Abstract:Improving feed efficiency (FE) is a major goal for the livestock industry. Previously, we have identified 48 SNP markers distributed over 32 genes significantly associated with residual feed intake (RFI) in Israeli Holstein male calves, the most significant of which are located in the bovine FABP4 gene. In the present study, we tested associations of eight of the FABP4 markers with RFI and feed conversion ratio (FCR), along with milk composition and feeding behavioral traits, in 114 lactating Israeli Holstein … Show more
“…Equipped with an individual feeding system, the experimental dairy farm of ARO has been monitoring the RFI of lactating cows [ 12 ]. To further validate the findings of a QTL for RFI on BTA14 that have been based on a sample of 114 cows [ 12 ], we enlarged this sample to 192 cows all genotyped with the Illumina BovineHD BeadChip (777K SNPs). We also performed whole genome sequencing (WGS) for 19 Israeli Holstein sires, representing major lineages of the Israeli herd [ 20 ] with no RFI evaluations.…”
Section: Resultsmentioning
confidence: 99%
“…The indication that FABP4 has a large effect on RFI mostly relies on the fourth and fifth SNPs ( FABP4_4 and FABP4_5 ) of 10 SNPs detected in gene FABP4 , of which FABP4_4 is capable of encoding a conservative substitution of hydrophobic amino acids [ 12 ] ( Table 1 ). To infer unavailable genotypes for these SNPs in the enlarged test sample of cows and re-evaluate previous results, we examined an additional 15 SNPs within a short interval (~35 Kbp) of this gene locus ( Table 2 ).…”
Section: Resultsmentioning
confidence: 99%
“…To investigate why the predicted effect of FABP4 locus on RFI differs between studies, we compared the imputed genotypes to those previously recorded for the sample of 114 cows using the HRM and TaqMan methods [ 12 ]. Imputed genotypes were identical for the tightly linked FABP4_4 and FABP4_5 SNPs that are only 3387 bp apart.…”
Section: Resultsmentioning
confidence: 99%
“…A total of 192 Israeli Holstein multiparous dairy cows from the Agricultural Research Organization (ARO) dairy herd (Rishon-LeTsiyon, Israel) were used in the present study of which 114 cows were used in previous studies [ 12 ]. The RFI values were evaluated as previously described [ 12 ]. Briefly, the cows were healthy, multiparous, high yielding (35 kg/day), and 60–180 days in milking.…”
Section: Methodsmentioning
confidence: 99%
“…Thoroughly reviewing this approach, Lashmar et al [ 10 ] listed 14 imputation software programs commonly used in animal genetics research [ 10 ]. Of these, in the current work, we used Findhap.f90 and PLINK to compare and re-evaluate genotyping data of RFI studies indicating that BTA14 fatty-acid-binding protein 4 ( FABP4 ) has a large effect on this trait [ 11 , 12 ]. We demonstrate the superiority of genotyping by imputation over the TaqMan, HRM, and even Sanger sequencing methods concluding that the relevance of the FABP4 gene to RFI is smaller than has been previously estimated [ 11 , 12 ], compared to an additional gene candidate on BTA14.…”
In dairy cattle, identifying polymorphisms that contribute to complex economical traits such as residual feed intake (RFI) is challenging and demands accurate genotyping. In this study, we compared imputed genotypes (n = 192 cows) to those obtained using the TaqMan and high-resolution melting (HRM) methods (n = 114 cows), for mutations in the FABP4 gene that had been suggested to have a large effect on RFI. Combining the whole genome sequence (n = 19 bulls) and the cows’ BovineHD BeadChip allowed imputing genotypes for these mutations that were verified by Sanger sequencing, whereas, an error rate of 11.6% and 10.7% were encountered for HRM and TaqMan, respectively. We show that this error rate seriously affected the linkage-disequilibrium analysis that supported this gene candidacy over other BTA14 gene candidates. Thus, imputation produced superior genotypes and should also be regarded as a method of choice to validate the reliability of the genotypes obtained by other methodologies that are prone to genotyping errors due to technical conditions. These results support the view that RFI is a complex trait and that searching for the causative sequence variation underlying cattle RFI should await the development of statistical methods suitable to handle additive and epistatic interactions.
