P0656 Extensive Genetic Diversity and Sub-structuring among Zebrafish Strains Revealed through Copy Number Variant Analysis

Kim Brown , Brigham and Women’s Hospital
Kim Dobrinski , Brigham and Women's Hospital
Arthur Lee , Washington University
Omer Gokcumen , Brigham and Women's Hospital
Ryan Mills , Brigham and Women's Hospital
Xinghua Shi , Brigham and Women's Hospital
Wilson Chong , Brigham and Women's Hospital
Helen Chen , Brigham and Women's Hospital
Sthuthie David , Brigham and Women's Hospital
Paulo Yoo , Brigham and Women's Hospital
Samuel Peterson , Purdue University
Towfique Raj , Brigham and Women's Hospital
Kwong Wai Choy , The Chinese University of Hong Kong
Barbara Stranger , Brigham and Women's Hospital
Robin Williamson , Harvard Medical School
Leonard Zon , Childrens Hospital Boston
Jennifer Freeman , Purdue University
Charles Lee , Brigham and Women's Hospital
Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly-used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising of 6,080 CNV elements (CNVE) and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of the CNVEs exhibited strain-specificity with the highest number observed for Tubingen. This variation likely arose, in part, from Tubingen’s large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and sub-structure of these commonly-used laboratory strains. This extensive variation among and within zebrafish strains may have functional effects that impact phenotype. If not properly addressed, such extensive levels of germ-line variation and population sub-structure in this commonly-used model organism can potentially confound studies intended for translation to human diseases.