Identification of alternative splicing events in cows with A1A1 and A2A2 β-casein genotypes using large gap read mapping
Bibliographic record
Abstract
BACKGROUND: The A2 β-casein milk variant has gained interest due to potential health benefits, which has contributed to the rise of A2A2 genotypes within dairy herds. Although the A1 to A2 amino acid substitution in β-casein does not directly regulate gene expression, selective breeding for the A2A2 genotype may have indirect transcriptomic consequences in the mammary gland. RESULTS: In this study, we investigated whether the A1A1 and A2A2 β-casein genotypes are associated with differential mRNA isoform expression in bovine milk fat globules (MFG) using RNA-Sequencing technology (RNA-Seq). A total of 619 million paired-end reads from 14 MFG cDNA libraries were analysed. In total, 3,454 DE mRNA isoforms were identified (FDR < 0.05, |FC|> 2), of which 823 were mRNA isoforms with annotated associated genes, 2,067 were mRNA isoforms with annotated associated genes but novel transcript lengths and 586 were novel mRNA isoforms with non-annotated associated genes. Functional analysis of the 2,954 DE mRNA isoforms with annotated gene names revealed 523 enriched metabolic pathways (p < 0.05). Among these pathways, patterns consistent with mitochondrial dysfunction and reduced mitochondrial fatty acid β-oxidation were observed in A2A2 cows, together with indications of reduced mitochondrial biogenesis and altered mitochondrial RNA degradation, suggesting adjustments in cellular energy metabolism. Additionally, differences in isoforms related to ER-Golgi communication, vesicle trafficking and protein folding pointed to subtle modifications in secretory pathway dynamics. Regarding lipid metabolism, A2A2 cows showed signs of increased fatty acid uptake but reduced capacity for de novo synthesis of fatty acids, triglyceride and cholesterol synthesis, as well as for lipid droplet formation. CONCLUSIONS: These findings suggest that the A2A2 genotype would be associated with isoform level changes likely driven by alternative splicing events. Further functional validation will be necessary to assess the biological relevance of the observed differences and their potential implications for genetic selection for the A2 β-casein variant.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".