“…Equipped with an individual feeding system, the experimental dairy farm of ARO has been monitoring the RFI of lactating cows [ 12 ]. To further validate the findings of a QTL for RFI on BTA14 that have been based on a sample of 114 cows [ 12 ], we enlarged this sample to 192 cows all genotyped with the Illumina BovineHD BeadChip (777K SNPs). We also performed whole genome sequencing (WGS) for 19 Israeli Holstein sires, representing major lineages of the Israeli herd [ 20 ] with no RFI evaluations.…”
Section: Resultsmentioning
confidence: 99%
“…The indication that FABP4 has a large effect on RFI mostly relies on the fourth and fifth SNPs ( FABP4_4 and FABP4_5 ) of 10 SNPs detected in gene FABP4 , of which FABP4_4 is capable of encoding a conservative substitution of hydrophobic amino acids [ 12 ] ( Table 1 ). To infer unavailable genotypes for these SNPs in the enlarged test sample of cows and re-evaluate previous results, we examined an additional 15 SNPs within a short interval (~35 Kbp) of this gene locus ( Table 2 ).…”
Section: Resultsmentioning
confidence: 99%
“…To investigate why the predicted effect of FABP4 locus on RFI differs between studies, we compared the imputed genotypes to those previously recorded for the sample of 114 cows using the HRM and TaqMan methods [ 12 ]. Imputed genotypes were identical for the tightly linked FABP4_4 and FABP4_5 SNPs that are only 3387 bp apart.…”
Section: Resultsmentioning
confidence: 99%
“…A total of 192 Israeli Holstein multiparous dairy cows from the Agricultural Research Organization (ARO) dairy herd (Rishon-LeTsiyon, Israel) were used in the present study of which 114 cows were used in previous studies [ 12 ]. The RFI values were evaluated as previously described [ 12 ]. Briefly, the cows were healthy, multiparous, high yielding (35 kg/day), and 60–180 days in milking.…”
Section: Methodsmentioning
confidence: 99%
“…Thoroughly reviewing this approach, Lashmar et al [ 10 ] listed 14 imputation software programs commonly used in animal genetics research [ 10 ]. Of these, in the current work, we used Findhap.f90 and PLINK to compare and re-evaluate genotyping data of RFI studies indicating that BTA14 fatty-acid-binding protein 4 ( FABP4 ) has a large effect on this trait [ 11 , 12 ]. We demonstrate the superiority of genotyping by imputation over the TaqMan, HRM, and even Sanger sequencing methods concluding that the relevance of the FABP4 gene to RFI is smaller than has been previously estimated [ 11 , 12 ], compared to an additional gene candidate on BTA14.…”
In dairy cattle, identifying polymorphisms that contribute to complex economical traits such as residual feed intake (RFI) is challenging and demands accurate genotyping. In this study, we compared imputed genotypes (n = 192 cows) to those obtained using the TaqMan and high-resolution melting (HRM) methods (n = 114 cows), for mutations in the FABP4 gene that had been suggested to have a large effect on RFI. Combining the whole genome sequence (n = 19 bulls) and the cows’ BovineHD BeadChip allowed imputing genotypes for these mutations that were verified by Sanger sequencing, whereas, an error rate of 11.6% and 10.7% were encountered for HRM and TaqMan, respectively. We show that this error rate seriously affected the linkage-disequilibrium analysis that supported this gene candidacy over other BTA14 gene candidates. Thus, imputation produced superior genotypes and should also be regarded as a method of choice to validate the reliability of the genotypes obtained by other methodologies that are prone to genotyping errors due to technical conditions. These results support the view that RFI is a complex trait and that searching for the causative sequence variation underlying cattle RFI should await the development of statistical methods suitable to handle additive and epistatic interactions.
Purpose of Review
Fatty acid-binding protein 4 (FABP4) plays a role in lipid metabolism and cardiovascular health. In this paper, we cover FABP4 biology, its implications in atherosclerosis from observational studies, genetic factors affecting FABP4 serum levels, and ongoing drug development to target FABP4 and offer insights into future FABP4 research.
Recent Findings
FABP4 impacts cells through JAK2/STAT2 and c-kit pathways, increasing inflammatory and adhesion-related proteins. In addition, FABP4 induces angiogenesis and vascular smooth muscle cell proliferation and migration. FABP4 is established as a reliable predictive biomarker for cardiovascular disease in specific at-risk groups. Genetic studies robustly link PPARG and FABP4 variants to FABP4 serum levels. Considering the potential effects on atherosclerotic lesion development, drug discovery programs have been initiated in search for potent inhibitors of FABP4.
Summary
Elevated FABP4 levels indicate an increased cardiovascular risk and is causally related to acceleration of atherosclerotic disease, However, clinical trials for FABP4 inhibition are lacking, possibly due to concerns about available compounds’ side effects. Further research on FABP4 genetics and its putative causal role in cardiovascular disease is needed, particularly in aging subgroups.
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