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1.
Genes (Basel) ; 15(8)2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39202415

RESUMEN

Four dominant coat color phenotypes are found in fallow deer (Dama dama). Brown is the most common. Black, menil, and white occur with varying frequencies. In order to gain insights into the molecular genetic background of these phenotypes, 998 fallow animals (772 brown, 62 black, 126 menil, and 38 white) were examined for mutations in the ASIP, MC1R, TYR, and SLC45A2 genes. In ASIP, two mutations (ASIP-M-E2, located at the boundary from exon 2 to intron 2; and ASIP-M-E3, an InDel of five nucleotides) were found, leading to black fallow deer being either homozygous or heterozygous in combination. There were also two mutations found in MC1R. Whereby the mutation MC1R-M1 (leucine to proline, L48P) homozygous leads to a white coat, while the mutation MC1R-M2 (glycine to aspartic acid, G236D) homozygous is associated with the menil phenotype. When both mutations occur together in a heterozygous character state, it results in a menil coat. Since the mutations in the two genes are only present alternatively, 36 genotypes can be identified that form color clusters to which all animals can be assigned. No mutations were found in the TYR and SLC45A2 genes. Our investigations demonstrate that the four dominant coat colors in fallow deer can be explained by ASIP and MC1R mutations only.


Asunto(s)
Proteína de Señalización Agouti , Ciervos , Fenotipo , Receptor de Melanocortina Tipo 1 , Animales , Ciervos/genética , Receptor de Melanocortina Tipo 1/genética , Proteína de Señalización Agouti/genética , Mutación , Color del Cabello/genética , Pigmentación/genética
2.
Nat Genet ; 56(8): 1583-1591, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39048794

RESUMEN

Retrotransposons comprise about 45% of the human genome1, but their contributions to human trait variation and evolution are only beginning to be explored2,3. Here, we find that a sequence of SVA retrotransposon insertions in an early intron of the ASIP (agouti signaling protein) gene has probably shaped human pigmentation several times. In the UK Biobank (n = 169,641), a recent 3.3-kb SVA insertion polymorphism associated strongly with lighter skin pigmentation (0.22 [0.21-0.23] s.d.; P = 2.8 × 10-351) and increased skin cancer risk (odds ratio = 1.23 [1.18-1.27]; P = 1.3 × 10-28), appearing to underlie one of the strongest common genetic influences on these phenotypes within European populations4-6. ASIP expression in skin displayed the same association pattern, with the SVA insertion allele exhibiting 2.2-fold (1.9-2.6) increased expression. This effect had an unusual apparent mechanism: an earlier, nonpolymorphic, human-specific SVA retrotransposon 3.9 kb upstream appeared to have caused ASIP hypofunction by nonproductive splicing, which the new (polymorphic) SVA insertion largely eliminated. Extended haplotype homozygosity indicated that the insertion allele has risen to allele frequencies up to 11% in European populations over the past several thousand years. These results indicate that a sequence of retrotransposon insertions contributed to a species-wide increase, then a local decrease, of human pigmentation.


Asunto(s)
Proteína de Señalización Agouti , Retroelementos , Pigmentación de la Piel , Humanos , Retroelementos/genética , Proteína de Señalización Agouti/genética , Pigmentación de la Piel/genética , Mutagénesis Insercional , Alelos , Neoplasias Cutáneas/genética , Genoma Humano , Intrones/genética
3.
BMC Vet Res ; 20(1): 311, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38997753

