Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function
Background: Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mi...
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| Veröffentlicht in: | Journal of medical genetics 2006-03, Vol.43 (3), p.e13-e13 |
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| creator | Cao, X Eu, K W Kumarasinghe, M P Li, H H Loi, C Cheah, P Y |
| description | Background: Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis-carcinoma sequence in both hereditary and sporadic CRC. Methods/Results: We performed a genomewide linkage search on 15 members of a three-generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi-point logarithm of the odds (LOD) score of 4.6 (p |
| doi_str_mv | 10.1136/jmg.2005.034827 |
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Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis-carcinoma sequence in both hereditary and sporadic CRC. Methods/Results: We performed a genomewide linkage search on 15 members of a three-generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi-point logarithm of the odds (LOD) score of 4.6 (p<0.001). The 10q23.1–10q23.31 haplotypes segregate with the disease in both families. We screened for mutations in four candidate genes within the linkage region and identified an 11 bp deletion in the bone morphogenesis protein receptor 1A (BMPR1A) gene in one family. Conclusions: Our results indicate that BMPR1A mutation accounts for HMPS. The data suggest that inactivating BMPR1A can initiate colorectal tumourigenesis via the mixed polyposis-carcinoma sequence.</description><identifier>ISSN: 0022-2593</identifier><identifier>ISSN: 1468-6244</identifier><identifier>EISSN: 1468-6244</identifier><identifier>DOI: 10.1136/jmg.2005.034827</identifier><identifier>PMID: 16525031</identifier><identifier>CODEN: JMDGAE</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd</publisher><subject>Adenomatous Polyposis Coli - genetics ; Automation ; Bone Morphogenetic Protein Receptors, Type I - genetics ; Chromosome Mapping ; Chromosomes, Human, Pair 10 ; Colorectal cancer ; Colorectal Neoplasms - genetics ; CRC ; Deoxyribonucleic acid ; DNA ; Electronic Letter ; familial adenomatous polyposis ; FAP ; Female ; GDAS ; Genechip DNA Analysis ; Genes ; Genome, Human ; Genomes ; Genotype ; haplotype ; Haplotypes ; hereditary mixed polyposis syndrome ; Histology ; HMPS ; Humans ; intestinal stem cell ; ISC ; JPS ; juvenile polyposis syndrome ; linkage ; LOD ; logarithm of the odds ; Male ; Microsatellite Repeats ; mixed polyposis ; Morphology ; Mutation ; Patients ; PCR ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; SGH ; Singapore General Hospital ; Software ; Tumors ; whole-genome SNP genotyping</subject><ispartof>Journal of medical genetics, 2006-03, Vol.43 (3), p.e13-e13</ispartof><rights>Copyright 2006 Journal of Medical Genetics</rights><rights>Copyright: 2006 Copyright 2006 Journal of Medical Genetics</rights><rights>Copyright ©2006 BMJ Publishing Group Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b523t-85925f06aa47377c298ba7616c22d2cc284350c58317910b7e20633283cb2c1d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jmg.bmj.com/content/43/3/e13.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttps://jmg.bmj.com/content/43/3/e13.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,727,780,784,885,3196,23571,27924,27925,53791,53793,77600,77631</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16525031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, X</creatorcontrib><creatorcontrib>Eu, K W</creatorcontrib><creatorcontrib>Kumarasinghe, M P</creatorcontrib><creatorcontrib>Li, H H</creatorcontrib><creatorcontrib>Loi, C</creatorcontrib><creatorcontrib>Cheah, P Y</creatorcontrib><title>Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function</title><title>Journal of medical genetics</title><addtitle>J Med