{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:36:22Z","timestamp":1792564582624,"version":"4.5.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T00:00:00Z","timestamp":1462752000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2016,6]]},"DOI":"10.1038\/nsmb.3227","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T12:01:48Z","timestamp":1462795308000},"page":"566-573","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Lactase nonpersistence is directed by DNA-variation-dependent epigenetic aging"],"prefix":"10.1038","volume":"23","author":[{"given":"Viviane","family":"Labrie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orion J","family":"Buske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richie","family":"Jeremian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Ptak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giedrius","family":"Gasi\u016bnas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almantas","family":"Maleckas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u016bta","family":"Petereit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"\u017dvirbliene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u0119stutis","family":"Adamonis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edita","family":"Kriukien\u0117","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolis","family":"Koncevi\u010dius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juozas","family":"Gordevi\u010dius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhil","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha","family":"Ebrahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginijus","family":"\u0160ik\u0161nys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limas","family":"Kup\u010dinskas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brudno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturas","family":"Petronis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,9]]},"reference":[{"key":"BFnsmb3227_CR1","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1136\/gut.2005.077404","volume":"54","author":"H Rasinper\u00e4","year":"2005","unstructured":"Rasinper\u00e4, H. et al. Transcriptional downregulation of the lactase (LCT) gene during childhood. Gut 54, 1660\u20131661 (2005).","journal-title":"Gut"},{"key":"BFnsmb3227_CR2","doi-asserted-by":"publisher","first-page":"865","DOI":"10.3109\/00365528309182107","volume":"18","author":"T Sahi","year":"1983","unstructured":"Sahi, T., Launiala, K. & Laitinen, H. Hypolactasia in a fixed cohort of young Finnish adults: a follow-up study. Scand. J. Gastroenterol. 18, 865\u2013870 (1983).","journal-title":"Scand. J. Gastroenterol."},{"key":"BFnsmb3227_CR3","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s00439-008-0593-6","volume":"124","author":"CJ Ingram","year":"2009","unstructured":"Ingram, C.J., Mulcare, C.A., Itan, Y., Thomas, M.G. & Swallow, D.M. Lactose digestion and the evolutionary genetics of lactase persistence. Hum. Genet. 124, 579\u2013591 (2009).","journal-title":"Hum. Genet."},{"key":"BFnsmb3227_CR4","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/ng826","volume":"30","author":"NS Enattah","year":"2002","unstructured":"Enattah, N.S. et al. Identification of a variant associated with adult-type hypolactasia. Nat. Genet. 30, 233\u2013237 (2002).","journal-title":"Nat. Genet."},{"key":"BFnsmb3227_CR5","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1046\/j.1469-1809.2003.00048.x","volume":"67","author":"M Poulter","year":"2003","unstructured":"Poulter, M. et al. The causal element for the lactase persistence\/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans. Ann. Hum. Genet. 67, 298\u2013311 (2003).","journal-title":"Ann. Hum. Genet."},{"key":"BFnsmb3227_CR6","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1086\/421051","volume":"74","author":"T Bersaglieri","year":"2004","unstructured":"Bersaglieri, T. et al. Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111\u20131120 (2004).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnsmb3227_CR7","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1086\/520705","volume":"81","author":"NS Enattah","year":"2007","unstructured":"Enattah, N.S. et al. Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans. Am. J. Hum. Genet. 81, 615\u2013625 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnsmb3227_CR8","doi-asserted-by":"publisher","first-page":"e1000491","DOI":"10.1371\/journal.pcbi.1000491","volume":"5","author":"Y Itan","year":"2009","unstructured":"Itan, Y., Powell, A., Beaumont, M.A., Burger, J. & Thomas, M.G. The origins of lactase persistence in Europe. PLoS Comput. Biol. 5, e1000491 (2009).","journal-title":"PLoS Comput. Biol."},{"key":"BFnsmb3227_CR9","doi-asserted-by":"publisher","first-page":"5257","DOI":"10.1038\/ncomms6257","volume":"5","author":"C Gamba","year":"2014","unstructured":"Gamba, C. et al. Genome flux and stasis in a five millennium transect of European prehistory. Nat. Commun. 5, 5257 (2014).","journal-title":"Nat. Commun."