Biology subjects

Quintanilla, R.

Publications and source records attributed to Quintanilla, R..

9 recordsLinked to original sources

bioRxiv2026

Ruminosignatures associated with methane emissions and feed efficiency across geographies and cattle breeds

The cattle rumen microbiota represents a highly complex and dynamic ecosystem, whose organization and connection to host phenotypes are of the highest importance to food security and the environment. In this study, we analyzed the rumen microbiota, from 2,492 cattle belonging to five different breeds and production systems across five countries, categorizing them into microbial co-abundance groups referred to as Ruminosignatures. We identified twelve distinct Ruminosignatures, including two that were consistently observed across all populations and were dominated by the genus Prevotella and UBA2810. Additional Ruminosignatures showed breed-and diet-specific patterns and collectively explained 96-99% of the variance in rumen microbial composition. The abundances of several Ruminosignatures were associated with methane emissions and feed efficiency, and were influenced by host genetics, with heritability estimates ranging from 0.09 to 0.51. The Ruminosignature dominated by UAB2810 was negatively associated with methane emissions across all datasets and positively linked to feed efficiency in Holstein from Italy and crossbred from Ireland. Additionally, the type of production system affects both the occurrence of Ruminosignatures and their impact on host phenotypes, emphasizing the need for context-specific approaches to modulate the rumen microbiome. Overall, our results offer new perspectives on the assembly of ruminal microbes and underscore the potential of the Ruminosignatures framework for microbiome-informed precision agriculture and breeding initiatives aimed at enhancing feed efficiency and minimizing the environmental impact of cattle farming.

microbiology↗

bioRxiv2022

A compendium of genetic regulatory effects across pig tissues

The Farm animal Genotype-Tissue Expression (FarmGTEx, https://www.farmgtex.org/) project has been established to develop a comprehensive public resource of genetic regulatory variants in domestic animal species, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biology discovery and exploitation in animal breeding and human biomedicine. Here we present results from the pilot phase of PigGTEx (http://piggtex.farmgtex.org/), where we processed 9,530 RNA-sequencing and 1,602 whole-genome sequencing samples from pigs. We build a pig genotype imputation panel, characterize the transcriptional landscape across over 100 tissues, and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We study interactions between genotype and breed/cell type, evaluate tissue specificity of regulatory effects, and elucidate the molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying about 80% of the genetic associations for 207 pig complex phenotypes, and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, corroborating the importance of pigs as a human biomedical model.

genomics↗

bioRxiv2022

Copy number variation on ABCC2-DNMBP loci impacts the diversity and composition of the gut microbiota in pigs

BackgroundGenetic variation in the pig genome partially modulates the composition of porcine gut microbial communities. Previous studies have been focused on the association between single nucleotide polymorphisms (SNPs) and the gut microbiota, but little is known about the relationship between structural variants and gut microbial traits. ResultsThe main goal of this study was to assess the effect of porcine genome copy number variants (CNVs) on the diversity and composition of pig gut microbiota. For this purpose, we used whole-genome sequencing data to undertake a comprehensive identification of CNVs followed by a genome-wide association analysis between the estimated CNV status and the gut bacterial diversity in a commercial Duroc pig population. A CNV predicted as gain (DUP) partially harboring ABCC2-DNMBP loci was associated with richness (p-value=5.41x10-5) and Shannon -diversity (p-value=1.42x10-4). The in-silico predicted gain of copies was validated by real-time quantitative PCR (qPCR), and its segregation, and positive association with the richness and Shannon -diversity of the porcine gut bacterial ecosystem was confirmed in an unrelated F1 (DurocxIberian) cross. Furthermore, despite genetic and environmental differences between both populations, the gut microbiota of DUP samples showed a significant over-abundance of the Desulfovibrio, Blautia, Phascolarctobacterium, Faecalibacterium, Succinivibrio and Anaerovibrio genera. ConclusionsIn summary, this is the first study that evaluate the putative modulatory role of CNVs on pig gut microbiota. Our results advice the relevance of considering the role of host-genome structural variants as modulators of microbial ecosystems, and suggest the ABCC2-DNMBP CNV as a host-genetic factor for the modulation of the diversity and composition of the gut microbiota in pigs.

microbiology↗

bioRxiv2022

Discovering genomic regions associated with the phenotypic differentiation of European local pig breeds

