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A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants.

ABSTRACT: BACKGROUND: The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days). RESULTS: Analysis of data with mixed-model methods (EMMAX, GEMMA, GenABEL) and PLINK showed a low positional concordance between trait-associated regions (TARs) for serum lipids at 45 and 190 days. Besides, the proportion of phenotypic variance explained by SNPs at these two time points was also substantially different. The four analyses consistently detected two regions on SSC3 (124 Mb, CHOL and LDL at 190 days) and SSC6 (135 Mb, CHOL and TRIG at 190 days) with highly significant effects on the porcine blood lipid profile. Moreover, we have found that SNP variation within SSC3, SSC6, SSC10, SSC13 and SSC16 TARs is associated with the expression of several genes mapping to other chromosomes and related to lipid metabolism. CONCLUSIONS: Our data demonstrate that the effects of genomic determinants influencing lipid concentrations in pigs, as well as the amount of phenotypic variance they explain, are influenced by age-related factors.

SUBMITTER: Manunza A

PROVIDER: S-EPMC4164741 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants.

Manunza Arianna A Casellas Joaquim J Quintanilla Raquel R González-Prendes Rayner R Pena Ramona N RN Tibau Joan J Mercadé Anna A Castelló Anna A Aznárez Nitdia N Hernández-Sánchez Jules J Amills Marcel M

BMC genomics 20140904

<h4>Background</h4>The genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein c ...[more]

PMID: 25189197

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Project description:BackgroundThe comparison of expression QTL (eQTL) maps obtained in different tissues is an essential step to understand how gene expression is genetically regulated in a context-dependent manner. In the current work, we have compared the transcriptomic and eQTL profiles of two porcine tissues (skeletal muscle and liver) which typically show highly divergent expression profiles, in 103 Duroc pigs genotyped with the Porcine SNP60 BeadChip (Illumina) and with available microarray-based measurements of hepatic and muscle mRNA levels. Since structural variation could have effects on gene expression, we have also investigated the co-localization of cis-eQTLs with copy number variant regions (CNVR) segregating in this Duroc population.ResultsThe analysis of differential expresssion revealed the existence of 1204 and 1490 probes that were overexpressed and underexpressed in the gluteus medius muscle when compared to liver, respectively (|fold-change| > 1.5, q-value < 0.05). By performing genome scans in 103 Duroc pigs with available expression and genotypic data, we identified 76 and 28 genome-wide significant cis-eQTLs regulating gene expression in the gluteus medius muscle and liver, respectively. Twelve of these cis-eQTLs were shared by both tissues (i.e. 42.8% of the cis-eQTLs identified in the liver were replicated in the gluteus medius muscle). These results are consistent with previous studies performed in humans, where 50% of eQTLs were shared across tissues. Moreover, we have identified 41 CNVRs in a set of 350 pigs from the same Duroc population, which had been genotyped with the Porcine SNP60 BeadChip by using the PennCNV and GADA softwares, but only a small proportion of these CNVRs co-localized with the cis-eQTL signals.ConclusionDespite the fact that there are considerable differences in the gene expression patterns of the porcine liver and skeletal muscle, we have identified a substantial proportion of common cis-eQTLs regulating gene expression in both tissues. Several of these cis-eQTLs influence the mRNA levels of genes with important roles in meat (CTSF) and carcass quality (TAPT1), lipid metabolism (TMEM97) and obesity (MARC2), thus evidencing the practical importance of dissecting the genetic mechanisms involved in their expression.

Dataset Information

A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants.

Publications

A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants.

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