Identification of a candidate gene associated with isoflavone content in soybean seeds using genome-wide association and linkage mapping.
Identifieur interne : 000162 ( Main/Exploration ); précédent : 000161; suivant : 000163Identification of a candidate gene associated with isoflavone content in soybean seeds using genome-wide association and linkage mapping.
Auteurs : Depeng Wu [République populaire de Chine] ; Dongmei Li [République populaire de Chine] ; Xue Zhao [République populaire de Chine] ; Yuhang Zhan [République populaire de Chine] ; Weili Teng [République populaire de Chine] ; Lijuan Qiu [République populaire de Chine] ; Hongkun Zheng [République populaire de Chine] ; Wenbin Li [République populaire de Chine] ; Yingpeng Han [République populaire de Chine]Source :
- The Plant journal : for cell and molecular biology [ 1365-313X ] ; 2020.
Abstract
Isoflavone, a secondary metabolite produced by Glycine max (L.) Merr. (soybean), is valuable for human and plant health. The genetic architecture of soybean isoflavone content remains unclear, however, despite several mapping studies. We generated genomic data for 200 soybean cultivars and 150 recombinant inbred lines (RILs) to localize putative loci associated with soybean seed isoflavone content. Using a genome-wide association study (GWAS), we identified 87 single-nucleotide polymorphisms (SNPs) that were significantly associated with isoflavone concentration. Using linkage mapping, we identified 37 quantitative trait loci (QTLs) underlying the content of four isoflavones found in the RILs. A major locus on chromosome 8 (qISO8-1) was co-located by both the GWAS and linkage mapping. qISO8-1 was fine mapped to a 99.5-kb region, flanked by SSR_08_1651 and SSR_08_1656, in a BC2 F5 population. GmMPK1, encoding a mitogen-activated protein kinase, was identified as the causal gene in qISO8-1, and two natural GmMPK1 polymorphisms were significantly associated with isoflavone content. Overexpression of GmMPK1 in soybean hairy roots resulted in increased isoflavone concentrations. Overexpressing GmMPK1 in transgenic soybeans had greater resistance to Phytophthora root rot, suggesting that GmMPK1 might increase soybean resistance to biotic stress by influencing isoflavone content. Our results not only increase our understanding of the genetic architecture of soybean seed isoflavone content, but also provide a framework for the future marker-assisted breeding of high isoflavone content in soybean cultivars.
DOI: 10.1111/tpj.14972
PubMed: 32862479
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150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Qiu, Lijuan" sort="Qiu, Lijuan" uniqKey="Qiu L" first="Lijuan" last="Qiu">Lijuan Qiu</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Crop Science, National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI), Chinese Academy of Agricultural Sciences, Beijing, 100081, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Crop Science, National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI), Chinese Academy of Agricultural Sciences, Beijing, 100081</wicri:regionArea><wicri:noRegion>100081</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Hongkun" sort="Zheng, Hongkun" uniqKey="Zheng H" first="Hongkun" last="Zheng">Hongkun Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Bioinformatics Division, Biomarker Technologies Corporation, Beijing, 101300, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bioinformatics Division, Biomarker Technologies Corporation, Beijing, 101300</wicri:regionArea><wicri:noRegion>101300</wicri:noRegion></affiliation></author><author><name sortKey="Li, Wenbin" sort="Li, Wenbin" uniqKey="Li W" first="Wenbin" last="Li">Wenbin Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Han, Yingpeng" sort="Han, Yingpeng" uniqKey="Han Y" first="Yingpeng" last="Han">Yingpeng Han</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32862479</idno><idno 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China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Li, Dongmei" sort="Li, Dongmei" uniqKey="Li D" first="Dongmei" last="Li">Dongmei Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Xue" sort="Zhao, Xue" uniqKey="Zhao X" first="Xue" last="Zhao">Xue Zhao</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Zhan, Yuhang" sort="Zhan, Yuhang" uniqKey="Zhan Y" first="Yuhang" last="Zhan">Yuhang Zhan</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Teng, Weili" sort="Teng, Weili" uniqKey="Teng W" first="Weili" last="Teng">Weili Teng</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Qiu, Lijuan" sort="Qiu, Lijuan" uniqKey="Qiu L" first="Lijuan" last="Qiu">Lijuan Qiu</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Crop Science, National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI), Chinese Academy of Agricultural Sciences, Beijing, 100081, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Crop Science, National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI), Chinese