RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease
Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the develo...
Gespeichert in:
Veröffentlicht in: | PloS one 2014-06, Vol.9 (6), p.e98957-e98957 |
---|---|
Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | e98957 |
---|---|
container_issue | 6 |
container_start_page | e98957 |
container_title | PloS one |
container_volume | 9 |
creator | Vaclavikova, Eliska Dvorakova, Sarka Skaba, Richard Pos, Lucie Sykorova, Vlasta Halkova, Tereza Vcelak, Josef Bendlova, Bela |
description | Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p |
doi_str_mv | 10.1371/journal.pone.0098957 |
format | Article |
fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1532653305</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A416975561</galeid><doaj_id>oai_doaj_org_article_751acbf3bec54d5083d9e5825014d151</doaj_id><sourcerecordid>A416975561</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</originalsourceid><addsrcrecordid>eNqNk01v1DAQhiMEomXhHyCIhITgsIsdfyS5IFWrQleqVKkULhysWWeycZWNUzspLL8ep5tWG9QD8iG287yvZ8aeKHpNyYKylH66tr1roF60tsEFIXmWi_RJdExzlsxlQtjTg_lR9ML7a0IEy6R8Hh0lPMtTmsjj6Ofl6VV8C85A0_kYmiKuoK1tt2sxrKDeeeNj08QQa1tZ18W2jJd_UFdxC53BQfTLdFV8ZpzXlW9d32ziwngEjy-jZyXUHl-N31n0_cvp1fJsfn7xdbU8OZ9rmSfdvEhzzoUgAIRjRgjJpF6ngicslVgIypCBlDxP2DrDIgdKy7VIATWC4LlM2Sx6u_cNgXs11sUrKlgiBWMh61m02hOFhWvVOrMFt1MWjLrbsG6jwHVG16hSQUGvS7ZGLXghSMaKHEWWCEJ5QUM0s-jzeFq_3mKhQw0c1BPT6Z_GVGpjbxUnXGREBoMPo4GzNz36Tm2N11jX0KDt7-LmlIQxxP3uH_Tx7EZqAyEB05Q2nKsHU3XCqcxTIeQQ9-IRKowCt0aHR1SasD8RfJwIAtPh724Dvfdq9e3y_9mLH1P2_QFbIdRd5W3dd8Y2fgryPaid9d5h-VBkStTQA_fVUEMPqLEHguzN4QU9iO4fPfsLAyEAQg</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1532653305</pqid></control><display><type>article</type><title>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Vaclavikova, Eliska ; Dvorakova, Sarka ; Skaba, Richard ; Pos, Lucie ; Sykorova, Vlasta ; Halkova, Tereza ; Vcelak, Josef ; Bendlova, Bela</creator><contributor>Miao, Xiaoping</contributor><creatorcontrib>Vaclavikova, Eliska ; Dvorakova, Sarka ; Skaba, Richard ; Pos, Lucie ; Sykorova, Vlasta ; Halkova, Tereza ; Vcelak, Josef ; Bendlova, Bela ; Miao, Xiaoping</creatorcontrib><description>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p<0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0098957</identifier><identifier>PMID: 24897126</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alleles ; Analysis ; Biology and Life Sciences ; Case-Control Studies ; Chromosomes ; Clustering ; Congenital diseases ; Czech Republic ; Endocrinology ; Exons ; Female ; Females ; Follow-Up Studies ; Gene expression ; Genetic Markers ; Genetics ; Genotype ; Genotyping ; Haplotypes ; Haplotypes - genetics ; Hirschsprung Disease - genetics ; Hirschsprung's disease ; Humans ; Intestine ; Kinases ; Male ; Males ; Medicine and Health Sciences ; Mutation ; Pathogenesis ; Patients ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide - genetics ; Population genetics ; Prognosis ; Prospective Studies ; Proto-Oncogene Proteins c-ret - genetics ; Pruning ; Ret protein ; Retrospective Studies ; Risk ; Sequence Analysis, DNA ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Statistical tests ; Thyroid cancer</subject><ispartof>PloS one, 2014-06, Vol.9 (6), p.e98957-e98957</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Vaclavikova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Vaclavikova et al 2014 Vaclavikova et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</citedby><cites>FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045806/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045806/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24897126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Miao, Xiaoping</contributor><creatorcontrib>Vaclavikova, Eliska</creatorcontrib><creatorcontrib>Dvorakova, Sarka</creatorcontrib><creatorcontrib>Skaba, Richard</creatorcontrib><creatorcontrib>Pos, Lucie</creatorcontrib><creatorcontrib>Sykorova, Vlasta</creatorcontrib><creatorcontrib>Halkova, Tereza</creatorcontrib><creatorcontrib>Vcelak, Josef</creatorcontrib><creatorcontrib>Bendlova, Bela</creatorcontrib><title>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p<0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</description><subject>Alleles</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Case-Control