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

Abitbol M, Legrand R, Tiret L - Genet. Sel. Evol. (2015)

Bottom Line: This variant results in a cysteine to arginine substitution at position 117 in the ASIP protein.Altogether, our results strongly support that the identified mutation is causative of the NLP phenotype.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.

View Article: PubMed Central - PubMed

Affiliation: Inra, Unité de Génétique Fonctionnelle et Médicale, Ecole nationale vétérinaire d'Alfort, Maisons-Alfort, 94700, France. m.abitbol@vet-alfort.fr.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Alignment between ASIP protein sequences from 10 vertebrate species. ASIP amino acid sequences from various species were collected from Ensembl (mouse: ENSMUST00000109697; horse: ENSECAT00000004772; cow: ENSBTAT00000048322; sheep: ENSOART00000010128; dog: ENSCAFT00000038625; cat: ENSFCAT00000011040; human: ENST00000568305; chicken: ENSGALT00000044768; zebrafish: ENSDART00000113083). ASIP sequences are identified with the name of the species on the left. The mouse ASIP sequence (reference sequence) is at the top of the alignment. Non-conserved residues in the 10 species analyzed are shown in grey. Conserved residues are indicated in black within the reference sequence and represented by black dots in other sequences. Dashes represent deletions. The conserved C117 residue in donkey ASIP that corresponds to the murine C113 residue is circled. The 10 functional cysteine residues that have been shown to be involved in the activity of ASIP are indicated with stars. Non-agouti mutations identified in other domestic mammalian species are reported above the corresponding position. Dog and alpaca mutations consist in missense mutations and a 19 amino acids (aa) in-frame deletion. Rabbit, rat, cat and horse mutations are frameshifts. Mouse and sheep regulatory mutations are not shown.
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Fig2: Alignment between ASIP protein sequences from 10 vertebrate species. ASIP amino acid sequences from various species were collected from Ensembl (mouse: ENSMUST00000109697; horse: ENSECAT00000004772; cow: ENSBTAT00000048322; sheep: ENSOART00000010128; dog: ENSCAFT00000038625; cat: ENSFCAT00000011040; human: ENST00000568305; chicken: ENSGALT00000044768; zebrafish: ENSDART00000113083). ASIP sequences are identified with the name of the species on the left. The mouse ASIP sequence (reference sequence) is at the top of the alignment. Non-conserved residues in the 10 species analyzed are shown in grey. Conserved residues are indicated in black within the reference sequence and represented by black dots in other sequences. Dashes represent deletions. The conserved C117 residue in donkey ASIP that corresponds to the murine C113 residue is circled. The 10 functional cysteine residues that have been shown to be involved in the activity of ASIP are indicated with stars. Non-agouti mutations identified in other domestic mammalian species are reported above the corresponding position. Dog and alpaca mutations consist in missense mutations and a 19 amino acids (aa) in-frame deletion. Rabbit, rat, cat and horse mutations are frameshifts. Mouse and sheep regulatory mutations are not shown.

Mentions: To estimate the functional importance of the donkey ASIP cysteine 117 amino acid, we aligned the donkey ASIP protein sequence with the ASIP sequences of nine vertebrates and found that is was fully conserved (Figure 2). This result confirmed the 100% conservation previously reported for the 10 cysteine amino acids of the C-terminal Cys-rich domain of ASIP [18-21] the functional role of which was investigated by mutagenesis experiments. Perry and collaborators reported that in mouse, 13 mutated ASIP proteins displayed a partial (n = 4) or a total (n = 9) loss of activity [21]. In particular, they found that eight of the 10 cysteines located in the Cys-rich C-terminal tail of ASIP, including the murine cysteine 113 that corresponds to the donkey cysteine 117, were critical for protein activity [21]. Altogether these results strongly support that, in donkeys, the ASIP cysteine 117 has an essential role for ASIP function.Figure 2


