Signature of Balancing Selection at the MC1R Gene in Kunming Dog Populations

Wang, Guodong; Cheng, Lu-Guang; Fan, Ruoxi; Irwin, David M.; Tang, Shusheng; Peng, Jian‐Guo; Zhang, Yaping

doi:10.1371/journal.pone.0055469

Cited by 18 publications

(18 citation statements)

References 45 publications

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“…Moreover, SNPs on commercial arrays are generally thought to be selectively neutral since they are usually chosen to provide even chromosomal coverage [7]. Unfortunately, very little is known about balancing selection in either dogs or seals, other than the fact that this may be operating at the canine MHC [45] and MC1R [46]. Moreover, classical tests for balancing selection cannot be applied in the context of this study because they require data on intraspecific and/or interspecific sequence variation [47] that are not available.…”

Section: Discussionmentioning

confidence: 99%

Cross-Amplification and Validation of SNPs Conserved over 44 Million Years between Seals and Dogs

et al. 2013

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High-density SNP arrays developed for humans and their companion species provide a rapid and convenient tool for generating SNP data in closely-related non-model organisms, but have not yet been widely applied to phylogenetically divergent taxa. Consequently, we used the CanineHD BeadChip to genotype 24 Antarctic fur seal (Arctocephalus gazella) individuals. Despite seals and dogs having diverged around 44 million years ago, 33,324 out of 173,662 loci (19.2%) could be genotyped, of which 173 were polymorphic and clearly interpretable. Two SNPs were validated using KASP genotyping assays, with the resulting genotypes being 100% concordant with those obtained from the high-density array. Two loci were also confirmed through in silico visualisation after mapping them to the fur seal transcriptome. Polymorphic SNPs were distributed broadly throughout the dog genome and did not differ significantly in proximity to genes from either monomorphic SNPs or those that failed to cross-amplify in seals. However, the nearest genes to polymorphic SNPs were significantly enriched for functional annotations relating to energy metabolism, suggesting a possible bias towards conserved regions of the genome.

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Section: Discussionmentioning

confidence: 99%

Cross-Amplification and Validation of SNPs Conserved over 44 Million Years between Seals and Dogs

et al. 2013

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“…14 They have natural high BP, 15 and are therefore ideal experimental animals used for this study. Eligible dogs were older than 3 years and had a systolic BP (SBP) of ≥140 mm Hg (under anesthesia and via invasive BP monitoring).…”

Section: Animalsmentioning

confidence: 99%

Selective Proximal Renal Denervation Guided by Autonomic Responses Evoked via High-Frequency Stimulation in a Preclinical Canine Model

Wang

Zhou

et al. 2015

Circ: Cardiovascular Interventions

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R esistant hypertension has been linked to chronic excessive sympathetic drive, especially elevation of renal sympathetic activity in some groups of patients.1,2 Against this background, renal artery ablation selectively denervating the kidneys emerges as an alternative treatment for such patients. Although initial trials 3,4 showed promising results with regard to large reductions in blood pressure (BP), disappointingly, the potential therapeutic role of renal denervation (RDN) in lowering BP is being challenged after the failure of recent SYMPLICITY HTN-3 trial 5 to show a benefit of RDN over the optimal medical therapy.The concept of RDN is supported by both experimental and early human evidence when surgical sympathectomy procedures were done and found to have huge effect on BP. [6][7][8] However, for the time being, the BP-lowering effect of catheter-based RDN is highly variable (the rates of nonresponse to RDN vary between 8% and 37%).9 Kaiser et al 10 reported that repeated RDN could significantly decrease BP in nonresponders to previous radiofrequency ablation procedure. These findings suggest that lack of BP reductions after RDN may be the results of incomplete denervation. Therefore, to minimize treatment failure of blind ablation, a method that could convert what is currently a purely anatomic procedure to one that involves quantifying the efficacy of RDN intraprocedurally and mapping the renal nerves to enable a targeted therapy is of great clinical significance.Background-Electric stimulation has been proved to be available to monitor the efficacy of renal denervation (RDN). This study was to evaluate the effectiveness of high-frequency stimulation (HFS)-guided proximal RDN. Methods and Results-A total of 13 Chinese Kunming dogs were included and allocated to proximal RDN group (n=8) and control group (n=5). HFS (20 Hz, 8 V, pulse width 2 ms) was performed from proximal to distal renal artery in all dogs. Radiofrequency ablations were delivered in proximal RDN group and only at the proximal positive sites where systolic blood pressure (BP) increased ≥10 mm Hg during HFS. Postablation HFS was performed over the previously stimulated sites. BP, heart rate, and plasma norepinephrine were analyzed. In 8 denervated dogs, preablation HFS caused significant BP increases of 6.0±5.0/3.4±5.5, 16.9±11.7/11.1±8.5, and 17.1±8.4/8.5±5.3 mm Hg during the first, second, and third 20 s of HFS at the proximal positive sites. After ablation, these sites showed a negative response to postablation HFS with increases of BP by 1.3±3.0/1.0±2.5, 0.8±3.9/1.5±3.

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“…To perform the percutaneous catheter-based RDN technique, large experimental animal model was required. As previously described, the Chinese Kunming dogs are larger, more aggressive and fierce than beagles, spaniels and mongrels, more importantly having high natural BP and sympathetic activity2526. Thus, this study was performed on Chinese Kunming dogs.…”

Section: Discussionmentioning

confidence: 97%

“…Eligible dogs were older than three years and had systolic BP of 140 mmHg or more. The Chinese Kunming dogs are larger, more aggressive and fierce than beagles, spaniels and mongrels, more importantly having high natural BP and sympathetic activity2526, which are ideal as the experimental animals for renal denervation studies. Using the Chinese Kunming dogs as the experimental animals, we had successfully performed a series of basic researches related to catheter-based RDN technique252728.…”

Section: Methodsmentioning

confidence: 99%

Renal Artery Vasodilation May Be An Indicator of Successful Sympathetic Nerve Damage During Renal Denervation Procedure

Chen

et al. 2016

Sci Rep

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Autonomic nervous system plays a crucial role in maintaining and regulating vessel tension. Renal denervation (RDN) may induce renal artery vasodilation by damaging renal sympathetic fibers. We conducted this animal study to evaluate whether renal artery vasodilation could be a direct indicator of successful RDN. Twenty-eight Chinese Kunming dogs were randomly assigned into three groups and underwent RDN utilizing temperature-controlled catheter (group A, n = 11) or saline-irrigated catheter (group B, n = 11) or sham procedure (group C, n = 6). Renal angiography, blood pressure (BP) and renal artery vasodilation measurements were performed at baseline, 30-minute, 1-month, and 3-month after interventions. Plasma norepinephrine concentrations were tested at baseline and 3-month after intervention. Results showed that, in addition to significant BP reduction, RDN induced significant renal artery vasodilation. Correlation analyses showed that the induced renal artery vasodilation positively correlated with SBP reduction and plasma norepinephrine reduction over 3 months after ablation. Post hoc analyses showed that saline-irrigated catheter was superior to TC catheter in renal artery vasodilation, especially for the acute dilatation of renal artery at 30-minute after RDN. In conclusion, renal artery vasodilation, induced by RDN, may be a possible indicator of successful renal nerve damage and a predictor of blood pressure response to RDN.

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Signature of Balancing Selection at the MC1R Gene in Kunming Dog Populations

Cited by 18 publications

References 45 publications

Cross-Amplification and Validation of SNPs Conserved over 44 Million Years between Seals and Dogs

Cross-Amplification and Validation of SNPs Conserved over 44 Million Years between Seals and Dogs

Selective Proximal Renal Denervation Guided by Autonomic Responses Evoked via High-Frequency Stimulation in a Preclinical Canine Model

Renal Artery Vasodilation May Be An Indicator of Successful Sympathetic Nerve Damage During Renal Denervation Procedure

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