Inheritance of coat colour in the Hovawart dog

The three recognised colour varieties of the Hovawart breed of dog, black, black and gold and blonde, are due primarily to combinations of the mutant alleles solid black (A ^s ), black and tan (a ^t ) of the agouti series and the non-extension of black allele (e). The e allele is epistatic to the agouti alleles, thereby reducing the four possible phenotypes to three.     

Inheritance of coat colour in the German Pinscher dog

The two primary colour varieties of the German Pinscher breed are the red and the black and tan. Respectively, these are produced by the dominant yellow allele A ^y and the black and tan allele a ^t of the agouti locus. The dilute gene d is present in the breed at a low frequency and produces the rarer isabella and blue and tan colours, with the genotypes A ^y -dd and a ^t dd, respectively.     

Agouti-Related Maturation and Tissue Distribution of oc-Melanocyte Stimulating Hormone in Wild-Type (AwJ/AwJ) and Mutant (Ay/a,a/a) Mice

Because of ectopic overproduction of agouti protein, yellow alleles (A^y and A^vy) of the murine agouti gene may secondarily modulate the synthesis, maturation (i.e., acetylation), and/or tissue deployment of α-Melanocyte Stimulating Hormone (MSH). We used HPLC to test the hypothesis that A^y/a mice exhibit altered concentrations of desacetyl-, monoacetyl-, and diacetyl-α-MSH in pituitaries, sera, and telogen hair bulbs when compared to black (a/a) mice. We also used RIA to measure total MSH in those same tissues of A^y/a, a/a, and white-bellied agouti (A^wJ/A^wJ) mice (Strain C57BL/6J). We found no evidence that A^y/a mice possessed an imbalance of des-, mono-, and diacetylated α-MSH species. However, radioimmunoassay (RIA) analyses of total MSH suggest that wild-type agouti mice (A^wJ/A^wJ) exhibited significantly decreased (P < 0.05) tissue levels of total α-MSH in pituitaries, sera, and regenerating hair bulbs when compared to those of mutant A^y/a and a/a mice.     

Inheritance of colour and coat in the Belgian Shepherd dog

The several colours and coats of the Belgian Shepherd dog are shown to be due primary to combinations of the following genes: dominant black (A ^s ), dominant yellow (A ^y ), chinchilla (ch), long hair (l) and wire hair (Wh). The gene for black and tan (a ^t ) is or has been present in the breed. All of the dominant yellow dogs exhibit a black facial mask and extensive suffusion of black guard hairs on the body.     

Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice

There is increasing evidence in both plants and animals that epigenetic marks are not always cleared between generations. Incomplete erasure at genes associated with a measurable phenotype results in unusual patterns of inheritance from one generation to the next, termed transgenerational epigenetic inheritance. The Agouti viable yellow (A^vy) allele is the best-studied example of this phenomenon in mice. The A^vy allele is the result of a retrotransposon insertion upstream of the Agouti gene. Expression at this locus is controlled by the long terminal repeat (LTR) of the retrotransposon, and expression results in a yellow coat and correlates with hypomethylation of the LTR. Isogenic mice display variable expressivity, resulting in mice with a range of coat colours, from yellow through to agouti. Agouti mice have a methylated LTR. The locus displays epigenetic inheritance following maternal but not paternal transmission; yellow mothers produce more yellow offspring than agouti mothers. We have analysed the DNA methylation in mature gametes, zygotes, and blastocysts and found that the paternally and maternally inherited alleles are treated differently. The paternally inherited allele is demethylated rapidly, and the maternal allele is demethylated more slowly, in a manner similar to that of nonimprinted single-copy genes. Interestingly, following maternal transmission of the allele, there is no DNA methylation in the blastocyst, suggesting that DNA methylation is not the inherited mark. We have independent support for this conclusion from studies that do not involve direct analysis of DNA methylation. Haplo-insufficiency for Mel18, a polycomb group protein, introduces epigenetic inheritance at a paternally derived A^vy allele, and the pedigrees reveal that this occurs after zygotic genome activation and, therefore, despite the rapid demethylation of the locus.     

The mouse ruby‐eye 2d (ru2d/Hps5ru2‐d) allele inhibits eumelanin but not pheomelanin synthesis

The novel mutation named ru2^d/Hps5^ru2‐d, characterized by light‐colored coats and ruby‐eyes, prohibits differentiation of melanocytes by inhibiting tyrosinase (Tyr) activity, expression of Tyr, Tyr‐related protein 1 (Tyrp1), Tyrp2, and Kit. However, it is not known whether the ru2^d allele affects pheomelanin synthesis in recessive yellow (e/Mc1r^e) or in pheomelanic stage in agouti (A) mice. In this study, effects of the ru2^d allele on pheomelanin synthesis were investigated by chemical analysis of melanin present in dorsal hairs of 5‐week‐old mice from F₂ generation between C57BL/10JHir (B10)‐co‐isogenic ruby‐eye 2^d and B10‐congenic recessive yellow or agouti. Eumelanin content was decreased in ruby‐eye 2^d and ruby‐eye 2^d agouti mice, whereas pheomelanin content in ruby‐eye 2^d recessive yellow and ruby‐eye 2^d agouti mice did not differ from the corresponding Ru2^d/‐ mice, suggesting that the ru2^d allele inhibits eumelanin but not pheomelanin synthesis.     

Dermal-epidermal interactions and the action of alleles at the agouti locus in the mouse

In the mouse, alleles at the agouti locus determine eumelanin or pheomelanin synthesis by the follicular melanocytes. Previous studies have identified the dermis as the site of action of these alleles. However, a recent investigation utilizing the yellow (A^y) allele suggested a possible role of the epidermis in the expression of agouti locus alleles. Using dermal-epidermal recombinations of embryonic skin of various agouti genotypes, the present investigation supports the role of both the dermis and epidermis. If nonagouti ($\text{a}\text{a}$) dermis is recombined with agouti ($\text{A}\text{A}$) epidermis, the resulting hairs are pigmented in the nonagouti pattern. The reciprocal recombination of agouti dermis and nonagouti epidermis results in hairs pigmented in the agouti pattern. The recombinations of yellow ($\text{A}{}^{\mathrm{y}}\text{a}$) dermis and agouti or extreme nonagouti ($\text{a}{}^{\mathrm{e}}\text{a}{}^{\mathrm{e}}$) epidermis result in hairs completely pigmented in the yellow pattern (pheomelanin). However, when extreme nonagouti or agouti dermis is recombined with yellow epidermis, the resulting hairs are completely pigmented with pheomelanin. Similar results occur in recombinations of “young” yellow epidermis (13 days) and “old” dermis (17 days) even though dermal papillae are present. The role of dermal-epidermal interactions in the expression of agouti alleles as well as possible explanations for the unique action of the yellow allele are discussed.     

Pleiotropic Effects of a Methyl Donor Diet in a Novel Animal Model

Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent prenatal neural tube defects. Several lines of evidence suggest that these supplements act through epigenetic mechanisms (e.g. altering DNA methylation). Primary among these are the experiments on the mouse viable yellow allele of the agouti locus (A^vy). In the A^vy allele, an Intracisternal A-particle retroelement has inserted into the genome adjacent to the agouti gene and is preferentially methylated. To further test these effects, we tested the same diet used in the A^vy studies on wild-derived Peromyscus maniculatus, a native North American rodent. We collected tissues from neonatal offspring whose parents were fed the high-methyl donor diet as well as controls. In addition, we assayed coat-color of a natural variant (wide-band agouti = A^Nb) that overexpresses agouti as a phenotypic biomarker. Our data indicate that these dietary components affected agouti protein production, despite the lack of a retroelement at this locus. Surprisingly, the methyl-donor diet was associated with defects (e.g. ovarian cysts, cataracts) and increased mortality. We also assessed the effects of the diet on behavior: We scored animals in open field and social interaction tests. We observed significant increases in female repetitive behaviors. Thus these data add to a growing number of studies that suggest that these ubiquitously added nutrients may be a human health concern.     

