A method for the allocation of sequencing resources in genotyped livestock populations

International audienceAbstractBackgroundThis paper describes a method, called AlphaSeqOpt, for the allocation of sequencing resources in livestock populations with existing phased genomic data to maximise the ability to phase and impute sequenced haplotypes into the whole population.MethodsWe present two algorithms. The first selects focal individuals that collectively represent the maximum possible portion of the haplotype diversity in the population. The second allocates a fixed sequencing budget among the families of focal individuals to enable phasing of their haplotypes at the sequence level. We tested the performance of the two algorithms in simulated pedigrees. For each pedigree, we evaluated the proportion of population haplotypes that are carried by the focal individuals and compared our results to a variant of the widely-used key ancestors approach and to two haplotype-based approaches. We calculated the expected phasing accuracy of the haplotypes of a focal individual at the sequence level given the proportion of the fixed sequencing budget allocated to its family.ResultsAlphaSeqOpt maximises the ability to capture and phase the most frequent haplotypes in a population in three ways. First, it selects focal individuals that collectively represent a larger portion of the population haplotype diversity than existing methods. Second, it selects focal individuals from across the pedigree whose haplotypes can be easily phased using family-based phasing and imputation algorithms, thus maximises the ability to impute sequence into the rest of the population. Third, it allocates more of the fixed sequencing budget to focal individuals whose haplotypes are more frequent in the population than to focal individuals whose haplotypes are less frequent. Unlike existing methods, we additionally present an algorithm to allocate part of the sequencing budget to the families (i.e. immediate ancestors) of focal individuals to ensure that their haplotypes can be phased at the sequence level, which is essential for enabling and maximising subsequent sequence imputation.ConclusionsWe present a new method for the allocation of a fixed sequencing budget to focal individuals and their families such that the final sequenced haplotypes, when phased at the sequence level, represent the maximum possible portion of the haplotype diversity in the population that can be sequenced and phased at that budget

The potential of shifting recombination hotspots to increase genetic gain in livestock breeding

International audienceAbstractBackgroundThis study uses simulation to explore and quantify the potential effect of shifting recombination hotspots on genetic gain in livestock breeding programs.MethodsWe simulated three scenarios that differed in the locations of quantitative trait nucleotides (QTN) and recombination hotspots in the genome. In scenario 1, QTN were randomly distributed along the chromosomes and recombination was restricted to occur within specific genomic regions (i.e. recombination hotspots). In the other two scenarios, both QTN and recombination hotspots were located in specific regions, but differed in whether the QTN occurred outside of (scenario 2) or inside (scenario 3) recombination hotspots. We split each chromosome into 250, 500 or 1000 regions per chromosome of which 10% were recombination hotspots and/or contained QTN. The breeding program was run for 21 generations of selection, after which recombination hotspot regions were kept the same or were shifted to adjacent regions for a further 80 generations of selection. We evaluated the effect of shifting recombination hotspots on genetic gain, genetic variance and genic variance.ResultsOur results show that shifting recombination hotspots reduced the decline of genetic and genic variance by releasing standing allelic variation in the form of new allele combinations. This in turn resulted in larger increases in genetic gain. However, the benefit of shifting recombination hotspots for increased genetic gain was only observed when QTN were initially outside recombination hotspots. If QTN were initially inside recombination hotspots then shifting them decreased genetic gain.DiscussionShifting recombination hotspots to regions of the genome where recombination had not occurred for 21 generations of selection (i.e. recombination deserts) released more of the standing allelic variation available in each generation and thus increased genetic gain. However, whether and how much increase in genetic gain was achieved by shifting recombination hotspots depended on the distribution of QTN in the genome, the number of recombination hotspots and whether QTN were initially inside or outside recombination hotspots.ConclusionsOur findings show future scope for targeted modification of recombination hotspots e.g. through changes in zinc-finger motifs of the PRDM9 protein to increase genetic gain in production species

Evaluation of bull fertility in Italian Brown Swiss dairy cattle using cow field data

Dairy bull fertility is traditionally evaluated using semen production and quality traits; however, these attributes explain only part of the differences observed in fertility among bulls. Alternatively, bull fertility can be directly evaluated using cow field data. The main objective of this study was to investigate bull fertility in the Italian Brown Swiss dairy cattle population using confirmed pregnancy records. The data set included a total of 397,926 breeding records from 1,228 bulls and 129,858 lactating cows between first and fifth lactation from 2000 to 2019. We first evaluated cow pregnancy success, including factors related to the bull under evaluation, such as bull age, bull inbreeding, and AI organization, and factors associated with the cow that receives the dose of semen, including herd-year-season, cow age, parity, and milk yield. We then estimated sire conception rate using only factors related to the bull. Model predictive ability was evaluated using 10-fold cross-validation with 10 replicates. Interestingly, our analyses revealed that there is a substantial variation in conception rate among Brown Swiss bulls, with more than 20% conception rate difference between high fertility and low-fertility bulls. We also showed that the prediction of bull fertility is feasible as our cross -validation analyses achieved predictive correlations equal to 0.30 for sire conception rate. Improving reproduction performance is one of the major challenges of the dairy industry worldwide, and for this, it is essential to have accurate predictions of service sire fertility. This study represents the foundation for the development of novel tools that will allow dairy producers, breeders, and artificial insemination companies to make enhanced management and selection decisions on Brown Swiss male fertility

Sustained virological response after treatment with direct-acting antivirals can help immune reconstitution in HIV-HCV coinfected patients even in case of persistent HIV low-level viremia

none9nononeBasso M.; Zago D.; Pozzetto I.; Battagin G.; Carlotto A.; Rossi M.C.; Panese S.; Sarmati L.; Parisi S.G.Basso, M.; Zago, D.; Pozzetto, I.; Battagin, G.; Carlotto, A.; Rossi, M. C.; Panese, S.; Sarmati, L.; Parisi, S. G