Academy of Agricultural Sciences, Beijing, 100081</wicri:regionArea><wicri:noRegion>100081</wicri:noRegion></affiliation></author><author><name sortKey="Zheng, Hongkun" sort="Zheng, Hongkun" uniqKey="Zheng H" first="Hongkun" last="Zheng">Hongkun Zheng</name><affiliation wicri:level="1"><nlm:affiliation>Bioinformatics Division, Biomarker Technologies Corporation, Beijing, 101300, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Bioinformatics Division, Biomarker Technologies Corporation, Beijing, 101300</wicri:regionArea><wicri:noRegion>101300</wicri:noRegion></affiliation></author><author><name sortKey="Li, Wenbin" sort="Li, Wenbin" uniqKey="Li W" first="Wenbin" last="Li">Wenbin Li</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author><author><name sortKey="Han, Yingpeng" sort="Han, Yingpeng" uniqKey="Han Y" first="Yingpeng" last="Han">Yingpeng Han</name><affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030</wicri:regionArea><wicri:noRegion>150030</wicri:noRegion></affiliation></author></analytic><series><title level="j">The Plant journal : for cell and molecular biology</title><idno type="eISSN">1365-313X</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Isoflavone, a secondary metabolite produced by Glycine max (L.) Merr. (soybean), is valuable for human and plant health. The genetic architecture of soybean isoflavone content remains unclear, however, despite several mapping studies. We generated genomic data for 200 soybean cultivars and 150 recombinant inbred lines (RILs) to localize putative loci associated with soybean seed isoflavone content. Using a genome-wide association study (GWAS), we identified 87 single-nucleotide polymorphisms (SNPs) that were significantly associated with isoflavone concentration. Using linkage mapping, we identified 37 quantitative trait loci (QTLs) underlying the content of four isoflavones found in the RILs. A major locus on chromosome 8 (qISO8-1) was co-located by both the GWAS and linkage mapping. qISO8-1 was fine mapped to a 99.5-kb region, flanked by SSR_08_1651 and SSR_08_1656, in a BC<sub>2</sub> F<sub>5</sub> population. GmMPK1, encoding a mitogen-activated protein kinase, was identified as the causal gene in qISO8-1, and two natural GmMPK1 polymorphisms were significantly associated with isoflavone content. Overexpression of GmMPK1 in soybean hairy roots resulted in increased isoflavone concentrations. Overexpressing GmMPK1 in transgenic soybeans had greater resistance to Phytophthora root rot, suggesting that GmMPK1 might increase soybean resistance to biotic stress by influencing isoflavone content. Our results not only increase our understanding of the genetic architecture of soybean seed isoflavone content, but also provide a framework for the future marker-assisted breeding of high isoflavone content in soybean cultivars.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32862479</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1365-313X</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Aug</Month><Day>30</Day></PubDate></JournalIssue><Title>The Plant journal : for cell and molecular biology</Title><ISOAbbreviation>Plant J</ISOAbbreviation></Journal><ArticleTitle>Identification of a candidate gene associated with isoflavone content in soybean seeds using genome-wide association and linkage mapping.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1111/tpj.14972</ELocationID><Abstract><AbstractText>Isoflavone, a secondary metabolite produced by Glycine max (L.) Merr. (soybean), is valuable for human and plant health. The genetic architecture of soybean isoflavone content remains unclear, however, despite several mapping studies. We generated genomic data for 200 soybean cultivars and 150 recombinant inbred lines (RILs) to localize putative loci associated with soybean seed isoflavone content. Using a genome-wide association study (GWAS), we identified 87 single-nucleotide polymorphisms (SNPs) that were significantly associated with isoflavone concentration. Using linkage mapping, we identified 37 quantitative trait loci (QTLs) underlying the content of four isoflavones found in the RILs. A major locus on chromosome 8 (qISO8-1) was co-located by both the GWAS and linkage mapping. qISO8-1 was fine mapped to a 99.5-kb region, flanked by SSR_08_1651 and SSR_08_1656, in a BC<sub>2</sub> F<sub>5</sub> population. GmMPK1, encoding a mitogen-activated protein kinase, was identified as the causal gene in qISO8-1, and two natural GmMPK1 polymorphisms were significantly associated with isoflavone content. Overexpression of GmMPK1 in soybean hairy roots resulted in increased isoflavone concentrations. Overexpressing GmMPK1 in transgenic soybeans had greater resistance to Phytophthora root rot, suggesting that GmMPK1 might increase soybean resistance to biotic stress by influencing isoflavone content. Our results not only increase our understanding of the genetic architecture of soybean seed isoflavone content, but also provide a framework for the future marker-assisted breeding of high isoflavone content in soybean cultivars.