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27 results for “MC1R”
Peripheral MC1R activation modulates immune responses and confers neuroprotection in a mouse model of Parkinson's disease
<p>Raw data sets for the manuscripts</p> <p>This work was supported by NIH grants R01NS102735 and R01NS110879, the Farmer Family Foundation Initiative for Parkinson’s Disease Research and the MJFF and ASAP [ASAP-000312].</p>
Using MC1R Genotype to Impact Melanoma Risk Behavior
ClinicalTrials.gov study NCT03509467. IPD Sharing: Not stated. Countries: 2. Publications: 5.
Data from: Survival by genotype: patterns at Mc1r are not black and white at the White Sands ecotone
Measuring links among genotype, phenotype and survival in the wild has long been a focus of studies of adaptation. We conducted a 4-year capture–recapture study to measure survival by genotype and phenotype in the Southwestern Fence Lizard (Sceloporus cowlesi) at the White Sands ecotone (transition area between white sands and dark soil habitats). We report several unanticipated findings. First, in contrast with previous work showing that cryptic blanched coloration in S. cowlesi from the heart of the dunes is associated with mutations in the melanocortin-1 receptor gene (Mc1r), ecotonal S. cowlesi showed minimal association between colour phenotype and Mc1r genotype. Second, the frequency of the derived Mc1r allele in ecotonal S. cowlesi appeared to decrease over time. Third, our capture–recapture data revealed a lower survival rate for S. cowlesi individuals with the derived Mc1r allele. Thus, our results suggest that selection at the ecotone may have favoured the wild-type allele in recent years. Even in a system where a genotype–phenotype association appeared to be black and white, our study suggests that additional factors – including phenotypic plasticity, epistasis, pleiotropy and gene flow – may play important roles at the White Sands ecotone. Our study highlights the importance of linking molecular, genomic and organismal approaches for understanding adaptation in the wild. Furthermore, our findings indicate that dynamics of natural selection can be particularly complex in transitional habitats like ecotones and emphasize the need for future research that examines the patterns of ongoing selection in other ecological 'grey' zones.
Data from: MC1R variants affect the expression of melanocortin and melanogenic genes and the association between melanocortin genes and coloration
The melanocortin-1 receptor (MC1R) gene influences coloration by altering the expression of genes acting downstream in the melanin synthesis. MC1R belongs to the melanocortin system, a genetic network coding for the ligands that regulate MC1R and other melanocortin receptors controlling different physiological and behavioural traits. The impact of MC1R variants on these regulatory melanocortin genes was never considered, even though MC1R mutations could alter the influence of these genes on coloration (e.g. by decreasing MC1R response to melanocortin ligands). Using barn owl growing feathers, we investigated the differences between MC1R genotypes in the (co)expression of six melanocortin and nine melanogenic-related genes and in the association between melanocortin gene expression and phenotype (feather pheomelanin content). Compared to the MC1R rufous allele, responsible for reddish coloration, the white allele was not only associated with an expected lower expression of melanogenic-related genes (TYR, TYRP1, OCA2, SLC45A2, KIT, DCT) but also with a lower MC1R expression and a higher expression of ASIP, the MC1R antagonist. More importantly, the expression of PCSK2, responsible for the maturation of the MC1R agonist, α-melanocyte-stimulating hormone, was positively related to pheomelanin content in MC1R white homozygotes but not in individuals carrying the MC1R rufous allele. These findings indicate that MC1R mutations not only alter the expression of melanogenic-related genes but also the association between coloration and the expression of melanocortin genes upstream of MC1R. This suggests that MC1R mutations can modulate the regulation of coloration by the pleiotropic melanocortin genes, potentially decoupling the often-observed associations between coloration and other phenotypes.
