investigation of the agouti gene for the identification of useful markers for coat colour association studies in domestic rabbits

AbstractIn wild-type mice, it is well known that Agouti is expressed in skin where it controls the banded-hair Agouti phenotype. Molecular genetics and pharmacological studies show that mutually exclusive binding of the melanocortin 1 receptor (MC1R) by the Agouti protein or by -melanocyte-stimulating hormone (a-MSH) signals hair-bulb melanocytes to synthesise preferentially either pheomelanin (yellow-red pigment) or eumelanin (black-brown pigment), respectively. In mice as well as in other species, loss-of-function mutations of the Agouti gene determine only the production of eumelanin while gain-of-function mutations lead to pheomelanin production. A variety of coat colours appear as a result of these alterations that show also epistatic interactions with MC1R mutations. In rabbit, classical studies have suggested the presence of three alleles at the Agouti locus: A (wild type allele), at (black and tan) and a (non-agouti). We recently showed that mutations in the rabbit MC1R gene are associated with c..

Conséquences de la mise en œuvre de la sélection génomique. Jeu de rôles

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Blood analysis parameters genetically associated with longevity of jumping horses

International audienceIn order to find early selection criteria to improve the longevity of show jumping horses in competition, a specific protocol was constructed. Before entering competition, young horses were measured for many traits. These horses were offspring of two groups of sires selected as having the highest and lowest estimated breeding values for functional longevity in jumping competition, as calculated from progeny. Functional longevity was defined as the time spent in competition corrected for the level of performance. The dataset included 952 horses (mainly French Saddlebred) and 77 blood parameters. Heritability was estimated using a mixed model including the effect of age, sex, place and date of collection, weight and animal random additive value with 10,280 horses in pedigree. Heritability of blood parameters was generally moderate to high: 21 values were higher than 0.5 and 39 were between 0.2 and 0.5. The most heritable traits were hematology and enzyme traits: mean corpuscular volume (0.90) and mean corpuscular hemoglobin concentration (0.92) but also traits as liver isozyme (0.72) or total alkaline phosphatase (0.68), small lymphocytes (0.67), superoxide dismutase (0.60). Principal Component Analysis reveals the low correlations between traits: 32 variables were required to achieve 90% of the variance explained. However, correlation patterns between variables in the same function group revealed functional relationships. Logistic regression to predict group of sires according to longevity revealed, in order of appearance, the effect of mean corpuscular hemoglobin concentration, leukocytes, liver isozyme of alkaline phosphatase, 2-globulin, monocytes, 1-globulin and aspartate transaminase. Biological explanations are underway

Comparaison des paramètres sanguins chez deux groupes de chevaux génétiquement différents pour la longévité fonctionnelle en saut d'obstacles

International audienceIn order to find early selection criteria to improve the longevity of show jumping horses, a specific protocol was designed. Before entering competition, young horses selected from extreme stallions for longevity were measured for many traits, including blood parameters. Blood samples were taken from 952 horses aged 2–4 years old, sired by two groups of stallions: one with unfavorable (U) and the other with favorable (F) extreme estimated breeding values for functional longevity. These breeding values were previously calculated from data on 202,320 horses that participated in show jumping competitions between 1985 and 2022. Functional longevity was defined as time spent in competition, adjusted for the level of performance. The 59 measured parameters included hematology, proteins, cytokines, liver and kidney function, bone and joint health, oxidative stress and endocrinology. Heritability was estimated using a mixed model that accounted for the effect of age, sex, estimated weight, visit (place and date of collection), and animal random additive value with 10,280 horses in pedigree. A Partial Least Square logistic regression was performed to predict the sire group. Age, sex and estimated weight significantly affected 36, 19 and 16 variables, respectively. The visit had a significant effect on all variables. Heritability estimates were high, with 75% higher than 0.20% and 30% higher than 0.50. The most heritable traits included mean corpuscular volume (0.92, se 0.11), mean corpuscular hemoglobin (0.90, se 0.11), white blood cells (0.55, se 0.13), total alkaline phosphatase (0.68, se 0.12) and percentage of γ-globulin (0.57, se 0.12). The logistic regression that predicted the group of sires favorable for longevity identified 16 significant variables. Key findings included: lower mean corpuscular hemoglobin ( p -value < 0.001), lower mean corpuscular volume ( p -value < 0.001), lower number of white blood cells ( p -value < 0.01), higher percentage of intestinal and bone alkaline phosphatase ( p -value < 0.01) for a lower total alkaline phosphatase ( p -value < 0.01), higher percentage of α2-globulin ( p -value < 0.001) and lower percentage of β1-globulin ( p -value < 0.01). Blood parameters measured at rest in young horses may be predictive of their genetic value for functional longevity in show jumping

Investigation of the premelanosome protein (PMEL or SILV) gene and identification of polymorphism excluding it as the determinant of the dilute locus in domestic rabbits (Oryctolagus cuniculus)

After the rediscovery of the Mendel's laws, the domesticated European rabbit (Orycolagus cuniculus) has been the objective of pioneering studies on coat colour genetics. However, despite the early role of this species in defining genetic mechanisms determining this phenotypic trait, only recently a few loci have been characterized at the molecular level analysing also in rabbits genes already shown to affect coat colour in mice. We herein investigated the rabbit premelanosome protein (PMEL) gene, also known as melanocyte protein Pmel 17 (PMEL17) or silver (SILV), as mutations in the homologous gene in mice and other species produce phenotypic effects similar to what is observed in the dilute coat colour in rabbit. The rabbit dilute locus is determined by a recessive coat colour mutation that dilutes the black to blue (grey) interacting with the basic colours influenced by the agouti and extension loci. To investigate this candidate gene, we isolated and sequenced cDNAs as well as portions of intronic and exonic regions of the PMEL gene in several rabbits with different coat colours and identified single nucleotide polymorphisms, including several missense mutations. One polymorphism, positioned in intron 7, was genotyped in a family in which there was segregation of the dilute coat colour. The results excluded PMEL as the causative gene for the dilute locus in rabbits, shortening the list of candidate genes that should be analysed to identify the mutation determining this phenotypic trait

Investigation of coat colour affecting genes in several european rabbit breeds and other leporid species

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A composite six bp in-frame deletion in the melanocortin 1 receptor (MC1R) gene is associated with the japanese brindling coat colour in rabbits (Oryctolagus Cuniculus)

Background: In the domestic rabbit (Oryctolagus cuniculus), classical genetic studies have identified five alleles at the Extension locus: ED (dominant black), ES (steel, weaker version of ED), E (wild type, normal extension of black), eJ(Japanese brindling, mosaic distribution of black and yellow) and e (non-extension of black, yellow/red with white belly). Sequencing almost the complete coding sequence (CDS) of the rabbit MC1R gene, we recently identified two in-frame deletions associated with dominant black (c.280_285del6; alleles ED or ES) and recessive red (c.304_333del30; allele e) coat colours. It remained to characterize the eJallele whose phenotypic effect is similar to the Orange and Sex-linked yellow loci of cat and Syrian hamster. [br/] Results: We sequenced the whole CDS in 25 rabbits of different coat colours including 10 Japanese and 10 Rhinelander (tricolour) rabbits and identified another 6 bp-in frame deletion flanked by a G > A transition in 5' (c.[124G>A;125_130del6]) that was present in all animals with Japanese brindling coat colour and pattern. These mutations eliminate two amino acids in the first transmembrane domain and, in addition, cause an amino acid substitution at position 44 of the wild type sequence. Genotyping 371 rabbits of 31 breeds with different coat colour this allele (eJ) was present in homozygous state in Japanese, Rhinelander and Dutch tricolour rabbits only (except one albino rabbit). Rabbits with eJ/eJ genotype were non fixed at the non-agouti mutation we previously identified in the ASIP gene. Segregation in F1 and F2 families confirmed the order of dominance already determined by classical genetic experiments with a possible dose effect evident comparing eJ/eJ and eJ/e animals. MC1R mRNA was expressed in black hair skin regions only. [br/] Conclusions: The c.[124A;125_130del6] allele may be responsible for a MC1R variant determining eumelanin production in the black areas. However, the mechanism determining the presence of both red and black hairs in the same animal seems more complex. Expression analyses of the c.[124A;125_130del6] allele suggest that MC1R transcription may be regulated epigenetically in rabbits with the Japanese brindling phenotype. Further studies are needed to clarify this issue

A first-generation microsatellite-based integrated genetic and cytogenetic map for the European rabbit ( Oryctolagus cuniculus) and localization of angora and albino

International audienceAlthough the European rabbit (Oryctolagus cuniculus) is used both in agronomics and in research, genomic resources for this species are still limited and no microsatellite-based genetic map has been reported. Our aim was to construct a rabbit genetic map with cytogenetically mapped microsatellites so as to build an integrated genetic and cytogenetic map. A reference population of 187 rabbits comprising eight three-generation families with 10–25 offspring per family was produced. One hundred and ninety-four of 305 previously identified microsatellites were included in this study. Of these, 158 were polymorphic with two to seven alleles. The map reported here comprises 111 markers, including 104 INRA microsatellites, five microsatellites from another source and two phenotypic markers (angora and albino). Ninety markers were integrated into 20 linkage groups. The remaining 21 microsatellites mapped to separate linkage groups, 19 with a precise cytogenetic position and two with only a chromosomal assignment. The genetic map spans 2766.6 cM and covers 20 rabbit chromosomes, excluding chromosomes 20, 21 and X. The density of this map is limited, but we used it to verify the location of angora and albino on chromosomes 15q and 1q, respectively, in agreement with previously published data. This first generation genetic/cytogenetic map will help gene identification and quantitative trait loci mapping projects in rabbit

Carte génétique du lapin : Etat des lieux et perspectives

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