A Genomewide Linkage Scan for Quantitative Trait Loci Influencing the Craniofacial Complex in Baboons (Papio hamadryas spp.)

Lifespan Health Research Center, Department of Community Health, Boonshoft School of Medicine, Wright State University, Dayton, Ohio 45420, USA.
Genetics (Impact Factor: 5.96). 09/2008; 180(1):619-28. DOI: 10.1534/genetics.108.090407
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Numerous studies have detected significant contributions of genes to variation in development, size, and shape of craniofacial traits in a number of vertebrate taxa. This study examines 43 quantitative traits derived from lateral cephalographs of 830 baboons (Papio hamadryas) from the pedigreed population housed at the Southwest National Primate Research Center. Quantitative genetic analyses were conducted using the SOLAR analytic platform, a maximum-likelihood variance components method that incorporates all familial information for parameter estimation. Heritability estimates were significant and of moderate to high magnitude for all craniofacial traits. Additionally, 14 significant quantitative trait loci (QTL) were identified for 12 traits from the three developmental components (basicranium, splanchnocranium, and neurocranium) of the craniofacial complex. These QTL were found on baboon chromosomes (and human orthologs) PHA1 (HSA1), PHA 2 (HSA3), PHA4 (HSA6), PHA11 (HSA12), PHA13 (HSA2), PHA16 (HSA17), and PHA17 (HSA13) (PHA, P. hamadryas; HSA, Homo sapiens). This study of the genetic architecture of the craniofacial complex in baboons provides the groundwork needed to establish the baboon as an animal model for the study of genetic and nongenetic influences on craniofacial variation.

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Available from: Laura A Cox, Oct 02, 2015
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    • "For at least one of these QTL, a likely causal variant (in BMP3) was identified. In primates, two studies also used GWAS and linear measurements from lateral cephalograms to map QTL responsible for the CF traits in baboons and humans, respectively (Sherwood et al., 2008, 2011). In a recent human GWAS, five candidate genes affecting facial shape variation in Europeans were identified (Liu et al., 2012). "
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    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 315MB and contained 2,476 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.
    Frontiers in Physiology 03/2015; 6:92. DOI:10.3389/fphys.2015.00092 · 3.53 Impact Factor
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    • "The first-generation linkage map was published in 2000 [35] and later improved in 2006 by the addition of more loci in chromosomal regions with insufficient marker density in the initial map [36]. This map has allowed scientists to localize and identify functionally significant genes that influence phenotypic variation related to human health or disease [11], [14], [37]–[42]. "
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    ABSTRACT: The baboon is an invaluable model for the study of human health and disease, including many complex diseases of the kidney. Although scientists have made great progress in developing this animal as a model for numerous areas of biomedical research, genomic resources for the baboon, such as a quality annotated genome, are still lacking. To this end, we characterized the baboon kidney transcriptome using high-throughput cDNA sequencing (RNA-Seq) to identify genes, gene variants, single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (InDels), cellular functions, and key pathways in the baboon kidney to provide a genomic resource for the baboon. Analysis of our sequencing data revealed 45,499 high-confidence SNPs and 29,813 InDels comparing baboon cDNA sequences with the human hg18 reference assembly and identified 35,900 cDNAs in the baboon kidney, including 35,150 transcripts representing 15,369 genic genes that are novel for the baboon. Gene ontology analysis of our sequencing dataset also identified numerous biological functions and canonical pathways that were significant in the baboon kidney, including a large number of metabolic pathways that support known functions of the kidney. The results presented in this study catalogues the transcribed mRNAs, noncoding RNAs, and hypothetical proteins in the baboon kidney and establishes a genomic resource for scientists using the baboon as an experimental model.
    PLoS ONE 04/2013; 8(4):e57563. DOI:10.1371/journal.pone.0057563 · 3.23 Impact Factor
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    • "Several groups have attempted to tackle the complexity of skull shape in mice using different approaches. While variations in natural or pedigreed populations have been used for example in plants [1] fishes [2] or primates [3], studies in mice have been made on either F2 progeny [4], or recombinant inbred strains [5], using classical measurements [6], or geometric morphometrics [7], [8]. Compared with segregating populations such as F2s, where every individual carries a unique genotype, recombinant inbred strains allow for replications, since a trait can be measured on a group of genetically identical, sex- and age-matched individuals, buffering between-individual noise. "
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    ABSTRACT: Genetic determinism of cranial morphology in the mouse is still largely unknown, despite the localization of putative QTLs and the identification of genes associated with Mendelian skull malformations. To approach the dissection of this multigenic control, we have used a set of interspecific recombinant congenic strains (IRCS) produced between C57BL/6 and mice of the distant species Mus spretus (SEG/Pas). Each strain has inherited 1.3% of its genome from SEG/Pas under the form of few, small-sized, chromosomal segments. The shape of the nasal bone was studied using outline analysis combined with Fourier descriptors, and differential features were identified between IRCS BcG-66H and C57BL/6. An F2 cross between BcG-66H and C57BL/6 revealed that, out of the three SEG/Pas-derived chromosomal regions present in BcG-66H, two were involved. Segments on chromosomes 1 (∼32 Mb) and 18 (∼13 Mb) showed additive effect on nasal bone shape. The three chromosomal regions present in BcG-66H were isolated in congenic strains to study their individual effect. Epistatic interactions were assessed in bicongenic strains. Our results show that, besides a strong individual effect, the QTL on chromosome 1 interacts with genes on chromosomes 13 and 18. This study demonstrates that nasal bone shape is under complex genetic control but can be efficiently dissected in the mouse using appropriate genetic tools and shape descriptors.
    PLoS ONE 05/2012; 7(5):e37721. DOI:10.1371/journal.pone.0037721 · 3.23 Impact Factor
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