Light whole genome sequence for SNP discovery across domestic cat breeds.

James C Mullikin ,Wei Tao,Lei Shen,Heather Ebling,Adrianne Brand,Pedro Cruz,Douglas R Smith ,William F Donahue ,Mary Locniskar ,Marc Rubenfield ,Victor A David ,Nancy F Hansen ,Mitchell S Abrahamsen ,Stephen J O’brien ,Samer Al-Murrani ,Carlos A Driscoll ,David J Saranga ,Alice C Young ,Jeffrey A Brockman

doi:10.1186/1471-2164-11-406

Abstract

BackgroundThe 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.DescriptionTo 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%.ConclusionsThese 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.

Highlights

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 that are homologues to human scourges
These data provide a large collection of mapped feline single nucleotide polymorphism (SNP) across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases
The availability of a sufficiently dense single-nucleotide polymorphism (SNP) map for a species provides a resource which enables the power of automated highthroughput genotyping to associate regions of the genome to hereditary diseases, quantitative traits, and other phenotypes

Summary

Background

The domestic cat enjoys extensive veterinary surveillance, more than any other animal. To supplement feline SNP map and the genome assembly, we created fosmid libraries and sequenced six additional cats of different breeds and one African wild cat. These sequences dramatically improve the SNP map by increasing the total number of useful SNPs and by filling in the long stretches of genomic homozygosity (~60% of the genome) reported in the 1.9X genome sequence of Cinnamon[4]. In order to make the best use of the additional sequence reads for SNP discovery, we generated a new assembly; the new reads increase the depth-of-coverage of the genome by 50%.

Findings

Utility and Discussion

Conclusions