Quantitative trait loci affecting the 3D skull shape and size in mouse and prioritization of candidate genes in-silico
Identifieur interne : 002936 ( Main/Exploration ); précédent : 002935; suivant : 002937Quantitative trait loci affecting the 3D skull shape and size in mouse and prioritization of candidate genes in-silico
Auteurs : A. Murat Maga [États-Unis] ; Nicolas Navarro [France] ; Michael L. Cunningham [États-Unis] ; Timothy C. Cox [États-Unis, Australie]Source :
- Frontiers in Physiology [ 1664-042X ] ; 2015.
Abstract
We describe the first application of high-resolution 3D micro-computed tomography, together with 3D landmarks and geometric morphometrics, to map QTL responsible for variation in skull shape and size using a backcross between C57BL/6J and A/J inbred strains. Using 433 animals, 53 3D landmarks, and 882 SNPs from autosomes, we identified seven QTL responsible for the skull size (SCS.qtl) and 30 QTL responsible for the skull shape (SSH.qtl). Size, sex, and direction-of-cross were all significant factors and included in the analysis as covariates. All autosomes harbored at least one SSH.qtl, sometimes up to three. Effect sizes of SSH.qtl appeared to be small, rarely exceeding 1% of the overall shape variation. However, they account for significant amount of variation in some specific directions of the shape space. Many QTL have stronger effect on the neurocranium than expected from a random vector that will parcellate uniformly across the four cranial regions. On the contrary, most of QTL have an effect on the palate weaker than expected. Combined interval length of 30 SSH.qtl was about 315 MB and contained 2476 known protein coding genes. We used a bioinformatics approach to filter these candidate genes and identified 16 high-priority candidates that are likely to play a role in the craniofacial development and disorders. Thus, coupling the QTL mapping approach in model organisms with candidate gene enrichment approaches appears to be a feasible way to identify high-priority candidates genes related to the structure or tissue of interest.
Url:
DOI: 10.3389/fphys.2015.00092
PubMed: 25859222
PubMed Central: 4374467
Affiliations:
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Cox</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Division of Craniofacial Medicine, Department of Pediatrics, University of Washington</institution><country>Seattle, WA, USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute</institution><country>Seattle, WA, USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Anatomy and Developmental Biology, Monash University</institution><country>Clayton, VIC, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation></author></analytic><series><title level="j">Frontiers in Physiology</title><idno type="eISSN">1664-042X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We describe the first application of high-resolution 3D micro-computed tomography, together with 3D landmarks and geometric morphometrics, to map QTL responsible for variation in skull shape and size using a backcross between C57BL/6J and A/J inbred strains. Using 433 animals, 53 3D landmarks, and 882 SNPs from autosomes, we identified seven QTL responsible for the skull size (SCS.qtl) and 30 QTL responsible for the skull shape (SSH.qtl). Size, sex, and direction-of-cross were all significant factors and included in the analysis as covariates. All autosomes harbored at least one SSH.qtl, sometimes up to three. Effect sizes of SSH.qtl appeared to be small, rarely exceeding 1% of the overall shape variation. However, they account for significant amount of variation in some specific directions of the shape space. Many QTL have stronger effect on the neurocranium than expected from a random vector that will parcellate uniformly across the four cranial regions. On the contrary, most of QTL have an effect on the palate weaker than expected. Combined interval length of 30 SSH.qtl was about 315 MB and contained 2476 known protein coding genes. We used a bioinformatics approach to filter these candidate genes and identified 16 high-priority candidates that are likely to play a role in the craniofacial development and disorders. Thus, coupling the QTL mapping approach in model organisms with candidate gene enrichment approaches appears to be a feasible way to identify high-priority candidates genes related to the structure or tissue of interest.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Adams, D C" uniqKey="Adams D">D. C. Adams</name></author><author><name sortKey="Rohlf, F J" uniqKey="Rohlf F">F. J. Rohlf</name></author><author><name sortKey="Slice, D E" uniqKey="Slice D">D. E. Slice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agrawal, P" uniqKey="Agrawal P">P. Agrawal</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Kim, S" uniqKey="Kim S">S. 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Murat Maga</name></noRegion><name sortKey="Cox, Timothy C" sort="Cox, Timothy C" uniqKey="Cox T" first="Timothy C." last="Cox">Timothy C. Cox</name><name sortKey="Cox, Timothy C" sort="Cox, Timothy C" uniqKey="Cox T" first="Timothy C." last="Cox">Timothy C. Cox</name><name sortKey="Cunningham, Michael L" sort="Cunningham, Michael L" uniqKey="Cunningham M" first="Michael L." last="Cunningham">Michael L. Cunningham</name><name sortKey="Cunningham, Michael L" sort="Cunningham, Michael L" uniqKey="Cunningham M" first="Michael L." last="Cunningham">Michael L. Cunningham</name><name sortKey="Maga, A Murat" sort="Maga, A Murat" uniqKey="Maga A" first="A. Murat" last="Maga">A. Murat Maga</name></country><country name="France"><noRegion><name sortKey="Navarro, Nicolas" sort="Navarro, Nicolas" uniqKey="Navarro N" first="Nicolas" last="Navarro">Nicolas Navarro</name></noRegion><name sortKey="Navarro, Nicolas" sort="Navarro, Nicolas" uniqKey="Navarro N" first="Nicolas" last="Navarro">Nicolas Navarro</name></country><country name="Australie"><noRegion><name sortKey="Cox, Timothy C" sort="Cox, Timothy C" uniqKey="Cox T" first="Timothy C." last="Cox">Timothy C. Cox</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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