Data from: Effect of the MC1R gene on sexual dimorphism in melanin-based colorations
Variants of the melanocortin-1 receptor (MC1R) gene result in abrupt, naturally selected colour morphs. These genetic variants may differentially affect sexual dimorphism if one morph is naturally selected in the two sexes but another morph is naturally or sexually selected only in one of the two sexes (e.g. to confer camouflage in reproductive females or confer mating advantage in males). Therefore, the balance between natural and sexual selections can differ between MC1R variants, as suggest studies showing interspecific correlations between sexual dimorphism and the rate of nonsynonymous vs. synonymous amino acid substitutions at the MC1R. Surprisingly, how MC1R is related to within-species sexual dimorphism, and thereby to sex-specific selection, has not yet been investigated. We tackled this issue in the barn owl (Tyto alba), a species showing pronounced variation in the degree of reddish pheomelanin-based coloration and in the number and size of black feather spots. We found that a valine (V)-to-isoleucine (I) substitution at position 126 explains up to 30% of the variation in the three melanin-based colour traits and in feather melanin content. Interestingly, MC1R genotypes also differed in the degree of sexual colour dimorphism, with individuals homozygous for the II MC1R variant being 2 times redder and 2.5 times less sexually dimorphic than homozygous individuals for the VV MC1R variant. These findings support that MC1R interacts with the expression of sexual dimorphism and suggest that a gene with major phenotypic effects and weakly influenced by variation in body condition can participate in sex-specific selection processes.
Data from: Effect of the MC1R gene on sexual dimorphism in melanin-based colorations
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Data from: Melanocortin 1 receptor (MC1R) gene sequence variation and melanism in the gray (Sciurus carolinensis), fox (Sciurus niger) and red (Sciurus vulgaris) squirrel
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Data from: Beyond mean allelic effects: a locus at the major color gene MC1R associates also with differing levels of phenotypic and genetic (co)variance for coloration in barn owls
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Data from: MC1R variants affect the expression of melanocortin and melanogenic genes and the association between melanocortin genes and coloration
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Data from: Survival by genotype: patterns at Mc1r are not black and white at the White Sands ecotone
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Data from: Ancient onset of geographic divergence, interpopulation genetic exchange, and natural selection on the Mc1r coat-color gene in the house mouse (Mus musculus) inferred from tandemly arranged nuclear gene markers
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Data from: Sex-specific allelic transmission bias suggests sexual conflict at MC1R
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Data from: Female-biased dispersal and non-random gene flow of MC1R variants do not result in a migration load in barn owls
Non-random gene flow is a widely neglected force in evolution and ecology. This genotype-dependent dispersal is difficult to assess, yet can impact the genetic variation of natural populations and their fitness. In this work, we demonstrate a high immigration rate of barn owls (Tyto alba) inside a Swiss population surveyed during 15 years. Using 10 microsatellite loci as an indirect method to characterize dispersal, two third of the genetic tests failed to detect a female-biased dispersal, and Monte-Carlo simulations confirmed a low statistical power to detect sex-biased dispersal in case of high dispersal rate of both sexes. The capture-recapture data revealed a female-biased dispersal associated with an excess of heterozygote for the melanocortin-1 receptor gene (MC1R), which is responsible for their ventral rufous coloration. Thus, female homozygotes for the MC1R_white allele might be negatively selected during dispersal. Despite the higher immigration of females that are heterozygote at MC1R, non-random gene flow should not lead to a migration load regarding this gene because we did not detect an effect of MC1R on survival and reproductive success in our local population. The present study highlights the usefulness of using multiple methods to correctly decrypt dispersal and gene flow. Moreover, despite theoretical expectations, we show that non-random dispersal of particular genotypes does not necessarily lead to migration load in recipient populations.
Data from: The MC1R and ASIP coat color loci may impact behavior in the horse
Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes.
Data from: The MC1R and ASIP coat color loci may impact behavior in the horse
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Data from: Female-biased dispersal and non-random gene flow of MC1R variants do not result in a migration load in barn owls
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Loss of MC1R signaling implicates TBX3 in pheomelanogenesis and melanoma predisposition
GEO Series GSE237004. Mus musculus; Homo sapiens. 13 samples. Type: Expression profiling by high throughput sequencing.
Capturing the biological impact of the melanoma susceptibility genes CDKN2A and MC1R in cocultured keratinocytes and melanocytes
GEO Series GSE44805. Homo sapiens. 12 samples. Type: Expression profiling by array.
Dysregulation of MITF in the context of defective MC1R and RB1/p16/CDK4 leads to melanocyte transformation [ChIP-Seq]
GEO Series GSE142014. Homo sapiens. 8 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
Loss of MC1R signaling implicates TBX3 in pheomelanogenesis and melanoma predisposition [scRNA-seq]
GEO Series GSE236918. Mus musculus. 4 samples. Type: Expression profiling by high throughput sequencing.
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Allen Brain Atlas
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