The natural course of a disease in a human may take years to manifest symptoms; to overcome this problem, tractable aquatic genome models employing organisms that can mimic a disease in shorter time periods with genetic power have been created. Going forward we believe attaining the highest possible genome reference quality that we propose here will have a profound effect on funded aquatic research. In essence high quality genome references are proven to be a necessity to enable research on so many levels of biological investigation including disease etiology, small molecule drug screening and interactions, canonical disease pathway manifestation, and so many others. To date very few genomes can be classified as near finished, defined as only missing small regions that are recalcitrant to known molecular biology methods. Previously we have built reference genomes for new aquatic models for human disease that have been immediately put to use by several labs whose experimental outcomes are dependent on this resource. We believe we have raised the level of interest in comparative biological scientific inquiry that employ these species and others where such resources did not exist before. The goal of this project is to considerably elevate targeted aquatic genome models in reference assembly quality and accompany each with near complete gene models. Most biologists wish to see genome quality sufficient to not hinder within species studies that rely on transcriptome, transgenic, RNA interference, or gene knockout data for hypothesis testing. Responding to community needs we will apply cutting edge sequencing technology, the newest de novo assembly algorithms and innovative optical mapping techniques to provide a grouping of the highest quality genome references to date. Outcomes include new genome references for Xiphophorus maculatus (platyfish), Astynanax mexicanus (blind cavefish), Fundulus heteroclitus (killifish), Xenopus tropicalis (frog), Aplysia californica (sea hare) and Oryzias latipes (medaka). With a defined series of specific aims we are confident the future for next generation sequencing based approaches to the discovery of aquatic traits linked to human disease and expose future scientists to excite their intellectual ambitions. Achieving these aims will advance our concept of evolutionary medicine, understanding the origins and complexity of various human maladies through our shared genetic past.

Public Health Relevance

There is a real need to continue to develop and understand non-human models of human disease. The primary goal of this resource-related research project is to replace existing aquatic genome references, each with vibrant communities and a wide variety of disease model applications. We fully believe such an effort will avoid loss of sequence information and reduce error propagation during genetic investigation. Equally important is our plans to add genetic diversity, not just fishes, to our list of aquatic model species. Finally, perhaps most critical to this proposal will be our demonstrations of genome model use through extensive collaborations and communicating our exciting findings by various venues.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD011198-05
Application #
9265976
Study Section
Special Emphasis Panel (ZRG1-BBBP-Y (45)R)
Program Officer
Contreras, Miguel A
Project Start
2011-09-15
Project End
2020-02-29
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
5
Fiscal Year
2017
Total Cost
$206,193
Indirect Cost
$41,895
Name
Washington University
Department
Genetics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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