BackgroundIntensive selection of modern pig breeds resulted in genetic improvement of productive traits while local pig breeds remained less performant. As they have been bred in extensive systems, they have adapted to specifical environmental conditions resulting in a rich genotypic and phenotypic diversity. This study is based on European local pig breeds genetically characterized using DNA-pool sequencing data and phenotypically characterized using breed level phenotypes related to stature, fatness, growth and reproductive performance traits. These data were analyzed using a dedicated approach to detect selection signatures linked to phenotypic traits in order to uncover potential candidate genes that may be under adaptation to specific environments. ResultsGenetic data analysis of European pig breeds revealed four main axes of genetic variation represented by Iberian and modern breeds (i.e. Large White, Landrace, and Duroc). In addition, breeds clustered according to their geographical origin, for example French Gascon and Basque breeds, Italian Apulo Calabrese and Casertana breeds, Spanish Iberian and Portuguese Alentejano breeds. Principal component analysis of phenotypic data distinguished between larger and leaner breeds with better growth potential and reproductive performance on one hand and breeds that were smaller, fatter, and had low growth and reproductive efficiency on the other hand. Linking selection signatures with phenotype identified 16 significant genomic regions associated with stature, 24 with fatness, 2 with growth and 192 with reproduction. Among them, several regions contained candidate genes with possible biological effect on stature, fatness, growth and reproduction performance traits. For example, strong associations were found for stature in two regions containing the ANXA4 and ANTXR1 genes, for fatness containing the DNMT3A and POMC genes and for reproductive performance containing the HSD17B7 gene. ConclusionsThe present study on European local pig breeds used a dedicated approach for searching selection signatures supported by phenotypic data at the breed level to identify potential candidate genes that may have adapted to different living environments and production systems. Results can be useful to define conservation programs of local pig breeds.

genetics↗

bioRxiv2021

An exon-intron split framework to prioritize transcriptional and post-transcriptional regulatory signals and its application to study energy homeostasis in pigs

The contribution of microRNAs (miRNAs) to mRNA regulation has often been explored by post hoc selection of downregulated genes and determining whether they harbor binding sites for miRNAs of interest. This approach, however, does not discriminate whether these mRNAs are also downregulated at the transcriptional level. Here, we have characterized the transcriptional and post-transcriptional changes of mRNA expression in two porcine tissues: gluteus medius muscle of fasted and fed Duroc gilts and adipose tissue of lean and obese Duroc-Gottingen minipigs. Exon-intron split analysis (EISA) of RNA-seq data allowed us to identify downregulated mRNAs with high post-transcriptional signals in fed or obese states, and we assessed whether they harbor binding sites for upregulated miRNAs in any of these two physiological states. We found 26 downregulated mRNAs with high post-transcriptional signals in the muscle of fed gilts and 21 of these were predicted targets of upregulated miRNAs also in the fed state. For adipose tissue, 44 downregulated mRNAs in obese minipigs displayed high post-transcriptional signals, and 25 of these were predicted targets of miRNAs upregulated in the obese state. These results suggest that the contribution of miRNAs to mRNA repression is more prominent in the skeletal muscle system. Finally, we identified several genes that may play relevant roles in the energy homeostasis of the pig skeletal muscle (DKK2 and PDK4) and adipose (SESN3 and ESRRG) tissues. By differentiating transcriptional from post-transcriptional changes in mRNA expression, EISA provides a valuable view about the regulation of gene expression, complementary to canonical differential expression analyses.

genomics↗

bioRxiv2021

Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs

The aim of the present work was to identify microbial biomarkers linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs. To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h2; proportion of phenotypic variance explained by the host genetics) and microbiability (m2; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that were dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m2 (0.275) compared to h2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r=0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r=-0.34) and between Megasphaera and serum concentration of haptoglobin (r=0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively. Overall, our findings reveal an important connection between immunity traits and gut microbiota in pigs and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs.

microbiology↗

bioRxiv2020

Variability in porcine microRNA genes and its association with mRNA expression phenotypes

