{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:11Z","timestamp":1772160071671,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T00:00:00Z","timestamp":1658620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFC1000700"],"award-info":[{"award-number":["2016YFC1000700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFC1000704"],"award-info":[{"award-number":["2016YFC1000704"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071066"],"award-info":[{"award-number":["82071066"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700900"],"award-info":[{"award-number":["81700900"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The frequency of the pathogenic allele of the autosomal recessive deafness gene GJB2 varies among different populations in the world, and accumulates to a sufficiently high frequency in certain population. The purpose of this study is to investigate the origin and evolution of GJB2 pathogenic alleles in Chinese deaf patients. Children with non\u2010syndromic hearing loss, and their parents, from 295 families were recruited. Customized capture probes targeted at 943 single nucleotide polymorphisms (SNPs) related to GJB2 gene were designed for sequencing of genomic DNA in blood samples. Haplotypes carrying pathogenic allele were analyzed through linkage disequilibrium block building, ancestry tracing, and extended haplotype heterozygosity calculation. Two pathogenic GJB2 alleles, c.235delC (18.41%) and c.109G\u2009&gt;\u2009A (15.57%), were observed in 867 donors. For c.235delC allele, three different core haplotypes with one major haplotype (97.32%) were found, and their core SNPs were 100% conserved. For c.109G\u2009&gt;\u2009A allele, six different haplotypes with one major haplotype (93.28%) were found and the major c.109G\u2009&gt;\u2009A allele evolved from a specific ancestral haplotype. Geographical origins of donors carrying GJB2 c.109G\u2009&gt;\u2009A and c.235delC core haplotypes centered between Qinghai and Neimenggu. GJB2 c.235delC has long\u2010range linkage disequilibrium. No positive selection signature was found for GJB2 c.235delC or c.109G\u2009&gt;\u2009A in the studied population. In conclusion, we discovered a single origin of GJB2 c.235delC allele and multiple independent origins of GJB2 c.109G\u2009&gt;\u2009A allele. Alternative to positive selection or multiple independent recurrent mutation event, population bottleneck effect might account for the observed high population frequency of these pathogenic alleles.<\/jats:p>","DOI":"10.1111\/cge.14191","type":"journal-article","created":{"date-parts":[[2022,7,16]],"date-time":"2022-07-16T06:38:44Z","timestamp":1657953524000},"page":"305-313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evolutionary origin of pathogenic\n                    <scp>GJB2<\/scp>\n                    alleles in China"],"prefix":"10.1111","volume":"102","author":[{"given":"Yi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Ear Institute Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Institute of Otolaryngology, Chinese PLA General Hospital  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery National Clinical Research Center for Otolaryngologic Diseases  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery Key Lab of Hearing Impairment Science of Ministry of Education  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery Key Lab of Hearing Impairment Prevention and Treatment of Beijing  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Research and Development Euler Technology  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Fang","sequence":"additional","affiliation":[{"name":"Research and Development Center Beijing Scisoon Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Research and Development Center Beijing Scisoon Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunchao","family":"Liu","sequence":"additional","affiliation":[{"name":"Research and Development Center Beijing Scisoon Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Bai","sequence":"additional","affiliation":[{"name":"Research and Development Center Beijing Scisoon Biotechnology Co., Ltd.  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Institute of Otolaryngology, Chinese PLA General Hospital  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery National Clinical Research Center for Otolaryngologic Diseases  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery Key Lab of Hearing Impairment Science of Ministry of Education  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery Key Lab of Hearing Impairment Prevention and Treatment of Beijing  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pu","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery Institute of Otolaryngology, Chinese PLA General Hospital  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery National Clinical Research Center for Otolaryngologic Diseases  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery Key Lab of Hearing Impairment Science of Ministry of Education  Beijing China"},{"name":"College of Otolaryngology Head and Neck Surgery Key Lab of Hearing Impairment Prevention and Treatment of Beijing  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.35.102401.091224"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/380205"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-1018-1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1779-6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.101"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11070833"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.8.515"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199811193392103"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36042"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.06.038"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/amiajnl-2011-000652"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4934"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.12969"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01140"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0003489415575060"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11030250"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.042051"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-7-26"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-6-12"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10060429"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209797"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125416"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01407.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.10.016"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba0909"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1113"}],"container-title":["Clinical 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