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De novo rates and selection of large copy number variation
Open accessAbstract
While copy number variation (CNV) is an active area of research, de novo mutation rates within human populations are not well characterized. By focusing on large (>100 kbp) events, we estimate the rate of de novo CNV formation in humans by analyzing 4394 transmissions from human pedigrees with and without neurocognitive disease. We show that a significant limitation in directly measuring genome-wide CNV mutation is accessing DNA derived from primary tissues as opposed to cell lines. We conservatively estimated the genome-wide CNV mutation rate using single nucleotide polymorphism (SNP) microarrays to analyze whole-blood derived DNA from asthmatic trios, a collection in which we observed no elevation in the prevalence of large CNVs. At a resolution of ∼30 kb, nine de novo CNVs were observed from 772 transmissions, corresponding to a mutation rate of μ = 1.2 × 10−2 CNVs per genome per transmission (μ = 6.5 × 10−3 for CNVs >500 kb). Combined with previous estimates of CNV prevalence and assuming a model of mutation-selection balance, we estimate significant purifying selection for large (>500 kb) events at the genome-wide level to be s = 0.16. Supporting this, we identify de novo CNVs in 717 multiplex autism pedigrees from the AGRE collection and observe a fourfold enrichment (P = 1.4 × 10−3) for de novo CNVs in cases of multiplex autism versus unaffected siblings, suggesting that many de novo CNV mutations contribute a subtle, but significant risk for autism. We observe no parental bias in the origin or transmission of CNVs among any of the cohorts studied.
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“The over-representation of large de novo CNVs in ASD has been replicated in studies ranging from 60 to 393 simplex trios (Itsara et al., 2010; Marshall et al., 2008; Pinto et al., 2010)”
From Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism (2011) · cites this paper as Itsara et al., 2010
In the citing paper
“Subsequent studies in larger samples have confirmed a high (5–10%) rate of de novo CNVs in ASD and further elucidated the extent of genetic heterogeneity in ASD (Itsara et al., 2010; Levy et al., 2011; Marshall et al., 2008; Pinto et al., 2010; Sanders et al., 2011).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Itsara et al., 2010
In the citing paper
“CNVs >10 Kb in size occur at a rate of ~0.01–0.02 per generation.(Itsara et al., 2010; Levy et al., 2011; Marshall et al., 2008; Sanders et al., 2011; Sebat et al., 2007).”
From CNVs: Harbingers of a Rare Variant Revolution in Psychiatric Genetics (2012) · cites this paper as Itsara et al., 2010
In the citing paper
“This rate is consistent with estimates from previous studies ranging from 0.5% to 3% (Conrad et al., 2010, Itsara et al., 2010, Levy et al., 2011, Sebat et al., 2007 and Xu et al., 2008).”
From High frequencies of de novo CNVs in bipolar disorder and schizophrenia (2011) · cites this paper as Itsara et al., 2010
In the citing paper
“Notably, the median size of SD and non-SD-mediated de novo CNVs was 722 kb and 67 kb respectively, consistent with previous studies that have found differences in CNV size related to the underlying mutational mechanism (Itsara et al., 2010 and Stefansson et al., 2008).”
From High frequencies of de novo CNVs in bipolar disorder and schizophrenia (2011) · cites this paper as Itsara et al., 2010
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Cites
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795
Initial sequence of the chimpanzee genome and comparison with the human genome
The Chimpanzee Sequencing and Analysis Consortium (2005) · Nature · doi:10.1038/nature04072 · Cited by 2,459
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449
Origins and functional impact of copy number variation in the human genome
The Wellcome Trust Case Control Consortium, Conrad, D. F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T. D., Barnes, C., et al. (2010) · Nature · doi:10.1038/nature08516 · Cited by 1,970
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800
Self-citationLarge recurrent microdeletions associated with schizophrenia.
GROUP, Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P. H., Ingason, A., Steinberg, S., Fossdal, R., Sigurdsson, E., Sigmundsson, T., et al. (2008) · Nature · doi:10.1038/nature07229 · Cited by 1,745
Association between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa075974 · Cited by 1,666
Rare chromosomal deletions and duplications increase risk of schizophrenia
The International Schizophrenia Consortium (2008) · Nature · doi:10.1038/nature07239 · Cited by 1,475
Mapping autism risk loci using genetic linkage and chromosomal rearrangements
The Autism Genome Project Consortium (2007) · Nature Genetics · doi:10.1038/ng1985 · Cited by 1,402
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Items 101–200 of 328
Celestino-Soper, P. B. S., Skinner, C. D., Schroer, R. J., Eng, P. A., Shenai, J. P., Nowaczyk, M. M. J., Terespolsky, D., Cushing, D., Patel, G. S., Immken, L. L., et al. (2012) · Molecular Cytogenetics · doi:10.1186/1755-8166-5-17 · Cited by 51
Copy Number Variants in Alzheimer’s Disease
Cuccaro, D., Marco, E. V. D., Cittadella, R., & Cavallaro, S. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160469 · Cited by 51
“CNVs can be familial or de novo, with de novo mutation rate being higher than single base-pair mutation rate [34] and contributing to the development of sporadic genomic disorders [35].”
