RT Journal Article
SR Electronic
T1 A domestic cat whole exome sequencing resource for trait discovery
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.01.128405
DO 10.1101/2020.06.01.128405
A1 Alana R. Rodney
A1 Reuben M. Buckley
A1 Robert S. Fulton
A1 Catrina Fronick
A1 Todd Richmond
A1 Christopher R. Helps
A1 Peter Pantke
A1 Dianne J. Trent
A1 Leslie A. Lyons
A1 Wesley C. Warren
YR 2020
UL http://biorxiv.org/content/early/2020/06/02/2020.06.01.128405.abstract
AB Over 94 million domestic cats are considered pets, who, as our companions, are also susceptible to cancers, common and rare diseases. Whole exome sequencing (WES) is a cost-effective strategy to study their putative disease-causing variants. Presented is ~35.8 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. WES was conducted on 41 cats from various breeds with known and unknown diseases and traits, including 10 cats with prior whole genome sequence (WGS) data available, to test WES capture probe performance. A WES and WGS comparison was completed to understand variant discovery capability of each platform. At ~80x exome coverage, the percent of on-target base coverage >20x was 96.4% with an average of 10.4% off-target. For variant discovery, greater than 98% of WGS SNPs were also discovered by WES. Platform specific variants were mainly restricted to a small number of sex chromosome and olfactory receptor genes. Within the 41 cats with ~31 diseases and normal traits, 45 previously known disease or trait causal variants were observed, such as Persian progressive retinal degeneration and hydrocephalus. Novel candidate variants for polycystic kidney disease and atrichia in the Peterbald breed were also identified as well as a new cat patient with a known variant for cystinuria. These results show the discovery potential of deep exome sequencing to validate existing disease gene models and identify novel gene candidate alleles for many common and rare diseases in cats.Competing Interest StatementThe authors have declared no competing interest.