title: Gene copy-number alterations: a cost-benefit analysis.
abstract: Changes in DNA copy number, whether confined to specific genes or affecting whole chromosomes, have been identified as causes of diseases and developmental abnormalities and as sources of adaptive potential. Here, we discuss the costs and benefits of DNA copy-number alterations. Changes in DNA copy number are largely detrimental. Amplifications or deletions of specific genes can elicit discrete defects. Large-scale changes in DNA copy number can also cause detrimental phenotypes that are due to the cumulative effects of copy-number alterations of many genes simultaneously. On the other hand, studies in microorganisms show that DNA copy-number alterations can be beneficial, increasing survival under selective pressure. As DNA copy-number alterations underlie many human diseases, we will end with a discussion of gene copy-number changes as therapeutic targets.
authors: David H. Koch Institute for Integrative Cancer Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 76-561, 500 Main Street, Cambridge, MA 02139, USA.
authors: Yun-Chi
authors: YC
authors: Tang
authors: Angelika
authors: A
authors: Amon
mesh_terms: D000782:Aneuploidy; D000818:Animals; D056915:DNA Copy Number Variations; D018628:Gene Dosage; D015870:Gene Expression; D056084:Genetic Fitness; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D010944:Plants / Q000235:genetics; D011123:Polyploidy; D015003:Yeasts / Q000235:genetics / Q000502:physiology
references: Chromosoma. 2007 Dec;116(6):497-505
references: 17639451
references: Science. 1994 Dec 23;266(5193):1999-2002
references: 17836517
references: Genome Res. 2004 Jul;14(7):1258-67
references: 15231742
references: Mol Cell. 2011 Sep 2;43(5):751-63
references: 21884976
references: Trends Biochem Sci. 2004 Jan;29(1):18-24
references: 14729328
references: Dev Cell. 2002 Sep;3(3):351-65
references: 12361599
references: Nature. 1981 Jul 16;292(5820):269-71
references: 7019717
references: Genes Dev. 2011 Jul 1;25(13):1384-98
references: 21724831
references: Am J Hum Genet. 2007 Jun;80(6):1037-54
references: 17503323
references: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12644-9
references: 22802626
references: Cell. 2011 Feb 18;144(4):499-512
references: 21315436
references: Science. 1968 Apr 19;160(3825):272-80
references: 4867987
references: Cell. 2011 Jan 7;144(1):67-78
references: 21215370
references: Nat Genet. 2004 Nov;36(11):1159-61
references: 15475955
references: Bioessays. 2002 Feb;24(2):175-84
references: 11835282
references: Cell. 2009 Jul 10;138(1):198-208
references: 19596244
references: Blood. 2002 Jul 1;100(1):29-35
references: 12070004
references: Science. 1987 Jan 9;235(4785):177-82
references: 3798106
references: Science. 2003 Oct 31;302(5646):841
references: 14593171
references: PLoS Genet. 2010 Apr 22;6(4):e1000919
references: 20421994
references: Cell. 1997 Mar 7;88(5):593-602
references: 9054499
references: Cell. 1981 Nov;27(1 Pt 2):193-201
references: 6799210
references: Genetika. 1986 Mar;22(3):434-41
references: 3957031
references: Yeast. 2006 Oct 15;23(13):937-50
references: 17072887
references: Genes Dev. 1998 Aug 1;12(15):2434-42
references: 9694807
references: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14188-93
references: 20663956
references: Cancer Cell. 2007 Jan;11(1):25-36
references: 17189716
references: EMBO Rep. 2012 Jun 01;13(6):501-14
references: 22565320
references: Trends Neurosci. 1998 Jul;21(7):282-6
references: 9683317
references: Annu Rev Genet. 1984;18:69-97
references: 6241455
references: Annu Rev Genomics Hum Genet. 2009;10:451-81
references: 19715442
references: N Engl J Med. 2005 Jun 16;352(24):2487-98
references: 15958804
references: Science. 2006 Jul 21;313(5785):367-70
references: 16857942
references: Genes Dev. 1998 Dec 15;12(24):3821-30
references: 9869636
references: Nat Genet. 2007 Jul;39(7 Suppl):S43-7
references: 17597781
references: J Neurosci. 2005 Mar 2;25(9):2176-80
references: 15745943
references: Cell. 2010 Oct 1;143(1):71-83
references: 20850176
references: Lancet. 2002 Mar 23;359(9311):1019-25
references: 11937181
references: EMBO Rep. 2012 Jun 01;13(6):515-27
references: 22614003
references: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18551-6
references: 20937885
references: Genome Biol. 2006;7(11):R107
references: 17105650
references: Proc Natl Acad Sci U S A. 1974 Aug;71(8):3082-6
references: 4606151
references: Cell. 2012 Mar 16;148(6):1223-41
references: 22424231
references: Nat Rev Genet. 2012 Jan 24;13(3):189-203
references: 22269907
references: Nat Rev Genet. 2006 Feb;7(2):85-97
references: 16418744
references: Nature. 2010 Nov 11;468(7321):321-5
references: 20962780
references: Proc Natl Acad Sci U S A. 1968 Jun;60(2):553-60
