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Light whole genome sequence for SNP discovery across domestic cat breeds

James C Mullikin1*, Nancy F Hansen1, Lei Shen2, Heather Ebling2, William F Donahue2, Wei Tao2, David J Saranga2, Adrianne Brand2, Marc J Rubenfield2, Alice C Young1, Pedro Cruz1, NISC Comparative Sequencing Program1, Carlos Driscoll3, Victor David3, Samer WK Al-Murrani4, Mary F Locniskar4, Mitchell S Abrahamsen4, Stephen J O'Brien3, Douglas R Smith2 and Jeffrey A Brockman4

Author Affiliations

1 Genome Technology Branch and NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

2 Agencourt Bioscience Corporation, Beverly, Massachusetts 01915, USA

3 Laboratory of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702, USA

4 Hill's Pet Nutrition Inc., PO Box 1658, Topeka, KS 66601, USA

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BMC Genomics 2010, 11:406  doi:10.1186/1471-2164-11-406

Published: 24 June 2010

Abstract

Background

The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus -- FeLV, feline coronavirus -- FECV, feline immunodeficiency virus - FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery.

Description

To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower-limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%.

Conclusions

These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases.