{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T06:30:03Z","timestamp":1763533803277},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Estimating the frequency distribution of copy number variants (CNVs) is an important aspect of the effort to characterize this new type of genetic variation. Currently, most studies report a strong skew toward low-frequency CNVs. In this article, our goal is to investigate the frequencies of CNVs. We employ a two-step procedure for the CNV frequency estimation process. We use family information a posteriori to select only the most reliable CNV regions, i.e. those showing high rates of Mendelian transmission.<\/jats:p>\n               <jats:p>Results: Our results suggest that the current skew toward low-frequency CNVs may not be representative of the true frequency distribution, but may be due, among other reasons, to the non-negligible false negative rates that characterize CNV detection methods. Moreover, false positives are also likely, as low-frequency CNVs are hard to detect with small sample sizes and technologies that are not ideally suited for their detection. Without appropriate validation methods, such as incorporation of biologically relevant information (for example, in our case, the transmission of heritable CNVs from parents to offspring), it is difficult to assess the validity of specific CNVs, and even harder to obtain reliable frequency estimates.<\/jats:p>\n               <jats:p>Availability: Software implementing the methods described in this article is available for download at the following address: http:\/\/www.isites.harvard.edu\/icb\/icb.do?keyword=k36162<\/jats:p>\n               <jats:p>Contact: \u00a0iionita@hsph.harvard.edu<\/jats:p>\n               <jats:p>Supplementary informantion: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn421","type":"journal-article","created":{"date-parts":[[2008,8,9]],"date-time":"2008-08-09T00:25:11Z","timestamp":1218241511000},"page":"2350-2355","source":"Crossref","is-referenced-by-count":8,"title":["On the frequency of copy number variants"],"prefix":"10.1093","volume":"24","author":[{"given":"Iuliana","family":"Ionita-Laza","sequence":"first","affiliation":[{"name":"1 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue and 2Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan M.","family":"Laird","sequence":"additional","affiliation":[{"name":"1 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue and 2Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin A.","family":"Raby","sequence":"additional","affiliation":[{"name":"1 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue and 2Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott T.","family":"Weiss","sequence":"additional","affiliation":[{"name":"1 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue and 2Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Lange","sequence":"additional","affiliation":[{"name":"1 Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue and 2Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,8,8]]},"reference":[{"key":"2023020211252310200_B1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0197-2456(98)00044-0","article-title":"The childhood asthma management program (CAMP): design, rationale, and methods","volume":"20","author":"Childhood Asthma Management Program Research Group","year":"1999","journal-title":"Control Clin. Trials"},{"key":"2023020211252310200_B2","first-page":"1054","article-title":"Long-term effects of budesonide or nedocromil in children with asthma","volume":"43","author":"Childhood Asthma Management Program Research Group","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"2023020211252310200_B3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/ng1697","article-title":"A high-resolution survey of deletion polymorphism in the human genome","volume":"38","author":"Conrad","year":"2006","journal-title":"Nat. Genet."},{"key":"2023020211252310200_B4","volume-title":"Introduction to Algorithms2nd Edn","author":"Cormen","year":"2001","edition":"2nd Edn"},{"key":"2023020211252310200_B5","doi-asserted-by":"crossref","first-page":"16292","DOI":"10.1073\/pnas.0407247101","article-title":"A versatile statistical analysis algorithm to detect genome copy number variation","volume":"101","author":"Daruwala","year":"2004","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020211252310200_B6","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1093\/hmg\/ddm208","article-title":"Array CGH analysis of copy number variation identifies 1284 new genes variant in healthy white males: implications for association studies of complex diseases","volume":"16","author":"de Smith","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"2023020211252310200_B7","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1086\/503632","article-title":"Breakpoint cloning and haplotype analysis indicate a single origin of the common Inv(10)(p11.2q21.2) mutation among northern Europeans","volume":"78","author":"Gilling","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"2023020211252310200_B8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/ng1695","article-title":"Common deletions and SNPs are in linkage disequilibrium in the human genome","volume":"38","author":"Hinds","year":"2006","journal-title":"Nat. Genet."},{"key":"2023020211252310200_B9","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/ng1416","article-title":"Detection of large-scale variation in the human genome","volume":"36","author":"Iafrate","year":"2004","journal-title":"Nat. Genet."},{"key":"2023020211252310200_B10","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/nature06742","article-title":"Genotype, haplotype and copy-number variation in worldwide human populations","volume":"451","author":"Jakobsson","year":"2008","journal-title":"Nature"},{"key":"2023020211252310200_B11","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1126\/science.1149504","article-title":"Paired-end mapping reveals extensive structural variation in the human genome","volume":"318","author":"Korbel","year":"2007","journal-title":"Science"},{"key":"2023020211252310200_B12","doi-asserted-by":"crossref","first-page":"R228","DOI":"10.1186\/gb-2007-8-10-r228","article-title":"Breaking the waves: improved detection of copy number variation from microarray-based comparative genomic hybridization","volume":"8","author":"Marioni","year":"2007","journal-title":"Genome Biol"},{"key":"2023020211252310200_B13","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/ng1696","article-title":"Common deletion polymorphisms in the human genome","volume":"38","author":"McCarroll","year":"2006","journal-title":"Nat. Genet."},{"key":"2023020211252310200_B14","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/biostatistics\/kxh008","article-title":"Circular binary segmentation for the analysis of array-based DNA copy number data","volume":"5","author":"Olshen","year":"2004","journal-title":"Biostatistics"},{"key":"2023020211252310200_B15","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1101\/gr.5402306","article-title":"High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotyping","volume":"16","author":"Peiffer","year":"2006","journal-title":"Genome Res."},{"key":"2023020211252310200_B16","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/hmg\/ddm241","article-title":"Copy-number variation in control population cohorts","volume":"2","author":"Pinto","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"2023020211252310200_B17","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nature05329","article-title":"Global variation in copy number in the human genome","volume":"444","author":"Redon","year":"2006","journal-title":"Nature"},{"key":"2023020211252310200_B18","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1126\/science.1098918","article-title":"Large-scale copy number polymorphism in the human genome","volume":"305","author":"Sebat","year":"2004","journal-title":"Science"},{"key":"2023020211252310200_B19","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/bioinformatics\/btl646","article-title":"A faster circular binary segmentation algorithm for the analysis of array CGH data","volume":"23","author":"Venkatraman","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020211252310200_B20","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1101\/gr.6861907","article-title":"PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data","volume":"17","author":"Wang","year":"2007","journal-title":"Genome Res."},{"key":"2023020211252310200_B21","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00439-007-0404-5","article-title":"Germ-line DNA copy number variation frequencies in a large North American population","volume":"122","author":"Zogopoulos","year":"2007","journal-title":"Hum. Genet."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/20\/2350\/49049988\/bioinformatics_24_20_2350.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/20\/2350\/49049988\/bioinformatics_24_20_2350.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T14:05:38Z","timestamp":1675346738000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/20\/2350\/258649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,8]]},"references-count":21,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2008,10,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btn421","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,10,15]]},"published":{"date-parts":[[2008,8,8]]}}}