BackgroundMature microRNAs (miRNAs) play an important role in repressing the expression of a wide range of mRNAs. The variability of miRNA genes and their corresponding 3UTR binding sites might disrupt canonical conserved miRNA-mRNA pairing, thus modifying gene expression patterns. The presence of polymorphic sites in miRNA genes and their association with gene expression phenotypes and complex traits has been poorly characterized in pigs so far. ResultsBy analyzing whole-genome sequences from 120 pigs and wild boars from Europe and Asia, we have identified 285 single nucleotide polymorphisms (SNPs) mapping to miRNA loci, as well as 109,724 SNPs located in predicted 7mer-m8 miRNA binding sites within porcine 3UTRs. Porcine miRNA genes show a reduced SNP density compared with their flanking non-miRNA regions. By sequencing the genomes of 5 Duroc boars, we have identified 12 miRNA SNPs that have been subsequently genotyped in their offspring (N = 345, Lipgen population). Association analyses between miRNA SNPs and 38 lipid-related traits as well as hepatic and muscle microarray expression phenotypes recorded in the Lipgen population were carried out. The most relevant association detected was the one between the genotype of the rs319154814 (G/A) SNP located in the apical loop of the ssc-miR-326 hairpin precursor and PPP1CC mRNA levels in the liver (q-value = 0.058). This result was subsequently confirmed by qPCR (P-value = 0.027). The rs319154814 (G/A) genotype was also associated with several fatty acid composition traits. ConclusionsPorcine miRNA genes show a reduced variability consistent with strong purifying selection, particularly in the seed region, which plays a critical role in miRNA binding. Although it is generally assumed that SNPs mapping to the seed region are the ones with the strongest consequences on mRNA expression, we show that a SNP mapping to the apical region of ssc-miR-326 is significantly associated with the hepatic mRNA levels of the PPP1CC gene, one of its predicted targets. Although experimental confirmation of such interaction has been obtained in humans but not in pigs, this result highlights the need of further investigating the functional effects of miRNA polymorphisms located outside the seed region on gene expression in pigs.

genomics↗

bioRxiv2020

Gut eukaryotic communities in pigs: diversity, composition and host genetics contribution

This study aims to characterize commensal fungi and protists inhabiting the gut of healthy pigs, and explore the putative host genetic control over diversity and composition of pig gut eukaryotes. Fecal fungi and protists communities from 514 Duroc pigs of two sexes and two different ages were characterized by 18S and ITS ribosomal RNA gene sequencing. The gut mycobiota was dominated by yeasts, with a high prevalence of Kazachstania spp. Regarding protists, representatives of four genera (Blastocystis, Neobalantidium, Tetratrichomonas and Trichomitus) persisted through more than the 80% of the pigs. Heritabilities for the diversity and abundance of gut eukaryotic communities were estimated with the subset of 60 days aged piglets (N=405). Obtained heritabilities ranged from 0.15 to 0.28, indicating a rather limited host-genetic control. A genome wide association study reported genetic variants associated with the fungal -diversity (SSC6) and with the abundance of Blastocystis spp. (SSC6, SSC17 and SSC18). Annotated candidate genes (IL23R, IL12RB2, PIK3C3, PIK3CD, HNF4A and TNFRSF9) were mainly related to immunity, gut homeostasis and metabolic processes. Our results point towards a minor and taxa specific genetic control over the diversity and composition of the pig gut eukaryotic communities.

genomics↗

bioRxiv2017

Investigating The Genetic Regulation Of The Expression Of 63 Lipid Metabolism Genes In The Pig Skeletal Muscle

Despite their potential involvement in the determination of fatness phenotypes, a comprehensive and systematic view about the genetic regulation of lipid metabolism genes is still lacking in pigs. Herewith, we have used a dataset of 104 pigs, with available genotypes for 62,163 single nucleotide polymorphisms and microarray gene expression measurements in the gluteus medius muscle, to investigate the genetic regulation of 63 genes with crucial roles in the uptake, transport, synthesis and catabolism of lipids. By performing an eQTL scan with the GEMMA software, we have detected 12 cis- and 18 trans-eQTL modulating the expression of 19 loci. Genes regulated by eQTL had a variety of functions such as the {beta}-oxidation of fatty acids, lipid biosynthesis and lipolysis, fatty acid activation and desaturation, lipoprotein uptake, apolipoprotein assembly and cholesterol trafficking. These data provide a first picture about the genetic regulation of loci involved in porcine lipid metabolism.

genomics↗