Genetic dissection of blood lipid traits by integrating genome-wide association study and gene expression profiling in a porcine model

Chen, Congying; Yang, Bin; Zeng, Zhijun; Yang, Hui; Liu, Chenlong; Ren, Jun; Huang, Lusheng

doi:10.1186/1471-2164-14-848

Cited by 30 publications

(49 citation statements)

References 48 publications

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“…As previously said, one of the most promising candidate genes is apolipoprotein B ( APOB , located at SSC3 125.2 Mb), which has been identified in our study as well as in the GWAS performed by Chen et al [9]. Apolipoprotein B is essential for the correct assembly of chylomicrons and the synthesis of very low density lipoproteins (VLDL), that transport TRIG from the intestine to other body tissues [35].…”

Section: Discussionmentioning

confidence: 62%

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

Manunza

Casellas

Quintanilla³

et al. 2014

BMC Genomics

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BackgroundThe 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).ResultsAnalysis 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-758) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 62%

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

Manunza

Casellas

Quintanilla³

et al. 2014

BMC Genomics

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“…In our GWAS (Chen et al . ), this QTL was evidenced in this F 2 population, but it achieved only a chromosomal‐wide significance level. Furthermore, in a Sutai population, we found that this QTL showed the most predominant effect on LDL‐C and TC in a GWAS (Chen et al .…”

Section: Introductionmentioning

confidence: 74%

“…Furthermore, in a Sutai population, we found that this QTL showed the most predominant effect on LDL‐C and TC in a GWAS (Chen et al . ). We also investigated the associations of whole‐genome gene expressions in liver with serum lipids.…”

Section: Introductionmentioning

confidence: 97%

Evaluation of the causality of the low‐density lipoprotein receptor gene (LDLR) for serum lipids in pigs

et al. 2014

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A significant quantitative trait locus (QTL) for low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) was identified around the LDLR gene on chromosome 2 (SSC2) in a White Duroc × Erhualian F2 resource population and Sutai pigs in our previous study. However, in previous reports, the causality of LDLR with serum lipids is controversial in pigs. To systematically assess the causality of LDLR with serum lipids, association analyses were successively performed in three populations: Sutai pigs, a White Duroc × Erhualian F2 resource population and a Duroc × (Landrace × Large White) population. We first performed a haplotype-based association study with 60K SNP genotyping data and evidenced the significant association with LDL-C and TC around the LDLR gene region. We also found that there is more than one QTL for LDL-C and TC on SSC2. Then, we evaluated the causalities of two missense mutations, c.1812C>T and c.1520A>G, with LDL-C and TC. We revealed that the c.1812C>T SNP showed the strongest association with LDL-C (P = 5.40 × 10(-11) ) and TC (P = 3.64 × 10(-8) ) and explained all the QTL effect in Sutai pigs. Haplotype analysis found that two missense SNPs locate within a 1.93-Mb haplotype block. One major haplotype showed the strongest significant association with LDL-C (P = 4.62 × 10(-18) ) and TC (P = 1.06 × 10(-9) ). However, the c.1812C>T SNP was not identified in the White Duroc × Erhualian intercross, and the association of c.1520A>G with both LDL-C and TC did not achieve significance in this F2 population, suggesting population heterogeneity. Both missense mutations were identified in the Duroc × (Landrace × Large White) population and showed significant associations with LDL-C and TC. Our data give evidence that the LDLR gene should be a candidate causative gene for LDL-C and TC in pigs, but heterogeneity exists in different populations.

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“…mcw.edu/) and mice (http://www.informatics.jax.org/), but few studies have investigated QTL for serum lipids in pigs. Recently, a number of QTLs have been mapped for porcine blood lipids using whole genome-linkage analysis (Gallardo et al 2008;Uddin et al 2011) and the genome-wide association approach (Chen et al 2013). To date, 43 QTL for total cholesterol (TC), 21 for high-density lipoprotein cholesterol (HDL-C), 68 for low-density lipoprotein cholesterol (LDL-C), 22 for HDL-C/LDL-C and 25 for triglycerides (TG) have been reported in the pig QTL database (http:// www.animalgenome.org/cgi-bin/QTLdb/SS/index).…”

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confidence: 99%

“…The samples were processed to measure serum TC (TC 45 , TC 300 ), LDL-C (LDL-C 45, LDL-C 300 ), HDL-C (HDL-C 45 , HDL-C 300 ) and TG (TG 45 , TG 300 ) concentrations as described by Chen et al (2013). Blood collection took place between 8:00 and 10:00 a.m. after an overnight fast (approximately 12 h).…”

mentioning

confidence: 99%

Functional and association studies of the cholesteryl ester transfer protein (CETP) gene in a Wannan Black pig model

Ding

Zhang

et al. 2015

Animal Genetics

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Some polymorphisms of the human CETP gene are causally and significantly associated with serum lipids levels; however, the information regarding this gene in pigs is sparse. To evaluate the effects of CETP on blood lipid traits and fat deposition in pig, porcine CETP tissue expression patterns were observed by quantitative real-time polymerase chain reaction (qPCR) first. High expression was detected in liver, spleen, gluteus medius (GM) muscle and backfat. A de novo polymorphism (AF333037:g.795C>T) in the intron 1 region of porcine CETP was identified. This polymorphism was further genotyped by direct sequencing of the PCR products of 390 Wannan Black pigs, a Chinese native breed population. Association analyses at 45 and 300 days of age revealed highly significant associations between CETP genotypes and serum lipid traits. Furthermore, this polymorphism was proved to be associated with differences in liver CETP mRNA levels: pigs at 300 days of age with the TT genotype had higher levels than did those with other genotypes (P = 0.021). Additionally, analysis at 300 days of age showed that GM CETP mRNA expression correlated positively with serum lipids levels as well as with carcass backfat thickness and intramuscular fat content in GM. These results indicate that CETP is involved in serum, adipose and muscle lipid metabolism in pigs. The mechanisms underlying such relationships and their functional implications are worthy of further research.

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Genetic dissection of blood lipid traits by integrating genome-wide association study and gene expression profiling in a porcine model

Cited by 30 publications

References 48 publications

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

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

Evaluation of the causality of the low‐density lipoprotein receptor gene (LDLR) for serum lipids in pigs

Functional and association studies of the cholesteryl ester transfer protein (CETP) gene in a Wannan Black pig model

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