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A non-human primate system for large-scale genetic studies of complex traits

Identifieur interne : 000871 ( Main/Exploration ); précédent : 000870; suivant : 000872

A non-human primate system for large-scale genetic studies of complex traits

Auteurs : Anna J. Jasinska [États-Unis] ; Michelle K. Lin [États-Unis, Allemagne] ; Susan Service [États-Unis] ; Oi-Wa Choi [États-Unis] ; Joseph Deyoung [États-Unis] ; Olivera Grujic [États-Unis] ; Sit-Yee Kong [États-Unis] ; Yoon Jung [États-Unis] ; Mathew J. Jorgensen [États-Unis] ; Lynn A. Fairbanks [États-Unis] ; Trudy Turner [États-Unis] ; Rita M. Cantor [États-Unis] ; Jessica Wasserscheid [États-Unis, Canada] ; Ken Dewar [États-Unis, Canada] ; Wesley Warren [États-Unis] ; Richard K. Wilson [États-Unis] ; George Weinstock [États-Unis] ; J. David Jentsch [États-Unis] ; Nelson B. Freimer [États-Unis]

Source :

RBID : Pascal:12-0303323

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Abstract

Non-human primates provide genetic model systems biologically intermediate between humans and other mammalian model organisms. Populations of Caribbean vervet monkeys (Chlorocebus aethiops sabaeus) are genetically homogeneous and large enough to permit well-powered genetic mapping studies of quantitative traits relevant to human health, including expression quantitative trait loci (eQTL). Previous transcriptome-wide investigation in an extended vervet pedigree identified 29 heritable transcripts for which levels of expression in peripheral blood correlate strongly with expression levels in the brain. Quantitative trait linkage analysis using 261 microsatellite markers identified significant (n = 8) and suggestive (n = 4) linkages for 12 of these transcripts, including both cis- and trans-eQTL. Seven transcripts, located on different chromosomes, showed maximum linkage to markers in a single region of vervet chromosome 9; this observation suggests the possibility of a master trans-regulator locus in this region. For one cis-eQTL (at B3GALTL, beta-1,3-glucosyltransferase), we conducted follow-up single nucleotide polymorphism genotyping and fine-scale association analysis in a sample of unrelated Caribbean vervets, localizing this eQTL to a region of <200 kb. These results suggest the value of pedigree and population samples of the Caribbean vervet for linkage and association mapping studies of quantitative traits. The imminent whole genome sequencing of many of these vervet samples will enhance the power of such investigations by providing a comprehensive catalog of genetic variation.

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<name sortKey="Kong, Sit Yee" sort="Kong, Sit Yee" uniqKey="Kong S" first="Sit-Yee" last="Kong">Sit-Yee Kong</name>
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<name sortKey="Jung, Yoon" sort="Jung, Yoon" uniqKey="Jung Y" first="Yoon" last="Jung">Yoon Jung</name>
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<region type="state">Californie</region>
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<author>
<name sortKey="Turner, Trudy" sort="Turner, Trudy" uniqKey="Turner T" first="Trudy" last="Turner">Trudy Turner</name>
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<s1>University of Wisconsin-Milwaukee</s1>
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<country>États-Unis</country>
<placeName>
<region type="state">Wisconsin</region>
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<author>
<name sortKey="Cantor, Rita M" sort="Cantor, Rita M" uniqKey="Cantor R" first="Rita M." last="Cantor">Rita M. Cantor</name>
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<s1>Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, University of California</s1>
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<region type="state">Californie</region>
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<author>
<name sortKey="Wasserscheid, Jessica" sort="Wasserscheid, Jessica" uniqKey="Wasserscheid J" first="Jessica" last="Wasserscheid">Jessica Wasserscheid</name>
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<wicri:noRegion>Research Institute of the McGill University Health Centre, McGill University and Genome Quebec Innovation Centre</wicri:noRegion>
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<s1>Department of Human Genetics and, McGill University</s1>
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<settlement type="city">Montréal</settlement>
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<orgName type="university">Université McGill</orgName>
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<s1>Department of Experimental Medicine, McGill University</s1>
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<settlement type="city">Montréal</settlement>
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<name sortKey="Dewar, Ken" sort="Dewar, Ken" uniqKey="Dewar K" first="Ken" last="Dewar">Ken Dewar</name>
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<s1>Research Institute of the McGill University Health Centre, McGill University and Genome Quebec Innovation Centre</s1>
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<wicri:noRegion>Research Institute of the McGill University Health Centre, McGill University and Genome Quebec Innovation Centre</wicri:noRegion>
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<s1>Department of Human Genetics and, McGill University</s1>
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<sZ>13 aut.</sZ>
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<country>Canada</country>
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<settlement type="city">Montréal</settlement>
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</placeName>
<orgName type="university">Université McGill</orgName>
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<s1>Department of Experimental Medicine, McGill University</s1>
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<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
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<country>Canada</country>
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<settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
<orgName type="university">Université McGill</orgName>
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<name sortKey="Warren, Wesley" sort="Warren, Wesley" uniqKey="Warren W" first="Wesley" last="Warren">Wesley Warren</name>
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<s1>The Genome Institute at Washington University</s1>
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<placeName>
<region type="state">Missouri (État)</region>
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<author>
<name sortKey="Wilson, Richard K" sort="Wilson, Richard K" uniqKey="Wilson R" first="Richard K." last="Wilson">Richard K. Wilson</name>
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<s1>The Genome Institute at Washington University</s1>
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<placeName>
<region type="state">Missouri (État)</region>
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<author>
<name sortKey="Weinstock, George" sort="Weinstock, George" uniqKey="Weinstock G" first="George" last="Weinstock">George Weinstock</name>
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<inist:fA14 i1="08">
<s1>The Genome Institute at Washington University</s1>
<s2>St Louis, MO 63108</s2>
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<placeName>
<region type="state">Missouri (État)</region>
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<author>
<name sortKey="David Jentsch, J" sort="David Jentsch, J" uniqKey="David Jentsch J" first="J." last="David Jentsch">J. David Jentsch</name>
<affiliation wicri:level="2">
<inist:fA14 i1="09">
<s1>Department of Psychology and Semel Institute for Neuroscience & Human Behavior, University of California</s1>
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<s3>USA</s3>
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</inist:fA14>
<country>États-Unis</country>
<placeName>
<region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Freimer, Nelson B" sort="Freimer, Nelson B" uniqKey="Freimer N" first="Nelson B." last="Freimer">Nelson B. Freimer</name>
<affiliation wicri:level="2">
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<s1>Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, University of California</s1>
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<region type="state">Californie</region>
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</analytic>
<series>
<title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
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<seriesStmt>
<title level="j" type="main">Human molecular genetics : (Print)</title>
<title level="j" type="abbreviated">Hum. mol. genet. : (Print)</title>
<idno type="ISSN">0964-6906</idno>
</seriesStmt>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Genetics</term>
<term>Nonhuman primate</term>
<term>Polygenic</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Génétique</term>
<term>Polygénique</term>
<term>Primate non humain</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Génétique</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">Non-human primates provide genetic model systems biologically intermediate between humans and other mammalian model organisms. Populations of Caribbean vervet monkeys (Chlorocebus aethiops sabaeus) are genetically homogeneous and large enough to permit well-powered genetic mapping studies of quantitative traits relevant to human health, including expression quantitative trait loci (eQTL). Previous transcriptome-wide investigation in an extended vervet pedigree identified 29 heritable transcripts for which levels of expression in peripheral blood correlate strongly with expression levels in the brain. Quantitative trait linkage analysis using 261 microsatellite markers identified significant (n = 8) and suggestive (n = 4) linkages for 12 of these transcripts, including both cis- and trans-eQTL. Seven transcripts, located on different chromosomes, showed maximum linkage to markers in a single region of vervet chromosome 9; this observation suggests the possibility of a master trans-regulator locus in this region. For one cis-eQTL (at B3GALTL, beta-1,3-glucosyltransferase), we conducted follow-up single nucleotide polymorphism genotyping and fine-scale association analysis in a sample of unrelated Caribbean vervets, localizing this eQTL to a region of <200 kb. These results suggest the value of pedigree and population samples of the Caribbean vervet for linkage and association mapping studies of quantitative traits. The imminent whole genome sequencing of many of these vervet samples will enhance the power of such investigations by providing a comprehensive catalog of genetic variation.</div>
</front>
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<li>Caroline du Nord</li>
<li>Missouri (État)</li>
<li>Québec</li>
<li>Rhénanie-Palatinat</li>
<li>Wisconsin</li>
</region>
<settlement>
<li>Montréal</li>
<li>Trèves (Allemagne)</li>
</settlement>
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<li>Université McGill</li>
<li>Université de Trèves</li>
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<name sortKey="Lin, Michelle K" sort="Lin, Michelle K" uniqKey="Lin M" first="Michelle K." last="Lin">Michelle K. Lin</name>
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</country>
<country name="Canada">
<region name="Québec">
<name sortKey="Wasserscheid, Jessica" sort="Wasserscheid, Jessica" uniqKey="Wasserscheid J" first="Jessica" last="Wasserscheid">Jessica Wasserscheid</name>
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<name sortKey="Dewar, Ken" sort="Dewar, Ken" uniqKey="Dewar K" first="Ken" last="Dewar">Ken Dewar</name>
<name sortKey="Dewar, Ken" sort="Dewar, Ken" uniqKey="Dewar K" first="Ken" last="Dewar">Ken Dewar</name>
<name sortKey="Wasserscheid, Jessica" sort="Wasserscheid, Jessica" uniqKey="Wasserscheid J" first="Jessica" last="Wasserscheid">Jessica Wasserscheid</name>
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   |texte=   A non-human primate system for large-scale genetic studies of complex traits
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