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Long-read assembly and annotation of rat genomes that are important models of complex genetic disease

大鼠基因组的长读组装和注释是复杂遗传疾病的重要模型

基本信息

批准号：
10449388
负责人：
PETER A DORIS
金额：
$ 42.53万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-12 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10449388
关键词：
Addictive Behavior Affect Agriculture Alternative Splicing Amylases Animal Model Animals Automated Annotation Behavior Behavioral Behavioral Research Biodiversity Biological Biological Process Biology Biomedical Research Brain Brain Diseases Carbohydrates Cardiovascular Physiology Characteristics Chromosomes Communities Complex Data Deposition Development Diet Digestion Disease Disease model Disease susceptibility Distant Drug Addiction Elements Ensure Event Evolution Experimental Models Funding Gene Duplication Gene Expression Genes Genetic Genetic Diseases Genetic Models Genetic Variation Genome Genomic DNA Genomics Grain Hi-C Human IGH@ gene cluster Inbred BN Rats Inbred Strains Rats Inbreeding Investigation Knowledge Laboratories Libraries Ligation Link Liquid substance Long-Evans Rats Manuals Medical Methods Modeling Molecular Conformation Mus Nature Neurosciences Norway Optics Organism Pathogenesis Phenotype Physiology Polishes Process Proteins Rat Genome Database Rat Strains Rattus Rattus norvegicus Renal function Research Research Personnel Resources Rodent Sampling Single Nucleotide Polymorphism Socialization Starch Structure System Tissues Transcript United States National Institutes of Health Variant Work base comparative cost disorder risk genome annotation genome sequencing genomic tools genomic variation hypertensive mRNA sequencing mammalian genome normotensive rat genome reference genome scaffold single molecule trait transcriptome sequencing transcriptomics whole genome

项目摘要

Project Summary: The rat is commonly used as an experimental model to investigate a wide diversity of biological processes of medical relevance. These include neuroscience and brain function, behavioral research, and drug dependency and addiction. Similarly, aspects of cardiovascular and renal function are more readily investigated in the rat where the volumes of fluid within these systems are on a much more manageable scale than in smaller rodents. The utility of rat models for investigation has led to the development of inbred rat strains that harbor medically relevant phenotypes. Such models have drawn on pre-existing, natural genetic variation to fix genomic diversity that creates traits such as disease susceptibility. The existence of such models has spurred genetic investigations that have sought to uncover genetic variation responsible for disease susceptibility traits and to utilize such knowledge to reveal mechanistic aspects of disease pathogenesis. However, rat studies can be impeded by the poor quality of existing rat genomic resources. For example, the rat genome reference sequence is very underdeveloped compared to that of human and mouse. Contiguity of the genome assembly is an order of magnitude smaller and gene annotation is much reduced. Further, the reference genome was generated from the Brown Norway inbred rat strain. This strain is biologically remote from many rat strains used in research. The rat is recognized as a highly adaptable species. Evolutionary biologists have recognized that an essential element of adaptation arises from structural variation events in the genome. For example, the adaptation of humans to high starch diets after the introduction of grain-based agriculture is associated with structural variation in the amylase gene. This structural variation results from gene duplication events that are adaptive in permitting increased carbohydrate digestion. These duplication and other large-scale events cannot be observed and understood simply by alignment of short read genome sequence to the reference genome. Long reads are required to capture structural variation events. The objective of our project is to advance rat genomics resources to increase their utility to ongoing studies of this animal model. To do so, we will use PacBio long read sequencing to capture all genomic variation (SNP and structural). We will assemble de novo the genomes of 9 widely used rat strains. We will also introduce additional annotation of the rat genome to increase the numbers of transcripts and proteins associated with the rat reference genome using long read RNA sequencing. The result of our work will be made available via the Rat Genome Database and by Ensembl and will provide essential research information to the many laboratories that employ rat models in their research.

项目总结: