comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33
Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Sinc...
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| Veröffentlicht in: | Human genetics 2010-01, Vol.127 (1), p.91-99 |
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| creator | Parikh, Hemang Deng, Zuoming Yeager, Meredith Boland, Joseph Matthews, Casey Jia, Jinping Collins, Irene White, Ariel Burdett, Laura Hutchinson, Amy Qi, Liqun Bacior, Jennifer A Lonsberry, Victor Rodesch, Matthew J Jeddeloh, Jeffrey A Albert, Thomas J Halvensleben, Heather A Harkins, Timothy T Ahn, Jiyoung Berndt, Sonja I Chatterjee, Nilanjan Hoover, Robert Thomas, Gilles Hunter, David J Hayes, Richard B Chanock, Stephen J Amundadottir, Laufey |
| description | Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r ² threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r ² threshold of 0.8 and MAF >5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression. |
| doi_str_mv | 10.1007/s00439-009-0751-5 |
| format | Article |
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Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r ² threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r ² threshold of 0.8 and MAF >5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression.</description><identifier>ISSN: 0340-6717</identifier><identifier>ISSN: 1432-1203</identifier><identifier>EISSN: 1432-1203</identifier><identifier>DOI: 10.1007/s00439-009-0751-5</identifier><identifier>PMID: 19823874</identifier><identifier>CODEN: HUGEDQ</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Analysis ; Antigens ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Chromosomes ; Chromosomes, Human, Pair 19 - genetics ; Classical genetics, quantitative genetics, hybrids ; Diagnosis ; Epidemiology ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Frequency ; Gene Function ; Genes ; Genetics of eukaryotes. Biological and molecular evolution ; Genomes ; Genomics ; Haplotypes ; Health aspects ; Human ; Human Genetics ; Humans ; INDEL Mutation ; Kallikrein ; Kallikreins - genetics ; Linkage Disequilibrium ; Male ; Medical screening ; Metabolic Diseases ; Molecular Medicine ; Mutation ; Original Investigation ; Polymorphism, Single Nucleotide ; Population genetics ; Prostate cancer ; Prostate-specific antigen ; Prostate-Specific Antigen - genetics ; Prostatic Neoplasms - ethnology ; Prostatic Neoplasms - genetics ; Proteins ; Sequence Analysis, DNA ; Tissue Kallikreins - genetics ; White People - genetics</subject><ispartof>Human genetics, 2010-01, Vol.127 (1), p.91-99</ispartof><rights>The Author(s) 2009</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Springer</rights><rights>Springer-Verlag 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c654t-20cdaf79152019a8b6d9a32540486eba121f35284398c0139a11ed53aaffb7c73</citedby><cites>FETCH-LOGICAL-c654t-20cdaf79152019a8b6d9a32540486eba121f35284398c0139a11ed53aaffb7c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00439-009-0751-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00439-009-0751-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22347304$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19823874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Parikh, Hemang</creatorcontrib><creatorcontrib>Deng, Zuoming</creatorcontrib><creatorcontrib>Yeager, Meredith</creatorcontrib><creatorcontrib>Boland, Joseph</creatorcontrib><creatorcontrib>Matthews, Casey</creatorcontrib><creatorcontrib>Jia, Jinping</creatorcontrib><creatorcontrib>Collins, Irene</creatorcontrib><creatorcontrib>White, Ariel</creatorcontrib><creatorcontrib>Burdett, Laura</creatorcontrib><creatorcontrib>Hutchinson, Amy</creatorcontrib><creatorcontrib>Qi, Liqun</creatorcontrib><creatorcontrib>Bacior, Jennifer A</creatorcontrib><creatorcontrib>Lonsberry, Victor</creatorcontrib><creatorcontrib>Rodesch, Matthew J</creatorcontrib><creatorcontrib>Jeddeloh, Jeffrey A</creatorcontrib><creatorcontrib>Albert, Thomas J</creatorcontrib><creatorcontrib>Halvensleben, Heather A</creatorcontrib><creatorcontrib>Harkins, Timothy T</creatorcontrib><creatorcontrib>Ahn, Jiyoung</creatorcontrib><creatorcontrib>Berndt, Sonja