BackgroundSimpson, N. H., Ceroni, F., Reader, R. H., Covill, L., Knight, J. C., Hennessy, E. R., Bolton, P., Conti‐Ramsden, G., O'Hare, A. E., Baird, G., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.296 · Cited by 50
Palmer, E. E., Speirs, H. J. L., Taylor, P. J., Mullan, G. L., Turner, G., Einfeld, S., Tonge, B. J., & Mowat, D. R. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.36279 · Cited by 49
“It is estimated that a de novo CNV occurs at a rate of 1.2 10 2 CNVs per genome per transmission from parent to child [Itsara et al., 2010]; therefore, just because aCNV isdenovo,doesnotmean that it is necessarily pathogenic.”
BackgroundInfluentialCNV Concordance in 1,097 MZ Twin Pairs
Abdellaoui, A., Ehli, E. A., Hottenga, J., Weber, Z. M., Mbarek, H., Willemsen, G. A. H. M., van Beijsterveldt, T., Brooks, A. I., Hudziak, J. J., Sullivan, P. F., et al. (2015) · Twin Research and Human Genetics · doi:10.1017/thg.2014.86 · Cited by 48
“CNVs have a higher mutation rate than single nucleotide polymorphisms (SNPs) and affect larger segments of the genome (Itsara et al., 2010; Lupski, 2007; van Ommen, 2005).”
BackgroundThe causality of de novo copy number variants is overestimated
Vermeesch, J. R., Balikova, I., Schrander-Stumpel, C. T. R. M., Fryns, J., & Devriendt, K. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.83 · Cited by 47
Boer, L. L., Schepens‐Franke, A. N., & Oostra, R. (2019) · Clinical Anatomy · doi:10.1002/ca.23387 · Cited by 46
“Copy-number variants account for a major portion of the genome and are strongly polymorphic and relatively unstable, with mutation rates 100 to 10,000 times higher than those for single base substitutions (Itsara et al., 2010).”
BackgroundQuenez, O., Cassinari, K., Coutant, S., Lecoquierre, F., Guennec, K. L., Rousseau, S., Richard, A., Vasseur, S., Bouvignies, E., Bou, J., et al. (2020) · European Journal of Human Genetics · doi:10.1038/s41431-020-0672-2 · Cited by 46
Forsberg, L. A., Absher, D., & Dumanski, J. P. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101322 · Cited by 44
Buizer‐Voskamp, J. E., Blauw, H. M., Boks, M. P., van Eijk, K. R., Veldink, J. H., Hennekam, E. A. M., Vorstman, J. A. S., Mulder, F., Tiemeier, H. W., Uitterlinden, A. G., et al. (2013) · Human Genetics · doi:10.1007/s00439-012-1261-4 · Cited by 44
Grossi, S., Regis, S., Biancheri, R., Mort, M. E., Lualdi, S., Bertini, E., Uziel, G., Boespflug‐Tanguy, O., Simonati, A., Corsolini, F., et al. (2011) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-6-40 · Cited by 43
The Evolving Diagnostic and Genetic Landscapes of Autism Spectrum Disorder
Ziats, M. N., & Rennert, O. M. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00065 · Cited by 48
Interpretation of Array Comparative Genome Hybridization Data: A Major Challenge
Gijsbers, A. C. J., Schoumans, J., & Ruivenkamp, C. A. L. (2011) · Cytogenetic and Genome Research · doi:10.1159/000334066 · Cited by 43
“As a consequence 20% of the de novo CNVs in the range of 200 kb are benign, and for smaller CNVs this frequency is likely higher [Itsara et al., 2010].”
