Distinct correlations between lipogenic gene expression and fatty acid composition of subcutaneous fat among cattle breeds.

BACKGROUND: The fatty acid (FA) composition of adipose tissue influences the nutritional quality of meat products. The unsaturation level of FAs is determined by fatty acid desaturases such as stearoyl-CoA desaturases (SCDs), which are under control of the transcription factor sterol regulatory element-binding protein (SREBP). Differences in SCD genotype may thus confer variations in lipid metabolism and FA content among cattle breeds. This study investigated correlations between FA composition and lipogenic gene expression levels in the subcutaneous adipose tissue of beef cattle breeds of different gender from the Basque region of northern Spain. Pirenaica is the most important beef cattle breed in northern Spain, while Salers cattle and Holstein-Friesian cull cows are also an integral part of the regional beef supply. RESULTS: Pirenaica heifers showed higher monounsaturated FA (MUFA) and conjugated linoleic acid (CLA) contents in subcutaneous adipose tissue than other breeds (P < 0.001). Alternatively, Salers bulls produced the highest oleic acid content, followed by Pirenaica heifers (P < 0.001). There was substantial variability in SCD gene expression among breeds, consistent with these differences in MUFA and CLA content. Correlations between SCD1 expression and most FA desaturation indexes (DIs) were positive in Salers (P < 0.05) and Pirenaica bulls, while, in general, SCD5 expression showed few significant correlations with DIs. There was a significant linear correlation between SCD1 and SRBEP1 in all breeds, suggesting strong regulation of SCD1 expression by SRBEP1. Pirenaica heifers showed a stronger correlation between SCD1 and SREBP1 than Pirenaica bulls. We also observed a opposite relationship between SCD1 and SCD5 expression levels and opposite associations of isoform expression levels with the ∆9 desaturation indexes. CONCLUSIONS: These results suggest that the relationships between FA composition and lipogenic gene expression are influenced by breed and sex. The opposite relationship between SCD isoforms suggests a compensatory regulation of total SCD activity, while opposite relationships between SCD isoforms and desaturation indexes, specially 9c-14:1 DI, previously reported as an indicator of SCD activity, may reflect distinct activities of SCD1 and SCD5 in regulation of FA content. These findings may be useful for beef/dairy breeding and feeding programs to supply nutritionally favorable products.

Effect of a genetic polymorphism in SREBP1 on fatty acid composition and related gene expression in subcutaneous fat tissue of beef cattle breeds.

Sterol regulatory element-binding factor 1 (SREBP1) plays an important role in the lipogenesis which affects fatty acid (FA) composition in backfat and consequently influences beef nutritional quality. This study analyzed the association of 84 bp-indel, both short (S) and long (L) alleles in intron 5 of SREBP1, with FA composition and gene expression of SREBP1 in backfat of northern Spanish beef breeds (Pirenaica, Salers and Holstein-Friesian). Phylogenetic analysis suggests that 84 bp-indel of ruminants is a highly conserved region compared with those in the full-length sequence of intron 5 or mRNA of SREBP1 among species. Overall, higher content of polyunsaturated FAs was observed in SL genotype compared to LL genotype of 84 bp-Indel (p < .05). In particular, in Pirenaica, SL genotype was associated with a higher content of stearic (18:0), α-linolenic (18:3n-3) acid, and total n-3 content (p < .05). However, the gene expression of SREBP1 did not differ among genotypes of 84 bp-Indel (p > .05).

Genetic Characterization of the Local Pirenaica Cattle for Parentage and Traceability Purposes.

Pirenaica is the most important autochthonous cattle breed within the Protected Geographic Indication (PGI) beef quality label in the Basque region, in northern Spain. The short tandem repeats (STRs) are powerful markers to elucidate forensic cases and traceability across the agri-food sector. The main objective of the present work was to study the phylogenetic relationships of Pirenaica cattle and other breeds typically raised in the region and provide the minimum number of STR markers for parentage and traceability purposes. The 30-STR panel recommended by the International Society of Animal Genetics-Food and Agriculture Organization of the United Nations (ISAG-FAO) was compared against other commercial STR panels. The 30-STR panel showed a combined matching probability of 1.89 × 10-25 and a power of exclusion for duos of 0.99998. However, commercial STR panels showed a limited efficiency for a reliable parentage analysis in Pirenaica, and at least a 21-STR panel is needed to reach a power of exclusion of 0.9999. Machine-learning analysis also demonstrated a 95% accuracy in assignments selecting the markers with the highest FST in Pirenaica individuals. Overall, the present study shows the genetic characterization of Pirenaica and its phylogeny compared with other breeds typically raised in the Basque region. Finally, a 21-STR panel with the highest FST markers is proposed for a confident parentage analysis and high traceability.

Population genetic data of 38 insertion-deletion markers in six populations of the northern fringe of the Iberian Peninsula.

Insertion-deletions have been reported very useful markers for forensic purposes. To further deepen in this matter, 38 non-coding bi-allelic autosomal indels were analyzed in 575 individuals representing six populations from the northern fringe of the Iberian Peninsula. Autochthonous populations from the Basque Country, northern Navarre, the Pas Valley in Cantabria and Aragon were analyzed, together with non-autochthonous populations from the Basque Country and northern Navarre. At the intra-population level, all loci analyzed were in Hardy-Weinberg equilibrium except for marker rs33917182 in autochthonous Basques. Linkage disequilibrium (LD) test did not reveal statistically significant allelic association between the different loci pairs in all six populations. Forensic parameters proved to be highly informative in the six populations analyzed, even if a scenario with population substructure and local inbreeding was considered for match probability calculations, and the potential of this indels set to be used in combination with other genetic markers is remarkable. As for inter-population analyses, in general terms the six populations showed low but statistically significant genetic distances. However, though this indels set efficiently differentiate between main ancestries, it does not allow an accurate separation at a local level and, for the time being, their combination with other informative markers is needed to maximize the power to accurately differentiate populations with close genetic ancestry.

New Q lineage found in bovine (Bos taurus) of Iberian Peninsula.

The northern Iberian Peninsula is home to a variety of autochthonous cattle breeds, such as the Terreña and Pirenaica. With the objective of characterizing the matrilineal lineages of these breeds, a study of mitochondrial DNA was performed. The D-loop of 155 individuals was analyzed and most of the individuals were carriers of the T3 haplogroup, while haplogroups T and T1 were much less frequent. A Pirenaica individual belonging to the Q haplogroup was found. To verify the presence of the Q haplogroup individual, the entire mitochondrial DNA was sequenced and compared with two descendants. The individuals were assigned to the Q1 sub-haplogroup. These findings extend the geographic distribution of the Q haplogroup to the south west of the European continent. This new Q1 lineage has seven polymorphisms in the coding region, so this lineage is probably as old as the Q lineages described to date.

Proteolytic enzymes involved in MHC class I antigen processing: A guerrilla army that partners with the proteasome.

Major histocompatibility complex class I proteins (MHC-I) load short peptides derived from proteolytic cleavage of endogenous proteins in any cell of the body, in a process termed antigen processing and presentation. When the source proteins are altered self or encoded by a pathogen, recognition of peptide/MHC-I complexes at the plasma membrane leads to CD8(+) T-lymphocyte responses that clear infections and probably underlie tumor immune surveillance. On the other hand, presentation of self peptides may cause some types of autoimmunity. The peptides that are presented determine the specificity and efficiency of pathogen clearance or, conversely, of immunopathology. In this review we highlight the growing number of peptidases which, as a by-product of their regular activity, can generate peptide epitopes for immune surveillance. These ∼20 peptidases collectively behave as a guerrilla army partnering with the regular proteasome army in generating a variety of peptides for presentation by MHC-I and thus optimally signaling infection.

Association of the C47T Polymorphism in SOD2 with Amnestic Mild Cognitive Impairment and Alzheimer's Disease in Carriers of the APOEε4 Allele.

Oxidative stress plays an important part in amnestic mild cognitive impairment (aMCI), the prodromal phase of Alzheimer's disease (AD). Recent evidence shows that polymorphisms in the SOD2 gene affect the elimination of the reactive oxygen species (ROS) generated in mitochondria. The aim of this study was to determine whether the functional rs4880 SNP in the SOD2 gene is a risk factor associated with aMCI and sporadic AD. 216 subjects with aMCI, 355 with AD, and 245 controls have been studied. The SNP rs4880 of the SOD2 gene was genotyped by RT-PCR and the APOE genotype was determined by PCR and RFLPs. Different multinomial logistic regression models were used to determine the risk levels for aMCI and AD. Although the T allele of the SOD2 rs4880 SNP gene (rs4880-T) is not an independent risk for aMCI or AD, this allele increases the risk to aMCI patients carrying at least one APOEε4 allele. Moreover, rs4880-T allele and APOEε4 allele combination has been found to produce an increased risk for AD compared to aMCI reference patients. These results suggest that APOEε4 and rs4880-T genotype may be a risk for aMCI and a predictor of progression from aMCI to AD.

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts.

The regulation of gene expression by microRNAs (miRNAs) is critical for normal development and physiology. Conversely, miRNA function is frequently impaired in cancer, and other pathologies, either by aberrant expression of individual miRNAs or dysregulation of miRNA synthesis. Here, we have investigated the impact of global disruption of miRNA biogenesis in primary fibroblasts of human or murine origin, through the knockdown of DGCR8, an essential mediator of the synthesis of canonical miRNAs. We find that the inactivation of DGCR8 in these cells results in a dramatic antiproliferative response, with the acquisition of a senescent phenotype. Senescence triggered by DGCR8 loss is accompanied by the upregulation of the cell-cycle inhibitor p21CIP1. We further show that a subset of senescence-associated miRNAs with the potential to target p21CIP1 is downregulated during DGCR8-mediated senescence. Interestingly, the antiproliferative response to miRNA biogenesis disruption is retained in human tumor cells, irrespective of p53 status. In summary, our results show that defective synthesis of canonical microRNAs results in cell-cycle arrest and cellular senescence in primary fibroblasts mediated by specific miRNAs, and thus identify global miRNA disruption as a novel senescence trigger.