references: 5248812
references: Chromosoma. 2011 Jun;120(3):213-25
references: 21505791
references: Genome Biol. 2010;11(8):216
references: 20804581
references: Hum Genet. 2011 Aug;130(2):237-45
references: 21614513
references: Mol Biol Cell. 2008 Jan;19(1):352-67
references: 17959824
references: Science. 2008 Oct 31;322(5902):703-9
references: 18974345
references: Mol Cell Biol. 1986 Jun;6(6):2213-22
references: 3537715
references: Science. 2004 Jul 23;305(5683):525-8
references: 15273396
references: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16144-9
references: 12446845
references: Mol Syst Biol. 2012;8:608
references: 22968442
references: Genome Res. 2010 Nov;20(11):1469-81
references: 20841430
references: Cytogenet Cell Genet. 1975;14(1):42-62
references: 1132247
references: J Clin Invest. 2012 Sep;122(9):3307-15
references: 22863619
references: Cancer Res. 2004 Oct 1;64(19):6941-9
references: 15466185
references: Annu Rev Cell Dev Biol. 2008;24:475-99
references: 18598214
references: Nature. 2010 Sep 9;467(7312):179-84
references: 20829789
references: Am J Hum Genet. 2009 Feb;84(2):148-61
references: 19166990
references: Cell. 2008 Nov 28;135(5):879-93
references: 19041751
references: Cell. 2012 Aug 17;150(4):842-54
references: 22901813
references: Cell. 2011 Jan 7;144(1):27-40
references: 21215367
references: Science. 2011 Sep 30;333(6051):1895-8
references: 21960636
references: J Comp Neurol. 2008 Apr 20;507(6):1944-51
references: 18273885
references: Mol Cell Biol. 1990 Oct;10(10):5286-94
references: 2204811
references: Annu Rev Genet. 2011;45:203-26
references: 21854229
references: Cell. 2000 Jun 9;101(6):635-45
references: 10892650
references: Am J Med Genet B Neuropsychiatr Genet. 2007 Apr 5;144B(3):259-65
references: 17357145
references: Nature. 2010 Oct 7;467(7316):707-10
references: 20861837
references: Science. 2007 Feb 9;315(5813):848-53
references: 17289997
references: PLoS Genet. 2008 Dec;4(12):e1000303
references: 19079573
references: Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13361-6
references: 11698687
references: Cell Mol Life Sci. 2006 Nov;63(22):2626-41
references: 16952055
references: Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):680-5
references: 21187411
references: Nat Genet. 2004 Jul;36(7):744-9
references: 15208629
references: Science. 2004 Jun 4;304(5676):1497-500
references: 15118125
references: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4500-5
references: 15755806
references: PLoS Genet. 2012;8(5):e1002719
references: 22615582
references: Genetics. 1981 Mar-Apr;97(3-4):639-66
references: 7297851
references: Nat Genet. 2006 Jan;38(1):47-53
references: 16341221
references: PLoS Genet. 2008 Oct;4(10):e1000226
references: 18927630
references: Mol Cell Biol. 2006 Aug;26(16):6223-38
references: 16880531
references: Mol Biol Cell. 2000 Dec;11(12):4241-57
references: 11102521
references: Nat Cell Biol. 2009 Apr;11(4):468-76
references: 19270693
references: Nat Genet. 2009 Apr;41(4):424-9
references: 19270705
references: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11296-301
references: 16055552
references: Nat Genet. 2008 Dec;40(12):1499-504
references: 19029899
references: Mol Biol Evol. 1998 Aug;15(8):931-42
references: 9718721
references: Development. 2012 Feb;139(3):455-64
references: 22223677
references: Nat Genet. 2004 Sep;36(9):949-51
references: 15286789
references: J Exp Med. 2010 Nov 22;207(12):2581-94
references: 21059853
references: Nature. 2006 Oct 5;443(7111):541-7
references: 17024086
references: Trends Mol Med. 2010 Nov;16(11):528-36
references: 20932800
references: Cancer Res. 1998 Jul 1;58(13):2825-31
references: 9661897
references: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6273-8
references: 11353870
references: J Cell Biol. 2010 Feb 8;188(3):369-81
references: 20123995
references: Genome Res. 2004 Jul;14(7):1268-74
references: 15231743
references: Nature. 2012 Jan 18;482(7383):53-8
references: 22258507
references: Genetics. 2008 Jun;179(2):737-46
references: 18558649
references: Science. 2007 Aug 17;317(5840):916-24
references: 17702937
references: Nat Rev Genet. 2011 May;12(5):363-76
references: 21358748
references: Yeast. 2007 Nov;24(11):961-76
references: 17605132
references: Trends Genet. 2005 Mar;21(3):149-62
references: 15734574
references: J Cell Biol. 2009 Jun 15;185(6):983-94
references: 19528295
references: Science. 2011 Aug 19;333(6045):1026-30
references: 21852501
references: PLoS Genet. 2011 Jun;7(6):e1002131
references: 21731501
references: Mol Cell Biol. 1989 Apr;9(4):1488-97
references: 2657397
references: Cell. 2009 May 15;137(4):609-22
references: 19450511
references: J Cell Biol. 2008 Feb 25;180(4):665-72
references: 18283116
references: Nat Rev Cancer. 2006 Dec;6(12):909-23
references: 17128209