BackgroundFrom De Novo Mutations to Personalized Therapeutic Interventions in Autism
Brandler, W. M., & Sebat, J. L. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-091113-024550 · Cited by 43
Rall, K., Eisenbeis, S., Barresi, G., Rückner, D., Walter, M. J., Poths, S., Wallwiener, D. R., Rieß, O., von Bonin, M., & Brucker, S. Y. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.10.053 · Cited by 40
Dubois, V., Bena, F. S., Cesbron, A., Hepkema, B. G., Gagne, K., Gimelli, S., Heim, D. A., Tichelli, A., Delaunay, J., Drouet, M., et al. (2012) · Leukemia · doi:10.1038/leu.2012.68 · Cited by 40
The case for DUF1220 domain dosage as a primary contributor to anthropoid brain expansion
Keeney, J., Dumas, L., & Sikela, J. M. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00427 · Cited by 38
Genetic Diversity of Seven Cattle Breeds Inferred Using Copy Number Variations
Pierce, M. D., Dzama, K., & Muchadeyi, F. C. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00163 · Cited by 39
“Itsara et al. (2010) determined different mutation processes to contribute disproportionately to CNVs dependant on the size of the de novo event.”
Copy Number Variation inTAS2RBitter Taste Receptor Genes: Structure, Origin, and Population Genetics
Roudnitzky, N., Risso, D. S., Drayna, D. T., Behrens, M., Meyerhof, W., & Wooding, S. (2016) · Chemical Senses · doi:10.1093/chemse/bjw067 · Cited by 38
Intellectual Disability & Rare Disorders: A Diagnostic Challenge
Kvarnung, M., & Nordgren, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67144-4_3 · Cited by 41
Deciphering the pathogenic consequences of chromosomal aberrations in human genetic disease
Kloosterman, W. P., & Hochstenbach, R. (2014) · Molecular Cytogenetics · doi:10.1186/s13039-014-0100-9 · Cited by 40
Menie, M. A. W. O. (2014) · Personality and Individual Differences · doi:10.1016/j.paid.2014.10.047 · Cited by 34
Ketelaar, M. E., Hofstra, R. M. W., & Hayden, M. R. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01795.x · Cited by 34
“The frequency of de novo occurrence of these larger alterations has been estimated as ∼5% per person per generation, indicating their relevance (10, 52).”
BackgroundA familial deletion of 16q21 characterized by an SNP array and associated with a normal phenotype
Kowalczyk, M., Tomaszewska, A., Podbiol‐Palenta, A., Remiszewska, B., Galjaard, R. H., Zajączek, S., & Srebniak, M. I. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35912 · Cited by 33
“The common use of advanced molecular cytogenetic techniques (high-resolution array) in recent times has shown that interstitial deletions of euchromatin with no phenotypic effect are not as rare, as one could expect [Itsara et al., 2010].”
BackgroundSG-ADVISER CNV: copy-number variant annotation and interpretation
Erikson, G. A., Deshpande, N. R., Kesavan, B. G., & Torkamani, A. (2014) · Genetics in Medicine · doi:10.1038/gim.2014.180 · Cited by 35
“(2) custom filters; (3) saving to file; (4) statistics; (5) help menu; (6) simple filter; (7) advanced filter; (8) stepping backward and forward through executed”
BackgroundCopy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula
Brosens, E., Marsch, F., de Jong, E. M., Zaveri, H. P., Hilger, A. C., Choinitzki, V., Hölscher, A., Hoffmann, P., Herms, S., Boemers, T. M., et al. (2016) · European Journal of Human Genetics · doi:10.1038/ejhg.2016.86 · Cited by 32
Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?
Matés, J., Mademont‐Soler, I., Fernández-Falgueras, A., Sarquella‐Brugada, G., César, S., Arbelo, E., García‐Álvarez, A., Jordà, P., Toro, R., Coll, M., et al. (2020) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2020.102281 · Cited by 34
Genome plasticity in Paramecium bursaria revealed by population genomics
Cheng, Y., Liu, C.-F. J., Yu, Y.-H., Jhou, Y., Fujishima, M., Tsai, I. J., & Leu, J. (2020) · BMC Biology · doi:10.1186/s12915-020-00912-2 · Cited by 31
“Most large-scale studies on CNV have been conducted on human populations, which show that de novo CNV frequently occurs in human genomes [9, 10] and accounts for 17.”
BackgroundNakatochi, M., Kushima, I., & Ozaki, N. (2020) · Journal of Human Genetics · doi:10.1038/s10038-020-00838-1 · Cited by 35
Genomic studies in fragile X premutation carriers
Lozano, R., Hagerman, R. J., Duyzend, M., Budimirovic, D. B., Eichler, E. E., & Tassone, F. (2014) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-6-27 · Cited by 32
Self-citationA Cell Type-Specific Expression Signature Predicts Haploinsufficient Autism-Susceptibility Genes
Zhang, C., & Shen, Y. (2016) · Human Mutation · doi:10.1002/humu.23147 · Cited by 25
“De novo CNVs detected in ASD probands typically span dozens or hundreds of genes [Itsara et al., 2010; Levy et al., 2011; Marshall et al., 2008; Pinto et al., 2010; Sanders et al., 2011; Sebat et al., 2007].”