RESUMEN

BACKGROUND: The pleiotropic effects of the melanocortin system show promise in overcoming limitations associated with large variations in opioid analgesic effectiveness observed in equine practice. Of particular interest is variation in the melanocortin-1-receptor (MC1R) gene, which dictates pigment type expression through its epistatic interaction with the agouti signalling protein (ASIP) gene. MC1R has previously been implicated in opioid efficacy in other species; however, this relationship is yet to be explored in horses. In this study, analgesic effectiveness was scored (1-3) based on noted response to dura penetration during the performance of cerebrospinal fluid centisis after sedation and tested for association with known genetic regions responsible for pigmentation variation in horses. RESULTS: The chestnut phenotype was statistically significant (P < 0.05) in lowering analgesic effectiveness when compared to the bay base coat colour. The 11bp indel in ASIP known to cause the black base coat colour was not significant (P>0.05); however, six single nucleotide polymorphisms (SNPs) within the genomic region encoding the ASIP gene and one within MC1R were identified as being nominally significant (P<0.05) in association with opioid analgesic effectiveness. This included the location of the known e MC1R variant resulting in the chestnut coat colour. CONCLUSIONS: The current study provides promising evidence for important links between pigmentation genes and opioid effectiveness in horses. The application of an easily identifiable phenotype indicating variable sensitivity presents a promising opportunity for accessible precision medicine in the use of analgesics and warrants further investigation.


Asunto(s)
Analgésicos Opioides , Polimorfismo de Nucleótido Simple , Receptor de Melanocortina Tipo 1 , Animales , Caballos , Analgésicos Opioides/farmacología , Analgésicos Opioides/uso terapéutico , Receptor de Melanocortina Tipo 1/genética , Pigmentación/genética , Proteína de Señalización Agouti/genética , Masculino , Femenino , Fenotipo , Líquido Cefalorraquídeo/metabolismo
4.
Cells Dev ; 179: 203930, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38815807

RESUMEN

The oocyte expresses certain genes during folliculogenesis to regulate the acquisition of oocyte competence. Oocyte competence, or oocyte quality, is directly related to the ability of the oocyte to result in a successful pregnancy following fertilization. Presently, approximately 40 % of bovine embryos will develop to the blastocyst stage in vitro. Characterization of factors regulating these processes is crucial to improve the efficiency of bovine in vitro embryo production. We demonstrated that the secreted protein, agouti-signaling protein (ASIP) is highly abundant in the bovine oocyte and aimed to characterize its spatiotemporal expression profile in the ovary and throughout early embryonic development. In addition to oocyte expression, ASIP was detected in granulosa, cumulus, and theca cells isolated from antral follicles. Both gene expression data and immunofluorescent staining indicated ASIP declines with oocyte maturation which may indicate a potential role for ASIP in the attainment of oocyte competence. Microinjection of zygotes using small interfering RNA targeting ASIP led to a 16 % reduction in the rate of development to the blastocyst stage. Additionally, we examined potential ASIP signaling mechanisms through which ASIP may function to establish oocyte developmental competence. The expression of melanocortin receptor 3 and 4 and the coreceptor attractin was detected in the oocyte and follicular cells. The addition of cortisol during in vitro maturation was found to increase significantly oocyte ASIP levels. In conclusion, these results suggest a functional role for ASIP in promoting oocyte maturation and subsequent embryonic development, potentially through signaling mechanisms involving cortisol.


Asunto(s)
Proteína de Señalización Agouti , Desarrollo Embrionario , Oocitos , Ovario , Animales , Bovinos , Femenino , Desarrollo Embrionario/genética , Oocitos/metabolismo , Ovario/metabolismo , Proteína de Señalización Agouti/metabolismo , Proteína de Señalización Agouti/genética , Regulación del Desarrollo de la Expresión Génica , Blastocisto/metabolismo , Transducción de Señal , Células del Cúmulo/metabolismo , Células Tecales/metabolismo
5.
Anim Genet ; 55(2): 249-256, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38194424

RESUMEN

The genetic foundation of chicken body plumage color has been extensively studied. However, little attention has been paid to the inheritance patterns and molecular mechanisms underlying the formation of distal feather colors (tail and wingtip). Differences in these colors are common; for example, the Chinese Huiyang Beard chicken has black tail feathers, but yellow body plumage. Here, the hybrid offspring of Huiyang Beard and White Leghorn chickens were used to study the inheritance patterns of tail-feather color. The expression levels of pigment genes in differently colored feather follicles were analyzed using quantitative real-time PCR. The results showed that genetic regulation of tail-feather color was independent of body-plumage color. The Dominant White locus inhibited eumelanin synthesis in tail feathers without affecting the formation of yellow body plumage, whereas the Silver locus had the opposite effect. The expression of agouti signaling protein (ASIP) gene class 1 transcripts was significantly lower in black tail-feather follicles than in yellow body follicles, whereas tyrosinase-related protein 1 (TYRP1) gene expression was significantly higher in black tail feathers. These differentially expressed genes were confirmed to exert an effect on eumelanin and pheomelanin formation in feathers, thus influencing the regulation of chicken tail-feather color. In conclusion, this study lays the foundation for further research on the genetic mechanisms of regional differences in feather color, contributing to a better understanding of plumage pigmentation in chickens.


