A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.National Natural Science Foundation of China [32022078]; National Key R&D Program of China [2022YFF1000900]; Local Innovative and Research Teams Project of Guangdong Province [2019BT02N630]; China Agriculture Research System [CARS-35]. Funding for open access charge: National Natural Science Foundation of China [32022078].Peer reviewe

Model Comparison of Heritability Enrichment Analysis in Livestock Population

Heritability enrichment analysis is an important means of exploring the genetic architecture of complex traits in human genetics. Heritability enrichment is typically defined as the proportion of an SNP subset explained heritability, divided by the proportion of SNPs. Heritability enrichment enables better study of underlying complex traits, such as functional variant/gene subsets, biological networks and metabolic pathways detected through integrating explosively increased omics data. This would be beneficial for genomic prediction of disease risk in humans and genetic values estimation of important economical traits in livestock and plant species. However, in livestock, factors affecting the heritability enrichment estimation of complex traits have not been examined. Previous studies on humans reported that the frequencies, effect sizes, and levels of linkage disequilibrium (LD) of underlying causal variants (CVs) would affect the heritability enrichment estimation. Therefore, the distribution of heritability across the genome should be fully considered to obtain the unbiased estimation of heritability enrichment. To explore the performance of different heritability enrichment models in livestock populations, we used the VanRaden, GCTA and &alpha; models, assuming different &alpha; values, and the LDAK model, considering LD weight. We simulated three types of phenotypes, with CVs from various minor allele frequency (MAF) ranges: genome-wide (0.005 &le; MAF &le; 0.5), common (0.05 &le; MAF &le; 0.5), and uncommon (0.01 &le; MAF &lt; 0.05). The performances of the models with two different subsets (one of which contained known CVs and the other consisting of randomly selected markers) were compared to verify the accuracy of heritability enrichment estimation of functional variant sets. Our results showed that models with known CV subsets provided more robust enrichment estimation. Models with different &alpha; values tended to provide stable and accurate estimates for common and genome-wide CVs (relative deviation 0.5&ndash;2.2%), while tending to underestimate the enrichment of uncommon CVs. As the &alpha; value increased, enrichments from 15.73% higher than true value (i.e., 3.00) to 48.93% lower than true value for uncommon CVs were observed. In addition, the long-range LD windows (e.g., 5000 kb) led to large bias of the enrichment estimations for both common and uncommon CVs. Overall, heritability enrichment estimations were sensitive for the &alpha; value assumption and LD weight consideration of different models. Accuracy would be greatly improved by using a suitable model. This study would be helpful in understanding the genetic architecture of complex traits and provides a reference for genetic analysis in the livestock population

Integration of non-additive genome-wide association study with a multi-tissue transcriptome analysis of growth and carcass traits in Duroc pigs

Growth and carcass traits are of economic importance in the pig production, which affect pork quality and profitability of finishing pig production. This study used whole-genome and transcriptome sequencing technologies to identify potential candidate genes affecting growth and carcass traits in Duroc pigs. The medium (50–60 k) single nucleotide polymorphism (SNP) arrays of 4 154 Duroc pigs from three populations were imputed to whole-genome sequence data, yielding 10 463 227 markers on 18 autosomes. The dominance heritabilities estimated for growth and carcass traits ranged from 0.000 ± 0.041 to 0.161 ± 0.054. Using non-additive genome-wide association study (GWAS), we identified 80 dominance quantitative trait loci for growth and carcass traits at genome-wide significance (false discovery rate < 5%), 15 of which were also detected in our additive GWAS. After fine mapping, 31 candidate genes for dominance GWAS were annotated, and 8 of them were highlighted that have been previously reported to be associated with growth and development (e.g. SNX14, RELN and ENPP2), autosomal recessive diseases (e.g. AMPH, SNX14, RELN and CACNB4) and immune response (e.g. UNC93B1 and PPM1D). By integrating the lead SNPs with RNA-seq data of 34 pig tissues from the Pig Genotype-Tissue Expression project (https://piggtex.farmgtex.org/), we found that the rs691128548, rs333063869, and rs1110730611 have significantly dominant effects for the expression of SNX14, AMPH and UNC93B1 genes in tissues related to growth and development for pig, respectively. Finally, the identified candidate genes were significantly enriched for biological processes involved in the cell and organ development, lipids catabolic process and phosphatidylinositol 3-kinase signalling (P < 0.05). These results provide new molecular markers for meat production and quality selection of pig as well as basis for deciphering the genetic mechanisms of growth and carcass traits

A compendium of genetic regulatory effects across pig tissues

Altres ajuts: Medical Research Council (MRC) MR/R025851/1 i MR/P015514/1. Biotechnology and Biological Sciences Research Council BBS/E/D/10002070 i BBS/E/D/30002275. United States Department of Agriculture 2019-67015-29321 i 2021-67015-33409. National Natural Science Foundation of China (National Science Foundation of China) 32022078.The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model. The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans

A compendium of genetic regulatory effects across pig tissues.

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model

Whole-genome sequencing of cultivated and wild peppers provides insights into <i>Capsicum</i> domestication and specialization

As an economic crop, pepper satisfies people’s spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded ∼0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of ∼81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs