Genetic analysis of fertility in the Italian Brown Swiss population using different models and trait definitions

AbstractThe aim of this study was to estimate genetic parameters for fertility and production traits in the Brown Swiss population reared in the Alps (Bolzano-Bozen province, Italy). Fertility indicators were interval from parturition to first service, interval from first service to conception (iFC), and interval from parturition to conception, either expressed as days and as number of potential 21-d estrus cycles (cPF, cFC, and cPC, respectively); number of inseminations to conception; conception rate at first service; and non-return rate at 56 d post-first service. Production traits were peak milk yield, lactation milk yield, lactation length, average lactation protein percentage, and average lactation fat percentage. Data included 71,556 lactations (parities 1 to 9) from 29,582 cows reared in 1,835 herds. Animals calved from 1999 to 2007 and were progeny of 491 artificial insemination bulls. Gibbs sampling and Metropolis algorithms were implemented to obtain (co)variance components using both univariate and bivariate censored threshold and linear sire models. All of the analyses accounted for parity and year-month of calving as fixed effects, and herd, permanent environmental cow, additive genetic sire, and residual as random effects. Heritability estimates for fertility traits ranged from 0.030 (iFC) to 0.071 (cPC). Strong genetic correlations were estimated between interval from parturition to first service and cPF (0.97), and interval from parturition to conception and cPC (0.96). The estimate of heritability for cFC (0.055) was approximately double compared with iFC (0.030), suggesting that measuring the elapsed time between first service and conception in days or potential cycles is not equivalent; this was also confirmed by the genetic correlation between iFC and cFC, which was strong (0.85), but more distant from unity than the other 2 pairs of fertility traits. Genetic correlations between number of inseminations to conception, conception rate at first service, non-return rate at 56 d post-first service, cPF, cFC, and cPC ranged from 0.07 to 0.82 as absolute value. Fertility was unfavorably correlated with production; estimates ranged from −0.26 (cPC with protein percentage) to 0.76 (cPC with lactation length), confirming the genetic antagonism between reproductive efficiency and milk production. Although heritability for fertility is low, the contemporary inclusion of several reproductive traits in a merit index would help to improve performance of dairy cows

Invited review:Novel methods and perspectives for modulating the rumen microbiome through selective breeding as a means to improve complex traits: Implications for methane emissions in cattle

The rumen microbiome is responsible for methane emission in ruminants. The study of microbes in the rumen has attracted great interest in the last decade. High-throughput sequencing technologies have been key in expanding the knowledge of the microorganisms that populate the rumen through metagenomic studies. There is substantial evidence that the composition of the rumen microbiota is influenced by host genotype. Therefore, modulation of the microbiota poses an important tool for breeding for lower emissions in large and small ruminants. The main challenges of metagenomic studies are addressed and some solutions are proposed when available, including the incorporation of metagenomic information into statistical models regularly used in animal breeding. To incorporate microbiome information into breeding programs, the particularities of the rumen microbiome must be considered, from sampling to inclusion in selection indices. The latest advances in this area are discussed in this review.Universidad de Costa RicaUCR::Vicerrectoría de Docencia::Ciencias Agroalimentarias::Facultad de Ciencias Agroalimentarias::Escuela de ZootecniaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Centro de Investigación en Nutrición Animal (CINA

Estimates of marker effects for measures of milk flow in the Italian brown Swiss dairy cattle population

Background: Milkability is a complex trait that is characterized by milk flow traits including average milk flow rate, maximum milk flow rate and total milking time. Milkability has long been recognized as an economically important trait that can be improved through selection. By improving milkability, management costs of milking decrease through reduced labor and improved efficiency of the automatic milking system, which has been identified as an important factor affecting net profit. The objective of this study was to identify markers associated with electronically measured milk flow traits, in the Italian Brown Swiss population that could potentially improve selection based on genomic predictions.Results: Sires (n = 1351) of cows with milk flow information were genotyped for 33,074 single nucleotide polymorphism (SNP) markers distributed across 29 Bos taurus autosomes (BTA). Among the six milk flow traits collected, ascending time, time of plateau, descending time, total milking time, maximum milk flow and average milk flow, there were 6,929 (time of plateau) to 14,585 (maximum milk flow) significant SNP markers identified for each trait across all BTA. Unique regions were found for each of the 6 traits providing evidence that each individual milk flow trait offers distinct genetic information about milk flow. This study was also successful in identifying functional processes and genes associated with SNPs that influences milk flow.Conclusions: In addition to verifying the presence of previously identified milking speed quantitative trait loci (QTL) within the Italian Brown Swiss population, this study revealed a number of genomic regions associated with milk flow traits that have never been reported as milking speed QTL. While several of these regions were not associated with a known gene or QTL, a number of regions were associated with QTL that have been formerly reported as regions associated with somatic cell count, somatic cell score and udder morphometrics. This provides further evidence of the complexity of milk flow traits and the underlying relationship it has with other economically important traits for dairy cattle. Improved understanding of the overall milking pattern will aid in identification of cows with lower management costs and improved udder health

Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation

Background: Spinocerebellar ataxia type 28 (SCA28) is a dominantly inherited neurodegenerative disease caused by pathogenic variants in AFG3L2. The AFG3L2 protein is a subunit of mitochondrial m-AAA complexes involved in protein quality control. Objective of this study was to determine the molecular mechanisms of SCA28, which has eluded characterisation to date. Methods: We derived SCA28 patient fibroblasts carrying different pathogenic variants in the AFG3L2 proteolytic domain (missense: the newly identified p.F664S and p.M666T, p.G671R, p.Y689H and a truncating frameshift p.L556fs) and analysed multiple aspects of mitochondrial physiology. As reference of residual m-AAA activity, we included SPAX5 patient fibroblasts with homozygous p.Y616C pathogenic variant, AFG3L2 +/\ue2 ' HEK293 T cells by CRISPR/Cas9-genome editing and Afg3l2 \ue2 '/\ue2 ' murine fibroblasts. Results: We found that SCA28 cells carrying missense changes have normal levels of assembled m-AAA complexes, while the cells with a truncating pathogenic variant had only half of this amount. We disclosed inefficient mitochondrial fusion in SCA28 cells caused by increased OPA1 processing operated by hyperactivated OMA1. Notably, we found altered mitochondrial proteostasis to be the trigger of OMA1 activation in SCA28 cells, with pharmacological attenuation of mitochondrial protein synthesis resulting in stabilised levels of OMA1 and OPA1 long forms, which rescued mitochondrial fusion efficiency. Secondary to altered mitochondrial morphology, mitochondrial calcium uptake resulted decreased in SCA28 cells. Conclusion: Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2 +/- cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants

Identification and validation of copy number variants in Italian Brown Swiss dairy cattle using Illumina Bovine SNP50 Beadchip®

The determination of copy number variation (CNV) is very important for the evaluation of genomic traits in several species because they are a major source for the genetic variation, influencing gene expression, phenotypic variation, adaptation and the development of diseases. The aim of this study was to obtain a CNV genome map using the Illumina Bovine SNP50 BeadChip data of 651 bulls of the Italian Brown Swiss breed. PennCNV and SVS7 (Golden Helix) software were used for the detection of the CNVs and Copy Number Variation Regions (CNVRs). A total of 5,099 and 1,289 CNVs were identified with PennCNV and SVS7 software, respectively. These were grouped at the population level into 1101 (220 losses, 774 gains, 107 complex) and 277 (185 losses, 56 gains and 36 complex) CNVR. Ten of the selected CNVR were experimentally validated with a qPCR experiment. The GO and pathway analyses were conducted and they identified genes (false discovery rate corrected) in the CNVR related to biological processes cellular component, molecular function and metabolic pathways. Among those, we found the FCGR2B, PPAR\u3b1, KATNAL1, DNAJC15, PTK2, TG, STAT family, NPM1, GATA2, LMF1, ECHS1 genes, already known in literature because of their association with various traits in cattle. Although there is variability in the CNVRs detection across methods and platforms, this study allowed the identification of CNVRs in Italian Brown Swiss, overlapping those already detected in other breeds and finding additional ones, thus producing new knowledge for association studies with traits of interest in cattle