Dataset Information

Genetic mapping of principal components of canine pelvic morphology.

ABSTRACT:

Background

Concentrated breeding effort to produce various body structures and behaviors of dogs to suit human demand has inadvertently produced unwanted traits and diseases that accompany the morphological and behavioral phenotypes. We explored the relationship between pelvic conformation and canine hip dysplasia (HD) because purebred dogs which are predisposed, or not, to HD share common morphologic features, respectively. Thirteen unique bilateral anatomical features of the pelvis were measured on 392 dogs of 51 breeds and 95 mixed breed dogs. Principal components (PCs) were derived to describe pelvic morphology. Dogs were genotyped at ~183,000 single nucleotide polymorphisms and their hip conformation was measured by the Norberg angle and angle of inclination between the femoral neck and diaphysis.

Results

No associations reached genome wide significance for the Norberg angle when averaged over both hips. PC1 was negatively correlated with the Norberg angle (r?=?-0.31; P?r?=?-0.08; P?>?0.05). PC1, 2, 4, and 5 differed significantly between male and female dogs confirming pelvic sexual dimorphism. With sex as a covariate, the eigenvector contribution to PC1 reflected the overall size of the pelvis and was significantly associated with the IGF-1 locus, a known contributor to canine body size. PC3, which represented a tradeoff between ilial length and ischial length in which a longer ischium is associated with a shorter ilium, was significantly associated with a marker on canine chromosome 16:5181388 bp. The closest candidate gene is TPK1, a thiamine-dependent enzyme and part of the PKA complex. Associations with the remaining PCs did not reach genome wide significance.

Conclusion

IGF-1 was associated with the overall size of the pelvis and sex is related to pelvic size. Ilial/ischial proportion is genetically controlled and the closest candidate gene is thiamine-dependent and affects birth weight and development of the nervous system. Dogs with larger pelves tend to have smaller NAs consistent with increased tendency toward HD in large breed dogs. Based on the current study, pelvic shape alone was not strongly associated with canine hip dysplasia.

SUBMITTER: Fealey MJ

PROVIDER: S-EPMC5364603 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Genetic mapping of principal components of canine pelvic morphology.

Fealey Mark J MJ Li Joy J Todhunter Rebel J E RJE Krotscheck Ursula U Hayashi Kei K McConkey Marina J MJ Boyko Adam R AR Hayward Jessica J JJ Todhunter Rory J RJ

Canine genetics and epidemiology 20170324

<h4>Background</h4>Concentrated breeding effort to produce various body structures and behaviors of dogs to suit human demand has inadvertently produced unwanted traits and diseases that accompany the morphological and behavioral phenotypes. We explored the relationship between pelvic conformation and canine hip dysplasia (HD) because purebred dogs which are predisposed, or not, to HD share common morphologic features, respectively. Thirteen unique bilateral anatomical features of the pelvis wer ...[more]

PMID: 28352471

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Project description:BackgroundFear/anxiety and anger/aggression greatly influence health, quality of life and social interactions. They are a huge burden to wellbeing, and personal and public economics. However, while much is known about the physiology and neuroanatomy of such emotions, little is known about their genetics - most importantly, why some individuals are more susceptible to pathology under stress.ResultsWe conducted genomewide association (GWA) mapping of breed stereotypes for many fear and aggression traits across several hundred dogs from diverse breeds. We confirmed those findings using GWA in a second cohort of partially overlapping breeds. Lastly, we used the validated loci to create a model that effectively predicted fear and aggression stereotypes in a third group of dog breeds that were not involved in the mapping studies. We found that i) known IGF1 and HMGA2 loci variants for small body size are associated with separation anxiety, touch-sensitivity, owner directed aggression and dog rivalry; and ii) two loci, between GNAT3 and CD36 on chr18, and near IGSF1 on chrX, are associated with several traits, including touch-sensitivity, non-social fear, and fear and aggression that are directed toward unfamiliar dogs and humans. All four genome loci are among the most highly evolutionarily-selected in dogs, and each of those was previously shown to be associated with morphological traits. We propose that the IGF1 and HMGA2 loci are candidates for identical variation being associated with both behavior and morphology. In contrast, we show that the GNAT3-CD36 locus has distinct variants for behavior and morphology. The chrX region is a special case due to its extensive linkage disequilibrium (LD). Our evidence strongly suggests that sociability (which we propose is associated with HS6ST2) and fear/aggression are two distinct GWA loci within this LD block on chrX, but there is almost perfect LD between the peaks for fear/aggression and animal size.ConclusionsWe have mapped many canine fear and aggression traits to single haplotypes at the GNAT3-CD36 and IGSF1 loci. CD36 is widely expressed, but areas of the amygdala and hypothalamus are among the brain regions with highest enrichment; and CD36-knockout mice are known to have significantly increased anxiety and aggression. Both of the other genes have very high tissue-specificity and are very abundantly expressed in brain regions that comprise the core anatomy of fear and aggression - the amygdala to hypothalamic-pituitary-adrenal (HPA) axis. We propose that reduced-fear variants at these loci may have been involved in the domestication process.

Project description:To decipher gene regulatory networks, we used systematic suppression of 97 transcription factors (TFs) and 7 other genes with shRNA in mouse embryonic stem (ES) cells, followed by global gene expression profiling. Meta-analysis of these data together with the earlier data obtained by the induction of 50 TFs and the existing genome-wide data on TF binding sites identified the sets of regulated target genes for 23 TFs. Principal component analysis shows different roles of two groups of TFs that are active in ES cells: Pou5f1 and Sox2 support the expression of their target genes and prevent the upregulation of trophectoderm-related genes, whereas Esrrb, Sall4, Nanog, Gbx2, Grhl2, Mtf2, Aff1, Tcfap4, and Cdc5l support the expression of targets of Esrrb, including glycolysis genes, and prevent upregulation of targets of Trp53 and Polycomb TFs. If TFs from the second group are downregulated while Pou5f1 and Sox2 are still active, then the cell state changes towards epiblast lineages. Sequences for shRNA were designed to target 3 untranslated region of genes (Supplementary Table S8). Gene expression change was checked with real time qPCR (Supplementary Figure S7) and Westerm blot. ES cells (ES[MC1R(20)], passage 20) were cultured without feeders and were co-transfected with 1.6 g of shRNA expression vector and 0.4 g of pPyCAG-EGFP-IP carrying expression cassettes for puromycin resistant genes and EGFP using Effectene (Qiagen). Transfected cells were cultured in presence of 1.5 g/ml of puromycin and were harvested at 72 h after transfection. Mock cells were treated with transfection reagent without DNA and cultured in the absence of puromycin. Experiments were done in 3 replications with 2 of them used for gene expression profiling with microarrays. Total RNA was isolated by TRIzol (Invitrogen) after 2 days. Cy3-CTP labeled sample targets were prepared with total RNA by Low RNA Input Fluorescent Linear Amplification Kit (Agilent). Cy5-CTP labeled reference target was Stratagene Universal Mouse Reference RNA. Note that the processed data in the paper, which is also attached as GSE26520_Table_data.txt.gz, is slightly different from the values columns in each sample. The original processed data are normalized with a batch method, as the new batches of arrays added in the set. The value columns in this submission reflect full normalization as described in the data processing fields in each sample.

Dataset Information

Genetic mapping of principal components of canine pelvic morphology.

Background

Results

Conclusion

Publications

Genetic mapping of principal components of canine pelvic morphology.

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