| RRC ID |
86218
|
| Author |
Lemoine L, Hoelzl S, Hasenbein TP, Graf E, Andergassen D.
|
| Title |
Long-read sequencing disentangles isoform complexity at allele-specific loci.
|
| Journal |
Sci Rep
|
| Abstract |
In recent years, long-read sequencing technologies have detected transcript isoforms with unprecedented accuracy and resolution. However, it remains unclear whether long-read sequencing can effectively disentangle the isoform landscape of complex allele-specific loci that arise from genetic or epigenetic differences between alleles. Here, we combine the PacBio Iso-Seq workflow with the established phasing approach WhatsHap to assign long reads to the corresponding allele in polymorphic F1 mouse hybrids. Upon comparing the long-read sequencing results with matched short reads, we observed general consistency in the allele-specific information and were able to confirm the imprinting status of known imprinted genes. We then explored the complex imprinted Gnas locus known for allele-specific non-coding and coding isoforms and were able to benchmark historical observations. This approach also allowed us to detect isoforms from both the active and inactive X chromosomes of genes that escape X chromosome inactivation. The described workflow offers a promising framework and demonstrates the power of long-read transcriptomic data to provide mechanistic insight into complex allele-specific loci.
|
| Volume |
15(1)
|
| Pages |
39389
|
| Published |
2025-11-11
|
| DOI |
10.1038/s41598-025-97362-z
|
| PII |
10.1038/s41598-025-97362-z
|
| PMID |
41219345
|
| PMC |
PMC12606347
|
| MeSH |
Alleles*
Animals
Genetic Loci*
Genomic Imprinting
High-Throughput Nucleotide Sequencing / methods
Mice
Protein Isoforms / genetics
X Chromosome Inactivation
|
| IF |
3.998
|
| Resource |
| Mice |
RBRC02655 |