Genet</addtitle><description>Background: Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis-carcinoma sequence in both hereditary and sporadic CRC. Methods/Results: We performed a genomewide linkage search on 15 members of a three-generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi-point logarithm of the odds (LOD) score of 4.6 (p<0.001). The 10q23.1–10q23.31 haplotypes segregate with the disease in both families. We screened for mutations in four candidate genes within the linkage region and identified an 11 bp deletion in the bone morphogenesis protein receptor 1A (BMPR1A) gene in one family. Conclusions: Our results indicate that BMPR1A mutation accounts for HMPS. The data suggest that inactivating BMPR1A can initiate colorectal tumourigenesis via the mixed polyposis-carcinoma sequence.</description><subject>Adenomatous Polyposis Coli - genetics</subject><subject>Automation</subject><subject>Bone Morphogenetic Protein Receptors, Type I - genetics</subject><subject>Chromosome Mapping</subject><subject>Chromosomes, Human, Pair 10</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - genetics</subject><subject>CRC</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Electronic Letter</subject><subject>familial adenomatous polyposis</subject><subject>FAP</subject><subject>Female</subject><subject>GDAS</subject><subject>Genechip DNA Analysis</subject><subject>Genes</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Genotype</subject><subject>haplotype</subject><subject>Haplotypes</subject><subject>hereditary mixed polyposis syndrome</subject><subject>Histology</subject><subject>HMPS</subject><subject>Humans</subject><subject>intestinal stem cell</subject><subject>ISC</subject><subject>JPS</subject><subject>juvenile polyposis syndrome</subject><subject>linkage</subject><subject>LOD</subject><subject>logarithm of the odds</subject><subject>Male</subject><subject>Microsatellite Repeats</subject><subject>mixed polyposis</subject><subject>Morphology</subject><subject>Mutation</subject><subject>Patients</subject><subject>PCR</subject><subject>Pedigree</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Single Nucleotide</subject><subject>SGH</subject><subject>Singapore General Hospital</subject><subject>Software</subject><subject>Tumors</subject><subject>whole-genome SNP genotyping</subject><issn>0022-2593</issn><issn>1468-6244</issn><issn>1468-6244</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</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><recordid>eNqFkl1v0zAUhiMEYmVwzR2yhIQ2pHT2cWKnN0hbBSvSOqq1wKXlOG7jLrGzOIH1v_HjcNRqfNzsyjrnfXy-9EbRa4LHhFB2tq03Y8A4HWOaZMCfRCOSsCxmkCRPoxHGADGkE3oUvfB-izGhnLDn0RFhKaSYklH0ay6bxtgNcmtU6lYXppPtDtXmXheocdWucd545He2aF2t0clsvlieos4hVYaE80OS4DugKN-hjbYh_mkKjUqzKeNCW2-6HfKhQ6WR7VWlXTfIQ-natU1pfI1OlteLU-SVtEjaAgXddmZtlOyMs8NkF_PFDTlHlfN-CNe9VYP0Mnq2lpXXrw7vcfT108fVdBZffbn8PD2_ivMUaBdn6QTSNWZSJpxyrmCS5ZIzwhRAAUpBltAUqzSjhE8IzrkGzCiFjKocFCnocfRhX7fp81oXKozXyko0ranDsYSTRvyrWFOKjfshIGUUEhoKvDsUaN1dr30nauOVrippteu9YJxToAl7FCScAFBKAvj2P3Dr-taGKwQmI4SFrjxQZ3tKteF0rV4_zEywGAwkgoHEYCCxN1D48ebvVf_wB8cEIN4Dxnf6_kGX7W3YgvJUXH-biovvS3a5ulmJWeDf7_m83j7a_Te1Wd8u</recordid><startdate>20060301</startdate><enddate>20060301</enddate><creator>Cao, X</creator><creator>Eu, K W</creator><creator>Kumarasinghe, M P</creator><creator>Li, H H</creator><creator>Loi, C</creator><creator>Cheah, P Y</creator><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060301</creationdate><title>Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function</title><author>Cao, X ; Eu, K W ; Kumarasinghe, M P ; Li, H H ; Loi, C ; Cheah, P Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b523t-85925f06aa47377c298ba7616c22d2cc284350c58317910b7e20633283cb2c1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adenomatous Polyposis Coli - genetics</topic><topic>Automation</topic><topic>Bone Morphogenetic Protein Receptors, Type I - genetics</topic><topic>Chromosome Mapping</topic><topic>Chromosomes, Human, Pair 