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Dog Coat Colour Genetics: A Review
Abstract and Figures
Canis lupus familiaris is one of the most beloved pet species with hundreds of worldwide recognized breeds, which can be differentiated from each other by specific morphological, behavioral and adoptive traits. Morphological characteristics of dog breeds get more attention which can be defined mostly by coat color and its texture, and considered to be incredibly lucrative traits in this valued species. Although the genetic foundation of coat color has been well stated in the literature, but still very little is known about the growth pattern, hair length and curly coat trait genes. Skin pigmentation is determined by eumelanin and pheomelanin switching phenomenon which is under the control of Melanocortin 1 Receptor and Agouti Signaling Protein genes. Genetic variations in the genes involved in pigmentation pathway provide basic understanding of melanocortin physiology and evolutionary adaptation of this trait. So in this review, we highlighted, gathered and comprehend the genetic mutations, associated and likely to be associated variants in the genes involved in the coat color and texture trait along with their phenotypes. Moreover, genetic diversity of other associated genes were also pointed out to understand this phenomena in detail along with their genotypes for better understanding the expression and mode of inheritance of this trait for describing dog breeds with more accuracy.
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... D lokusu alleller" "se p"gmentasyon yoğunluğunu etk"ler. Dom"nant allel formunda s"yah ve kahvereng" p"gmentler"n yoğunluğunu arttıran bu lokus, reses"f formda s"yah p"gmentler" mav"ye, kahvereng" p"gmentler" "se sarıya doğru seyrelt"r ve seyreltme lokusu olarak da "fade ed"l"r (24,25,26). ...
... Bu b"lg"ler ışığında veter"ner hek"mler köpek yet"şt"r"c"ler"ne yet"şt"rme kayıtları düzenl" tutuluyorsa doğacak yavrular hakkında b"lg" vereb"lecekt"r. Ayrıca her lokus "ç"n allell"k formlar genet"k test yapılarak moleküler olarak da tesp"t ed"leb"lmekted"r (26). ...
... Other key pigmentation genes have been identified and research on this topic is growing, but much of it is focused on domesticated animals, like livestock and dogs, and mice-predominantly laboratory mice (Daverio et al., 2016;Mallarino et al., 2016;Neves et al., 2017;Protas & Patel, 2008;Rees, 2003;Saif et al., 2020;Silvers, 2012;Yang et al., 2019;Zhao et al., 2018). Although these studies provide invaluable information, their methods and results can be difficult to transfer to wild, less-studied populations. ...
... Mutations of the KIT proto-oncogene, receptor tyrosine kinase (KIT), have been noted in mice, horses, cats, and other vertebrates and are attributed to white morphs as well as white spotting that can result in "masking" patterns on the face and spotting patterns throughout the body (Brookes & Bailey, 2005;David et al., 2014;De Sepulveda et al., 1995;Wong et al., 2013). In dogs, melanocyte-inducing transcription factor (MITF) is known to contribute to irregular white spotting, and numerous other canid genes have been identified that result in their color and pattern differences (Saif et al., 2020). Yet, few studies have examined these genes in wild populations, or explored the role of MC1R in color regulation in nondomesticated species, such as primates (c.f. ...
Organisms use color for camouflage, sexual signaling, or as a warning sign of danger. Primates are one of the most vibrantly colored Orders of mammals. However, the genetics underlying their coat color are poorly known, limiting our ability to study molecular aspects of its evolution. The role of the melanocortin 1 receptor (MC1R) in color evolution has been implicated in studies on rocket pocket mice (Chaetodipus intermediusi), toucans (Ramphastidae), and many domesticated animals. From these studies, we know that changes in MC1R result in a yellow/red or a brown/black morphology. Here, we investigate the evolution of MC1R in Lorisidae, a monophyletic nocturnal primate family, with some genera displaying high contrast variation in color patterns and other genera being monochromatic. Even more unique, the Lorisidae family has the only venomous primate: the slow loris (Nycticebus). Research has suggested that the contrasting coat patterns of slow lorises are aposematic signals for their venom. If so, we predict the MC1R in slow lorises will be under positive selection. In our study, we found that Lorisidae MC1R is under purifying selection (ω = 0.0912). In Lorisidae MC1R, there were a total of 75 variable nucleotides, 18 of which were nonsynonymous. Six of these nonsynonymous substitutions were found on the Perodicticus branch, which our reconstructions found to be the only member of Lorisidae that has predominantly lighter coat color; no substitutions were associated with Nycticebus. Our findings generate new insight into the genetics of pelage color and evolution among a unique group of nocturnal mammals and suggest putative underpinnings of monochromatic color evolution in the Perodicticus lineage.
