. Exome sequencing is also used to search the causal genes and variants in complex diseases. The successful use of exome sequencing in Mendelian disorders and complex diseases will facilitate the development of personalized genomic medicine.
Keywords : Mendelian disorders;Exome sequencing;Next-generation sequencing (NGS);
References
  1. Kaiser J. Affordable 'exomes' fill gaps in a catalog of rare diseases. Science 2010;330:903.
    Pubmed CrossRef
  2. 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 USA 2009;106:19096-19101.
    Pubmed KoreaMed CrossRef
  3. 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.
    Pubmed KoreaMed CrossRef
  4. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 2009;42:30-35.
    Pubmed KoreaMed CrossRef
  5. 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. Nat Genet 2010;42:790-793.
    Pubmed KoreaMed CrossRef
  6. Gilissen C, Arts HH, Hoischen A, Spruijt L, Mans DA, Arts P, et al. Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome. Am J Hum Genet 2010;87:418-423.
    Pubmed KoreaMed CrossRef
  7. Krawitz PM, Schweiger MR, 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 2010;42:827-829.
    Pubmed CrossRef
  8. Hoischen A, van Bon BWM, Gilissen C, Arts P, van Lier B, Steehouwer M, et al. De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. Nat Genet 2010;42:483-485.
    Pubmed CrossRef
  9. Bilguvar K, Ozt?rk 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.
    Pubmed KoreaMed CrossRef
  10. Johnston JJ, Teer JK, Cherukuri PF, Hansen NF, Loftus SK, et al. NIH Intramural sequencing center. Mssively 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 2010;86:743-748.
    Pubmed KoreaMed CrossRef
  11. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, et al. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet 2010;42:840-850.
    Pubmed KoreaMed CrossRef
  12. Lupski JR, Reid JG, Gonzaga-Jauregui C, Deiros DR, Chen DCY, Nazareth L, et al. Whole-genome sequencing in a patient with charcot-marie-tooth neuropathy. N Engl J Med 2010;362:1181-1191.
    Pubmed KoreaMed CrossRef
  13. Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 2010;363:2220-2227.
    Pubmed KoreaMed CrossRef


June 2017, 14 (1)