},{"key":"BFnsmb3227_CR10","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ajhg.2014.02.009","volume":"94","author":"A Ranciaro","year":"2014","unstructured":"Ranciaro, A. et al. Genetic origins of lactase persistence and the spread of pastoralism in Africa. Am. J. Hum. Genet. 94, 496\u2013510 (2014).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnsmb3227_CR11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/ng1946","volume":"39","author":"SA Tishkoff","year":"2007","unstructured":"Tishkoff, S.A. et al. Convergent adaptation of human lactase persistence in Africa and Europe. Nat. Genet. 39, 31\u201340 (2007).","journal-title":"Nat. Genet."},{"key":"BFnsmb3227_CR12","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.ajhg.2013.07.008","volume":"93","author":"BL Jones","year":"2013","unstructured":"Jones, B.L. et al. Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep. Am. J. Hum. Genet. 93, 538\u2013544 (2013).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnsmb3227_CR13","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1053\/j.gastro.2003.09.031","volume":"125","author":"JT Troelsen","year":"2003","unstructured":"Troelsen, J.T., Olsen, J., M\u00f8ller, J. & Sj\u00f6str\u00f6m, H. An upstream polymorphism associated with lactase persistence has increased enhancer activity. Gastroenterology 125, 1686\u20131694 (2003).","journal-title":"Gastroenterology"},{"key":"BFnsmb3227_CR14","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1093\/hmg\/ddg244","volume":"12","author":"LC Olds","year":"2003","unstructured":"Olds, L.C. & Sibley, E. Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum. Mol. Genet. 12, 2333\u20132340 (2003).","journal-title":"Hum. Mol. Genet."},{"key":"BFnsmb3227_CR15","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1007\/s00439-011-0966-0","volume":"130","author":"TG Jensen","year":"2011","unstructured":"Jensen, T.G. et al. The -14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1\u03b1 binding site and increases lactase promoter activity. Hum. Genet. 130, 483\u2013493 (2011).","journal-title":"Hum. Genet."},{"key":"BFnsmb3227_CR16","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1007\/s00439-012-1140-z","volume":"131","author":"L Fang","year":"2012","unstructured":"Fang, L., Ahn, J.K., Wodziak, D. & Sibley, E. The human lactase persistence-associated SNP -13910*T enables in vivo functional persistence of lactase promoter-reporter transgene expression. Hum. Genet. 131, 1153\u20131159 (2012).","journal-title":"Hum. Genet."},{"key":"BFnsmb3227_CR17","unstructured":"Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature 518, 317\u2013330 (2015)."},{"key":"BFnsmb3227_CR18","doi-asserted-by":"publisher","first-page":"6363","DOI":"10.1038\/ncomms7363","volume":"6","author":"G Elliott","year":"2015","unstructured":"Elliott, G. et al. Intermediate DNA methylation is a conserved signature of genome regulation. Nat. Commun. 6, 6363 (2015).","journal-title":"Nat. Commun."},{"key":"BFnsmb3227_CR19","doi-asserted-by":"publisher","first-page":"R115","DOI":"10.1186\/gb-2013-14-10-r115","volume":"14","author":"S Horvath","year":"2013","unstructured":"Horvath, S. DNA methylation age of human tissues and cell types. Genome Biol. 14, R115 (2013).","journal-title":"Genome Biol."},{"key":"BFnsmb3227_CR20","doi-asserted-by":"publisher","first-page":"e1002629","DOI":"10.1371\/journal.pgen.1002629","volume":"8","author":"JT Bell","year":"2012","unstructured":"Bell, J.T. et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 8, e1002629 (2012).","journal-title":"PLoS Genet."},{"key":"BFnsmb3227_CR21","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1038\/nn.3786","volume":"17","author":"PL De Jager","year":"2014","unstructured":"De Jager, P.L. et al. Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat. Neurosci. 17, 1156\u20131163 (2014).","journal-title":"Nat. Neurosci."},{"key":"BFnsmb3227_CR22","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nature14252","volume":"518","author":"E Gjoneska","year":"2015","unstructured":"Gjoneska, E. et al. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease. Nature 518, 365\u2013369 (2015).","journal-title":"Nature"},{"key":"BFnsmb3227_CR23","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1016\/S0021-9258(19)44141-0","volume":"248","author":"MM Weiser","year":"1973","unstructured":"Weiser, M.M. Intestinal epithelial cell surface membrane glycoprotein synthesis. I. An indicator of cellular differentiation. J. Biol. Chem. 248, 2536\u20132541 (1973).","journal-title":"J. Biol. Chem."},{"key":"BFnsmb3227_CR24","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1038\/ncomms3190","volume":"4","author":"E Kriukiene","year":"2013","unstructured":"Kriukiene, E. et al. DNA unmethylome profiling by covalent capture of CpG sites. Nat. Commun. 4, 2190 (2013).","journal-title":"Nat. Commun."},{"key":"BFnsmb3227_CR25","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.modgep.2005.09.003","volume":"6","author":"R Fang","year":"2006","unstructured":"Fang, R., Olds, L.C. & Sibley, E. Spatio-temporal patterns of intestine-specific transcription factor expression during postnatal mouse gut development. Gene Expr. Patterns 6, 426\u2013432 (2006).","journal-title":"Gene Expr. Patterns"},{"key":"BFnsmb3227_CR26","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/nmeth.1871","volume":"9","author":"D Diep","year":"2012","unstructured":"Diep, D. et al. Library-free methylation sequencing with bisulfite padlock probes. Nat. Methods 9, 270\u2013272 (2012).","journal-title":"Nat. Methods"},{"key":"BFnsmb3227_CR27","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1038\/nbt1010-1045","volume":"28","author":"BE Bernstein","year":"2010","unstructured":"Bernstein, B.E. et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat. Biotechnol. 28, 1045\u20131048 (2010).","journal-title":"Nat. Biotechnol."},{"key":"BFnsmb3227_CR28","doi-asserted-by":"crossref","unstructured":"ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57\u201374 (2012).","DOI":"10.1038\/nature11247"},{"key":"BFnsmb3227_CR29","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/molbev\/msr190","volume":"29","author":"I Gallego Romero","year":"2012","unstructured":"Gallego Romero, I. et al. Herders of Indian and European cattle share their predominant allele for lactase persistence. Mol. Biol. Evol. 29, 249\u2013260 (2012).","journal-title":"Mol. Biol. Evol."},{"key":"BFnsmb3227_CR30","doi-asserted-by":"publisher","first-page":"8790","DOI":"10.1038\/srep08790","volume":"5","author":"Y Li","year":"2015","unstructured":"Li, Y. et al. Genome-wide DNA methylome analysis reveals epigenetically dysregulated non-coding RNAs in human breast cancer. Sci. Rep. 5, 8790 (2015).","journal-title":"Sci. Rep."},{"key":"BFnsmb3227_CR31","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nature12598","volume":"503","author":"A Di Ruscio","year":"2013","unstructured":"Di Ruscio, A. et al. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature 503, 371\u2013376 (2013).","journal-title":"Nature"},{"key":"BFnsmb3227_CR32","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.tig.2012.03.013","volume":"28","author":"M Magistri","year":"2012","unstructured":"Magistri, M., Faghihi, M.A., St Laurent, G. III & Wahlestedt, C. Regulation of chromatin structure by long noncoding RNAs: focus on natural antisense transcripts. Trends Genet. 28, 389\u2013396 (2012).","journal-title":"Trends Genet."},{"key":"BFnsmb3227_CR33","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1128\/MCB.01124-12","volume":"33","author":"DH Yu","year":"2013","unstructured":"Yu, D.H. et al. Developmentally programmed 3\u2032 CpG island methylation confers tissue- and cell-type-specific transcriptional activation. Mol. Cell. Biol. 33, 1845\u20131858 (2013).","journal-title":"Mol. Cell. Biol."},{"key":"BFnsmb3227_CR34","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1016\/j.cell.2015.07.038","volume":"162","author":"Y Guo","year":"2015","unstructured":"Guo, Y. et al. CRISPR inversion of CTCF sites alters genome topology and enhancer\/promoter function. Cell 162, 900\u2013910 (2015).","journal-title":"Cell"},{"key":"BFnsmb3227_CR35","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nrg3663","volume":"15","author":"CT Ong","year":"2014","unstructured":"Ong, C.T. & Corces, V.G. CTCF: an architectural protein bridging genome topology and function. Nat. Rev. Genet. 15, 234\u2013246 (2014).","journal-title":"Nat. Rev. Genet."},{"key":"BFnsmb3227_CR36","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1101\/gad.230318.113","volume":"28","author":"KL Sheaffer","year":"2014","unstructured":"Sheaffer, K.L. et al. DNA methylation is required for the control of stem cell differentiation in the small intestine. Genes Dev. 28, 652\u2013664 (2014).","journal-title":"Genes Dev."},{"key":"BFnsmb3227_CR37","doi-asserted-by":"publisher","first-page":"R50","DOI":"10.1186\/gb-2013-14-5-r50","volume":"14","author":"LT Kaaij","year":"2013","unstructured":"Kaaij, L.T. et al. DNA methylation dynamics during intestinal stem cell differentiation reveals enhancers driving gene expression in the villus. Genome Biol. 14, R50 (2013).","journal-title":"Genome Biol."},{"key":"BFnsmb3227_CR38","doi-asserted-by":"publisher","first-page":"3945","DOI":"10.1093\/hmg\/ddi418","volume":"14","author":"RH Lewinsky","year":"2005","unstructured":"Lewinsky, R.H. et al. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro . Hum. Mol. Genet. 14, 3945\u20133953 (2005).","journal-title":"Hum. Mol. Genet."},{"key":"BFnsmb3227_CR39","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/nature16462","volume":"528","author":"S Domcke","year":"2015","unstructured":"Domcke, S. et al. Competition between DNA methylation and transcription factors determines binding of NRF1. Nature 528, 575\u2013579 (2015).","journal-title":"Nature"},{"key":"BFnsmb3227_CR40","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/cr.2014.35","volume":"24","author":"JF Xiang","year":"2014","unstructured":"Xiang, J.F. et al. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 24, 513\u2013531 (2014).","journal-title":"Cell Res."