Genome Architecture and Its Roles in Human Copy Number Variation

다국어 초록 (Multilingual Abstract)

Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations(CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases.
Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. Inthis review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats,including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNArecombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errorsand consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects thehigh-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genomearchitecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

참고문헌 (Reference)

1 Janoušek V, "The role of retrotransposons in gene family expansions: insights from the mouse Abp gene family" 13 : 107-, 2013

2 Conrad DF, "The population genetics of structural variation" 39 (39): S30-S36, 2007

3 Smit AF, "The origin of interspersed repeats in the human genome" 6 : 743-748, 1996

4 Lieber MR, "The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway" 79 : 181-211, 2010

5 Cordaux R, "The impact of retrotransposons on human genome evolution" 10 : 691-703, 2009

6 Lu J, "The distribution of genomic variations in human iPSCs is related to replication-timing reorganization during reprogramming" 7 : 70-78, 2014

7 Dangel AW, "The dichotomous size variation of human complement C4 genes is mediated by a novel family of endogenous retroviruses, which also establishes species-specific genomic patterns among Old World primates" 40 : 425-436, 1994

8 Lee C, "The clinical context of copy number variation in the human genome" 12 : e8-, 2010

9 Zhang F, "The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans" 41 : 849-853, 2009

10 Paylor R, "Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome" 103 : 7729-7734, 2006

11 Carvalho CM, "Structural variation of the human genome: mechanisms, assays, and role in male infertility" 57 : 3-16, 2011

12 Stankiewicz P, "Structural variation in the human genome and its role in disease" 61 : 437-455, 2010

13 Feuk L, "Structural variation in the human genome" 7 : 85-97, 2006

14 Watanabe Y, "Spatiotemporal regulation of DNA replication in the human genome and its association with genomic instability and disease" 17 : 222-233, 2010

15 Yao NY, "SnapShot: the replisome" 141 : 1088-, 2010

16 de Smith AJ, "Small deletion variants have stable breakpoints commonly associated with alu elements" 3 : e3104-, 2008

17 Olson MV, "Sequencing the chimpanzee genome: insights into human evolution and disease" 4 : 20-28, 2003

18 Sharp AJ, "Segmental duplications and copy-number variation in the human genome" 77 : 78-88, 2005

19 Yagi H, "Role of TBX1 in human del22q11.2syndrome" 362 : 1366-1373, 2003

20 Aran D, "Replication timing-related and gene body-specific methylation of active human genes" 20 : 670-680, 2011

21 Woodfine K, "Replication timing of the human genome" 13 : 191-202, 2004

22 Bechhoefer J, "Replication timing and its emergence from stochastic processes" 28 : 374-381, 2012

23 Grinberg-Rashi H, "Replication timing aberrations and aneuploidy in peripheral blood lymphocytes of breast cancer patients" 12 : 668-674, 2010

24 Shuvarikov A, "Recurrent HERV-H-mediated 3q13.2-q13.31deletions cause a syndrome of hypotonia and motor, language, and cognitive delays" 34 : 1415-1423, 2013

25 Bailey JA, "Recent segmental duplications in the human genome" 297 : 1003-1007, 2002

26 Eichler EE, "Recent duplication, domain accretion and the dynamic mutation of the human genome" 17 : 661-669, 2001

27 Bailey JA, "Primate segmental duplications: crucibles of evolution, diversity and disease" 7 : 552-564, 2006

28 Desprat R, "Predictable dynamic program of timing of DNA replication in human cells" 19 : 2288-2299, 2009

29 Itsara A, "Population analysis of large copy number variants and hotspots of human genetic disease" 84 : 148-161, 2009

30 Conrad DF, "Origins and functional impact of copy number variation in the human genome" 464 : 704-712, 2010

31 Dittwald P, "NAHR-mediated copy-number variants in a clinical population:mechanistic insights into both genomic disorders and Mendelizing traits" 23 : 1395-1409, 2013

32 Raghuraman MK, "Molecular analysis of the replication program in unicellular model organisms" 18 : 19-34, 2010

33 Chen X, "Molecular analysis of a deletion hotspot in the NRXN1region reveals the involvement of short inverted repeats in deletion CNVs" 92 : 375-386, 2013

34 Zhang F, "Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability" 86 : 892-903, 2010

35 Gu W, "Mechanisms for human genomic rearrangements" 1 : 4-, 2008

36 Mills RE, "Mapping copy number variation by population-scale genome sequencing" 470 : 59-65, 2011

37 Koh E, "Male infertility and genome disease -mechanism of microdeletions in azoospermia factor (AZF) regions and genomic diversification of the Y chromosome through analysis of human endogenous retrovirus" 85 : 445-, 2010

38 Sebat J, "Large-scale copy number polymorphism in the human genome" 305 : 525-528, 2004

39 Belancio VP, "LINE dancing in the human genome: transposable elements and disease" 1 : 97-, 2009

40 Yang N, "L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells" 13 : 763-771, 2006

41 Dittwald P, "Inverted low-copy repeats and genome instability: a genome-wide analysis" 34 : 210-220, 2013

42 Carvalho CM, "Inverted genomic segments and complex triplication rearrangements are mediated by inverted repeats in the human genome" 43 : 1074-1081, 2011

43 Smit AF, "Interspersed repeats and other mementos of transposable elements in mammalian genomes" 9 : 657-663, 1999

44 Lander ES, "Initial sequencing and analysis of the human genome" 409 : 860-921, 2001

45 Zhou W, "Increased genome instability in human DNA segments with self-chains:homology-induced structural variations via replicative mechanisms" 22 : 2642-2651, 2013

