Impact of strong selection for the PrP major gene on genetic variability of four French sheep breeds (Open Access publication)

Effective selection on the PrP gene has been implemented since October 2001 in all French sheep breeds. After four years, the ARR "resistant" allele frequency increased by about 35% in young males. The aim of this study was to evaluate the impact of this strong selection on genetic variability. It is focussed on four French sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3–4 years later. Genetic variability was assessed using genealogical and molecular data (29 microsatellite markers). The expected loss of genetic variability on the PrP gene was confirmed. Moreover, among the five markers located in the PrP region, only the three closest ones were affected. The evolution of the number of alleles, heterozygote deficiency within population, expected heterozygosity and the Reynolds distances agreed with the criteria from pedigree and pointed out that neutral genetic variability was not much affected. This trend depended on breed, i.e. on their initial states (population size, PrP frequencies) and on the selection strategies for improving scrapie resistance while carrying out selection for production traits

Multidirectional chromosome painting substantiates the occurrence of extensive genomic reshuffling within Accipitriformes.

BACKGROUND: Previous cross-species painting studies with probes from chicken (Gallus gallus) chromosomes 1-10 and a paint pool of nineteen microchromosomes have revealed that the drastic karyotypic reorganization in Accipitridae is due to extensive synteny disruptions and associations. However, the number of synteny association events and identities of microchromosomes involved in such synteny associations remain undefined, due to the lack of paint probes derived from individual chicken microchromosomes. Moreover, no genome-wide homology map between Accipitridae species and other avian species with atypical karyotype organization has been reported till now, and the karyotype evolution within Accipitriformes remains unclear. RESULTS: To delineate the synteny-conserved segments in Accipitridae, a set of painting probes for the griffon vulture, Gyps fulvus (2n = 66) was generated from flow-sorted chromosomes. Together with previous generated probes from the stone curlew, Burhinus oedicnemus (2n = 42), a Charadriiformes species with atypical karyotype organization, we conducted multidirectional chromosome painting, including reciprocal chromosome painting between B. oedicnemus and G. fulvus and cross-species chromosome painting between B. oedicnemus and two accipitrid species (the Himalayan griffon, G. himalayensis 2n = 66, and the common buzzard, Buteo buteo, 2n = 68). In doing so, genome-wide homology maps between B. oedicnemus and three Accipitridae species were established. From there, a cladistic analysis using chromosomal characters and mapping of chromosomal changes on a consensus molecular phylogeny were conducted in order to search for cytogenetic signatures for different lineages within Accipitriformes. CONCLUSION: Our study confirmed that the genomes of the diurnal birds of prey, especially the genomes of species in Accipitriformes excluding Cathartidae, have been extensively reshuffled when compared to other bird lineages. The chromosomal rearrangements involved include both fusions and fissions. Our chromosome painting data indicated that the Palearctic common buzzard (BBU) shared several common chromosomal rearrangements with some Old World vultures, and was found to be more closely related to other Accipitridae than to Neotropical buteonine raptors from the karyotypic perspective. Using both a chromosome-based cladistic analysis as well as by mapping of chromosomal differences onto a molecular-based phylogenetic tree, we revealed a number of potential cytogenetic signatures that support the clade of Pandionidae (PHA) + Accipitridae. In addition, our cladistic analysis using chromosomal characters appears to support the placement of osprey (PHA) in Accipitridae

Insights into gene expression profiling of natural resistance to coccidiosis in contrasting chicken lines

Coccidiosis is a parasitic disease with major economic impact, one of whose main causative agents is Eimeria tenella. Chicken breeds display variable natural resistance to this disease. Unravelling the genetic bases of such variations could provide new clues for protection strategies. Transcriptomic experiments were conducted comparing resistant (Fayoumi) and susceptible (Leghorn) lines. Caecum and caecal tonsils were analysed. A global increase in differential gene expression following infection was observed for caecum comparisons, whereas a global decrease following infection was observed for caecal tonsils

Microsatellite mapping of QTLs affecting resistance to coccidiosis (Eimeria tenella) in a Fayoumi × White Leghorn cross

<p>Abstract</p> <p>Background</p> <p>Avian coccidiosis is a major parasitic disease of poultry, causing severe economical loss to poultry production by affecting growth and feed efficiency of infected birds. Current control strategies using mainly drugs and more recently vaccination are showing drawbacks and alternative strategies are needed. Using genetic resistance that would limit the negative and very costly effects of the disease would be highly relevant. The purpose of this work was to detect for the first time QTL for disease resistance traits to <it>Eimeria tenella </it>in chicken by performing a genome scan in an F2 cross issued from a resistant Fayoumi line and a susceptible Leghorn line.</p> <p>Results</p> <p>The QTL analysis detected 21 chromosome-wide significant QTL for the different traits related to disease resistance (body weight growth, plasma coloration, hematocrit, rectal temperature and lesion) on 6 chromosomes. Out of these, a genome-wide very significant QTL for body weight growth was found on GGA1, five genome-wide significant QTL for body weight growth, plasma coloration and hematocrit and one for plasma coloration were found on GGA1 and GGA6, respectively. Two genome-wide suggestive QTL for plasma coloration and rectal temperature were found on GGA1 and GGA2, respectively. Other chromosme-wide significant QTL were identified on GGA2, GGA3, GGA6, GGA15 and GGA23. Parent-of-origin effects were found for QTL for body weight growth and plasma coloration on GGA1 and GGA3. Several QTL for different resistance phenotypes were identified as co-localized on the same location.</p> <p>Conclusion</p> <p>Using an F2 cross from resistant and susceptible chicken lines proved to be a successful strategy to identify QTL for different resistance traits to <it>Eimeria tenella</it>, opening the way for further gene identification and underlying mechanisms and hopefully possibilities for new breeding strategies for resistance to coccidiosis in the chicken. From the QTL regions identified, several candidate genes and relevant pathways linked to innate immune and inflammatory responses were suggested. These results will be combined with functional genomics approaches on the same lines to provide positional candidate genes for resistance loci for coccidiosis. Results suggested also for further analysis, models tackling the complexity of the genetic architecture of these correlated disease resistance traits including potential epistatic effects.</p

Issues and special features of animal health research

In the rapidly changing context of research on animal health, INRA launched a collective discussion on the challenges facing the field, its distinguishing features, and synergies with biomedical research. As has been declared forcibly by the heads of WHO, FAO and OIE, the challenges facing animal health, beyond diseases transmissible to humans, are critically important and involve food security, agriculture economics, and the ensemble of economic activities associated with agriculture. There are in addition issues related to public health (zoonoses, xenobiotics, antimicrobial resistance), the environment, and animal welfare

A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken

Author summaryVertebrates possess two types of melanin, red/yellow pheomelanin and black/brown eumelanin. In this study, we report that the recessive Inhibitor of gold phenotype in chicken, which causes a severe defect in pheomelanin pigmentation, is associated with a mutation that most likely inactivates the COMTD1 gene. This gene encodes an O-methyltransferase enzyme and is present throughout vertebrate evolution, but is one of the many genes in vertebrate genomes for which the biological function is still poorly understood. This is the first report of a COMTD1 mutation associated with a phenotypic effect. We show that the COMTD1 protein is present in mitochondria in pigment cells. Furthermore, inactivation of the gene in a mouse pigment cell line results in a significant reduction in metabolites that are important for the synthesis of pheomelanin. We hypothesize that COMTD1 activity protects pigment cells from oxidative stress and that inactivation of this function impairs the production of pheomelanin. It is likely that COMTD1 has a similar function in other cell types. This study establishes this chicken mutation as a model for further studies of COMTD1 function.The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5(th) exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin

The Rose-comb Mutation in Chickens Constitutes a Structural Rearrangement Causing Both Altered Comb Morphology and Defective Sperm Motility

Rose-comb, a classical monogenic trait of chickens, is characterized by a drastically altered comb morphology compared to the single-combed wild-type. Here we show that Rose-comb is caused by a 7.4 Mb inversion on chromosome 7 and that a second Rose-comb allele arose by unequal crossing over between a Rose-comb and wild-type chromosome. The comb phenotype is caused by the relocalization of the MNR2 homeodomain protein gene leading to transient ectopic expression of MNR2 during comb development. We also provide a molecular explanation for the first example of epistatic interaction reported by Bateson and Punnett 104 years ago, namely that walnut-comb is caused by the combined effects of the Rose-comb and Pea-comb alleles. Transient ectopic expression of MNR2 and SOX5 (causing the Pea-comb phenotype) occurs in the same population of mesenchymal cells and with at least partially overlapping expression in individual cells in the comb primordium. Rose-comb has pleiotropic effects, as homozygosity in males has been associated with poor sperm motility. We postulate that this is caused by the disruption of the CCDC108 gene located at one of the inversion breakpoints. CCDC108 is a poorly characterized protein, but it contains a MSP (major sperm protein) domain and is expressed in testis. The study illustrates several characteristic features of the genetic diversity present in domestic animals, including the evolution of alleles by two or more consecutive mutations and the fact that structural changes have contributed to fast phenotypic evolution

The "silver" Japanese quail and the MITF gene: causal mutation, associated traits and homology with the "blue" chicken plumage

<p>Abstract</p> <p>Background</p> <p>The <it>MITF </it>(<it>microphthalmia-associated transcription factor</it>) gene has been investigated in mice and various vertebrates but its variations and associated effects have not yet been explored much in birds. The present study describes the causal mutation <it>B </it>at the <it>MITF </it>gene responsible for the "silver" plumage colour in the Japanese quail (<it>Coturnix japonica</it>), and its associated effects on growth and body composition, and tests its allelism with the "blue" plumage colour mutation <it>Bl </it>in <it>Gallus gallus</it>.</p> <p>Results</p> <p>The semi dominant <it>B </it>mutation results from a premature stop codon caused by a 2 bp deletion in exon 11 of <it>MITF</it>. Homozygous "white" (<it>B/B</it>) quail which have a white plumage also show a slightly lower growth, lower body temperature, smaller heart, and lighter <it>pectoralis </it>muscles but more abdominal adipose tissue than the recessive homozygous "wild-type" (<it>+/+</it>) and heterozygous "silver" (<it>B/+</it>) quail. Similar observations on cardiac and body growth were made on mice (<it>Mus musculus</it>) homozygous for mutations at <it>MITF</it>. The production of chicken-quail hybrids with a white plumage obtained by crossing <it>Bl/+ </it>chicken heterozygous for the <it>blue </it>mutation with <it>B/B </it>white quail indicated that the mutations were allelic.</p> <p>Conclusion</p> <p>The "silver" Japanese quail is an interesting model for the comparative study of the effects of <it>MITF </it>in birds and mammals. Further investigation using a chicken family segregating for the "blue" plumage and molecular data will be needed to confirm if the "blue" plumage in chicken results from a mutation in <it>MITF</it>.</p

Structural and functional annotation of the porcine immunome

Background: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.[br/] Results: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.[br/] Conclusions: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response