Meiotic segregation analysis in cows heterozygous for the T(1;29) Robertsonian translocation.

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Meiotic segregation analysis in cow heterozygotes for the t(1;29) Robertsonian translocation

Heterozygotes for Robertsonian translocations have usually a normal phenotype but show variable decrease in fertility. In humans, meiotic segregation studies carried out in male carriers reveal a majority of balanced spermatozoa. The rate of unbalanced segregation products appears higher in females than in males, but the number of human oocytes analysed so far remains limited (about 100). The occurrence of the t(1;29) translocation in several cattle breeds makes bovines an interesting animal model to study the meiotic segregation in female carrier of Robertsonian translocations. The aim of our project is thus to assess the rates of unbalanced oocytes produced by four cows and to compare these values with those obtained in bulls carriers of the same translocation. The superstimulated cows were subjected to twenty um pick up (OPU) sessions. Dual colour whole chromosome painting probes for BTA1 and 29 were hybridized on oocytes preparations. To date, 649 oocytes have been matured in vitro and 500 successfully spread. Among the 266 oocytes analysed by FISH so far: 201 (75,5%) are balanced, including 105 translocated and 96 normal, 55 are diploid (20.7%), and 10 unbalanced (3.8%). The proportion of balanced oocytes is lower than the average proportion of balanced spermatozoa estimated for two heterozygous bulls (97.1%). This difference is essentially due to a higher rate of diploid oocytes (20.7% vs 0.04% diploid spermatozoa). The origin of observed differences in the segregation profiles of the two sexes, as well as the practical implications of these results for genetic counselling and cattle breeding are discussed

Contrôle chromosomique des populations animales d'élevage

Le contrôle chromosomique des populations animales d’élevage a pour principal objectif d’éviter la mise à la reproduction d’individus porteurs d’anomalies chromosomiques, ces dernières étant généralement responsables d’une dégradation importante des performances de reproduction des individus porteurs ou de leurs conjoint(e)s. La quasi totalité des contrôles (2000/an environ pour l’ensemble des espèces) est réalisée, en France, au sein de l’Unité mixte de recherches INRA-ENVT de Cytogénétique des Populations Animales. Ils concernent principalement les espèces bovine et porcine. Chez les bovins, la recherche de translocation Robertsonienne 1/29 concerne 1000 individus par an environ, dont 90 % sont des jeunes taureaux candidats à l’insémination artificielle. La fréquence de l’anomalie est la plus élevée en race Blonde d’Aquitaine (10,9 %). L’application des techniques de coloration en bandes des chromosomes a permis de mettre en évidence quatre anomalies chromosomiques nouvelles dans cette espèce. Chez le porc, environ 650 contrôles sont effectués annuellement. 80 % sont réalisés avant la mise à la reproduction des animaux et concernent majoritairement les verrats de race pure utilisés dans les centres d’insémination artificielle. Deux systèmes complémentaires de détection des verrats hypoprolifiques complètent le dispositif de contrôle. Vingt-quatre anomalies chromosomiques nouvelles ont été diagnostiquées dans ce laboratoire pour l’espèce porcine, dont 10 au cours des trois dernières années.The main objective of the chromosomal control of domestic animal populations is to avoid the reproduction of individuals carrying chromosomal abnormalities. Indeed, these latter are generally responsible for an important decrease of reproductive abilities of carrier animals or of their mates. In France, almost all the analyses (2000/year) are carried out at the UMR INRA-ENVT de Cytogenetique des Populations Animales. They mainly concern the bovine and the porcine species. In bovines, 1000 individuals are controlled per year for the presence/absence of the 1/29 Robertsonian translocation. 90 % of them are young bull candidates for use in artificial insemination centers. The estimated frequency of the anomaly is the use of chromosome banding techniques allowed us to identify several new chromosomal abnormalities in this species. In pigs, 650 analyses are carried out each year. 80 % of them concern young animals controlled before reproduction (mainly young purebred boar candidates for use in artificial insemination centers). Two systems aimed at detecting the hypoprolific boars have been designed and are used to complement the population control programme. 24 new chromosomal abnormalities have been identified in our laboratory, including 10 during the last three years

Meiotic segregation analysis in cows carrying the t(1;29) Robertsonian translocation.

Heterozygous carriers of Robertsonian translocations generally have a normal phenotype but present reproductive failure. In cattle, the t(1;29) Robertsonian translocation is very common and carriers show a 3-5% decrease in fertility. Some data suggest that female carriers have a higher decrease than male carriers but no direct studies of the chromosome content of oocytes from a t(1;29) carrier cow have been performed so far. Four heterozygous carrier cows underwent hormonal stimulations and follicles punctions and about 800 oocytes were matured in vitro. Six hundred metaphase II preparations were obtained and analysed by fluorescent in situ hybridization with bovine chromosome 1 and 29 painting probes. Proportions of different kinds of oocytes were assessed: 74.11% (292/394) were normal and balanced, 4.06% (16/394) unbalanced and 21.83% (86/394) diploid. For all cows, the number of normal oocytes was not significantly different from the number of translocated oocytes but the diploidy and unbalanced rate were significantly different between them. As found in bulls, the meiotic segregation pattern in cows has shown a preponderance of alternate products. However, the frequency of unbalanced gametes determined in females (4.06%) was significantly higher than the frequency observed in males (2.76%). The divergence in the rate of diploid gametes (0.04% vs. 21.83%) is mainly explained by the difference between males and females

Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity

Broad T cell and B cell responses to multiple HCV antigens are observed early in individuals who control or clear HCV infection. The prevailing hypothesis has been that similar immune responses induced by prophylactic immunization would reduce acute virus replication and protect exposed individuals from chronic infection. Here, we demonstrate that immunization of naïve chimpanzees with a multicomponent HCV vaccine induced robust HCV-specific immune responses, and that all vaccinees exposed to heterologous chimpanzee-adapted HCV 1b J4 significantly reduced viral RNA in serum by 84%, and in liver by 99% as compared to controls (P=0.024 and 0.028, respectively). However, despite control of HCV in plasma and liver in the acute period, in the chronic phase, 3 of 4 vaccinated animals developed persistent infection. Analysis of expression levels of proinflammatory cytokines in serial hepatic biopsies failed to reveal an association with vaccine outcome. However, expression of IDO, CTLA-4 [corrected] and PD-1 levels in liver correlated with clearance or chronicity. CONCLUSION: Despite early control of virus load, a virus-associated tolerogenic-like state can develop in certain individuals independent of vaccination history