... Por ejemplo, en otras especies de animales domésticos, se tienen identificados el número de los genes responsables del color de la capa: 13 en el caballo (Bartolomé et al., 2008;Thiruvenkadan et al., 2008); y 8 en el perro (Saif et al., 2020); y además de sus múltiples alelos para cada gen (multialélico), que son las que determinan su diversidad de colores. Consecuentemente: ...
El presente boletín tiene como finalidad compartir los avances en el conocimiento de la influencia genética en la coloración del vellón en alpacas; es decir, identificar la contribución de los genes involucrados en las expresiones del color y su diversidad de matices, apreciadas en los rebaños.
... breeds [9] and Agouti-signaling protein (ASIP) which regulates the type, amount, and distribution pattern of the eumelanin (brown/ black) and pheomelanin (yellow/red) [3,12,21,23]. ...
To assess factors for canine skin extensibility, our study investigated associations between the dogs’ skin extension index and the following factors, gender, age, neuter status, weight, coat color and six coat color related gene polymorphisms. Swab samples were collected from 69 toy poodles to extract DNA. The skin extension indices of the lower back and the neck were measured using the following formula: vertical height of the skin fold divided by body length multiplied by 100. The dogs’ age, weight, gender, neuter status and coat color were also recorded, as well as polymorphisms of the following six selected coat color related genes, Melanocortin 1 receptor, Tyrosinase-related protein 1, Melanophilin, Canine β-defensin-1, Major Facilitator Superfamily Domain Containing 12 and Agouti-signaling protein (ASIP). Univariable analysis showed there was a meaningful association between the lower back skin extension index and both gender and age (P<0.001 and P=0.048, respectively). Also, there was a possible association between the lower back skin extension index and ASIP Single nucleotide polymorphism (SNP) (R96C) (P=0.078). Linear model analysis showed there was a significant association between the lower back skin extension index and gender (P<0.001), and there was a tendency of the association between the lower back skin extension index and ASIP SNP (R96C) (P=0.098). In addition, there was an association between gender and age for the skin extension index. (P=0.048). Therefore, these results suggest that a greater risk of skin extensibility in toy poodle could be related to being female and the ASIP SNP (R96C), because these factors were associated with higher lower back skin extension index.
Simple Summary
Domestic dogs have a wide variety of colorations, and previous research has found that, in certain breeds, coat color can be linked to behavior. However, it is unknown if coloration is connected to dogs’ stress responses. To explore this question, we studied dogs living under stressful conditions: an animal shelter. We analyzed their urinary levels of cortisol, a stress hormone, to explore whether values from the shelter and on outings with people correlated with their coloration, specifically, their coat color/pattern, nose color, and extent of white spotting. In this preliminary study, we did not find a connection between their cortisol levels and coloration. While more research is needed, these initial findings do not suggest that dogs differ in their stress responses as a result of coloration alone.
Abstract
Previous research has found connections between pigmentation, behavior, and the physiological stress response in both wild and domestic animals; however, to date, no extensive research has been devoted to answering these questions in domestic dogs. Modern dogs are exposed to a variety of stressors; one well-studied stressor is residing in an animal shelter. To explore the possible relationships between dogs’ responses to stress and their pigmentation, we conducted statistical analyses of the cortisol:creatinine ratios of 208 American shelter dogs as a function of their coat color/pattern, eumelanin pigmentation, or white spotting. These dogs had been enrolled in previous welfare studies investigating the effect of interventions during which they left the animal shelter and spent time with humans. In the current investigation, we visually phenotype dogs based on photographs in order to classify their pigmentation and then conduct post hoc analyses to examine whether they differentially experience stress as a function of pigmentation. We found that the dogs did not differ significantly in their urinary cortisol:creatinine ratios based on coat color/pattern, eumelanin pigmentation, or white spotting, either while they were residing in the animal shelter or during the human interaction intervention. These preliminary data suggest that pigmentation alone does not predict the stress responses of shelter dogs; however, due to the small sample size and retrospective nature of the study, more research is needed.
Coat color genetics has been studied in many mammalian species. However, in the dromedary camel, there are only few efforts reported three genes that associated with coat color (MC1R, ASIP and KIT). Saudi dromedaries vary in color from white, light brown, brown, dark brown and black. Tyrosinase (encoded by TYR gene) is a key enzyme responsible for converting tyrosine to melanin in the melanin pathway. TYR is known as the albino locus as it causes albinism in several mammalian species. TYR variants are also associated with diluted coat color phenotypes in rabbits and mice. Here, we investigated the possibility of TYR contribution in the dromedary coat color variations. Dromedary TYR exon 1 gene was studies in the dromedary and two SNPs were detected at position c.200 C>T associated with shoulder height in one study and suggested to be associated with coat color and c.523 T>C associated with black dromedaries. Here, we sequenced TYR all coding regions and identified 3 single nucleotide polymorphisms (SNPs) in exon 1, 2 and 3 respectively. Our finding shows that TYR c.200 C>T is significantly associated with light brown coat color phenotype in the dromedary (P<0.05) suggesting codominant inheritance. This variant substitutes a proline with leucine at position 67 (p.P67L). Two synonymous SNPs variants were discovered in exon 2 c.861 G>A and exon3 c.950 C>T. The finding will contribute to the generation of coat color genetic test in the species.
Dark-haired dogs are predisposed to the development of digital squamous cell carcinoma (DSCC). This may potentially suggest an underlying genetic predisposition not yet completely elucidated. Some authors have suggested a potential correlation between the number of copies KIT Ligand (KITLG) and the predisposition of dogs to DSCC, containing a higher number of copies in those affected by the neoplasm. In this study, the aim was to evaluate a potential correlation between the number of copies of the KITLG and the histological grade of malignancy in dogs with DSCC. For this, 72 paraffin-embedded DSCCs with paired whole blood samples of 70 different dogs were included and grouped according to their haircoat color as follow: Group 0/unknown haircoat color (n = 11); Group 1.a/black non-Schnauzers (n = 15); group 1.b/black Schnauzers (n = 33); group 1.c/black and tan dogs (n = 7); group 2/tan animals (n = 4). The DSCCs were histologically graded. Additionally, KITLG Copy Number Variation (CNV) was determined by ddPCR. A significant correlation was observed between KITLG copy number and the histological grade and score value. This finding may suggest a possible factor for the development of canine DSCC, thus potentially having an impact on personalized veterinary oncological strategies and breeding programs.
Molecular cloning and expression analysis of agouti signaling protein (ASIP) gene in Canis Lupus
Association of SKG13 gene with hairlessness in domestic dogs
The popularity of dogs as human companions explains why these pets regularly come into focus in forensic cases such as bite attacks or accidents. Canine evidence, e.g., dog hairs, can also act as a link between the victim and suspect in a crime case due to the close contact between dogs and their owners. In line with human DNA identification, dog individualization from crime scene evidence is mainly based on the analysis of short tandem repeat (STR) markers. However, when the DNA profile does not match a reference, additional information regarding the appearance of the dog may provide substantial intelligence value. Key features of the dog’s appearance, such as the body size and coat colour are well-recognizable and easy to describe even to non-dog experts, including most investigating officers and eyewitnesses. Therefore, it is reasonable to complement eyewitnesses’ testimonies with externally visible traits predicted from associated canine DNA samples. Here, the feasibility and suitability of canine DNA phenotyping is explored from scratch in the form of a proof of concept study. To predict the overall appearance of an unknown dog from its DNA as accurately as possible, the following six traits were chosen: (1) coat colour, (2) coat pattern, (3) coat structure, (4) body size, (5) ear shape, and (6) tail length. A total of 21 genetic markers known for high predicting values for these traits were selected from previously published datasets, comprising 15 SNPs and six INDELS. Three of them belonged to SINE insertions. The experiments were designed in three phases. In the first two stages, the performance of the markers was tested on DNA samples from dogs with well-documented physical characteristics from different breeds. The final blind test, including dogs with initially withheld appearance information, showed that the majority of the selected markers allowed to develop composite sketches, providing a realistic impression of the tested dogs. We regard this study as the first attempt to evaluate the possibilities and limitations of forensic canine DNA phenotyping.