},{"key":"BFnsmb3227_CR41","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/nbt.3199","volume":"33","author":"IB Hilton","year":"2015","unstructured":"Hilton, I.B. et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat. Biotechnol. 33, 510\u2013517 (2015).","journal-title":"Nat. Biotechnol."},{"key":"BFnsmb3227_CR42","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1353\/foc.2012.0003","volume":"22","author":"L Delaney","year":"2012","unstructured":"Delaney, L. & Smith, J.P. Childhood health: trends and consequences over the life course. Future Child. 22, 43\u201363 (2012).","journal-title":"Future Child."},{"key":"BFnsmb3227_CR43","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/S2213-2600(13)70101-2","volume":"1","author":"DW Belsky","year":"2013","unstructured":"Belsky, D.W. et al. Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study. Lancet Respir. Med. 1, 453\u2013461 (2013).","journal-title":"Lancet Respir. Med."},{"key":"BFnsmb3227_CR44","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nbt.2884","volume":"32","author":"H Yin","year":"2014","unstructured":"Yin, H. et al. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat. Biotechnol. 32, 551\u2013553 (2014).","journal-title":"Nat. Biotechnol."},{"key":"BFnsmb3227_CR45","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.cell.2014.09.014","volume":"159","author":"RJ Platt","year":"2014","unstructured":"Platt, R.J. et al. CRISPR-Cas9 knockin mice for genome editing and cancer modeling. Cell 159, 440\u2013455 (2014).","journal-title":"Cell"},{"key":"BFnsmb3227_CR46","first-page":"G379","volume":"260","author":"KY Yeh","year":"1991","unstructured":"Yeh, K.Y., Yeh, M. & Holt, P.R. Intestinal lactase expression and epithelial cell transit in hormone-treated suckling rats. Am. J. Physiol. 260, G379\u2013G384 (1991).","journal-title":"Am. J. Physiol."},{"key":"BFnsmb3227_CR47","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1093\/jn\/129.6.1107","volume":"129","author":"T Goda","year":"1999","unstructured":"Goda, T., Yasutake, H., Tanaka, T. & Takase, S. Lactase-phlorizin hydrolase and sucrase-isomaltase genes are expressed differently along the villus-crypt axis of rat jejunum. J. Nutr. 129, 1107\u20131113 (1999).","journal-title":"J. Nutr."},{"key":"BFnsmb3227_CR48","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/1471-2105-8-186","volume":"8","author":"TE Royce","year":"2007","unstructured":"Royce, T.E., Carriero, N.J. & Gerstein, M.B. An efficient pseudomedian filter for tiling microrrays. BMC Bioinformatics 8, 186 (2007).","journal-title":"BMC Bioinformatics"},{"key":"BFnsmb3227_CR49","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","volume":"27","author":"F Krueger","year":"2011","unstructured":"Krueger, F. & Andrews, S.R. Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27, 1571\u20131572 (2011).","journal-title":"Bioinformatics"},{"key":"BFnsmb3227_CR50","doi-asserted-by":"crossref","unstructured":"1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56\u201365 (2012).","DOI":"10.1038\/nature11632"},{"key":"BFnsmb3227_CR51","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A.R. & Hall, I.M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842 (2010).","journal-title":"Bioinformatics"},{"key":"BFnsmb3227_CR52","doi-asserted-by":"publisher","first-page":"i54","DOI":"10.1093\/bioinformatics\/btp190","volume":"25","author":"M Garber","year":"2009","unstructured":"Garber, M. et al. Identifying novel constrained elements by exploiting biased substitution patterns. Bioinformatics 25, i54\u2013i62 (2009).","journal-title":"Bioinformatics"},{"key":"BFnsmb3227_CR53","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","volume":"8","author":"FA Ran","year":"2013","unstructured":"Ran, F.A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281\u20132308 (2013).","journal-title":"Nat. Protoc."},{"key":"BFnsmb3227_CR54","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.cell.2013.08.021","volume":"154","author":"FA Ran","year":"2013","unstructured":"Ran, F.A. et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154, 1380\u20131389 (2013).","journal-title":"Cell"},{"key":"BFnsmb3227_CR55","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1101\/gr.092759.109","volume":"19","author":"M Krzywinski","year":"2009","unstructured":"Krzywinski, M. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639\u20131645 (2009).","journal-title":"Genome Res."}],"container-title":["Nature Structural & Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nsmb.3227.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb.3227","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nsmb.3227.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:39:52Z","timestamp":1684456792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nsmb.3227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,9]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["BFnsmb3227"],"URL":"https:\/\/doi.org\/10.1038\/nsmb.3227","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,9]]},"assertion":[{"value":"15 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}