I</creatorcontrib><creatorcontrib>Chatterjee, Nilanjan</creatorcontrib><creatorcontrib>Hoover, Robert</creatorcontrib><creatorcontrib>Thomas, Gilles</creatorcontrib><creatorcontrib>Hunter, David J</creatorcontrib><creatorcontrib>Hayes, Richard B</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Amundadottir, Laufey</creatorcontrib><title>comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33</title><title>Human genetics</title><addtitle>Hum Genet</addtitle><addtitle>Hum Genet</addtitle><description>Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r ² threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r ² threshold of 0.8 and MAF >5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression.</description><subject>Analysis</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 19 - genetics</subject><subject>Classical genetics, quantitative genetics, hybrids</subject><subject>Diagnosis</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Frequency</subject><subject>Gene Function</subject><subject>Genes</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Human</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>INDEL Mutation</subject><subject>Kallikrein</subject><subject>Kallikreins - genetics</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Medical screening</subject><subject>Metabolic Diseases</subject><subject>Molecular Medicine</subject><subject>Mutation</subject><subject>Original Investigation</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population genetics</subject><subject>Prostate cancer</subject><subject>Prostate-specific antigen</subject><subject>Prostate-Specific Antigen - genetics</subject><subject>Prostatic Neoplasms - ethnology</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Proteins</subject><subject>Sequence Analysis, DNA</subject><subject>Tissue Kallikreins - genetics</subject><subject>White People - genetics</subject><issn>0340-6717</issn><issn>1432-1203</issn><issn>1432-1203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp9kl9r2zAUxc3YWLNuH2Avm9nYxh6c6epKlvUyKGV_SgODdXkWiiInLraUSnZpv31lHNpljCIkge_vHuseTpa9BjIHQsSXSAhDWRCStuBQ8CfZDBjSAijBp9mMICNFKUAcZS9ivCQEuKT8eXYEsqJYCTbLlsZ3u2C31sXm2ubBRns1WGdsrp1ub2MTc1_n_dbm54tz4EU6cTxo3nozpKLLzTb4zkff2RzkFeAc8WX2rNZttK_293G2_P7tz-nPYvHrx9npyaIwJWd9QYlZ61pI4JSA1NWqXEuNlDPCqtKuNFCokdMqDVkZAig1gF1z1LquV8IIPM6-Trq7YdXZtbGuD7pVu9B0Otwqrxt1WHHNVm38taJCIooqCXzaCwSf5o696ppobNtqZ_0QlUBGOWVAE_nxUZICFSWh45ve_QNe-iEkM0eGcyJliQl6P0Eb3VrVuNqn55lRUZ1gybgQyZNEzf9DpbW2XWO8s3WTvh80fD5oSExvb_qNHmJUZxe_D1mYWBN8jMHW97YBUWO81BQvleKlxngpnnre_O33Q8c-Twn4sAd0NLqtg3amifccpcgEkpGjExdTyW1seDDpsb-_nZpq7ZXehCS8vEjJQQJpIiEQ7wDce-st</recordid><startdate>20100101</startdate><enddate>20100101</enddate><creator>Parikh, Hemang</creator><creator>Deng, Zuoming</creator><creator>Yeager, Meredith</creator><creator>Boland, Joseph</creator><creator>Matthews, Casey</creator><creator>Jia, Jinping</creator><creator>Collins, Irene</creator><creator>White, Ariel</creator><creator>Burdett, Laura</creator><creator>Hutchinson, Amy</creator><creator>Qi, Liqun</creator><creator>Bacior, Jennifer A</creator><creator>Lonsberry, Victor</creator><creator>Rodesch, Matthew J</creator><creator>Jeddeloh, Jeffrey A</creator><creator>Albert, Thomas J</creator><creator>Halvensleben, Heather A</creator><creator>Harkins, Timothy T</creator><creator>Ahn, Jiyoung</creator><creator>Berndt, Sonja I</creator><creator>Chatterjee, Nilanjan</creator><creator>Hoover, Robert</creator><creator>Thomas, Gilles</creator><creator>Hunter, David J</creator><creator>Hayes, Richard B</creator><creator>Chanock, Stephen J</creator><creator>Amundadottir, Laufey</creator><general>Berlin/Heidelberg : Springer-Verlag</general><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>C6C</scope><scope>IQODW</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</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>CCPQU</scope><scope>DWQXO</scope><scope>FR3</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>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100101</creationdate><title>comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33</title><author>Parikh, Hemang ; Deng, Zuoming ; Yeager, Meredith ; Boland, Joseph ; Matthews, Casey ; Jia, Jinping ; Collins, Irene ; White, Ariel ; Burdett, Laura ; Hutchinson, Amy ; Qi, Liqun ; Bacior, Jennifer A ; Lonsberry, Victor ; Rodesch, Matthew J ; Jeddeloh, Jeffrey A ; Albert, Thomas J ; Halvensleben, Heather A ; Harkins, Timothy T ; Ahn, Jiyoung ; Berndt, Sonja I ; Chatterjee, Nilanjan ; Hoover, Robert ; Thomas, Gilles ; Hunter, David J ; Hayes, Richard B ; Chanock, Stephen J ; Amundadottir, Laufey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c654t-20cdaf79152019a8b6d9a32540486eba121f35284398c0139a11ed53aaffb7c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analysis</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 19 - genetics</topic><topic>Classical genetics, quantitative genetics, hybrids</topic><topic>Diagnosis</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Frequency</topic><topic>Gene Function</topic><topic>Genes</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Human</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>INDEL Mutation</topic><topic>Kallikrein</topic><topic>Kallikreins - genetics</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medical screening</topic><topic>Metabolic Diseases</topic><topic>Molecular Medicine</topic><topic>Mutation</topic><topic>Original Investigation</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population genetics</topic><topic>Prostate cancer</topic><topic>Prostate-specific antigen</topic><topic>Prostate-Specific Antigen - genetics</topic><topic>Prostatic Neoplasms - ethnology</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Proteins</topic><topic>Sequence Analysis, DNA</topic><topic>Tissue Kallikreins - genetics</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Parikh, Hemang</creatorcontrib><creatorcontrib>Deng, Zuoming</creatorcontrib><creatorcontrib>Yeager, Meredith</creatorcontrib><creatorcontrib>Boland, Joseph</creatorcontrib><creatorcontrib>Matthews, Casey</creatorcontrib><creatorcontrib>Jia, Jinping</creatorcontrib><creatorcontrib>Collins, Irene</creatorcontrib><creatorcontrib>White, Ariel</creatorcontrib><creatorcontrib>Burdett, Laura</creatorcontrib><creatorcontrib>Hutchinson, Amy</creatorcontrib><creatorcontrib>Qi, Liqun</creatorcontrib><creatorcontrib>Bacior, Jennifer A</creatorcontrib><creatorcontrib>Lonsberry, Victor</creatorcontrib><creatorcontrib>Rodesch, Matthew J</creatorcontrib><creatorcontrib>Jeddeloh, Jeffrey A</creatorcontrib><creatorcontrib>Albert, Thomas J</creatorcontrib><creatorcontrib>Halvensleben, Heather A</creatorcontrib><creatorcontrib>Harkins, Timothy T</creatorcontrib><creatorcontrib>Ahn, Jiyoung</creatorcontrib><creatorcontrib>Berndt, Sonja I</creatorcontrib><creatorcontrib>Chatterjee, Nilanjan</creatorcontrib><creatorcontrib>Hoover, Robert</creatorcontrib><creatorcontrib>Thomas, Gilles</creatorcontrib><creatorcontrib>Hunter, David J</creatorcontrib><creatorcontrib>Hayes, Richard B</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Amundadottir, Laufey</creatorcontrib><collection>AGRIS</collection><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</collection><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: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</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>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research 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>ProQuest One Community College</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>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>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Parikh, Hemang</au><au>Deng, Zuoming</au><au>Yeager, Meredith</au><au>Boland, Joseph</au><au>Matthews, Casey</au><au>Jia, Jinping</au><au>Collins, Irene</au><au>White, Ariel</au><au>Burdett, Laura</au><au>Hutchinson, Amy</au><au>Qi, Liqun</au><au>Bacior, Jennifer A</au><au>Lonsberry, Victor</au><au>Rodesch, Matthew J</au><au>Jeddeloh, Jeffrey A</au><au>Albert, Thomas J</au><au>Halvensleben, Heather A</au><au>Harkins, Timothy T</au><au>Ahn, Jiyoung</au><au>Berndt, Sonja I</au><au>Chatterjee, Nilanjan</au><au>Hoover, Robert</au><au>Thomas, Gilles</au><au>Hunter, David