10</topic><topic>Colorectal cancer</topic><topic>Colorectal Neoplasms - genetics</topic><topic>CRC</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Electronic Letter</topic><topic>familial adenomatous polyposis</topic><topic>FAP</topic><topic>Female</topic><topic>GDAS</topic><topic>Genechip DNA Analysis</topic><topic>Genes</topic><topic>Genome, Human</topic><topic>Genomes</topic><topic>Genotype</topic><topic>haplotype</topic><topic>Haplotypes</topic><topic>hereditary mixed polyposis syndrome</topic><topic>Histology</topic><topic>HMPS</topic><topic>Humans</topic><topic>intestinal stem cell</topic><topic>ISC</topic><topic>JPS</topic><topic>juvenile polyposis syndrome</topic><topic>linkage</topic><topic>LOD</topic><topic>logarithm of the odds</topic><topic>Male</topic><topic>Microsatellite Repeats</topic><topic>mixed polyposis</topic><topic>Morphology</topic><topic>Mutation</topic><topic>Patients</topic><topic>PCR</topic><topic>Pedigree</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Single Nucleotide</topic><topic>SGH</topic><topic>Singapore General Hospital</topic><topic>Software</topic><topic>Tumors</topic><topic>whole-genome SNP genotyping</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, X</creatorcontrib><creatorcontrib>Eu, K W</creatorcontrib><creatorcontrib>Kumarasinghe, M P</creatorcontrib><creatorcontrib>Li, H H</creatorcontrib><creatorcontrib>Loi, C</creatorcontrib><creatorcontrib>Cheah, P Y</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science 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>ProQuest Central Basic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, X</au><au>Eu, K W</au><au>Kumarasinghe, M P</au><au>Li, H H</au><au>Loi, C</au><au>Cheah, P Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function</atitle><jtitle>Journal of medical genetics</jtitle><addtitle>J Med Genet</addtitle><date>2006-03-01</date><risdate>2006</risdate><volume>43</volume><issue>3</issue><spage>e13</spage><epage>e13</epage><pages>e13-e13</pages><issn>0022-2593</issn><issn>1468-6244</issn><eissn>1468-6244</eissn><coden>JMDGAE</coden><abstract>Background: Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis-carcinoma sequence in both hereditary and sporadic CRC. Methods/Results: We performed a genomewide linkage search on 15 members of a three-generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi-point logarithm of the odds (LOD) score of 4.6 (p<0.001). The 10q23.1–10q23.31 haplotypes segregate with the disease in both families. We screened for mutations in four candidate genes within the linkage region and identified an 11 bp deletion in the bone morphogenesis protein receptor 1A (BMPR1A) gene in one family. Conclusions: Our results indicate that BMPR1A mutation accounts for HMPS. The data suggest that inactivating BMPR1A can initiate colorectal tumourigenesis via the mixed polyposis-carcinoma sequence.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd</pub><pmid>16525031</pmid><doi>10.1136/jmg.2005.034827</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adenomatous Polyposis Coli - genetics Automation Bone Morphogenetic Protein Receptors, Type I - genetics Chromosome Mapping Chromosomes, Human, Pair 10 Colorectal cancer Colorectal Neoplasms - genetics CRC Deoxyribonucleic acid DNA Electronic Letter familial adenomatous polyposis FAP Female GDAS Genechip DNA Analysis Genes Genome, Human Genomes Genotype haplotype Haplotypes hereditary mixed polyposis syndrome Histology HMPS Humans intestinal stem cell ISC JPS juvenile polyposis syndrome linkage LOD logarithm of the odds Male Microsatellite Repeats mixed polyposis Morphology Mutation Patients PCR Pedigree Polymerase Chain Reaction Polymorphism, Single Nucleotide SGH Singapore General Hospital Software Tumors whole-genome SNP genotyping |
| title | Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function |
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