BackgroundMethodInfluentialGenetic dissection identifies Necdin as a driver gene in a mouse model of paternal 15q duplications
Tamada, K., Fukumoto, K., Toya, T., Nakai, N., Awasthi, J. R., Tanaka, S., Okabe, S., Spitz, F., Saitow, F., Suzuki, H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24359-3 · Cited by 27
The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross
Samarakoon, U., Gonzales, J. M., Patel, J. J., Tan, A., Checkley, L. A., & Ferdig, M. T. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-457 · Cited by 29
A Preliminary Study of Copy Number Variation in Tibetans
Zhang, Y., Li, X., Zhang, F., Wang, D.-M., & Yu, J. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041768 · Cited by 27
“DNA copy number variation is an important type of genomic variation that can influence phenotype through gene dosage effect and/or alteration of the genomic architecture [10], and is a good candidate for natural selection [11].”
BackgroundCassinari, K., Quenez, O., Joly‐Hélas, G., Beaussire, L., Meur, N. L., Castelain, M., Goldenberg, A., Guerrot, A., Bréhin, A., Deleuze, J., et al. (2019) · Clinical Chemistry · doi:10.1373/clinchem.2019.304246 · Cited by 28
Du, H., Jolly, A., Grochowski, C. M., Yuan, B., Dawood, M., Jhangiani, S. N., Li, H., Muzny, D. M., Fatih, J. M., Coban‐Akdemir, Z., et al. (2022) · Genome Medicine · doi:10.1186/s13073-022-01123-w · Cited by 27
Aging genomes: A necessary evil in the logic of life
Vijg, J. (2014) · BioEssays · doi:10.1002/bies.201300127 · Cited by 25
Signals of Historical Interlocus Gene Conversion in Human Segmental Duplications
Dumont, B. L., & Eichler, E. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075949 · Cited by 26
“than per site rates of non-allelic crossing over [69,70].”
BackgroundSelf-citationSibbons, C. M., Morris, J. K., Crolla, J. A., Jacobs, P. A., & Thomas, N. S. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.182 · Cited by 24
Mouse Models of 22q11.2-Associated Autism Spectrum Disorder
Hiroi, N. (2012) · Autism - Open Access · doi:10.4172/2165-7890.s1-001 · Cited by 25
Costa, E., Pinto, I. P., Gonçalves, M. W., da Silva, J. F., Oliveira, L. G., da Cruz, A. S., Silva, D. D. M. E., da Silva, C. C., Pereira, R. W., & da Cruz, A. D. (2018) · Scientific Reports · doi:10.1038/s41598-018-23813-5 · Cited by 25
Origins and Long-Term Patterns of Copy-Number Variation in Rhesus Macaques
Thomas, G. W. C., Wang, R. J., Nguyen, J., Harris, R. A., Raveendran, M., Rogers, J., & Hahn, M. W. (2020) · Molecular Biology and Evolution · doi:10.1093/molbev/msaa303 · Cited by 21
“2016), though the origin of CNVs have been studied less often than singlenucleotide mutations (Sebat et al. 2007; Itsara et al. 2010; Schrider et al. 2013; MacArthur et al. 2014; Kloosterman et al. 2015; Brandler et al. 2016; Girard et al. 2016; Werling et al. 2018).”
BackgroundIdentification of structural variation in mouse genomes
Keane, T., Wong, K., Adams, D. J., Flint, J., Reymond, A., & Yalcin, B. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00192 · Cited by 24
Ma, R., Deng, L., Xia, Y., Wei, X., Cao, Y., Guo, R., Zhang, R., Guo, J., Liang, D., & Wu, L. (2017) · Scientific Reports · doi:10.1038/srep44446 · Cited by 22
Ravel, J., Renaud, M., Muller, J., Becker, A., Renard, É., Rémen, T., Lefort, G., Dexheimer, M., Jonveaux, P., Leheup, B., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01191-6 · Cited by 23
McCole, R. B., Fonseka, C. Y., Koren, A., & Wu, C.-T. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004646 · Cited by 23
“One study [70] included asthmatic individuals as healthy controls, and we did likewise.”
