Large-scale association study for structural soundness and leg locomotion traits in the pig

<p>Abstract</p> <p>Background</p> <p>Identification and culling of replacement gilts with poor skeletal conformation and feet and leg (FL) unsoundness is an approach used to reduce sow culling and mortality rates in breeding stock. Few candidate genes related to soundness traits have been identified in the pig.</p> <p>Methods</p> <p>In this study, 2066 commercial females were scored for 17 traits describing body conformation and FL structure, and were used for association analyses. Genotyping of 121 SNPs derived from 95 genes was implemented using Sequenom's MassARRAY system.</p> <p>Results</p> <p>Based on the association results from single trait and principal components using mixed linear model analyses and false discovery rate testing, it was observed that <it>APOE, BMP8, CALCR, COL1A2, COL9A1, DKFZ, FBN1 </it>and <it>VDBP </it>were very highly significantly (P < 0.001) associated with body conformation traits. The genes <it>ALOX5, BMP8</it>, <it>CALCR, OPG</it>, <it>OXTR </it>and <it>WNT16 </it>were very highly significantly (P < 0.001) associated with FL structures, and <it>APOE, CALCR, COL1A2, GNRHR, IHH</it>, <it>MTHFR </it>and <it>WNT16 </it>were highly significantly (P < 0.01) associated with overall leg action. Strong linkage disequilibrium between <it>CALCR </it>and <it>COL1A2 </it>on SSC9 was detected, and haplotype -ACGACC- was highly significantly (P < 0.01) associated with overall leg action and several important FL soundness traits.</p> <p>Conclusion</p> <p>The present findings provide a comprehensive list of candidate genes for further use in fine mapping and biological functional analyses.</p

Genome-Wide Association Study Identifies Loci for Body Composition and Structural Soundness Traits in Pigs

Background The recent completion of the swine genome sequencing project and development of a high density porcine SNP array has made genome-wide association (GWA) studies feasible in pigs. Methodology/Principal Findings Using Illumina\u27s PorcineSNP60 BeadChip, we performed a pilot GWA study in 820 commercial female pigs phenotyped for backfat, loin muscle area, body conformation in addition to feet and leg (FL) structural soundness traits. A total of 51,385 SNPs were jointly fitted using Bayesian techniques as random effects in a mixture model that assumed a known large proportion (99.5%) of SNPs had zero effect. SNP annotations were implemented through the Sus scrofa Build 9 available from pig Ensembl. We discovered a number of candidate chromosomal regions, and some of them corresponded to QTL regions previously reported. We not only have identified some well-known candidate genes for the traits of interest, such as MC4R (for backfat) and IGF2 (for loin muscle area), but also obtained novel promising genes, including CHCHD3 (for backfat), BMP2 (for loin muscle area, body size and several FL structure traits), and some HOXA family genes (for overall leg action). The candidate regions responsible for body conformation and FL structure soundness did not overlap greatly which implied that these traits were controlled by different genes. Functional clustering analyses classified the genes into categories related to bone and cartilage development, muscle growth and development or the insulin pathway suggesting the traits are regulated by common pathways or gene networks that exert roles at different spatial and temporal stages. Conclusions/Significance This study is one of the earliest GWA reports on important quantitative traits in pigs, and the findings will contribute to the further biological function analysis of the identified candidate genes and potential utilization of them in marker assisted selection

Whole-genome association analyses for lifetime reproductive traits in the pig

Profits for commercial pork producers vary in part because of sow productivity or sow productive life (SPL) and replacement costs. During the last decade, culling rates of sows have increased to more than 50% in the United States. Both SPL and culling rates are influenced by genetic and nongenetic factors. A whole-genome association study was conducted for pig lifetime reproductive traits, including lifetime total number born (LTNB), lifetime number born alive (LNBA), removal parity, and the ratio between lifetime nonproductive days and herd life. The proportion of phenotypic variance explained by markers was 0.15 for LTNB and LNBA, 0.12 for removal parity, and 0.06 for the ratio between lifetime nonproductive days and herd life. Several informative QTL regions (e.g., 14 QTL regions for LTNB) and genes within the regions (e.g., SLC22A18 on SSC2 for LTNB) were associated with lifetime reproductive traits in this study. Genes associated with LTNB and LNBA were similar, reflecting the high genetic correlation (0.99 ± 0.003) between these traits. Functional annotation revealed that many genes at the associated regions are expressed in reproductive tissues. For instance, the SLC22A18 gene on SSC2 associated with LTNB has been shown to be expressed in the placenta of mice. Many of the QTL regions showing associations coincided with previously identified QTL for fat deposition. This reinforces the role of fat regulation for lifetime reproductive traits. Overall, this whole-genome association study provides a list of genomic locations and markers associated with pig lifetime reproductive traits that could be considered for SPL in future studies

Analyses of pig genomes provide insight into porcine demography and evolution

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model

Data from: A missense mutation in AGTPBP1 was identified in sheep with a lower motor neuron disease