The genetics of colour-patterns in the grasshopper Chorthippus brunneus

Several alleles were found to determine the colour of the dorsal pronotum in Chorthippus brunneus; there was evidence for at least two loci (C and V). Brown (C^B)was the universal recessive and green (C^C) was dominant to all other colours. The white allele (C^W)was codominant with green(C^G)and purple (C^P). Wing-patterns were determined by a separate, probably linked locus (W). A dominant plain wing-pattern (W^P) was associated with colours other than brown. Striped(W^S)and mottled(W^mo) were codominant and a plain recessive allele (W^P) was also found. All three alleles were associated with the brown phenotype. A purple-sided allele (S^Pu) was sometimes obmd with C^pu.. S^Pu was dominant to brown sides (S^B), A series of markings on the dorsal and lateral pronotum (linea intermedia, fascia postocularis, linea media, carina media and zona lateralis) were investigated and found to be controlled at separate loci which may be linked to W. These characters were expressed by dominant alleles. Epistatic effects by modifier loci were shown to have an important effect on the determination of wing phenotype. Allele Wo⁺, for example, suppressed the stripe-wing pattern, linea media, carina media and zona lateralis. It was concluded that colour patterns appear to be under genetic control and that dominant alleles were rare in the wild. Changes in shades of colours were shown to be age-dependent and minor.     

Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed

Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2‐bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty‐seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non‐synonymous exonic SNPs, as well as 19 intronic variants, including a 42‐bp deletion in intron 4. Fifty‐six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A^Pbe) and domestic cat non‐agouti (a) haplotypes. Twenty‐four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non‐agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats.     

What weta want: colour preferences of a frugivorous insect

Plants use colours as signals to attract mutualists and repel antagonists. Fleshy-fruits are often conspicuously coloured to signal different types of information including fruit maturity and spatial location. Previous work on fruit colour selection focus on large diurnal vertebrates, yet fruit colours are perceived differently by frugivores with different types of visual systems. Here, we tested whether a nocturnal, frugivorous, seed-dispersing insect selects fruits based on their pigmentation and whether different lighting conditions affect fruit colour selection. We captured 20 Wellington tree weta (Hemideina crassidens) from a forest reserve on the North Island of New Zealand and brought them into laboratory conditions to test their fruit colour preferences. The fruits of Coprosma acerosa, a native shrub species that naturally produces translucent, blue-streaked fruits, were dyed either red or blue. Fruits were then offered to weta in a binary (y-maze) choice test in two light conditions, either at night during a full moon or under artificial light conditions in the lab. Weta preferred unmanipulated, naturally blue-streaked fruits and artificially-blue coloured fruits over those dyed red. Furthermore, their colour preferences were unaffected by light environment. Our results therefore suggest that weta can discriminate between colours (using colour vision) in both light and dark light environments. Their consistent preferences for colours other than red indicate that weta might be responsible for the unusual colours of fleshy-fruits in New Zealand.     

Tyrosinase Activity (TH,DO, PAGE-Defined Isozymes) and Melanin Production in Regenerating Hairbulb Melanocytes of Lethal Yellow (Ay/a), Black (a/a), Agouti (AwJ/AwJ) and Albino (a/a/c2J/c2J) Mice (C57BL/6J)

We compared tyrosinase activity (TH, DO, and native PAGE-defined isozymes) and melanin production in participate and soluble fractions of hairbulb melanocytes of lethal yellow (A^y/a C/C), nonagouti black (a/a C/C), and albino (a/a c^2J/c^2J) of 3-, 6-, 9-, and 12-day regenerating hairbulbs. With respect to tyrosine hydroxylase (TH) and dopa oxidase (DO) activities, A^y/a melanocytes possessed only 25-35% of the activity of a/a; there were no genotype differences in either the subcellular distribution of activity in soluble and particulate fractions or in the relative increases of activity over the 12-day developmental period. TH data on wild-type agouti (A^wJ/A^wJ) mice over the 3-11 day regeneration interval showed an activity intermediate between that of a/a and A^y/a; the rate of TH increase reflected black and yellow phases of the agouti hair cycle. Analyses of the number and densities of dopa-sensitive bands following native PAGE of 3-, 6-, 9-, and 12-day hairbulb fractions of a/a and A^y/a mice suggested stage-dependent patterns. A comparison of rates and amounts of melanin production in 3-, 6-, 9-, and 12-day fractions showed consistent melanin production in A^y/a to be 10-20% that of a/a; however, fold increases in melanin production over the four stages were similar between genotypes. Overall, tyrosinase activity data support the notion that agouti locus modification of tyrosinase activity is a graded or quantitative rather than a qualitative phenomenon.     