BackgroundResultA new era in the discovery of de novomutations underlying human genetic disease
Ku, C., Vasiliou, V., & Cooper, D. N. (2012) · Human Genomics · doi:10.1186/1479-7364-6-27 · Cited by 25
Risk of meningomyelocele mediated by the common 22q11.2 deletion
Vong, K. I., Lee, S., Au, K. S., Crowley, T. B., Capra, V., Martino, J., Haller, M., Araújo, C., Machado, H. R., George, R. D., et al. (2024) · Science · doi:10.1126/science.adl1624 · Cited by 21
Wang, B., Ji, T., Zhou, X., Wang, J., Wang, X., Wang, J., Zhu, D., Zhang, X., Sham, P. C., Zhang, X., et al. (2016) · Scientific Reports · doi:10.1038/srep25954 · Cited by 25
Jia, Y., Xu, M., Hu, H., Chapman, B., Watt, C., Buerte, B., Han, N., Zhu, M., Bian, H., Li, C., et al. (2023) · BMC Biology · doi:10.1186/s12915-022-01503-z · Cited by 21
Cooper, N. J., Shtir, C. J., Smyth, D. J., Guo, H., Swafford, A. D.-E., Zanda, M., Hurles, M. E., Walker, N. M., Plagnol, V., Cooper, J. D., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu581 · Cited by 20
Jeffares, D. C., Jolly, C., Hoti, M., Speed, D., Shaw, L. P., Rallis, C., Balloux, F., Dessimoz, C., Bähler, J., & Sedlazeck, F. J. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/047266 · Cited by 21
Characterization of copy number‐stable regions in the human genome
Johansson, A., & Feuk, L. (2011) · Human Mutation · doi:10.1002/humu.21524 · Cited by 19
“Interpretation of CNV data in clinical studies has focused on the identification of de novo CNVs that are large and overlap genes, as the rate of de novo creation of CNVs in the general population is low [Itsara et al., 2010; Lupski, 2007; Redon et al., 2006; Sebat et al., 2007; Turner et al., 2008].”
BackgroundInfluentialZhuang, J., & Weng, Z. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv831 · Cited by 18
“Considering that the spontaneous mutation rate for point mutations is much higher than for SVs (46), we hypothesize that tumorigenesis is often initiated by point mutations and that most SVs occur later during cancer development, when DNA repair mechanisms are compromised.”
BackgroundLamarckian evolution explains human brain evolution and psychiatric disorders
Barry, G. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00224 · Cited by 17
“Copy number variations arising from de novo mutations also play a significant role in sporadic cases of autism (Itsara et al., 2010; Sanders et al., 2011; Devlin and Scherer, 2012) and schizophrenia (Rees et al., 2012).”
Sokolowski, M., Wasserman, J., & Wasserman, D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168531 · Cited by 19
A Computational Framework Discovers New Copy Number Variants with Functional Importance
Banerjee, S., Oldridge, D. A., Poptsova, M. S., Hussain, W. M., Chakravarty, D., & Demichelis, F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017539 · Cited by 17
Rare copy number variants in patients with congenital conotruncal heart defects
Xie, H. M., Werner, P., Stambolian, D., Wilson, J., Hakonarson, H. H., White, P. S., Taylor, D. M., & Goldmuntz, E. (2017) · Birth Defects Research · doi:10.1002/bdra.23609 · Cited by 17
“Previous work had established bias towards Type II error using the protocol proposed by (Itsara et al., 2010).”
MethodConnolly, J. J., Glessner, J., Almoguera, B., Crosslin, D. R., Jarvik, G. P., Abou‐Sleiman, P. M., & Hakonarson, H. H. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00051 · Cited by 16
Discovery of genomic variation across a generation
Trost, B., Loureiro, L. O., & Scherer, S. W. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab209 · Cited by 20
Copy Number Variation Burden on Asthma Subgenome in Normal Cohorts Identifies Susceptibility Markers
Vishweswaraiah, S., Veerappa, A. M., Mahesh, P. A., Jahromi, S. R., & Ramachandra, N. B. (2015) · Allergy Asthma and Immunology Research · doi:10.4168/aair.2015.7.3.265 · Cited by 15
Dimensional Deconstruction and Reconstruction of CNV-Associated Neuropsychiatric Disorders
Hiroi, N., & Nishi, A. (2015) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-800981-9.00017-1 · Cited by 16
Diversity and regulatory impact of copy number variation in the primate Macaca fascicularis
Gschwind, A. R., Singh, A., Certa, U., Reymond, A., & Heckel, T. (2017) · BMC Genomics · doi:10.1186/s12864-017-3531-y · Cited by 16
“Furthermore, short CNVs are more frequently generated de novo than large CNVs (>500 kb) [42], which indicates that they are not under strong purifying selection in contrast to deleterious large CNVs [19].”
Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions
Neuhäusler, L., Summerer, A., Cooper, D. N., Mautner, V., & Kehrer‐Sawatzki, H. (2018) · Human Genetics · doi:10.1007/s00439-018-1888-x · Cited by 15
“Type-3 NF1 deletions are characterized by breakpoints located within NF1-REPb and NF1-REPc and are also mediated by NAHR (Bengesser et al. 2010; Pasmant et al. 2010; Zickler et al., 2012).”