</AbstractText><CopyrightInformation>© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Depeng</ForeName><Initials>D</Initials><Identifier Source="ORCID">https://orcid.org/0000-0002-3905-7587</Identifier><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Dongmei</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Xue</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhan</LastName><ForeName>Yuhang</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Teng</LastName><ForeName>Weili</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qiu</LastName><ForeName>Lijuan</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Institute of Crop Science, National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI), Chinese Academy of Agricultural Sciences, Beijing, 100081, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Hongkun</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Bioinformatics Division, Biomarker Technologies Corporation, Beijing, 101300, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Wenbin</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Yingpeng</ForeName><Initials>Y</Initials><Identifier Source="ORCID">https://orcid.org/0000-0002-9829-6588</Identifier><AffiliationInfo><Affiliation>Key Laboratory of Soybean Biology in Chinese Ministry of Education (Key Laboratory of Soybean Biology and Breeding/Genetics of Chinese Agriculture Ministry), Northeast Agricultural University, Harbin, 150030, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>The National Ten-thousand Talents Program</Agency><Country></Country></Grant><Grant><GrantID>2015RA228</GrantID><Agency>the Youth Leading Talent Project of the Ministry of Science and Technology in China</Agency><Country></Country></Grant><Grant><GrantID>2014BAD22B01</GrantID><Agency>the National Project</Agency><Country></Country></Grant><Grant><GrantID>2016ZX08004001-007</GrantID><Agency>the National Project</Agency><Country></Country></Grant><Grant><GrantID>CARS-04-PS04</GrantID><Agency>the National Project</Agency><Country></Country></Grant><Grant><GrantID>31471517</GrantID><Agency>the Chinese National Natural Science Foundation</Agency><Country></Country></Grant><Grant><GrantID>31671717</GrantID><Agency>the Chinese National Natural Science Foundation</Agency><Country></Country></Grant><Grant><GrantID>31871650</GrantID><Agency>the Chinese National Natural Science Foundation</Agency><Country></Country></Grant><Grant><GrantID>31971967</GrantID><Agency>the Chinese National Natural Science Foundation</Agency><Country></Country></Grant><Grant><GrantID>C2018016</GrantID><Agency>Heilongjiang Provincial Project</Agency><Country></Country></Grant><Grant><GrantID>GJ2018GJ0098</GrantID><Agency>Heilongjiang Provincial Project</Agency><Country></Country></Grant><Grant><GrantID>GX17B002</GrantID><Agency>Heilongjiang Provincial Project</Agency><Country></Country></Grant><Grant><GrantID>JC2018007</GrantID><Agency>Heilongjiang Provincial Project</Agency><Country></Country></Grant><Grant><GrantID>17XG22</GrantID><Agency>the 'Academic Backbone' Project of Northeast Agricultural University</Agency><Country></Country></Grant><Grant><GrantID>LBH-Q17015</GrantID><Agency>Postdoctoral Fund in Heilongjiang Province</Agency><Country></Country></Grant><Grant><GrantID>LBH-Z15017</GrantID><Agency>Postdoctoral Fund in Heilongjiang Province</Agency><Country></Country></Grant><Grant><GrantID>2016YFD0100304</GrantID><Agency>National Key R & D Project</Agency><Country></Country></Grant><Grant><GrantID>2017YFD0101302</GrantID><Agency>National Key R & D Project</Agency><Country></Country></Grant><Grant><GrantID>2017YFD0101306</GrantID><Agency>National Key R & D Project</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>08</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Plant J</MedlineTA><NlmUniqueID>9207397</NlmUniqueID><ISSNLinking>0960-7412</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MPK
</Keyword><Keyword MajorTopicYN="N">GWAS</Keyword><Keyword MajorTopicYN="N">QTL</Keyword><Keyword MajorTopicYN="N">isoflavone</Keyword><Keyword MajorTopicYN="N">linkage maps</Keyword><Keyword MajorTopicYN="N">soybean</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>12</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>07</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>08</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>8</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>8</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>8</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>aheadofprint</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32862479</ArticleId><ArticleId IdType="doi">10.1111/tpj.14972</ArticleId></ArticleIdList><ReferenceList><Title>REFERENCES</Title><Reference><Citation>Akond, M., Liu, S., Kantartzi, S.K., Meksem, K., Bellaloui, N., Lightfoot, D.A., Yuan, J., Wang, D., Anderson, J. and Kassem, M.A.J.P.B. 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