46 Fu W, "Identification of copy number variation hotspots in human populations" 87 : 494-504, 2010

47 Matejas V, "Identification of Alu elements mediating a partial PMP22 deletion" 7 : 119-126, 2006

48 Schwartz S, "Human-mouse alignments with BLASTZ" 13 : 103-107, 2003

49 Stamatoyannopoulos JA, "Human mutation rate associated with DNA replication timing" 41 : 393-395, 2009

50 Nelson PN, "Human endogenous retroviruses: transposable elements with potential?" 138 : 1-9, 2004

51 Higashimoto K, "Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome" 21 : 1316-1319, 2013

52 Arruda JT, "Homologous recombination between HERVs causes duplications in the AZFa region of men accidentally exposed to cesium-137 in Goiania" 7 : 1063-1069, 2008

53 Kazazian HH Jr, "Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man" 332 : 164-166, 1988

54 Hiratani I, "Global reorganization of replication domains during embryonic stem cell differentiation" 6 : e245-, 2008

55 Farkash-Amar S, "Global organization of replication time zones of the mouse genome" 18 : 1562-1570, 2008

56 Lupski JR, "Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits" 14 : 417-422, 1998

57 Farkash-Amar S, "Genome-wide analysis of the replication program in mammals" 18 : 115-125, 2010

58 Ryba T, "Genome-scale analysis of replication timing: from bench to bioinformatics" 6 : 870-895, 2011

59 Alkan C, "Genome structural variation discovery and genotyping" 12 : 363-376, 2011

60 Sasaki M, "Genome destabilization by homologous recombination in the germ line" 11 : 182-195, 2010

61 Stankiewicz P, "Genome architecture, rearrangements and genomic disorders" 18 : 74-82, 2002

62 Warren WC, "Genome analysis of the platypus reveals unique signatures of evolution" 453 : 175-183, 2008

63 Liu P, "Frequency of nonallelic homologous recombination is correlated with length of homology: evidence that ectopic synapsis precedes ectopic crossing-over" 89 : 580-588, 2011

64 Kriegs JO, "Evolutionary history of 7SL RNA-derived SINEs in Supraprimates" 23 : 158-161, 2007

65 Ryba T, "Evolutionarily conserved replication timing profiles predict long-range chromatin interactions and distinguish closely related cell types" 20 : 761-770, 2010

66 Kent WJ, "Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes" 100 : 11484-11489, 2003

67 Bosch E, "Duplications of the AZFa region of the human Y chromosome are mediated by homologous recombination between HERVs and are compatible with male fertility" 12 : 341-347, 2003

68 Cardoso-Moreira M, "Drosophila duplication hotspots are associated with late-replicating regions of the genome" 7 : e1002340-, 2011

69 Miki Y, "Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer" 52 : 643-645, 1992

70 Koren A, "Differential relationship of DNA replication timing to different forms of human mutation and variation" 91 : 1033-1040, 2012

71 Iafrate AJ, "Detection of large-scale variation in the human genome" 36 : 949-951, 2004

72 Donley N, "DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability" 23 : 80-89, 2013

73 Rhind N, "DNA replication timing" 5 : a010132-, 2013

74 Lupski JR, "DNA duplication associated with Charcot-Marie-Tooth disease type 1A" 66 : 219-232, 1991

75 Peng Z, "Correlation between frequency of non-allelic homologous recombination and homology properties: evidence from homology-mediated CNV mutations in the human genome" 2014

76 MacAlpine DM, "Coordination of replication and transcription along a Drosophila chromosome" 18 : 3094-3105, 2004

77 Breckpot J, "Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1" 158A : 574-580, 2012

78 Kamp C, "Complex human Y-chromosomal HERV sequence structure in the AZFa region:new candidate genes for the control of early germ cell proliferation?" 9 (9): C044-, 2001

79 Chen JM, "Complex gene rearrangements caused by serial replication slippage" 56 : 125-134, 2005

80 McDonald-McGinn DM, "Chromosome 22q11.2deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome)" 90 : 1-18, 2011

81 Moore JK, "Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae" 16 : 2164-2173, 1996

82 Litmanovitch T, "Asynchronous replication of homologous alpha-satellite DNA loci in man is associated with nondisjunction" 81 : 26-35, 1998

83 Hansen RS, "Association of fragile X syndrome with delayed replication of the FMR1 gene" 73 : 1403-1409, 1993

84 Jiang Z, "Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution" 39 : 1361-1368, 2007

85 Kim PM, "Analysis of copy number variants and segmental duplications in the human genome: Evidence for a change in the process of formation in recent evolutionary history" 18 : 1865-1874, 2008

86 Erez A, "Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder" 10 : 363-369, 2009

87 Batzer MA, "Alu repeats and human genomic diversity" 3 : 370-379, 2002

88 Fritz A, "Alterations in replication timing of cancer-related genes in malignant human breast cancer cells" 114 : 1074-1083, 2013

89 Hermetz KE, "A recurrent translocation is mediated by homologous recombination between HERV-H elements" 5 : 6-, 2012

90 Hastings PJ, "A microhomology-mediated break-induced replication model for the origin of human copy number variation" 5 : e1000327-, 2009

91 Marques-Bonet T, "A burst of segmental duplications in the genome of the African great ape ancestor" 457 : 877-881, 2009