Massively parallel sequencing: the next big thing in genetic medicine.
Massively parallel sequencing has reduced the cost and increased the throughput of genomic sequencing by more than three orders of magnitude, and it seems likely that costs will fall and throughput improve even more in the next few years. Clinical use of massively parallel sequencing will provide a way to identify the cause of many diseases of unknown etiology through simultaneous screening of thousands of loci for pathogenic mutations and by sequencing biological specimens for the genomic signatures of novel infectious agents. In addition to providing these entirely new diagnostic capabilities, massively parallel sequencing may also replace arrays and Sanger sequencing in clinical applications where they are currently being used. Routine clinical use of massively parallel sequencing will require higher accuracy, better ways to select genomic subsets of interest, and improvements in the functionality, speed, and ease of use of data analysis software. In addition, substantial enhancements in laboratory computer infrastructure, data storage, and data transfer capacity will be needed to handle the extremely large data sets produced. Clinicians and laboratory personnel will require training to use the sequence data effectively, and appropriate methods will need to be developed to deal with the incidental discovery of pathogenic mutations and variants of uncertain clinical significance. Massively parallel sequencing has the potential to transform the practice of medical genetics and related fields, but the vast amount of personal genomic data produced will increase the responsibility of geneticists to ensure that the information obtained is used in a medically and socially responsible manner.
Tucker
Tracy
T
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. tbtucker@interchange.ubc.ca
Marra
Marco
M
Friedman
Jan M
JM
D001483:Base Sequence; D005826:Genetics, Medical; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000295:instrumentation / Q000379:methods
Trends Genet. 2008 Mar;24(3):133-41
18262675
Nat Methods. 2009 Jul;6(7):507-10
19543287
Curr Opin Genet Dev. 2007 Jun;17(3):182-92
17467974
Circulation. 2007 Nov 27;116(22):2563-70
17989110
Pharmacogenet Genomics. 2006 Feb;16(2):101-10
16424822
Br J Cancer. 2009 Feb 24;100(4):571-7
19223907
Cell. 2007 May 18;129(4):823-37
17512414
J Chromatogr. 1990 Sep 7;516(1):61-7
2286629
N Engl J Med. 2008 Mar 6;358(10):991-8
18256387
Anal Biochem. 1996 Nov 1;242(1):84-9
8923969
Genet Med. 2008 Apr;10(4):294-300
18414213
Curr Opin Gastroenterol. 2008 Jan;24(1):4-10
18043225
BMC Genomics. 2009 Mar 19;10:116
19298667
J Mol Diagn. 2009 Jan;11(1):25-34
19074592
Nat Methods. 2007 Nov;4(11):931-6
17934468
Anal Bioanal Chem. 2009 Jan;393(1):171-5
18958448
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3960-4
12651960
Nat Genet. 2007 Dec;39(12):1522-7
17982454
Genes Chromosomes Cancer. 2009 Jan;48(1):55-68
18828157
Nat Methods. 2007 Nov;4(11):903-5
17934467
Nature. 1973 Jun 1;243(5405):290-3
4126434
Hum Mol Genet. 2005 Jan 1;14(1):95-102
15537666
Genome Res. 2008 Nov;18(11):1844-50
18849522
Nature. 2007 Aug 2;448(7153):553-60
17603471
Nucleic Acids Res. 2005 Apr 28;33(8):e71
15860768
Nat Biotechnol. 2008 Oct;26(10):1135-45
18846087
Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9296-301
18599465
PLoS Biol. 2007 Sep 4;5(10):e254
17803354
Hum Mol Genet. 1995 Dec;4(12):2379-85
8634713
PLoS Genet. 2008 Aug 01;4(8):e1000139
18670626
Cytogenet Genome Res. 2008;123(1-4):17-26
19287135
Nat Genet. 2009 May;41(5):535-43
19377476
Blood. 2005 Jan 15;105(2):645-9
15358623
Cell Host Microbe. 2008 Jun 12;3(6):417-27
18541218
Nat Biotechnol. 2008 Mar;26(3):256
18327223
Cancer Res. 2007 Sep 15;67(18):8511-8
17875690
Genome Res. 2008 Jul;18(7):1143-9
18326688
Genes Chromosomes Cancer. 2009 Jan;48(1):39-54
18828156
Nature. 2008 May 1;453(7191):56-64
18451855
Genome Res. 2008 May;18(5):763-70
18212088
Nucleic Acids Res. 2006 Feb 09;34(3):e22
16473845
Genome Res. 2009 Sep;19(9):1606-15
19525355
Nat Biotechnol. 2009 Feb;27(2):182-9
19182786
Int J Cancer. 1976 Jan 15;17(1):47-56
946170
Nature. 2008 Nov 6;456(7218):60-5
18987735
Proc Natl Acad Sci U S A. 1977 Feb;74(2):560-4
265521
Hum Mol Genet. 2007 Dec 1;16(23):2783-94
17666407
Nature. 2008 Nov 6;456(7218):53-9
18987734
Am J Hum Genet. 2008 Dec;83(6):663-74
18992858
Science. 2008 Apr 4;320(5872):106-9
18388294
JAMA. 2008 Dec 17;300(23):2715
19088343
Nat Biotechnol. 2008 Oct;26(10):1146-53
18846088
Virol J. 2008 Dec 22;5:159
19102772
Nature. 2007 Oct 18;449(7164):804-10
17943116
Genome Res. 2008 Nov;18(11):1851-8
18714091
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
271968
Am J Med Genet C Semin Med Genet. 2007 Nov 15;145C(4):335-45
17910076
BMC Bioinformatics. 2009 Feb 24;10:69
19239711
JAMA. 1998 Apr 15;279(15):1200-5
9555760
Hum Mutat. 2009 May;30(5):852-6
19260058
Science. 2007 Oct 19;318(5849):420-6
17901297
J Mol Diagn. 2008 Nov;10(6):484-92
18832462
Nature. 2008 Nov 6;456(7218):66-72
18987736
Nat Med. 2006 Jul;12(7):852-5
16799556
Am J Hum Genet. 2000 Aug;67(2):476-82
10856193
Nat Methods. 2008 Feb;5(2):179-81
18193056
Thromb Haemost. 2006 Feb;95(2):205-11
16493479
Science. 2005 Sep 9;309(5741):1728-32
16081699
Genet Med. 2007 Oct;9(10):665-74
18073579
PLoS One. 2008;3(12):e4012
19107202
PLoS Genet. 2009 Feb;5(2):e1000373
19197363
Science. 2009 Jan 2;323(5910):133-8
19023044
Nat Protoc. 2009;4(6):960-74
19478811
Am J Med Genet B Neuropsychiatr Genet. 2009 Sep 5;150B(6):808-16
19086053