BackgroundInfluentialCNVs with adaptive potential in Rangifer tarandus: genome architecture and new annotated assembly
Prunier, J., Carrier, A., Gilbert, I., Poisson, W., Albert, V., Taillon, J., Bourret, V., Côté, S. D., Droit, A., & Robert, C. (2021) · Life Science Alliance · doi:10.26508/lsa.202101207 · Cited by 14
“…genomes involve more nucleotides than single-nucleotide polymorphisms (Sebat et al, 2004; Carson et al, 2006; Redon et al, 2006; Conrad et al, 2010; Itsara et al, 2010), an increasing number of studies even suggested that CNVs account for higher genetic differentiation than SNPs (Dorant et al,…”
CNAsim: improved simulation of single-cell copy number profiles and DNA-seq data from tumors
Weiner, S., & Bansal, M. S. (2023) · Bioinformatics · doi:10.1093/bioinformatics/btad434 · Cited by 14
de Oliveira, H. R., Chud, T. C. S., Júnior, G. A. O., Hermisdorff, Í. D. C., Narayana, S. G., Rochus, C. M., Butty, A. M., Malchiodi, F., Stothard, P., Miglior, F., et al. (2024) · Journal of Dairy Science · doi:10.3168/jds.2023-24295 · Cited by 13
Fast detection of de novo copy number variants from SNP arrays for case-parent trios
Scharpf, R. B., Beaty, T. H., Schwender, H. R., Younkin, S. G., Scott, A. F., & Ruczinski, I. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-330 · Cited by 12
“Secondly, a recent study failed to identify de novo CNVs in HapMap, identifying instead somatic changes or possible problems with the cell lines [38].”
BackgroundMethodNumber of rare germline CNVs and TP53 mutation types
Silva, A. G., Achatz, M. I., Krepischi, A. C. V., Pearson, P. L., & Rosenberg, C. (2012) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-7-101 · Cited by 12
“Under the assumption that pathogenic variants would only remain in the population at low frequency, the selection against new pathogenic CNVs (in the context of studies on schizophrenia and autism, respectively) is extremely high [29,30].”
BackgroundUltra-rare renal diseases diagnosed with whole-exome sequencing: Utility in diagnosis and management
Jung, J., Lee, J. H., Park, Y. S., Seo, G. H., Keum, C., Kang, H. G., Lee, H., Lee, S. K., Lee, S. T., Cho, H., et al. (2021) · BMC Medical Genomics · doi:10.1186/s12920-021-01026-6 · Cited by 12
“On average, as 74 germline single-nucleotide variants (SNVs), 3 indels, and 0.02 de novo copy number variants (CNVs) occur in one person’s genome, one de novo mutation can develop per exome [23].”
BackgroundInfluentialFitness Consequences of Advanced Ancestral Age over Three Generations in Humans
Hayward, A. D., Lummaa, V., & Bazykin, G. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128197 · Cited by 12
“Besides single-nucleotide mutations, the number of copy-number variants is also enriched in cases of autism [13] and intellectual disability [14] and increases with paternal age [14], although it is not associated with intelligence in healthy individuals [15].”
BackgroundComprehensive inbred variation discovery in Bama pigs using de novo assemblies
Zhang, L., Huang, Y., Si, J., Wu, Y., Wang, M., Jiang, Q., Guo, Y., Liang, J., & Lan, G. (2018) · Gene · doi:10.1016/j.gene.2018.08.051 · Cited by 12
The Role of De Novo Variants in Patients with Congenital Diaphragmatic Hernia
Bendixen, C., & Reutter, H. M. (2021) · Genes · doi:10.3390/genes12091405 · Cited by 12
“5–3% [36,37], about 2–12 times lower than the rate of de novo CNVs in CDH patients.”
BackgroundThe Landscape of Structural Variation in Aye-Ayes (Daubentonia madagascariensis)
Versoza, C. J., Jensen, J. D., & Pfeifer, S. P. (2025) · Genome Biology and Evolution · doi:10.1093/gbe/evaf167 · Cited by 11
“…associated with deleterious fitness effects and are thus purged from the population, with purifying selection having been observed to be acting more strongly on longer deletions which more easily perturb protein function (Taylor et al. 2004; Itsara et al. 2010; Mills et al. 2011; Yang et al. 2024).”