J</au><au>Hayes, Richard B</au><au>Chanock, Stephen J</au><au>Amundadottir, Laufey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33</atitle><jtitle>Human genetics</jtitle><stitle>Hum Genet</stitle><addtitle>Hum Genet</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>127</volume><issue>1</issue><spage>91</spage><epage>99</epage><pages>91-99</pages><issn>0340-6717</issn><issn>1432-1203</issn><eissn>1432-1203</eissn><coden>HUGEDQ</coden><abstract>Single nucleotide polymorphisms (SNPs) in the KLK3 gene on chromosome 19q13.33 are associated with serum prostate-specific antigen (PSA) levels. Recent genome wide association studies of prostate cancer have yielded conflicting results for association of the same SNPs with prostate cancer risk. Since the KLK3 gene encodes the PSA protein that forms the basis for a widely used screening test for prostate cancer, it is critical to fully characterize genetic variation in this region and assess its relationship with the risk of prostate cancer. We have conducted a next-generation sequence analysis in 78 individuals of European ancestry to characterize common (minor allele frequency, MAF >1%) genetic variation in a 56 kb region on chromosome 19q13.33 centered on the KLK3 gene (chr19:56,019,829-56,076,043 bps). We identified 555 polymorphic loci in the process including 116 novel SNPs and 182 novel insertion/deletion polymorphisms (indels). Based on tagging analysis, 144 loci are necessary to tag the region at an r ² threshold of 0.8 and MAF of 1% or higher, while 86 loci are required to tag the region at an r ² threshold of 0.8 and MAF >5%. Our sequence data augments coverage by 35 and 78% as compared to variants in dbSNP and HapMap, respectively. We observed six non-synonymous amino acid or frame shift changes in the KLK3 gene and three changes in each of the neighboring genes, KLK15 and KLK2. Our study has generated a detailed map of common genetic variation in the genomic region surrounding the KLK3 gene, which should be useful for fine-mapping the association signal as well as determining the contribution of this locus to prostate cancer risk and/or regulation of PSA expression.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>19823874</pmid><doi>10.1007/s00439-009-0751-5</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6717 |
| ispartof | Human genetics, 2010-01, Vol.127 (1), p.91-99 |
| issn | 0340-6717 1432-1203 1432-1203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2793378 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Analysis Antigens Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Chromosomes Chromosomes, Human, Pair 19 - genetics Classical genetics, quantitative genetics, hybrids Diagnosis Epidemiology Female Fundamental and applied biological sciences. Psychology Gene Frequency Gene Function Genes Genetics of eukaryotes. Biological and molecular evolution Genomes Genomics Haplotypes Health aspects Human Human Genetics Humans INDEL Mutation Kallikrein Kallikreins - genetics Linkage Disequilibrium Male Medical screening Metabolic Diseases Molecular Medicine Mutation Original Investigation Polymorphism, Single Nucleotide Population genetics Prostate cancer Prostate-specific antigen Prostate-Specific Antigen - genetics Prostatic Neoplasms - ethnology Prostatic Neoplasms - genetics Proteins Sequence Analysis, DNA Tissue Kallikreins - genetics White People - genetics |
| title | comprehensive resequence analysis of the KLK15-KLK3-KLK2 locus on chromosome 19q13.33 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T21%3A17%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=comprehensive%20resequence%20analysis%20of%20the%20KLK15-KLK3-KLK2%20locus%20on%20chromosome%2019q13.33&rft.jtitle=Human%20genetics&rft.au=Parikh,%20Hemang&rft.date=2010-01-01&rft.volume=127&rft.issue=1&rft.spage=91&rft.epage=99&rft.pages=91-99&rft.issn=0340-6717&rft.eissn=1432-1203&rft.coden=HUGEDQ&rft_id=info:doi/10.1007/s00439-009-0751-5&rft_dat=%3Cgale_pubme%3EA364577152%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=215509963&rft_id=info:pmid/19823874&rft_galeid=A364577152&rfr_iscdi=true |