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Simulating the Collaborative Cross: Power of Quantitative Trait Loci Detection and Mapping Resolution in Large Sets of Recombinant Inbred Strains of Mice
It has been suggested that the collaborative cross, a large set of recombinant inbred strains derived from eight inbred mouse strains, would be a powerful resource for the dissection of complex phenotypes. Here we use simulation to investigate the power of the collaborative cross to detect and map s...
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| Published in: | Genetics (Austin) 2006-03, Vol.172 (3), p.1783-1797 |
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| container_title | Genetics (Austin) |
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| creator | Valdar, William Flint, Jonathan Mott, Richard |
| description | It has been suggested that the collaborative cross, a large set of recombinant inbred strains derived from eight inbred mouse strains, would be a powerful resource for the dissection of complex phenotypes. Here we use simulation to investigate the power of the collaborative cross to detect and map small genetic effects. We show that for a fixed population of 1000 individuals, 500 RI lines bred using a modified version of the collaborative cross design are adequate to map a single additive locus that accounts for 5% of the phenotypic variation to within 0.96 cM. In the presence of strong epistasis more strains can improve detection, but 500 lines still provide sufficient resolution to meet most goals of the collaborative cross. However, even with a very large panel of RILs, mapping resolution may not be sufficient to identify single genes unambiguously. Our results are generally applicable to the design of RILs in other species. |
| doi_str_mv | 10.1534/genetics.104.039313 |
| format | article |
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Here we use simulation to investigate the power of the collaborative cross to detect and map small genetic effects. We show that for a fixed population of 1000 individuals, 500 RI lines bred using a modified version of the collaborative cross design are adequate to map a single additive locus that accounts for 5% of the phenotypic variation to within 0.96 cM. In the presence of strong epistasis more strains can improve detection, but 500 lines still provide sufficient resolution to meet most goals of the collaborative cross. However, even with a very large panel of RILs, mapping resolution may not be sufficient to identify single genes unambiguously. Our results are generally applicable to the design of RILs in other species.</description><identifier>ISSN: 0016-6731</identifier><identifier>ISSN: 1943-2631</identifier><identifier>EISSN: 1943-2631</identifier><identifier>DOI: 10.1534/genetics.104.039313</identifier><identifier>PMID: 16361245</identifier><identifier>CODEN: GENTAE</identifier><language>eng</language><publisher>United States: Genetics Soc America</publisher><subject>Animals ; Chromosomes ; Computer Simulation ; Confidence intervals ; Crosses, Genetic ; Design ; Epistasis, Genetic ; Genetic diversity ; Genetic Drift ; Genetic Markers ; Genomics ; Haplotypes ; Inbreeding ; Investigations ; Mice ; Mice, Inbred A ; Mice, Inbred AKR ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Inbred DBA ; Models, Genetic ; Physical Chromosome Mapping - methods ; Population ; Quantitative Trait Loci ; Studies</subject><ispartof>Genetics (Austin), 2006-03, Vol.172 (3), p.1783-1797</ispartof><rights>Copyright Genetics Society of America Mar 2006</rights><rights>Copyright © 2006 by the Genetics Society of America 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-ad378c1c149cb7419e4e10ba5f1846f6746627d9fe607d9d02b4dd894d8bd9f63</citedby><cites>FETCH-LOGICAL-c590t-ad378c1c149cb7419e4e10ba5f1846f6746627d9fe607d9d02b4dd894d8bd9f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16361245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valdar, William</creatorcontrib><creatorcontrib>Flint, Jonathan</creatorcontrib><creatorcontrib>Mott, Richard</creatorcontrib><title>Simulating the Collaborative Cross: Power of Quantitative Trait Loci Detection and Mapping Resolution in Large Sets of Recombinant Inbred Strains of Mice</title><title>Genetics (Austin)</title><addtitle>Genetics</addtitle><description>It has been suggested that the collaborative cross, a large set of recombinant inbred strains derived from eight inbred mouse strains, would be a powerful resource for the dissection of complex phenotypes. Here we use simulation to investigate the power of the collaborative cross to detect and map small genetic effects. We show that for a fixed population of 1000 individuals, 500 RI lines bred using a modified version of the collaborative cross design are adequate to map a single additive locus that accounts for 5% of the phenotypic variation to within 0.96 cM. In the presence of strong epistasis more strains can improve detection, but 500 lines still provide sufficient resolution to meet most goals of the collaborative cross. However, even with a very large panel of RILs, mapping resolution may not be sufficient to identify single genes unambiguously. Our results are generally applicable to the design of RILs in other species.</description><subject>Animals</subject><subject>Chromosomes</subject><subject>Computer Simulation</subject><subject>Confidence intervals</subject><subject>Crosses, Genetic</subject><subject>Design</subject><subject>Epistasis, Genetic</subject><subject>Genetic diversity</subject><subject>Genetic Drift</subject><subject>Genetic Markers</subject><subject>Genomics</subject><subject>Haplotypes</subject><subject>Inbreeding</subject><subject>Investigations</subject><subject>Mice</subject><subject>Mice, Inbred A</subject><subject>Mice, Inbred AKR</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CBA</subject><subject>Mice, Inbred DBA</subject><subject>Models, Genetic</subject><subject>Physical Chromosome Mapping - methods</subject><subject>Population</subject><subject>Quantitative Trait Loci</subject><subject>Studies</subject><issn>0016-6731</issn><issn>1943-2631</issn><issn>1943-2631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkk1vEzEQhlcIRNPAL0BCFgd6SvCsvd5dDpVQ-KqUCmjK2fJ6ZxNXu3awvY34KfxbnCZ8XnoaeeaZV-OZN8ueAZ1DwfirNVqMRoc5UD6nrGbAHmQTqDmb5YLBw2xCKYiZKBmcZKch3FBKRV1Uj7MTEExAzotJ9mNlhrFX0dg1iRskC9f3qnE-ZW7Ty7sQXpPPboeeuI58GZWNJh6K116ZSJZOG_IWI-ponCXKtuRSbbd7vSsMrh_v0saSpfJrJCuMYa90hdoNjbFJj1zYxmNLVjEJ2rvqpdH4JHvUqT7g02OcZl_fv7tefJwtP324WLxZznRR0zhTLSsrDRp4rZuSQ40cgTaq6KDiohMlFyIv27pDQVNoad7wtq1q3lZNygo2zc4PutuxGbDVaNMcvdx6Myj_XTpl5L8VazZy7W4l8EIwWiWBl0cB776NGKIcTNCY9mjRjUGKshR1Sfm9IKTj5HUF94Ml8JzmLIEv_gNv3OhtWpfMgQMAS9Q0YwdI76_psfv9N6By7yT5y0kpweXBSanr-d9r-dNztE4Czg7Axqw3O-NRhkH1fcJB7nY7KHPJ0qQVYz8BdRrWgA</recordid><startdate>20060301</startdate><enddate>20060301</enddate><creator>Valdar, William</creator><creator>Flint, Jonathan</creator><creator>Mott, Richard</creator><general>Genetics Soc America</general><general>Genetics Society of America</general><general>Copyright © 2006 by the Genetics Society of America</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>3V.</scope><scope>4T-</scope><scope>4U-</scope><scope>7QP</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</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>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</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>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060301</creationdate><title>Simulating the Collaborative Cross: Power of Quantitative Trait Loci Detection and Mapping Resolution in Large Sets of Recombinant Inbred Strains of Mice</title><author>Valdar, William ; Flint, Jonathan ; Mott, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c590t-ad378c1c149cb7419e4e10ba5f1846f6746627d9fe607d9d02b4dd894d8bd9f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Chromosomes</topic><topic>Computer Simulation</topic><topic>Confidence intervals</topic><topic>Crosses, Genetic</topic><topic>Design</topic><topic>Epistasis, Genetic</topic><topic>Genetic diversity</topic><topic>Genetic Drift</topic><topic>Genetic Markers</topic><topic>Genomics</topic><topic>Haplotypes</topic><topic>Inbreeding</topic><topic>Investigations</topic><topic>Mice</topic><topic>Mice, Inbred A</topic><topic>Mice, Inbred AKR</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CBA</topic><topic>Mice, Inbred DBA</topic><topic>Models, Genetic</topic><topic>Physical Chromosome Mapping - methods</topic><topic>Population</topic><topic>Quantitative Trait Loci</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valdar, William</creatorcontrib><creatorcontrib>Flint, Jonathan</creatorcontrib><creatorcontrib>Mott, Richard</creatorcontrib><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>Docstoc</collection><collection>University Readers</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_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>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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest 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>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest_Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>Research Library (Corporate)</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>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genetics (Austin)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valdar, William</au><au>Flint, Jonathan</au><au>Mott, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simulating the Collaborative Cross: Power of Quantitative Trait Loci Detection and Mapping Resolution in Large Sets of Recombinant Inbred Strains of Mice</atitle><jtitle>Genetics (Austin)</jtitle><addtitle>Genetics</addtitle><date>2006-03-01</date><risdate>2006</risdate><volume>172</volume><issue>3</issue><spage>1783</spage><epage>1797</epage><pages>1783-1797</pages><issn>0016-6731</issn><issn>1943-2631</issn><eissn>1943-2631</eissn><coden>GENTAE</coden><abstract>It has been suggested that the collaborative cross, a large set of recombinant inbred strains derived from eight inbred mouse strains, would be a powerful resource for the dissection of complex phenotypes. 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| identifier | ISSN: 0016-6731 |
| ispartof | Genetics (Austin), 2006-03, Vol.172 (3), p.1783-1797 |
| issn | 0016-6731 1943-2631 1943-2631 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1456308 |
| source | Freely Accessible Science Journals - check A-Z of ejournals; Oxford Journals Online; Alma/SFX Local Collection |
| subjects | Animals Chromosomes Computer Simulation Confidence intervals Crosses, Genetic Design Epistasis, Genetic Genetic diversity Genetic Drift Genetic Markers Genomics Haplotypes Inbreeding Investigations Mice Mice, Inbred A Mice, Inbred AKR Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred CBA Mice, Inbred DBA Models, Genetic Physical Chromosome Mapping - methods Population Quantitative Trait Loci Studies |
| title | Simulating the Collaborative Cross: Power of Quantitative Trait Loci Detection and Mapping Resolution in Large Sets of Recombinant Inbred Strains of Mice |
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