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Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population.

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dc.contributor.author김현숙-
dc.date.accessioned2018-07-20T08:30:09Z-
dc.date.available2018-07-20T08:30:09Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/161248-
dc.description.abstractThe diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the "a" determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of "a" determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly underappreciated.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherPublic Library of Science-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAmino Acid Substitution-
dc.subject.MESHGenotype-
dc.subject.MESHGlobal Health*-
dc.subject.MESHHepatitis B Surface Antigens/chemistry-
dc.subject.MESHHepatitis B Surface Antigens/genetics*-
dc.subject.MESHHepatitis B virus/immunology*-
dc.subject.MESHHigh-Throughput Nucleotide Sequencing*-
dc.subject.MESHHumans-
dc.subject.MESHHydrophobic and Hydrophilic Interactions-
dc.subject.MESHMutation*-
dc.titleUltra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Laboratory Medicine-
dc.contributor.googleauthorMikael Genca-
dc.contributor.googleauthorKirsten HuÈbner-
dc.contributor.googleauthorPeter Gohl-
dc.contributor.googleauthorAnja Seffner-
dc.contributor.googleauthorMichael Weizenegger-
dc.contributor.googleauthorDionysios Neofytos-
dc.contributor.googleauthorRichard Batrla-
dc.contributor.googleauthorAndreas Woeste-
dc.contributor.googleauthorHyon-suk Kim-
dc.contributor.googleauthorGaston Westergaard-
dc.contributor.googleauthorChristine Reinsch Eva Brill-
dc.contributor.googleauthorPham Thi Thu Thuy-
dc.contributor.googleauthorBui Huu Hoang-
dc.contributor.googleauthorMark Sonderup-
dc.contributor.googleauthorC. Wendy Spearman-
dc.contributor.googleauthorStephan Pabinger-
dc.contributor.googleauthorJeÂreÂmie Gautier-
dc.contributor.googleauthorGiuseppina Brancaccio-
dc.contributor.googleauthorMassimo Fasano-
dc.contributor.googleauthorTeresa Santantonio-
dc.contributor.googleauthorGiovanni B. Gaeta-
dc.contributor.googleauthorMarkus Nauck-
dc.contributor.googleauthorWolfgang E. Kaminski-
dc.identifier.doi10.1371/journal.pone.0172101-
dc.contributor.localIdA01117-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid28472040-
dc.contributor.alternativeNameKim, Hyon Suk-
dc.contributor.affiliatedAuthorKim, Hyon Suk-
dc.citation.volume12-
dc.citation.number5-
dc.citation.startPagee0172101-
dc.identifier.bibliographicCitationPLOS ONE, Vol.12(5) : e0172101, 2017-
dc.identifier.rimsid61170-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers

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