Background: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease. Methods: The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, using NCBI automated protocols. We also generated orthogonal single molecule transcript sequence reads (Iso-Seq) from 8 tissues and used them to validate the coding assembly, to annotate the assembly with RNA transcripts representing unique full length transcript isoforms for each gene and to determine whether divergences between RefSeq sequences and the assembly were attributable to assembly errors or polymorphisms. Results: The assembly analysis indicates that this assembly is comparable in contiguity and completeness to the current rat reference assembly, while the use of HiFi sequencing yields an assembly that is more correct at the single base level. Synteny analysis was performed to uncover the extent of synteny and the presence and distribution of chromosomal rearrangements between the reference and this assembly. Conclusion: The resulting genome assembly is reference quality and captures significant structural variation.
|Number of pages||9|
|State||Published - Jan 1 2023|
Bibliographical noteFunding Information:
This work was supported in part by the National Center for Biotechnology Information of the National Library of Medicine (NLM) at the National Institutes of Health. This work was also supported by National Institutes of Health (Award Numbers: NIH R01HG011252 to PAD/MLS/TSK and R01DK081866 to PAD).
© 2023 Lippincott Williams and Wilkins. All rights reserved.
- cardiovascular diseases
- spontaneously hypertensive rat
- whole genome sequencing
ASJC Scopus subject areas
- Internal Medicine