The apartheid regime in South Africa was notorious for its gratuitous display of authority in the form of brutality and human rights excesses. Those who partook in the struggle against apartheid did so in an attempt to realise fundamental human rights and a conclusion to all forms of discrimination. The end of apartheid in South Africa in early 1994, therefore, heralded a new era and, indeed, a new political and economic dispensation in which the human rights (political and economic freedoms) of all people would become paramount. The victory of the anti-apartheid forces at the end of race-based politics was characterised by joyance, hope, and expectation for many, including foreign nationals from mostly contiguous countries. Sadly, however, South Africa is today known for being a highly iniquitous country with high poverty and unemployment levels. Tolmay (2019), for instance, reported that unemployment in South Africa had stood at 29% in the first quarter thus affecting mostly young people. This treatise has as its prime motif the interrogation of the efficacy of the concept of Ubuntu in the face of widespread xenophobic violence against African migrants and their businesses in South Africa.
Background
The inheritance of different coat colours in the Cane Corso Italiano dog has not been described thus far. We analysed data from 23,271 dogs and bitches using the Cane Corso Italiano Pedigree Database. We are describing for the first time the coat colour segregation ratios in Cane Corso Italiano offspring arising from crosses between parents of all possible coat colour combinations.
Results
Segregation ratios that do not follow a Mendelian pattern suggest that additional genes are active in the determination of coat colour. Segregation ratios of offspring produced by parental crossing (male colour A x female colour B) were compared with the ratios of offspring produced by reciprocal crossing (male colour B x female colour A) in all possible coat colour combinations.
Most of the segregation ratios were the same, but some segregation ratios in reciprocal crosses differed. This result suggests that at least one gene responsible for coat colour is located on a sex chromosome. The sex ratio was analysed in the offspring of all colour groups. A ratio of 1:1 was not confirmed in 8 colour groups by the chi-square test.
Conclusions
We described for the first time coat colour segregation ratios in Cane Corso Italiano dogs. Furthermore, we present the hypothesis that at least one gene responsible for coat colour is located on a sex chromosome.
We investigated a German Spitz family where the mating of a black male to a white female had yielded three puppies with an unexpected light brown coat color, lightly pigmented lips and noses, and blue eyes. Combined linkage and homozygosity analysis based on a fully penetrant monogenic autosomal recessive mode of inheritance identified a critical interval of 15 Mb on chromosome 3. We obtained whole genome sequence data from one affected dog, three wolves, and 188 control dogs. Filtering for private variants revealed a single variant with predicted high impact in the critical interval in LOC100855460 (XM_005618224.1:c.377+2T>G LT844587.1:c.-45+2T>G). The variant perfectly co-segregated with the phenotype in the family. We genotyped 181 control dogs with normal pigmentation from diverse breeds including 22 unrelated German Spitz dogs, which were all homozygous wildtype. Comparative sequence analyses revealed that LOC100855460 actually represents the 5’-end of the canine OCA2 gene. The CanFam 3.1 reference genome assembly is incorrect and separates the first two exons from the remaining exons of the OCA2 gene. We amplified a canine OCA2 cDNA fragment by RT-PCR and determined the correct full-length mRNA sequence (LT844587.1). Variants in the OCA2 gene cause oculocutaneous albinism type 2 (OCA2) in humans, pink-eyed dilution in mice, and similar phenotypes in corn snakes, medaka and Mexican cave tetra fish. We therefore conclude that the observed oculocutaneous albinism in German Spitz is most likely caused by the identified variant in the 5’-splice site of the first intron of the canine OCA2 gene.
An extraordinary amount of genomic variation is contained within the chromosomes of domestic dogs, manifesting as dramatic differences in morphology, behaviour and disease susceptibility. Morphology, in particular, has been a topic of enormous interest as biologists struggle to understand the small window of dog domestication from wolves, and the division of dogs into pure breeding, closed populations termed breeds. Many traits related to morphology, including body size, leg length and skull shape, have been under selection as part of the standard descriptions for the nearly 400 breeds recognized worldwide. Just as important, however, are the minor traits that have undergone selection by fanciers and breeders to define dogs of a particular appearance, such as tail length, ear position, back arch and variation in fur (pelage) growth patterns. In this paper, we both review and present new data for traits associated with pelage including fur length, curl, growth, shedding and even the presence or absence of fur. Finally, we report the discovery of a new gene associated with the absence of coat in the American Hairless Terrier breed.