A type of lower motor neuron (LMN) disease inherited as autosomal recessive in Romney sheep was characterized with normal appearance at birth, but with progressive weakness and tetraparesis after the first week of life. Here, we carried out genome-wide homozygosity mapping using Illumina Ovine SNP50 BeadChips on lambs descended from one carrier ram, including 19 sheep diagnosed as affected and 11 of their parents that were therefore known carriers. A homozygous region of 136 consecutive single-nucleotide polymorphism (SNP) loci on chromosome 2 was common to all affected sheep and it was the basis for searching for the positional candidate genes. Other homozygous regions shared by all affected sheep spanned eight or fewer SNP loci. The 136-SNP region contained the sheep ATP/GTP-binding protein 1 (AGTPBP1) gene. Mutations in this gene have been shown to be related to Purkinje cell degeneration (pcd) phenotypes including ataxia in mice. One missense mutation c.2909G>C on exon 21 of AGTPBP1 was discovered, which induces an Arg to Pro substitution (p.Arg970Pro) at amino-acid 970, a conserved residue for the catalytic activity of AGTPBP1. Genotyping of this mutation showed 100% concordant rate with the recessive pattern of inheritance in affected, carrier, phenotypically normal and unrelated normal individuals. This is the first report showing a mutant AGTPBP1 is associated with a LMN disease in a large mammal animal model. Our finding raises the possibility of human patients with the same etiology caused by this gene or other genes in the same pathway of neuronal development

Whole Genome Association Studies of Residual Feed Intake and Related Traits in the Pig

<div><p>Background</p><p>Residual feed intake (RFI), a measure of feed efficiency, is the difference between observed feed intake and the expected feed requirement predicted from growth and maintenance. Pigs with low RFI have reduced feed costs without compromising their growth. Identification of genes or genetic markers associated with RFI will be useful for marker-assisted selection at an early age of animals with improved feed efficiency.</p><p>Methodology/Principal findings</p><p>Whole genome association studies (WGAS) for RFI, average daily feed intake (ADFI), average daily gain (ADG), back fat (BF) and loin muscle area (LMA) were performed on 1,400 pigs from the divergently selected ISU-RFI lines, using the Illumina PorcineSNP60 BeadChip. Various statistical methods were applied to find SNPs and genomic regions associated with the traits, including a Bayesian approach using GenSel software, and frequentist approaches such as allele frequency differences between lines, single SNP and haplotype analyses using PLINK software. Single SNP and haplotype analyses showed no significant associations (except for LMA) after genomic control and FDR. Bayesian analyses found at least 2 associations for each trait at a false positive probability of 0.5. At generation 8, the RFI selection lines mainly differed in allele frequencies for SNPs near (<0.05 Mb) genes that regulate insulin release and leptin functions. The Bayesian approach identified associations of genomic regions containing insulin release genes (e.g., <i>GLP1R, CDKAL, SGMS1</i>) with RFI and ADFI, of regions with energy homeostasis (e.g., <i>MC4R</i>, <i>PGM1</i>, <i>GPR81</i>) and muscle growth related genes (e.g., <i>TGFB1</i>) with ADG, and of fat metabolism genes (e.g., <i>ACOXL</i>, <i>AEBP1</i>) with BF. Specifically, a very highly significantly associated QTL for LMA on SSC7 with skeletal myogenesis genes (e.g., <i>KLHL31</i>) was identified for subsequent fine mapping.</p><p>Conclusions/significance</p><p>Important genomic regions associated with RFI related traits were identified for future validation studies prior to their incorporation in marker-assisted selection programs.</p></div

LMNSNPdata

This data achieve including all the genotypes for each SNP for each animal. The files were created from the original genotyping file using "awk" or "sort" commands

Whole genome association studies for residual feed intake (RFI).

<p><b>Part A</b> depicts association analyses performed by the PLINK software for each SNP. The X axis shows SNPs across chromosomes 1 to X, unassigned contigs, Y and completely unmapped SNP. The Y axis represents the negative logarithm of the P-values corrected for genomic control. Each spot is a SNP. The green color SNPs are those located in 1 Mb window regions that explain more than 0.2% of genetic variance in part B. <b>Part B</b> illustrates results from the Bayes B model averaging approach used in the GenSel software. Different colors on the X axis indicate genome wide 1 Mb SNP windows from chromosome 1 to X, unassigned contigs, Y and completely unmapped SNP. The markers from completely unmapped and unassigned contigs were not included in the cumulative genetic variance. The Y axis represents percent genetic variance explained by each 1 Mb window. <b>Part C</b> shows association analyses with the PLINK software based on haplotypes, which were derived for 1 Mb windows that explained a higher than 0.2% of genetic variance in part B. The X axis shows chromosomal positions of the haplotypes. The Y axis shows the negative logarithm of the P-values corrected by genomic control. The arrows in parts A, B and C show the similarities in the significant locations. The 1 Mb windows that explained a higher than 0.2% percent of genetic variance in the Bayesian analyses and/or were significant in the PLINK analyses were considered to be important putative QTL for RFI. <i>GNG4</i>: guanine nucleotide binding protein 4; <i>GLP1R</i>: glucagon-like peptide 1 receptor; <i>CDKAL1:</i> cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1.</p

Population sampled.

<p>The animals in blue boxes were phenotyped and genotyped and included in the analyses. G: Generation; P: Parity. Please refer to references <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061756#pone.0061756-Cai1" target="_blank">[2]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061756#pone.0061756-Young1" target="_blank">[10]</a> for the population structure, which defines generation and parity.</p

Allele frequency differences between the Low and High residual feed intake lines at generation 8.

<p>The X axis indicates in different colors from left to right, SNP locations from chromosomes 1 to X, unassigned contigs, Y, and completely unmapped SNPs, using <i>Sus scrofa</i> genome build10.2. The Y axis represents the minus log of the P-value for the allele frequency difference between the two lines for each SNP,. The dashed line shows the P-value threshold. SSC: Pig chromosome; FDR: False discovery rate; <i>KCNJ15:</i> Potassium inwardly rectifying channel, subfamily J, member 15; <i>ELOVL2</i>: Elongation of very long chain fatty acids 2; <i>TFAP2A</i>: Transcription factor AP-2 (Activating enhancer binding protein 2)—alpha; <i>GPX2</i>: Glutathione peroxidase 2.</p