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

Abitbol M, Legrand R, Tiret L - Genet. Sel. Evol. (2015)

Alignment between ASIP protein sequences from 10 vertebrate species. ASIP amino acid sequences from various species were collected from Ensembl (mouse: ENSMUST00000109697; horse: ENSECAT00000004772; cow: ENSBTAT00000048322; sheep: ENSOART00000010128; dog: ENSCAFT00000038625; cat: ENSFCAT00000011040; human: ENST00000568305; chicken: ENSGALT00000044768; zebrafish: ENSDART00000113083). ASIP sequences are identified with the name of the species on the left. The mouse ASIP sequence (reference sequence) is at the top of the alignment. Non-conserved residues in the 10 species analyzed are shown in grey. Conserved residues are indicated in black within the reference sequence and represented by black dots in other sequences. Dashes represent deletions. The conserved C117 residue in donkey ASIP that corresponds to the murine C113 residue is circled. The 10 functional cysteine residues that have been shown to be involved in the activity of ASIP are indicated with stars. Non-agouti mutations identified in other domestic mammalian species are reported above the corresponding position. Dog and alpaca mutations consist in missense mutations and a 19 amino acids (aa) in-frame deletion. Rabbit, rat, cat and horse mutations are frameshifts. Mouse and sheep regulatory mutations are not shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4389795&req=5

Fig2: Alignment between ASIP protein sequences from 10 vertebrate species. ASIP amino acid sequences from various species were collected from Ensembl (mouse: ENSMUST00000109697; horse: ENSECAT00000004772; cow: ENSBTAT00000048322; sheep: ENSOART00000010128; dog: ENSCAFT00000038625; cat: ENSFCAT00000011040; human: ENST00000568305; chicken: ENSGALT00000044768; zebrafish: ENSDART00000113083). ASIP sequences are identified with the name of the species on the left. The mouse ASIP sequence (reference sequence) is at the top of the alignment. Non-conserved residues in the 10 species analyzed are shown in grey. Conserved residues are indicated in black within the reference sequence and represented by black dots in other sequences. Dashes represent deletions. The conserved C117 residue in donkey ASIP that corresponds to the murine C113 residue is circled. The 10 functional cysteine residues that have been shown to be involved in the activity of ASIP are indicated with stars. Non-agouti mutations identified in other domestic mammalian species are reported above the corresponding position. Dog and alpaca mutations consist in missense mutations and a 19 amino acids (aa) in-frame deletion. Rabbit, rat, cat and horse mutations are frameshifts. Mouse and sheep regulatory mutations are not shown.
Mentions: To estimate the functional importance of the donkey ASIP cysteine 117 amino acid, we aligned the donkey ASIP protein sequence with the ASIP sequences of nine vertebrates and found that is was fully conserved (Figure 2). This result confirmed the 100% conservation previously reported for the 10 cysteine amino acids of the C-terminal Cys-rich domain of ASIP [18-21] the functional role of which was investigated by mutagenesis experiments. Perry and collaborators reported that in mouse, 13 mutated ASIP proteins displayed a partial (n = 4) or a total (n = 9) loss of activity [21]. In particular, they found that eight of the 10 cysteines located in the Cys-rich C-terminal tail of ASIP, including the murine cysteine 113 that corresponds to the donkey cysteine 117, were critical for protein activity [21]. Altogether these results strongly support that, in donkeys, the ASIP cysteine 117 has an essential role for ASIP function.Figure 2

Bottom Line: This variant results in a cysteine to arginine substitution at position 117 in the ASIP protein.Altogether, our results strongly support that the identified mutation is causative of the NLP phenotype.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.

View Article: PubMed Central - PubMed

Affiliation: Inra, Unité de Génétique Fonctionnelle et Médicale, Ecole nationale vétérinaire d'Alfort, Maisons-Alfort, 94700, France. m.abitbol@vet-alfort.fr.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus