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Cet article retrace les principales étapes et la contribution de l’INRA au développement de la génomique, qui révolutionne depuis deux décennies les connaissances sur la structure et le fonctionnement du génome des animaux d’élevage. L’élaboration, dans les années 90, des premières cartes de marqueurs microsatellites a rapidement permis de mettre en évidence de nombreux locus à effets quantitatifs et de localiser les premiers gènes majeurs. En parallèle, les travaux de cytogénétique et de génomique comparative permettaient de tirer parti de l’avancée des connaissances sur le génome de l’homme et de la souris. A la fin des années 90, la construction d’outils de cartographie à haute densité, cartes d’hybrides d’irradiation et banques de grands fragments, a permis l’essor des travaux de cartographie fine et l’identification des premières mutations causales. Le début des années 2000 a été marqué par le développement des outils d’étude systématique de l’expression des gènes, micro-réseaux et puces à ADN, le démarrage du séquençage des premiers génomes d’animaux d’élevage, et l’essor des bases de données génomiques et de la bioinformatique. La connaissance des séquences permet ensuite de détecter in silico leurs variations, en particulier les très nombreuses variations ponctuelles (SNP) et de caractériser finement la structure des génomes des populations animales. La génomique a également renouvelé les méthodes d’amélioration génétique des populations, avec la mise en place de programmes de sélection assistée par marqueurs, de caractérisation et de gestion de la variabilité génétique et le développement d’applications en matière de contrôle de généalogie ou de traçabilité., This article outlines the main steps and the contribution of INRA to the development of genomics, which has revolutionised over the last two decades the knowledge of livestock genome structure and function. The development in the 1990’s of the first microsatellite marker maps quickly allowed the first major genes to be localised and numerous quantitative trait loci to be detected. Meanwhile, cytogenetics and comparative genomics studies allowed livestock genomics to benefit from advances in the knowledge of human and mouse genomes. At the end of the 1990’s, the construction of high-density mapping tools such as radiation hybrid maps and large insert libraries made it possible to develop fine mapping programmes and to identify the first causative mutations. The early 2000’s have been marked by the development of systematic gene expression tools, i.e. micro-arrays and DNA chips, the start of the first animal genome sequencing projects, and the rise of genomic databases and bioinformatics. Available sequence data then made it possible to detect in silico their variations, in particular the numerous single point polymorphisms (SNP) and to finely characterise the structure of livestock population genomes. Genomics has also renewed breeding programmes, with the development of programmes for marker-assisted selection, for the characterisation and the management of genetic variability and of parentage control or traceability applications.

Characterisation of genetic diversity in a large number of European pig populations has been undertaken with EC support. The populations sampled included local (rare) breeds, national varieties of the major international breeds, commercial lines and the Chinese Meishan breed. A second phase of the project will sample a further 50 Chinese breeds. Neutral genetic markers (AFLP and microsatellites), with individual or bulk typing, were used and compared.DNA from 59 European pig populations was extracted on samples of about 50 individuals per population. Individuals were typed for 50 microsatellites and for 148 AFLP bands. A subset of 25 populations was typed for 20 microsatellites on pools of DNA. Allele frequencies were estimated by direct allele counting for the co-dominant markers. Frequencies of AFLP negative alleles (absent bands) were obtained by taking the square root of absent band frequencies. Within-breed variability was summarised using standard statistics: expected and observed heterozygosity, mean observed and effective numbers of alleles, and F statistics. Between-breed diversity analysis was based on a bootstrapped Neighbor-Joining (NJ) tree derived from Reynolds distances (DR). The standard distance of Nei (DS) was also calculated.

Two genes coding for Na[sup +],K[sup +] -ATPase [alpha] and [beta] subunits are localized on pig chromosome 4, to the q1.6[yields]q2.3 and 1.3[yields]q2.1 regions, respectively, by radioactive in situ hybridization. According to nucleotide and amino acid sequence comparisons with different human isoforms of Na[sup +] ,K[sup +]-ATPase, these pig [alpha] and [beta] ATPase genes show strong homologies with human [alpha]1 and [beta] subunit ATPase genes, respectively. These results are discussed with respect to comparative mapping data of conserved genes in mammalian species. We showed that the pig cDNA probes encoding ATPase [alpha] and, [beta] genes reveal DNA polymorphism in Meishan an Large White pigs. 35 refs., 4 figs., 2 tabs.

Chantier qualité GA; International audience; Atlantic salmon Salmo salar microsatellite markers from a large database were analysed and selected with technical, economic and genetic criteria to provide an optimized set of polymorphic DNA markers for the analysis of the genetic diversity and the structure of anadromous Atlantic salmon populations. A set of 37 microsatellite markers was identified that are easy to use and provide a high level of differentiation power.

We investigate the use of markers to hasten the recovery of the recipient genome during an introgression breeding program. The effects of time and intensity of selection, population size, number and position of selected markers are studied for chromosomes either carrying or not carrying the introgressed gene. We show that marker assisted selection may lead to a gain in time of about two generations, an efficiency below previous theoretical predictions. Markers are most useful when their map position is known. In the early generations, it is shown that increasing the number of markers over three per non-carrier chromosome is not efficient, that the segment surrounding the introgressed gene is better controlled by rather distant markers unless high selection intensity can be applied, and that selection on this segment first can reduce the selection intensity available for selection on non-carrier chromosomes. These results are used to propose an optimal strategy for selection on the whole genome, making the most of available material and conditions (e.g., population size and fertility, genetic map).