Asunto(s)
Pollos , Cola (estructura animal) , Animales , Pollos/genética , Proteína de Señalización Agouti/genética , Plumas/fisiología , Expresión Génica , Pigmentación/genética
6.
J Pineal Res ; 76(1): e12939, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38241679

RESUMEN

Temporal signals such as light and temperature cycles profoundly modulate animal physiology and behaviour. Via endogenous timing mechanisms which are regulated by these signals, organisms can anticipate cyclic environmental changes and thereby enhance their fitness. The pineal gland in fish, through the secretion of melatonin, appears to play a critical role in the circadian system, most likely acting as an element of the circadian clock system. An important output of this circadian clock is the locomotor activity circadian rhythm which is adapted to the photoperiod and thus determines whether animals are diurnal or nocturnal. By using a genetically modified zebrafish strain known as Tg (Xla.Eef1a1:Cau.asip1)iim04, which expresses a higher level of the agouti signalling protein 1 (Asip1), an endogenous antagonist of the melanocortin system, we observed a complete disruption of locomotor activity patterns, which correlates with the ablation of the melatonin daily rhythm. Consistent with this, in vitro experiments also demonstrated that Asip1 inhibits melatonin secretion from the zebrafish pineal gland, most likely through the melanocortin receptors expressed in this gland. Asip1 overexpression also disrupted the expression of core clock genes, including per1a and clock1a, thus blunting circadian oscillation. Collectively, these results implicate the melanocortin system as playing an important role in modulating pineal physiology and, therefore, circadian organisation in zebrafish.


Asunto(s)
Melanocortinas , Melatonina , Glándula Pineal , Animales , Proteína de Señalización Agouti/genética , Proteína de Señalización Agouti/metabolismo , Ritmo Circadiano/fisiología , Locomoción/fisiología , Melatonina/metabolismo , Glándula Pineal/metabolismo , Pez Cebra/genética , Melanocortinas/metabolismo
7.
Pigment Cell Melanoma Res ; 37(2): 259-264, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37874775

RESUMEN

MFSD12 functions as a transmembrane protein required for import of cysteine into melanosomes and lysosomes. The MFSD12 locus has been associated with phenotypic variation in skin color across African, Latin American, and East Asian populations. The frequency of a particular MFSD12 coding variant, rs2240751 (MAF = 0.08), has been reported to correlate with solar radiation and occur at highest frequency in Peruvian (PEL MAF = 0.48) and Han Chinese (CHB MAF = 0.40) populations, suggesting it could be causative for associated phenotypic variation in skin color. We have generated a mouse knock-in allele, Mfsd12Y182H , to model the human missense p.Tyr182His human variant. We demonstrate that the variant transcript is stably expressed and that agouti mice homozygote for the variant allele are viable with an altered coat color. This in vivo data confirms that the MFSD12 p.Tyr182His variant functions as a hypomorphic allele sufficient to alter mammalian pigmentation.


Asunto(s)
Proteínas de la Membrana , Pigmentación de la Piel , Animales , Ratones , Proteína de Señalización Agouti/genética , Alelos , Color del Cabello/genética , Homocigoto , Proteínas de la Membrana/genética , Mutación Missense/genética , Pigmentación de la Piel/genética
8.
Curr Protein Pept Sci ; 24(4): 329-338, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36941814

RESUMEN

BACKGROUND: The brain melanocortin system regulates numerous physiological functions and kinds of behavior. The agouti protein inhibits melanocortin receptors in melanocytes. The lethal yellow (AY) mutation puts the Agouti gene under the control of the Raly gene promotor and causes the agouti protein expression in the brain. In the present article, we investigated the effects of the AY mutation on brain mRNA levels of Agouti, Raly, and melanocortin-related genes such as Agrp, Pomc, Mc3r, Mc4r, and their relationship to behavior. METHODS: The experiment was performed on 6-month-old males and females of AY/a and a/a (control) mice. Anxiety and obsessive-compulsive behavior were studied in elevated plus-maze and marble- burying tests. The mRNA levels were quantified by qPCR. RESULTS: AY mutation caused anxiety in males and obsessive-compulsive behavior in females. Positive correlation between Agouti and Raly genes mRNA levels were shown in the hypothalamus, hippocampus, and frontal cortex in AY/a mice. Reduced RNA concentrations of Mc3r and Mc4r genes were found respectively in the hypothalamus and frontal cortex in AY/a males. The Raly gene expression positively correlates with mRNA concentrations of the Mc3r gene in the hypothalamus and the Mc4r gene in the hypothalamus and frontal cortex. CONCLUSION: Possible association of obsessive-compulsive behavior with reduced Raly, Mc3r, or Mc4r gene expression is suggested.


Asunto(s)
Trastorno Obsesivo Compulsivo , Animales , Femenino , Masculino , Ratones , Proteína de Señalización Agouti/genética , Proteína de Señalización Agouti/metabolismo , Ansiedad/genética , Encéfalo/metabolismo , Melanocortinas/metabolismo , Mutación , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/metabolismo , Receptores de Melanocortina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo
9.
Science ; 379(6638): 1238-1242, 2023 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-36952420

RESUMEN

The genetic basis of adaptive traits has rarely been used to predict future vulnerability of populations to climate change. We show that light versus dark seasonal pelage in white-tailed jackrabbits (Lepus townsendii) tracks snow cover and is primarily determined by genetic variation at endothelin receptor type B (EDNRB), corin serine peptidase (CORIN), and agouti signaling protein (ASIP). Winter color variation was associated with deeply divergent alleles at these genes, reflecting selection on both ancestral and introgressed variation. Forecasted reductions in snow cover are likely to induce widespread camouflage mismatch. However, simulated populations with variation for darker winter pelage are predicted to adapt rapidly, providing a trait-based genetic framework to facilitate evolutionary rescue. These discoveries demonstrate how the genetic basis of climate change adaptation can inform conservation.


Asunto(s)
Aclimatación , Mimetismo Biológico , Cambio Climático , Liebres , Animales , Aclimatación/genética , Liebres/genética , Liebres/fisiología , Estaciones del Año , Mimetismo Biológico/genética , Receptor de Endotelina B/genética , Variación Genética , Serina Endopeptidasas/genética , Proteína de Señalización Agouti/genética
10.
Transgenic Res ; 32(1-2): 143-152, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36637628

RESUMEN

The mouse Agouti gene encodes a paracrine signaling factor which promotes melanocytes to produce yellow instead of black pigment. It has been reported that Agouti mRNA is confined to the dermal papilla after birth in various mammalian species. In this study, we created and characterized a knockin mouse strain in which Cre recombinase was expressed in-frame with endogenous Agouti coding sequence. The Agouti-Cre mice were bred with reporter mice (Rosa26-tdTomato or Rosa26-ZsGreen) to trace the lineage of Agouti-expressing cells during development. In skin, the reporter was detected in some dermal fibroblasts at the embryonic stage and in all dermal fibroblasts postnatally. It was also expressed in all mesenchymal lineage cells in other organs/tissues, including eyes, tongue, muscle, intestine, adipose, prostate and testis. Interestingly, the reporter expression was excluded from epithelial cells in the above organs/tissues. In brain, the reporter was observed in the outermost meningeal fibroblasts. Our work helps to illustrate the Agouti expression pattern during development and provides a valuable mouse strain for conditional gene targeting in mesenchymal lineage cells in multiple organs.