Blue-eyed albino: A new albino allele in the domestic cat

A new albinistic allele in the cat is described and designated blue-eyed albino (symbol c ^a ). The coat is completely white. The eyes possess a dull red pupil in reduced light and a pale translucent blue iris. Reasons are given for regarding the allele as less extreme than complete albinism. The inheritance of three members of the albino series in the cat has now been reported. In decreasing order of dominance these are full colour (C), Burmese (c ^b ), Siamese (c ^s ) and blue-eyed albino (c ^a ).     

Genetic heterogeneity and selection signature at the KIT gene in pigs showing different coat colours and patterns

Mutations in the porcine KIT gene (Dominant white locus) have been shown to affect coat colours and colour distribution in pigs. We analysed this gene in several pig breeds and populations (Sicilian black, completely black or with white patches; Cinta Senese; grey local population; Large White; Duroc; Hampshire; Pietrain; wild boar; Meishan) with different coat colours and patterns, genotyping a few polymorphisms. The 21 exons and parts of the intronic regions were sequenced in these pigs and 69 polymorphisms were identified. The grey-roan coat colour observed in a local grey population was completely associated with a 4-bp deletion of intron 18 in a single copy KIT gene, providing evidence that this mutation characterizes the I^d allele described in the early genetic literature. The white patches observed in black Sicilian pigs were not completely associated with the presence of a duplicated KIT allele (I^p), suggesting that genetic heterogeneity is a possible cause of different coat colours in this breed. Selection signature was evident at the KIT gene in two different belted pig breeds, Hampshire and Cinta Senese. The same mutation(s) may cause the belted phenotype in these breeds that originated in the 18th–19th centuries from English pigs (Hampshire) and in Tuscany (Italy) in the 14th century (Cinta Senese). Phylogenetic relationships of 28 inferred KIT haplotypes indicated two clades: one of Asian origin that included Meishan and a few Sicilian black haplotypes and another of European origin.     

Genetic Regulation of Plasma Corticosterone Concentration and its Response to Castration and Allogeneic Tumour Growth in the Mouse

EXCESS fat deposition after castration is thought to be a response to hyperinsulinism induced by an increased level of adrenal glucocorticoids¹. Two mutant alleles, lethal yellow (A^y) and viable yellow (A^vy), at the agouti locus in the mouse induce excess fat deposition; the A^y allele has also been found to induce insulin resistance². Katsh³ concluded that in adrenalectomized KL strain mice a considerable portion of the high insulin tolerance depended on normal adrenal function. In the inbred YS/Wf and VY/Wf strains, both yellow pheno-types modulate serum insulin concentration⁴. Castration of inbred YS strain males causes a large decrease in serum insulin⁴, suggesting a possible relationship¹ to the concentration of adrenal glucocorticoids. Growth of allogeneic tumour cells has different effects on the serum insulin concentrations of YS and VY strain mice⁴.     

Association of Xmv-10 and the non-agouti (a) mutation explained by close linkage instead of causality

In a previous survey of endogenous proviruses among inbred mouse strains, the Xmv-10 provirus was found only in strains that carried the non-agouti (a) mutation (Frankel et al. J. Virol. 63: 1763–1774, 1989). To determine whether insertion of Xmv-10 caused the a mutation, we cloned a portion of Xmv-10 and its insertion site. Using a fragment of flanking cellular DNA as a Southern hybridization probe, we found that the Xmv-10 provirus was still present in revertant alleles of a to a ^tor A W.A restriction fragment length variant (RFLV) in cellular DNA at the Xmv-10 insertion site was found to be correlated with the presence or absence of the provirus among inbred strains of laboratory mice regardless of their agouti allele. This correlation did not extend to wild mice, however, in which none of the samples contained Xmv-10, yet one, Mus domesticus poschiavinus, contained the insertion site RFLV correlated with Xmv-10 in laboratory mice. Analysis of an intersubspecific backcross with RFLVs at the insertion sites of Xmv-10 and Emv-15 (an endogenous provirus associated with A ^y)revealed the following genetic map information: cen-A-0.31±0.31 cM-Emv-15-0.62±0.27 cM-Xmv-10-tel. Haplotype analysis of inbred strains in which a was not associated with Xmv-10 and in which A ^ywas not associated with Emv-15 demonstrated that these exceptions were explained most simply by a single recombination that disturbed the linkage relationships evident in most inbred strains. These results demonstrate that Xmv-10 did not cause the a mutation, suggest that insertion of Xmv-10 occurred recently in the evolution of laboratory mice, and show that the associations between agouti alleles and endogenous proviruses are due to linkage disequilibrium.     

