35 ANALYSIS OF EPIGENETIC MODIFICATIONS AND GENOMIC IMPRINTING IN NUCLEAR TRANSFER DERIVED BOS GAURUS × B. TAURUS CONCEPTI
Bibliographic record
Abstract
Somatic cell nuclear transfer in cattle is an inefficient process hindered by low pregnancy rates and fetal placental abnormalities. Improper or incomplete epigenetic reprogramming of the donor genome has been implicated as a cause for these aberrations and has been investigated extensively in mice. Here we report the use of a bovine interspecies model (Bos gaurus × B. taurus) for the assessment and characterization of epigenetic modifications and genomic imprinting in 40-day-old female nuclear transfer (NT)-derived fetuses and placentas. Previously, we identified genomic imprinting at the IGF2, GTL2 and XIST loci in the Bos gaurus × B. taurus fetuses. These results indicated maternal and paternal imprinting of the IGF2 and GTL2 loci, respectively, in the chorion, allantois, liver, lung and brain, whereas the XIST locus was maternally imprinted solely in the chorion of females. We extended this analysis to 40-day-old NT fetuses derived from a hybrid lung fibroblast cell line (female). Analysis of the donor cell line indicated conservation of imprinting of the IGF2 and GTL2 loci and bialleic expression of the XIST locus, presumably from the random patterns of X-chromosome inactivation. Analysis of three NT and three control pregnancies indicated disruption of genomic imprinting at the XIST locus in the chorions of all three clones compared to controls. In contrast, proper allelic expression of the IGF2 and GTL2 loci was observed in all fetuses and placentas. Quantification of maternal and paternal XIST transcripts in the chorion of clones and controls demonstrated a significant skewing from preferential paternal expression in controls (95.0 ± 0.882, mean ± S.E.) to mixed paternal and maternal expression in clones (73.6 ± 5.2), (t-test; P < 0.05). In an attempt to determine the cause for the abnormal allelic expression of the XIST locus in the chorion of the clones, methylation analysis of the XIST Differentially Methylated Region (DMR) was performed. Methylation-sensitive restriction digests and subsequent PCR of the XIST DMR indicated patterns were not different between controls and clones. However, when genome-wide and promoter-specific methylation analysis (bisulfite sequencing) was extended to the satellite I repeat element and epidermal cytokeratin promoter, hypermethylation was observed in the chorion of clones. These results demonstrate disruption of genomic imprinting in XIST locus in the placenta of 40-day-old clones independent of DMR methylation. They also indicate that cloning is associated with increased levels of methylation in selected genomic regions in the chorion.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".