Asunto(s)
Proteína de Señalización Agouti , Animales , Masculino , Ratones , Marcación de Gen , Integrasas/genética , Integrasas/metabolismo , Ratones Transgénicos , Proteína de Señalización Agouti/genética
12.
Nat Metab ; 4(12): 1697-1712, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36536132

RESUMEN

Here we report a heterozygous tandem duplication at the ASIP (agouti signaling protein) gene locus causing ubiquitous, ectopic ASIP expression in a female patient with extreme childhood obesity. The mutation places ASIP under control of the ubiquitously active itchy E3 ubiquitin protein ligase promoter, driving the generation of ASIP in patient-derived native and induced pluripotent stem cells for all germ layers and hypothalamic-like neurons. The patient's phenotype of early-onset obesity, overgrowth, red hair and hyperinsulinemia is concordant with that of mutant mice ubiquitously expressing the homolog nonagouti. ASIP represses melanocyte-stimulating hormone-mediated activation as a melanocortin receptor antagonist, which might affect eating behavior, energy expenditure, adipocyte differentiation and pigmentation, as observed in the index patient. As the type of mutation escapes standard genetic screening algorithms, we rescreened the Leipzig Childhood Obesity cohort of 1,745 patients and identified four additional patients with the identical mutation, ectopic ASIP expression and a similar phenotype. Taken together, our data indicate that ubiquitous ectopic ASIP expression is likely a monogenic cause of human obesity.


Asunto(s)
Obesidad Infantil , Niño , Humanos , Femenino , Animales , Ratones , Proteína de Señalización Agouti/genética , Proteína de Señalización Agouti/metabolismo , Pigmentación/genética , Mutación , Fenotipo
13.
Genes (Basel) ; 13(9)2022 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-36140707

RESUMEN

Goats have become one of the most adaptive and important livestock species distributed in developing countries in recent years. The Hainan Black goat is a native goat breed of the Hainan region that is generally well-liked by the local population and is thus raised in large numbers. However, the genomic diversity and selective signals of the Hainan Black goat have not been clearly elucidated yet. Therefore, in this study, we performed whole-genome resequencing of 16 Hainan Black goats and compared the results with those of 71 goats of 6 other breeds from different geographic regions. Principal component analysis (PCA) and phylogenetic analysis identified seven lineages for all goats. Hainan Black goats showed the most similarity with Leizhou goats and the least similarity with Boer goats. Selective sweep analysis identified candidate genes associated with various functions, including immune resistance to disease (TNFAIP2 (TNF alpha induced protein 2) and EXOC3L4 (exocyst complex component 3 like 4)), melanin biosynthetic process (CDH15 (cadherin 15), ASIP (agouti signaling protein), and PARD3 (par-3 family cell polarity regulator)), and light sensitivity (CNGB3 (cyclic nucleotide gated channel subunit beta 3) and CNBD1 (cyclic nucleotide binding domain containing 1)), underlying strong selection signatures in Hainan Black goats. The melanin biosynthetic process, circadian entrainment, regulation of cyclic adenosine 3,5-monophosphate (cAMP)-mediated signaling, and the Rap-1 signaling pathway were significantly enriched in Hainan Black and Alashan Cashmere goats. This result may be important for understanding each trait. Selection signature analysis revealed candidate single nucleotide polymorphisms (SNPs) and genes correlated with the traits of Hainan Black goats. Collectively, our results provide valuable insights into the genetic basis of specific traits correlated with the Hainan island climate, artificial selection in certain local goat breeds, and the importance of protecting breed resources.


Asunto(s)
Cabras , Selección Genética , Adenosina , Proteína de Señalización Agouti/genética , Animales , Canales Catiónicos Regulados por Nucleótidos Cíclicos/genética , Genómica , Cabras/genética , Melaninas/genética , Nucleótidos Cíclicos , Filogenia , Factor de Necrosis Tumoral alfa/genética
14.
Genomics ; 114(3): 110361, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35378242

RESUMEN

Deciphering the molecular architecture of coat coloration for a better understanding of the biological mechanisms underlying pigmentation still remains a challenge. We took advantage of a rabbit French experimental population in which both a pattern and a gradient of coloration from white to brown segregated within the himalayan phenotype. The whole experimental design was genotyped using the high density Affymetrix® AxiomOrcun™ SNP Array and phenotyped into 6 different groups ordered from the lighter to the darker. Genome-wide association analyses pinpointed an oligogenic determinism, under recessive and additive inheritance, involving genes already known in melanogenesis (ASIP, KIT, MC1R, TYR), and likely processed pseudogenes linked to ribosomal function, RPS20 and RPS14. We also identified (i) gene-gene interactions through ASIP:MC1R affecting light cream/beige phenotypes while KIT:RPS responsible of dark chocolate/brown colors and (ii) a genome-wide epistatic network involving several others coloration genes such as POT1 or HPS5. Finally, we determined the recessive inheritance of the English spotting phenotype likely involving a copy number variation affecting at least the end of the coding sequence of the KIT gene. Our analyses of coloration as a continuous trait allowed us to go beyond much of the established knowledge through the detection of additional genes and gene-gene interactions that may contribute to the molecular architecture of the coloration phenotype.


Asunto(s)
Variaciones en el Número de Copia de ADN , Estudio de Asociación del Genoma Completo , Animales , Conejos , Proteína de Señalización Agouti/genética , Pigmentación/genética , Fenotipo , Extremidades
15.
Genes Genet Syst ; 96(6): 271-284, 2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35283410

RESUMEN

While the house mouse (Mus musculus), widely distributed in Eurasia, is known to have substantial coat color variation between and within local populations, in both primary and secondary distribution areas, including the Japanese archipelago, the evolutionary history of the color variation is poorly understood. To address the ventral fur color variation, we quantified the lightness of museum skin specimens, and found that the southern subspecies, M. m. castaneus (CAS), has high and low lightness in dry and rainy geographic regions, respectively. The northern subspecies, M. m. musculus (MUS), has low and high levels of lightness in the high and middle latitudes of northern Eurasia, respectively. We examined sequence variation of the agouti signaling protein gene (Asip), which is known to be responsible for the ventral fur color. We performed phylogenetic analyses with 196 haplotype sequences of Asip (~180 kb) generated by phasing the whole-genome data of 98 wild mice reported previously. Network and phylogenetic tree construction revealed clustering of haplotypes representing the two subspecies, MUS and CAS. A number of subclusters with geographic affinities appeared within the subspecies clusters, in which the essential results were consistent with those reconstructed with whole mitochondrial genome data, indicating that the phased haplotype genome sequences of the nuclear genome can be a useful tool for tracing the dispersal of geographical lineages. The results of phylogeographic analysis showed that CAS mice with darker ventral fur possessed similar Asip haplotypes across the geographic distribution, suggesting that these haplotypes are major causes of the historical introduction of Asip haplotypes for darker ventral fur in mice from northern India to the peripheral areas, including the Japanese archipelago. Similarly, MUS in East Asia, which has a white abdomen, formed an Asip haplogroup with that from northern Iran, also with a white abdomen.


Asunto(s)
Proteína de Señalización Agouti , Genoma Mitocondrial , Color del Cabello , Ratones , Proteína de Señalización Agouti/genética , Pelaje de Animal , Animales , Color del Cabello/genética , Haplotipos , Ratones/genética , Filogenia , Filogeografía
16.
Gene ; 809: 146018, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34655720

RESUMEN

The Agouti gene (ASIP) is one of the most important genes for coat color determination in mammals. It has a complex structure with several promoters and alternative non-coding first exons that are transcribed into mRNAs with different 5'UTR. These mRNA isoforms regulate the temporal and spatial expression of the gene, producing diverse pigmentation patterns. Here, we studied ASIP transcriptional variants and their expression in the skin of llamas with different coat color phenotypes. We also described the ASIP locus, including promoter usage and the splicing events that originate each transcript variant. Using 5'RACE-PCR we isolated seven ASIP transcripts with alternative 5'UTR, where exons 1A, 1A', 1C, 1D, and a novel non-coding exon 1A" were identified. Additionally, new alternative spliced forms were found. The diversity of ASIP 5'UTRs is originated by a complex pattern of alternative promoter usage, multiple transcription start sites and splicing events that include exon skipping and alternative 3' splicing site selection. We found that ASIP was highly expressed in llamas with white and brown phenotypes while black animals presented very low expression. The main responsible for this difference was a fusion transcript between ASIP and NCOA6 genes, which was present in the skin of white and brown llamas but not in the black ones. The rest of ASIP transcripts presented very low expression in the skin, indicating that the main regulation point for ASIP gene expression is at the transcriptional level. Nevertheless, the characteristics of the 5'UTRs sequences suggest that alternative transcripts could be regulated differently at the protein synthesis level.


Asunto(s)
Regiones no Traducidas 5' , Proteína de Señalización Agouti/genética , Camélidos del Nuevo Mundo/genética , Pigmentación/genética , Empalme Alternativo , Animales , Camélidos del Nuevo Mundo/fisiología , Exones , Expresión Génica , Fenotipo , Regiones Promotoras Genéticas , Pigmentación de la Piel/genética
17.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34607956

RESUMEN

Melanotic (Ml) is a mutation in chickens that extends black (eumelanin) pigmentation in normally brown or red (pheomelanin) areas, thus affecting multiple within-feather patterns [J. W. Moore, J. R. Smyth Jr, J. Hered. 62, 215-219 (1971)]. In the present study, linkage mapping using a back-cross between Dark Cornish (Ml/Ml) and Partridge Plymouth Rock (ml+/ml+ ) chickens assigned Ml to an 820-kb region on chromosome 1. Identity-by-descent mapping, via whole-genome sequencing and diagnostic tests using a diverse set of chickens, refined the localization to the genomic region harboring GJA5 encoding gap-junction protein 5 (alias connexin 40) previously associated with pigmentation patterns in zebrafish. An insertion/deletion polymorphism located in the vicinity of the GJA5 promoter region was identified as the candidate causal mutation. Four different GJA5 transcripts were found to be expressed in feather follicles and at least two showed differential expression between genotypes. The results showed that Melanotic constitutes a cis-acting regulatory mutation affecting GJA5 expression. A recent study established the melanocortin-1 receptor (MC1R) locus and the interaction between the MC1R receptor and its antagonist agouti-signaling protein as the primary mechanism underlying variation in within-feather pigmentation patterns in chickens. The present study advances understanding the mechanisms underlying variation in plumage color in birds because it demonstrates that the activity of connexin 40/GJA5 can modulate the periodic pigmentation patterns within individual feathers.


Asunto(s)
Proteína de Señalización Agouti/genética , Pollos/genética , Conexinas/genética , Plumas/fisiología , Pigmentación/genética , Receptor de Melanocortina Tipo 1/genética , Animales , Mutación INDEL/genética , Queratinocitos/metabolismo , Melaninas/genética , Regiones Promotoras Genéticas/genética , Proteína alfa-5 de Unión Comunicante
18.
Poult Sci ; 100(11): 101440, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34547619

RESUMEN

The objective of this study was to investigate the effect of breed, sex, and age on the gene expression level of melanocortin 1 receptor (MC1R), DOPA chrome tautomerase (DCT), tyrosinase-related protein 1 (TYRP1), tyrosinase (TYR), and agouti signaling protein (ASIP) genes in Thai commercial chicken lines. All chicken have received Newscastle vaccination, and no antibiotics or any drugs were used in this study. Four chicken breeds including Black-Chinese, KU-Phuparn, Sri Mok, and Pradu Hang Dam were used in this study. These breeds can be classified by their skin color into 3 group including black (Black Chinese and KU-Phuparn), light black (Sri Mok), and yellowish white (Pradu Hang Dam). One hundred chickens per breed were used in this study. Breast skin tissue was randomly collected from 8 chickens (4 males, 4 females) per breed at 4, 8, 12, and 16 wk of age. The mRNA expression was analyzed using qRT-PCR and the gene expression level was calculated as 2-ΔΔCT. From the results, breed significantly (P < 0.01) affected the expression level for the 5 genes evaluated. Birds with the black skin color had greater TYRP1 and TYR gene expression when compared to chickens with light black and yellowish-white skin color, respectively. Whereas, chickens with yellowish-white skin color had greater ASIP gene expression when compared to chickens having the other skin colors. Sex significantly affected DCT, TYRP1, and TYR gene expression where the gene expression in males was greater when compared to females (P < 0.05). Age affected all gene expression levels (P < 0.01). At 4 wk of age, MC1R, DCT, TYRP1, and TYR gene expression was the highest and decreased as bird age increased (P < 0.05); however, ASIP gene expression was greatest at 8 wk of age. After 8 wk of age all gene expression for the genes evaluated in this study decreased as age increased. In addition, an interaction between breed and sex (P < 0.05) impacted DCT and ASIP gene expression. The results from this study showed that all genes evaluated can be used as candidate markers to further improve the blackness of the chicken's skin because the most desired skin color is black in the Thai black-bone chicken population.


Asunto(s)
Pollos , Pigmentación de la Piel , Proteína de Señalización Agouti/genética , Animales , Pollos/genética , Color , Femenino , Expresión Génica , Masculino , Pigmentación de la Piel/genética , Tailandia
19.
Genet Sel Evol ; 53(1): 40, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33910501

RESUMEN

BACKGROUND: Nellore cattle (Bos indicus) are well-known for their adaptation to warm and humid environments. Hair length and coat color may impact heat tolerance. The Nellore breed has been strongly selected for white coat, but bulls generally exhibit darker hair ranging from light grey to black on the head, neck, hump, and knees. Given the potential contribution of coat color variation to the adaptation of cattle populations to tropical and sub-tropical environments, our aim was to map positional and functional candidate genetic variants associated with darkness of hair coat (DHC) in Nellore bulls. RESULTS: We performed a genome-wide association study (GWAS) for DHC using data from 432 Nellore bulls that were genotyped for more than 777 k single nucleotide polymorphism (SNP) markers. A single major association signal was detected in the vicinity of the agouti signaling protein gene (ASIP). The analysis of whole-genome sequence (WGS) data from 21 bulls revealed functional variants that are associated with DHC, including a structural rearrangement involving ASIP (ASIP-SV1). We further characterized this structural variant using Oxford Nanopore sequencing data from 13 Australian Brahman heifers, which share ancestry with Nellore cattle; we found that this variant originates from a 1155-bp deletion followed by an insertion of a transposable element of more than 150 bp that may impact the recruitment of ASIP non-coding exons. CONCLUSIONS: Our results indicate that the variant ASIP sequence causes darker coat pigmentation on specific parts of the body, most likely through a decreased expression of ASIP and consequently an increased production of eumelanin.


Asunto(s)
Proteína de Señalización Agouti/genética , Bovinos/genética , Pigmentación/genética , Polimorfismo Genético , Pelaje de Animal/metabolismo , Animales , Elementos Transponibles de ADN , Mutación INDEL , Melaninas/genética , Melaninas/metabolismo
20.
J Exp Zool B Mol Dev Evol ; 336(5): 443-450, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33755299

RESUMEN

While color patterns are highly diverse across the animal kingdom, certain patterns such as countershading and stripe patterns have evolved repeatedly. Across vertebrates, agouti-signaling genes have been associated with the evolution of both patterns. Here we study the functional conservation and divergence by investigating the expression patterns of the two color-pattern-related agouti-signaling genes, agouti-signaling protein 1 (asip1) and agouti-signaling protein 2b (asip2b, also known as agrp2) in Teleostei. We show that the dorsoventral expression profile of asip1 and the role of the "stripe repressor" asip2b are shared across multiple teleost lineages and uncover a previously unknown association between stripe-interstripe patterning and both asip1 and asip2b expression. In some species, including the zebrafish (Danio rerio), these two genes show complementary and overlapping expression patterns in line with functional redundancy. Our results thus suggest how conserved and novel functions of agouti-signaling genes might have shaped the evolution of color patterns across teleost fishes.


Asunto(s)
Proteína de Señalización Agouti/metabolismo , Peces/fisiología , Regulación de la Expresión Génica/fisiología , Pigmentación/fisiología , Proteína de Señalización Agouti/clasificación , Proteína de Señalización Agouti/genética , Animales , Peces/anatomía & histología , Peces/clasificación , Peces/genética , Filogenia , Pigmentación/genética , Pigmentos Biológicos
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