Developmental psychopathology: The role of structural variation in the genome
Gill, M. (2012) · Development and Psychopathology · doi:10.1017/s0954579412000739 · Cited by 11
“Itsara et al. (2010) suggest that multiaffected autism pedigrees segregate an existing inherited mutation of low penetrance, which, by itself, is rarely sufficient to cause disease.”
BackgroundMethodForsberg, L. A., Absher, D., & Dumanski, J. P. (2013) · Postgraduate Medical Journal · doi:10.1136/postgradmedj-2012-101322rep · Cited by 12
Copy number variation genotyping using family information
Chu, J., Rogers, A. J., Ionita‐Laza, I., Darvishi, K., Mills, R. E., Lee, C., & Raby, B. A. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-157 · Cited by 11
“have suggested that de novo CNV mutation is likely rare (about 1% in healthy controls) [35-37].”
BackgroundCNV analysis in the Lithuanian population
Urnikytė, A., Domarkienė, I., Stoma, S., Ambrozaitytė, L., Uktverytė, I., Meškienė, R., Kasiulevičius, V., Burokienė, N., & Kučinskas, V. (2016) · BMC Genetics · doi:10.1186/s12863-016-0373-6 · Cited by 12
Ma, J., Xie, F., Tian, X.-Y., Chen, L.-N., Fan, X.-Y., Guo, L., Li, S., Yin, S., Luo, S., & Ou, X. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz156 · Cited by 10
Ashitha, S. N. M., & Ramachandra, N. B. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.04.051 · Cited by 10
Singh, V. K., Singh, S., Nandhini, P. B., Bhatia, A. K., Dixit, S. P., & Ganguly, I. (2023) · Animal Biotechnology · doi:10.1080/10495398.2022.2162910 · Cited by 11
“However, significant differences in CNV count reported in human, 38 cattle, 17,39 – 41 and goat 14 may be due to various population phenomena like population history, size of the population, adaptation, migration, selection, mutation, etc. Similarly, higher number of deletion CNVs reported in this…”
BackgroundAdvanced Whole-Genome Sequencing and Analysis of Fetal Genomes from Amniotic Fluid
Mao, Q., Chin, R. G., Xie, W., Deng, Y., Zhang, W., Xu, H., Zhang, R. Y. U., Shi, Q., Peters, E. E., Gulbahce, N., et al. (2018) · Clinical Chemistry · doi:10.1373/clinchem.2017.281220 · Cited by 12
Binversie, E. E., Baker, L. A., Engelman, C. D., Hao, Z., Moran, J. J. M., Piazza, A. M., Sample, S. J., & Muir, P. (2020) · PLoS ONE · doi:10.1371/journal.pone.0244075 · Cited by 12
Molekulare Karyotypisierung in der Diagnostik neurokognitiver Entwicklungsstörungen
Oneda, B., & Rauch, A. M. (2012) · Medizinische Genetik · doi:10.1007/s11825-012-0327-y · Cited by 10
Autosomal Reciprocal Translocations
Gardner, R. J. M., & Amor, D. J. (2018) · Oxford University Press eBooks · doi:10.1093/med/9780199329007.003.0005 · Cited by 10
Mutational Processes Shaping the Genome in Early Human Embryos
Voet, T., & Vermeesch, J. R. (2017) · Cell · doi:10.1016/j.cell.2017.02.008 · Cited by 10
Haplotype Phasing and Inheritance of Copy Number Variants in Nuclear Families
Palta, P., Kaplinski, L., Nagirnaja, L., Veidenberg, A., Möls, M., Nelis, M., Esko, T., Metspalu, A., Laan, M., & Remm, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122713 · Cited by 12
“, Reference [49]) Illumina HumanCNV370K”
BackgroundMethodInfluentialGenome integrity as a potential index of longevity in Ashkenazi Centenarian’s families
Andrawus, M., David, G. B., Terziyska, I., Sharvit, L. E., Bergman, A., Barzilai, N., Raj, S. M., Govindaraju, D. R., & Atzmon, G. (2024) · GeroScience · doi:10.1007/s11357-024-01178-0 · Cited by 8
Soni, V., Pfeifer, S. P., & Jensen, J. D. (2025) · American Journal of Primatology · doi:10.1002/ajp.70105 · Cited by 7
“As longer deletions are likely to experience stronger purifying selection, owing to the increased likelihood of functionally altering expressed proteins, this relatively diminutive length may be expected (Taylor et al. 2004; Itsara et al. 2010; Mills et al. 2011; Y. Yang et al. 2024).”
Jakubek, Y., & Cutler, D. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-737 · Cited by 14
“In the field of human genetics, DNA microarrays are used to investigate disease [4,11,12], to study variation [5,8], and to detect variants in clinical samples [9].”
