The dog is becoming an increasingly important biomedical model for human diseases such as cancer, inflammatory, cardiovascular and behavioural diseases. The unique breed structure makes trait mapping particularly efficient. While a genome, basic annotation and SNP catalog have been available since 2004, improved genomic resources would allow a more efficient identification of disease genes, pathways and mutations. In this project we aim to improve the canine genomic resources by creating a more comprehensive genome annotation along with extensive genomic data from the dog genetic community as a track data hub on the UCSC Genome Browser. Six dogs, euthanized for other medical reasons, will donate 30 tissues each for RNA- sequencing and 11 primary cell cultures for both RNA-sequencing and ChIP-sequencing for five histone antibodies. A sample will also be obtained for whole genome sequencing of each dog. This will yield an extensive transcriptome resource for 30 tissues and the first genome-wide catalog of regulatory elements in the dog. Embryonic dog tissue will also be obtained for RNA- sequencing from embryos already sacrificed for other scientific studies.The RNA-sequencing data will be combined with previous human and dog gene annotations in a custom annotation pipeline, to result in an improved dog gene annotation, based largely on species-specific information. All of the above data, along with the new gene annotation and data gathered from the dog genetics community will be hosted at the Broad Institute on the UCSC Genome Browser, enabling access to these resources by dog scientists around the world. These genomic resources will vastly increase the utility of the dog as a biomedical model and will accelerate dog genetics, and translational research arising from the study of the dog model. Collaborators for this important project include Drs Sharp and Ferrer, veterinary specialists at Tufts Veterinary School, Dr. Meyers-Wallen, an expert in dog embryonic development, Dr Lander and the Broad Institute Genomics Platform, experts in sequencing, Drs Regev and Grabherr, experts at transcriptomics and genome regulation and Drs Haussler and Kent, leaders of the UCSC genome browser.

Public Health Relevance

The dog is an excellent model for human disease; the recent breed creation and strong selection for particular traits has made the canine genome structure outstanding for disease gene mapping. While both monogenic and complex traits of relevance to humans have been mapped, scientists would be greatly assisted by a better annotation of the canine genome. This research aims to create a better genome annotation and collect an abundance of genomic data in a comprehensive and easily accessible fashion, thus enabling canine and human disease genetics.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD018250-03
Application #
9238508
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Zou, Sige
Project Start
2015-08-17
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2019-04-30
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Broad Institute, Inc.
Department
Type
DUNS #
623544785
City
Cambridge
State
MA
Country
United States
Zip Code
02142