Genetic analysis of the coloured mutants ofAspergillus niger

Seven different classes of coloured mutants were produced in anAspergillus niger strain: brown (B), cinnamon (C), dark brown (DB), fawn (F), green (G), yellow (Y) and white (W). A few of these recurrent colour mutants were allelic and the rest was non-allelic. These were tested by complementation test in heterocaryons. A few colour mutants failed to form heterocaryons. The incompatibility is suggested to be under genetic control. Conidial size of the heterocaryotic heads was measured and found to be significantly larger than that of their parental homocaryons. It is believed that the larger size is due to heterocaryotic vigor manifested in the conidia from heterocaryotic mycelium. It is termed haploid inherited vigor.     

Explicit evidence for a missense mutation in exon 4 of SLC45A2 gene causing the pearl coat dilution in horses

Four loci seem responsible for the dilution of the basic coat colours in horse: Dun (D), Silver Dapple (Z), Champagne (CH) and Cream (C). Apart from the current phenotypes ascribed to these loci, pearl has been described as yet another diluted coat colour in this species. To date, this coat colour seems to segregate only in the Iberian breeds Purebred Spanish horse and Lusitano and has also been described in breeds of Iberian origin, such as Quarter Horses and Paint Horse, where it is referred to as the ‘Barlink Factor’. This phenotype segregates in an autosomal recessive manner and resembles some of the coat colours produced by the champagne CH^CH and cream C^Cr alleles, sometimes being difficult to distinguish among them. The interaction between compound heterozygous for the pearl C^prl and cream C^Cr alleles makes SLC45A2 the most plausible candidate gene for the pearl phenotype in horses. Our results provide documented evidence for the missense variation in exon 4 [SLC45A2:c.985G>A; SLC45A2:p.(Ala329Thr)] as the causative mutation for the pearl coat colour. In addition, it is most likely involved as well in the cremello, perlino and smoky cream like phenotypes associated with the compound C^Cr and C^prl heterozygous genotypes (known as cream pearl in the Purebred Spanish horse breed). The characterization of the pearl mutation allows breeders to identify carriers of the C^prl allele and to select this specific coat colour according to personal preferences, market demands or studbook requirements as well as to verify segregation within particular pedigrees.     

A missense mutation in the agouti signaling protein gene (ASIP) is associated with the no light points coat phenotype in donkeys

Background

Seven donkey breeds are recognized by the French studbook and are characterized by a black, bay or grey coat colour including light cream-to-white points (LP). Occasionally, Normand bay donkeys give birth to dark foals that lack LP and display the no light points (NLP) pattern. This pattern is more frequent and officially recognized in American miniature donkeys. The LP (or pangare) phenotype resembles that of the light bellied agouti pattern in mouse, while the NLP pattern resembles that of the mammalian recessive black phenotype; both phenotypes are associated with the agouti signaling protein gene (ASIP).

Findings

We used a panel of 127 donkeys to identify a recessive missense c.349 T > C variant in ASIP that was shown to be in complete association with the NLP phenotype. This variant results in a cysteine to arginine substitution at position 117 in the ASIP protein. This cysteine is highly-conserved among vertebrate ASIP proteins and was previously shown by mutagenesis experiments to lie within a functional site. Altogether, our results strongly support that the identified mutation is causative of the NLP phenotype.

Conclusions

Thus, we propose to name the c.[349 T > C] allele in donkeys, the a^nlp allele, which enlarges the panel of coat colour alleles in donkeys and ASIP recessive loss-of-function alleles in animals.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0112-x) contains supplementary material, which is available to authorized users.