BackgroundMethodGenetic Approaches to Understanding Psychiatric Disease
Michaelson, J. J. (2017) · Neurotherapeutics · doi:10.1007/s13311-017-0551-x · Cited by 11
Chen, Z., Long, H., Guo, J., Wang, Y., He, K., Tao, C., Li, X., Jiang, K., Guo, S., & ., Y. P. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.901682 · Cited by 9
Chromosome Instability Syndromes
Gardner, R. J. M., & Amor, D. J. (2018) · Oxford University Press eBooks · doi:10.1093/med/9780199329007.003.0016 · Cited by 9
Technical strategy for monozygotic twin discrimination by single-nucleotide variants
Sun, W., Wang, Z., Wen, S., Huang, A., Li, H., Jiang, L., Feng, Q., Fan, D., Tian, Q., Han, D., et al. (2024) · International Journal of Legal Medicine · doi:10.1007/s00414-023-03150-7 · Cited by 7
“Copy number variants (CNVs), which account for a substantial portion of the genetic variation, are strongly polymorphic and relatively unstable, with mutation rates 100 to 10,000 times higher than those for single base substitutions [26].”
Fox, K., Johnsen, J. M., Coe, B. P., Frazar, C. D., Reiner, A., Eichler, E. E., & Nickerson, D. (2016) · Transfusion · doi:10.1111/trf.13797 · Cited by 8
“Previous studies have suggested that SDs are capable of driving increased copy number variation mutation rates, not only through flanking direct orientation repeats (nonallelic homologous recombination), but also through a replication or repair-based mechanism in regions adjacent to duplications.(22) To this end we ex…”
BackgroundSelf-citationJain, Y., Chandradoss, K. R., Anjoom, A. V., Bhattacharya, J., Lal, M., Bagadia, M., Singh, H., & Sandhu, K. S. (2021) · npj Aging and Mechanisms of Disease · doi:10.1038/s41514-021-00072-9 · Cited by 7
Tan, R., & Shen, Y. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac788 · Cited by 7
“Meanwhile, based on recent studies, the real de novo CNV rate in the human genome is very low (30-32).”
BackgroundRare Variants in Complex Traits: Novel Identification Strategies and the Role of de novo Mutations
Jouan, L., Gauthier, J., Dion, P. A., & Rouleau, G. A. (2012) · Human Heredity · doi:10.1159/000346478 · Cited by 7
Functional Comparison between Genes Dysregulated in Ulcerative Colitis and Colorectal Carcinoma
Zhao, W., Qi, L., Qin, Y., Wang, H., Chen, B., Wang, R., Gu, Y., Liu, C., Wang, C., & Guo, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0071989 · Cited by 8
“We defined the GO BP term ‘‘response to stimulus’’ and its offspring terms as the stimulus-related terms, and found the stimulus-related terms which significantly enriched with UC-related DE genes with FDR,1%, termed as ‘‘UC-stimulus-functions’’.”
Mokhtar, S. S., Marshall, C. R., Phipps, M. E., Thiruvahindrapuram, B., Lionel, A. C., Scherer, S. W., & Hoh, B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100371 · Cited by 7
Metadata
- Authors
- Itsara, A., Wu, H., Smith, J. D., Nickerson, D. A., Romieu, I., London, S. J., & Eichler, E. E.
- Affiliations
- University of Washington (US)
- National Institutes of Health (US)
- Instituto Nacional de Salud Pública (MX)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-09-14
- Volume
- 20
- Issue
- 11
- Pages
- 1469-1481
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC2963811
- OpenAlex
- W2158959870
- Cited by
- 328
- References
- 65
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 16 · 2019: 10 · 2018: 43 · 2017: 19 · 2016: 30 · 2015: 25 · 2014: 25 · 2013: 36 · 2012: 43
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- U.S. Department of Health and Human Services
- Autism Speaks
- Simons Foundation
- Simons Foundation Autism Research Initiative (137578)
- Consejo Nacional de Ciencia y Tecnología (26206-M)
- National Institutes of Health (26206-M)
- National Institute of Mental Health (U24MH081810)
- National Institute of General Medical Sciences (T32GM007266)
- National Institute of Environmental Health Sciences (26206-M, ES049019, ES025045, ZIAES049019, ZIAES025045)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- copy number variation, de novo mutations, mutation rate, purifying selection, mutation-selection balance, autism spectrum disorder, human pedigrees, SNP array, parental bias
- MeSH terms
- Adolescent, Asthma, Autistic Disorder, Base Sequence, Child, Child, Preschool, Female, Gene Frequency, Humans, Male, Pedigree, Selection, Genetic, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Genome-Wide Association Study, DNA Copy Number Variations
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