On discute une possibilité d’utiliser des marqueurs polymorphes pour contrebalancer, dans une population d’effectif limité, les effets de la dérive aléatoire des fréquences alléliques. Le critère de sélection utilisé est un index favorisant le maintien de l’hétérozygotie aux locus marqueurs. Dans des populations d’effectif petit (moins de 100 reproducteurs efficaces) il semble qu’un marquage peu dense mais uniformément réparti (3 marqueurs pour 100 centimorgans) permette des gains sensables pour le maintien de l’hétérozygotie sur l’ensemble du génome avec une intensité de sélection faible. Par ailleurs la réponse observée aux marqueurs s’avère très élevée même avec un assez grand nombre de marqueurs sélectionnés simultanément.

Following Robertson (1970a) it is generally considered that for mass selection the selected proportion that maximises ultimate response is 0.5. This prediction has been partly tested by different authors. Here we explicitly address the question using computer simulations of selection in finite populations with linkage. The results show that the response achieved is always lower than the one predicted by standard methods, and that optimum selection intensity may be much lower than predicted unless population size is small.

The M13.13 minisatellite probe, consisting of a polymer of the M13 VNTR consensus sequence, cross-hybridized to ovine DNA and allowed detection of several polymorphic loci. Individual specific patterns were obtained in sheep using this probe. Pedigree analysis showed that individuals were heterozygous for most of the DNA fragments detected (88%). By studying the segregation of male's variable DNA fragments, a minimum of 10 loci were defined. The ovine DNA 'fingerprint' obtained with M13.13 is polymorphic enough to be used efficiently in animal identification, paternity testing, and possibly as a source of genetic markers for linkage analysis.

Predicting the genetic drift in small populations is considered over a short interval of time. A detailed description of the dynamic and spatial structure of the population is used, together with several measures of the change of genetic variability with time: mean inbreeding and kinship coefficients within and between groups of animals; percentages of genes contributed by the various foundation groups that made up the initial population; rate of loss of founder genes; joint distribution and random fluctuations of allelic frequencies. This approach is illustrated by means of two theoretical populations that model actual cattle breeds, and is applied to two problems: the conservation of a small population with or without freezing of semen, and the conflict between diffusion of genetic progress and random drift in a selected population conducted with or without superovulation and embryo transfer. Two main conclusions were drawn from these examples: 1. (a) Drift should not be characterized by single values (genetic effective size, or mean inbreeding coefficients), but rather by a set of criteria that have differentiated sensitivities to variations in demographic structure, mating scheme and gene diffusion. 2. (b) Quite large random variations in gene frequencies can be promoted by selection in seemingly large populations.

The syntenic α and β casein genes were localized in the rabbit by chromosomal in situ hybridization, using a mixture of two radioactive cDNA probes corresponding to these two genes. Highly significant labeling was observed on chromosome 12. A total of 175 silver grains was found on chromosomes in the 193 mitoses studied; 18% of the grains were on chromosome 12, and 42% of the grains on this chromosome were localized to the 12q24 region. Statistical analysis revealed that this labeling was highly significant.

Properties of identity relation between genes are discussed, and a derivation of recurrent equations of identity coefficients in a random mating, diploid dioecious population is presented. Computations are run by repeated matrix multiplication. Results show that for effective population size (Ne) larger than 16 and no mutation, a given identity coefficient at any time t can be expressed approximately as a function of (1—f), (1—f)3 and (1—f)6, where f is the mean inbreeding coefficient at time t. Tables are presented, for small Ne values and extreme sex ratios, showing the pattern of change in the identity coefficients over time. The pattern of evolution of identity coefficients is also presented and discussed with respect to N eu, where u is the mutation rate. Applications of these results to the evolution of genetic variability within and between inbred lines are discussed.

Data on the segregation of human markers in somatic hybrids between permanent rodent cell lines and primary human cells were gathered and statistically analyzed, using various criteria of association. The analysis provides evidence that human chromosomes do not segregate independently in somatic cell hybrids. A statistical decision rule concerning synteny or independence between markers is proposed, and its utility in developing the gene maps of other species by means of somatic cell hybridization is explored.

The syntenic alpha and beta casein genes were localized in the rabbit by chromosomal in situ hybridization, using a mixture of two radioactive cDNA probes corresponding to these two genes. Highly significant labeling was observed on chromosome 12. A total of 175 silver grains was found on chromosomes in the 193 mitoses studied; 18% of the grains were on chromosome 12, and 42% of the grains on this chromosome were localized to the 12q24 region. Statistical analysis revealed that this labeling was highly significant.

In the south-east of France, local honey bees possess only the B allele at the MDH locus, whereas the races which are usually imported into this area do not have this allele. The proportion of non-B genes in a sample of drones was used to measure the “genetic pollution” in the local population. Within the course of a breeding scheme of local bees, 99 queens, whose genotypes are BB, were naturally mated between April 25 and June 10, 1985 at la Tave (Gard, France). Twenty daughters-workers of each queen were analysed at the MDH locus. The frequency of the B allele in drones that mated with these queens is estimated by the proportion of workers with genotype BB and the genetic pollution by the cumulated frequency of the other alleles. The sampling variances of these frequencies involve a coefficient which is a function of the average number of drones mated with a queen. This latter parameter is estimated through the maximum likelihood method. In addition to the three well-known alleles, a rare allele (frequency=0.0055), possibly equivalent to the S1 allele described by Badino et al. (1983), has been found in three different colonies. Cumulating the frequencies of the non-B alleles results in an estimation of the genetic pollution equal to 0.0394 (±0.0071). This low value allows us to proceed to the next step of the selection project. The mean number of drones mated to a queen is 12.4 with a (10.4–19.3) confidence interval at the 90% level.