Confirmation and Fine Mapping of Chromosomal Regions Influencing Peak Bone Mass in Mice
Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysi...
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| Veröffentlicht in: | Journal of bone and mineral research 2001-11, Vol.16 (11), p.1953-1961 |
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| container_issue | 11 |
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| container_title | Journal of bone and mineral research |
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| creator | Klein, Robert F. Carlos, Amy S. Vartanian, Kristina A. Chambers, Virginia K. Turner, Renn J. Phillips, Tamara J. Belknap, John K. Orwoll, Eric S. |
| description | Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (RI‐BXD). The distribution of BMD values among these strains indicated strong genetic influences and a number of chromosomal sites linked to BMD were identified provisionally. Using three additional independent mapping populations derived from the same progenitors, we have confirmed loci on chromosomes 1, 2, and 4, and 11 that contain genes that influence peak BMD. Using a novel fine‐mapping approach (RI segregation testing [RIST]), we have substantially narrowed two of the BMD‐related chromosomal regions and in the process eliminated a number of candidate genes. The homologous regions in the human genome for each of these murine QTLs have been identified in recent human genetic studies. In light of this, we believe that findings in mice should aid in the identification of specific candidate genes for study in humans. |
| doi_str_mv | 10.1359/jbmr.2001.16.11.1953 |
| format | Article |
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The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (RI‐BXD). The distribution of BMD values among these strains indicated strong genetic influences and a number of chromosomal sites linked to BMD were identified provisionally. Using three additional independent mapping populations derived from the same progenitors, we have confirmed loci on chromosomes 1, 2, and 4, and 11 that contain genes that influence peak BMD. Using a novel fine‐mapping approach (RI segregation testing [RIST]), we have substantially narrowed two of the BMD‐related chromosomal regions and in the process eliminated a number of candidate genes. The homologous regions in the human genome for each of these murine QTLs have been identified in recent human genetic studies. In light of this, we believe that findings in mice should aid in the identification of specific candidate genes for study in humans.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1359/jbmr.2001.16.11.1953</identifier><identifier>PMID: 11697791</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>Washington, DC: John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</publisher><subject>Animals ; Biological and medical sciences ; Bone Density - genetics ; bone mineral density ; Chromosome Mapping ; Crosses, Genetic ; Diseases of the osteoarticular system ; Female ; heredity ; Humans ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Microsatellite Repeats ; osteoporosis ; Osteoporosis. Osteomalacia. Paget disease ; Phenotype ; quantitative trait ; quantitative trait locus analysis ; Quantitative Trait, Heritable ; Species Specificity</subject><ispartof>Journal of bone and mineral research, 2001-11, Vol.16 (11), p.1953-1961</ispartof><rights>Copyright © 2001 ASBMR</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5333-e8d367fe87a8536824c9ac8e1e7cd1af0ab6c4e1273963b6cfe73e2c5d1733433</citedby><cites>FETCH-LOGICAL-c5333-e8d367fe87a8536824c9ac8e1e7cd1af0ab6c4e1273963b6cfe73e2c5d1733433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1359%2Fjbmr.2001.16.11.1953$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1359%2Fjbmr.2001.16.11.1953$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14106737$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11697791$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klein, Robert F.</creatorcontrib><creatorcontrib>Carlos, Amy S.</creatorcontrib><creatorcontrib>Vartanian, Kristina A.</creatorcontrib><creatorcontrib>Chambers, Virginia K.</creatorcontrib><creatorcontrib>Turner, Renn J.</creatorcontrib><creatorcontrib>Phillips, Tamara J.</creatorcontrib><creatorcontrib>Belknap, John K.</creatorcontrib><creatorcontrib>Orwoll, Eric S.</creatorcontrib><title>Confirmation and Fine Mapping of Chromosomal Regions Influencing Peak Bone Mass in Mice</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (RI‐BXD). The distribution of BMD values among these strains indicated strong genetic influences and a number of chromosomal sites linked to BMD were identified provisionally. Using three additional independent mapping populations derived from the same progenitors, we have confirmed loci on chromosomes 1, 2, and 4, and 11 that contain genes that influence peak BMD. Using a novel fine‐mapping approach (RI segregation testing [RIST]), we have substantially narrowed two of the BMD‐related chromosomal regions and in the process eliminated a number of candidate genes. The homologous regions in the human genome for each of these murine QTLs have been identified in recent human genetic studies. In light of this, we believe that findings in mice should aid in the identification of specific candidate genes for study in humans.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone Density - genetics</subject><subject>bone mineral density</subject><subject>Chromosome Mapping</subject><subject>Crosses, Genetic</subject><subject>Diseases of the osteoarticular system</subject><subject>Female</subject><subject>heredity</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><subject>Microsatellite Repeats</subject><subject>osteoporosis</subject><subject>Osteoporosis. Osteomalacia. Paget disease</subject><subject>Phenotype</subject><subject>quantitative trait</subject><subject>quantitative trait locus analysis</subject><subject>Quantitative Trait, Heritable</subject><subject>Species Specificity</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1vEzEQhi0EoqHwDxDyBW4bPJ71x96gEYWiRqAKxNFyvLPFZddO141Q_z0OidQjXGbm8LzvSA9jL0EsAVX39mYzzUspBCxBL6HOTuEjtgAlsWm1hcdsIaxtG9EinLBnpdwIIbTS-ik7AdCdMR0s2I9VTkOcJ38Xc-I-9fw8JuJrv93GdM3zwFc_5zzlkic_8iu6rljhF2kYd5TCHvlK_hc_y39DpfCY-DoGes6eDH4s9OK4T9n38w_fVp-ayy8fL1bvL5ugELEh26M2A1njrUJtZRs6HywBmdCDH4Tf6NASSIOdxnoPZJBkUD0YxBbxlL059G7nfLujcuemWAKNo0-Ud8UZKZVVxv4TBCtRS60q2B7AMOdSZhrcdo6Tn-8dCLc37_bm3d68A-2gzmq-xl4d-3ebifqH0FF1BV4fAV-CH4fZV3_lgWtBaIOmcu8O3O840v1_PXefz9ZXSisBGkAg_gEx8Z8D</recordid><startdate>200111</startdate><enddate>200111</enddate><creator>Klein, Robert F.</creator><creator>Carlos, Amy S.</creator><creator>Vartanian, Kristina A.</creator><creator>Chambers, Virginia K.</creator><creator>Turner, Renn J.</creator><creator>Phillips, Tamara J.</creator><creator>Belknap, John K.</creator><creator>Orwoll, Eric S.</creator><general>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</general><general>American Society for Bone and Mineral Research</general><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>7QP</scope><scope>7X8</scope></search><sort><creationdate>200111</creationdate><title>Confirmation and Fine Mapping of Chromosomal Regions Influencing Peak Bone Mass in Mice</title><author>Klein, Robert F. ; Carlos, Amy S. ; Vartanian, Kristina A. ; Chambers, Virginia K. ; Turner, Renn J. ; Phillips, Tamara J. ; Belknap, John K. ; Orwoll, Eric S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5333-e8d367fe87a8536824c9ac8e1e7cd1af0ab6c4e1273963b6cfe73e2c5d1733433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone Density - genetics</topic><topic>bone mineral density</topic><topic>Chromosome Mapping</topic><topic>Crosses, Genetic</topic><topic>Diseases of the osteoarticular system</topic><topic>Female</topic><topic>heredity</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><topic>Microsatellite Repeats</topic><topic>osteoporosis</topic><topic>Osteoporosis. Osteomalacia. Paget disease</topic><topic>Phenotype</topic><topic>quantitative trait</topic><topic>quantitative trait locus analysis</topic><topic>Quantitative Trait, Heritable</topic><topic>Species Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klein, Robert F.</creatorcontrib><creatorcontrib>Carlos, Amy S.</creatorcontrib><creatorcontrib>Vartanian, Kristina A.</creatorcontrib><creatorcontrib>Chambers, Virginia K.</creatorcontrib><creatorcontrib>Turner, Renn J.</creatorcontrib><creatorcontrib>Phillips, Tamara J.</creatorcontrib><creatorcontrib>Belknap, John K.</creatorcontrib><creatorcontrib>Orwoll, Eric S.</creatorcontrib><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>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klein, Robert F.</au><au>Carlos, Amy S.</au><au>Vartanian, Kristina A.</au><au>Chambers, Virginia K.</au><au>Turner, Renn J.</au><au>Phillips, Tamara J.</au><au>Belknap, John K.</au><au>Orwoll, Eric S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Confirmation and Fine Mapping of Chromosomal Regions Influencing Peak Bone Mass in Mice</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2001-11</date><risdate>2001</risdate><volume>16</volume><issue>11</issue><spage>1953</spage><epage>1961</epage><pages>1953-1961</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (RI‐BXD). The distribution of BMD values among these strains indicated strong genetic influences and a number of chromosomal sites linked to BMD were identified provisionally. Using three additional independent mapping populations derived from the same progenitors, we have confirmed loci on chromosomes 1, 2, and 4, and 11 that contain genes that influence peak BMD. Using a novel fine‐mapping approach (RI segregation testing [RIST]), we have substantially narrowed two of the BMD‐related chromosomal regions and in the process eliminated a number of candidate genes. 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| subjects | Animals Biological and medical sciences Bone Density - genetics bone mineral density Chromosome Mapping Crosses, Genetic Diseases of the osteoarticular system Female heredity Humans Male Medical sciences Mice Mice, Inbred C57BL Mice, Inbred DBA Microsatellite Repeats osteoporosis Osteoporosis. Osteomalacia. Paget disease Phenotype quantitative trait quantitative trait locus analysis Quantitative Trait, Heritable Species Specificity |
| title | Confirmation and Fine Mapping of Chromosomal Regions Influencing Peak Bone Mass in Mice |
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