Studies</subject><subject>Chromosomes</subject><subject>Clustering</subject><subject>Congenital diseases</subject><subject>Czech Republic</subject><subject>Endocrinology</subject><subject>Exons</subject><subject>Female</subject><subject>Females</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Genetic Markers</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Hirschsprung Disease - genetics</subject><subject>Hirschsprung's disease</subject><subject>Humans</subject><subject>Intestine</subject><subject>Kinases</subject><subject>Male</subject><subject>Males</subject><subject>Medicine and Health Sciences</subject><subject>Mutation</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Population genetics</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Proto-Oncogene Proteins c-ret - genetics</subject><subject>Pruning</subject><subject>Ret protein</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Sequence Analysis, DNA</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical tests</subject><subject>Thyroid cancer</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEomXhHyCIhITgsIsdfyS5IFWrQleqVKkULhysWWeycZWNUzspLL8ep5tWG9QD8iG287yvZ8aeKHpNyYKylH66tr1roF60tsEFIXmWi_RJdExzlsxlQtjTg_lR9ML7a0IEy6R8Hh0lPMtTmsjj6Ofl6VV8C85A0_kYmiKuoK1tt2sxrKDeeeNj08QQa1tZ18W2jJd_UFdxC53BQfTLdFV8ZpzXlW9d32ziwngEjy-jZyXUHl-N31n0_cvp1fJsfn7xdbU8OZ9rmSfdvEhzzoUgAIRjRgjJpF6ngicslVgIypCBlDxP2DrDIgdKy7VIATWC4LlM2Sx6u_cNgXs11sUrKlgiBWMh61m02hOFhWvVOrMFt1MWjLrbsG6jwHVG16hSQUGvS7ZGLXghSMaKHEWWCEJ5QUM0s-jzeFq_3mKhQw0c1BPT6Z_GVGpjbxUnXGREBoMPo4GzNz36Tm2N11jX0KDt7-LmlIQxxP3uH_Tx7EZqAyEB05Q2nKsHU3XCqcxTIeQQ9-IRKowCt0aHR1SasD8RfJwIAtPh724Dvfdq9e3y_9mLH1P2_QFbIdRd5W3dd8Y2fgryPaid9d5h-VBkStTQA_fVUEMPqLEHguzN4QU9iO4fPfsLAyEAQg</recordid><startdate>20140604</startdate><enddate>20140604</enddate><creator>Vaclavikova, Eliska</creator><creator>Dvorakova, Sarka</creator><creator>Skaba, Richard</creator><creator>Pos, Lucie</creator><creator>Sykorova, Vlasta</creator><creator>Halkova, Tereza</creator><creator>Vcelak, Josef</creator><creator>Bendlova, Bela</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140604</creationdate><title>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</title><author>Vaclavikova, Eliska ; Dvorakova, Sarka ; Skaba, Richard ; Pos, Lucie ; Sykorova, Vlasta ; Halkova, Tereza ; Vcelak, Josef ; Bendlova, Bela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-d7944550aa04e800086cb7542376ed513e3a664923b8ed9a11fb57aecea549673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alleles</topic><topic>Analysis</topic><topic>Biology and Life Sciences</topic><topic>Case-Control Studies</topic><topic>Chromosomes</topic><topic>Clustering</topic><topic>Congenital diseases</topic><topic>Czech Republic</topic><topic>Endocrinology</topic><topic>Exons</topic><topic>Female</topic><topic>Females</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Genetic Markers</topic><topic>Genetics</topic><topic>Genotype</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Hirschsprung Disease - genetics</topic><topic>Hirschsprung's disease</topic><topic>Humans</topic><topic>Intestine</topic><topic>Kinases</topic><topic>Male</topic><topic>Males</topic><topic>Medicine and Health Sciences</topic><topic>Mutation</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Population genetics</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Proto-Oncogene Proteins c-ret - genetics</topic><topic>Pruning</topic><topic>Ret protein</topic><topic>Retrospective Studies</topic><topic>Risk</topic><topic>Sequence Analysis, DNA</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical tests</topic><topic>Thyroid cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vaclavikova, Eliska</creatorcontrib><creatorcontrib>Dvorakova, Sarka</creatorcontrib><creatorcontrib>Skaba, Richard</creatorcontrib><creatorcontrib>Pos, Lucie</creatorcontrib><creatorcontrib>Sykorova, Vlasta</creatorcontrib><creatorcontrib>Halkova, Tereza</creatorcontrib><creatorcontrib>Vcelak, Josef</creatorcontrib><creatorcontrib>Bendlova, Bela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vaclavikova, Eliska</au><au>Dvorakova, Sarka</au><au>Skaba, Richard</au><au>Pos, Lucie</au><au>Sykorova, Vlasta</au><au>Halkova, Tereza</au><au>Vcelak, Josef</au><au>Bendlova, Bela</au><au>Miao, Xiaoping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-06-04</date><risdate>2014</risdate><volume>9</volume><issue>6</issue><spage>e98957</spage><epage>e98957</epage><pages>e98957-e98957</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses in variable length of the intestine. This study investigated the influence and a possible modifying function of RET proto-oncogene's single nucleotide polymorphisms (SNPs) and haplotypes in the development and phenotype of the disease in Czech patients. Genotyping of 14 SNPs was performed using TaqMan Genotyping Assays and direct sequencing. The frequencies of SNPs and generated haplotypes were statistically evaluated using chi-square test and the association with the risk of HSCR was estimated by odds ratio. SNP analysis revealed significant differences in frequencies of 11 polymorphic RET variants between 162 HSCR patients and 205 unaffected controls. Particularly variant alleles of rs1864410, rs2435357, rs2506004 (intron 1), rs1800858 (exon 2), rs1800861 (exon 13), and rs2565200 (intron 19) were strongly associated with increased risk of HSCR (p<0.00000) and were over-represented in males vs. females. Conversely, variant alleles of rs1800860, rs1799939 and rs1800863 (exons 7, 11, 15) had a protective role. The haploblock comprising variants in intron 1 and exon 2 was constructed. It represented a high risk of HSCR, however, the influence of other variants was also found after pruning from effect of this haploblock. Clustering patients according to genotype status in haploblock revealed a strong co-segregation with several SNPs and pointed out the differences between long and short form of HSCR. This study involved a large number of SNPs along the entire RET proto-oncogene with demonstration of their risk/protective role also in haplotype and diplotype analysis in the Czech population. The influence of some variant alleles on the aggressiveness of the disease and their role in gender manifestation differences was found. These data contribute to worldwide knowledge of the genetics of HSCR.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24897126</pmid><doi>10.1371/journal.pone.0098957</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2014-06, Vol.9 (6), p.e98957-e98957 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1532653305 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Alleles Analysis Biology and Life Sciences Case-Control Studies Chromosomes Clustering Congenital diseases Czech Republic Endocrinology Exons Female Females Follow-Up Studies Gene expression Genetic Markers Genetics Genotype Genotyping Haplotypes Haplotypes - genetics Hirschsprung Disease - genetics Hirschsprung's disease Humans Intestine Kinases Male Males Medicine and Health Sciences Mutation Pathogenesis Patients Polymerase Chain Reaction Polymorphism, Single Nucleotide - genetics Population genetics Prognosis Prospective Studies Proto-Oncogene Proteins c-ret - genetics Pruning Ret protein Retrospective Studies Risk Sequence Analysis, DNA Single nucleotide polymorphisms Single-nucleotide polymorphism Statistical tests Thyroid cancer |
title | RET variants and haplotype analysis in a cohort of Czech patients with Hirschsprung disease |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T06%3A23%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=RET%20variants%20and%20haplotype%20analysis%20in%20a%20cohort%20of%20Czech%20patients%20with%20Hirschsprung%20disease&rft.jtitle=PloS%20one&rft.au=Vaclavikova,%20Eliska&rft.date=2014-06-04&rft.volume=9&rft.issue=6&rft.spage=e98957&rft.epage=e98957&rft.pages=e98957-e98957&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0098957&rft_dat=%3Cgale_plos_%3EA416975561%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1532653305&rft_id=info:pmid/24897126&rft_galeid=A416975561&rft_doaj_id=oai_doaj_org_article_751acbf3bec54d5083d9e5825014d151&rfr_iscdi=true |