This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.
The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.
The first white Doberman pinscher (WDP) dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA) and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1) produce a detailed description of the ocular phenotype of WDPs, (2) objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3) determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs); cutaneous tumors were noted in 12/20 WDP (<5 years of age: 4/12; >5 years of age: 8/8) and 1/20 SDPs (p<0.00001). Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968-77,067,051). This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model.
Curly fur is a common phenotype in many dog breeds, known to result from a missense variant (c.451C>T) in exon 2 of the keratin 71 (KRT71) gene. During screening for this variant across various breeds, we found that Curly Coated Retrievers (CCRs) fixed with the trait did not carry the known variant. By analysis of whole‐genome sequencing data of one CCR we identified a novel genetic cause for curly fur. We found a novel structural variant in exon 7 of the KRT71 gene (c.1266_1273delinsACA) that was predicted to result in a frameshift and stop loss, therefore significantly affecting the structure of the protein, if translated. The variant was also found at lower frequencies in five other breeds, including Lagotto Romagnolo, Bichon Frise, Spanish Water Dog, Chesapeake Bay Retriever and Irish Terrier. One curly‐coated Lagotto carried neither of the two KRT71 variants. These results identify a second variant for curly coat in KRT71 and suggest the existence of additional alleles. This study enables the development of an additional KRT71 gene test for breeders to understand and manage coat types.
Major characteristics of coat variation in dogs can be explained by variants in only a few genes. Until now, only one missense variant in the KRT71 gene, p.Arg151Trp, has been reported to cause curly hair in dogs. However, this variant does not explain the curly coat in all breeds as the mutant ¹⁵¹Trp allele, for example, is absent in Curly Coated Retrievers. We sequenced the genome of a Curly Coated Retriever at 22× coverage and searched for variants in the KRT71 gene. Only one protein‐changing variant was present in a homozygous state in the Curly Coated Retriever and absent or present in a heterozygous state in 221 control dogs from different dog breeds. This variant, NM_001197029.1:c.1266_1273delinsACA, was an indel variant in exon 7 that caused a frameshift and an altered and probably extended C‐terminus of the KRT71 protein NP_001183958.1:p.(Ser422ArgfsTer?). Using Sanger sequencing, we found that the variant was fixed in a cohort of 125 Curly Coated Retrievers and segregating in five of 14 additionally tested breeds with a curly or wavy coat. KRT71 variants cause curly hair in humans, mice, rats, cats and dogs. Specific KRT71 variants were further shown to cause alopecia. Based on this knowledge from other species and the predicted molecular consequence of the newly identified canine KRT71 variant, it is a compelling candidate causing a second curly hair allele in dogs. It might cause a slightly different coat phenotype than the previously published p.Arg151Trp variant and could potentially be associated with follicular dysplasia in dogs.
Coat colour dilution may be the result of altered melanosome transport in melanocytes. Loss-of-function variants in the melanophilin gene (MLPH) cause a recessively inherited form of coat colour dilution in many mammalian and avian species including the dog. MLPH corresponds to the D locus in many domestic animals, and recessive alleles at this locus are frequently denoted with d. In this study, we investigated dilute coloured Chow Chows whose coat colour could not be explained by their genotype at the previously known MLPH:c.–22G>A variant. Whole genome sequencing of such a dilute Chow Chow revealed another variant in the MLPH gene: MLPH:c.705G>C. We propose to designate the corresponding mutant alleles at these two variants d1 and d2. We performed an association study in a cohort of 15 dilute and 28 non-dilute Chow Chows. The dilute dogs were all either compound heterozygous d1/d2 or homozygous d2/d2, whereas the non-dilute dogs carried at least one wildtype allele D. The d2 allele did not occur in 417 dogs from diverse other breeds. However, when we genotyped a Sloughi family, in which a dilute coloured puppy had been born out of non-dilute parents, we again observed perfect co-segregation of the newly discovered d2 allele with coat colour dilution. Finally, we identified a blue Thai Ridgeback with the d1/d2 genotype. Thus, our data identify the MLPH:c.705G>C as a variant explaining a second canine dilution allele. Although relatively rare overall, this d2 allele is segregating in at least three dog breeds, Chow Chows, Sloughis and Thai Ridgebacks.