Genome-wide variations in a natural isolate of the nematode Caenorhabditis elegans

Ismael A Vergara,Maja Tarailo-Graovac,Ke Wang,Christian Frech,Jun Wang,Nansheng Chen,Jeffrey Sc Chu,Rong She,Ting Zhang,Zhaozhao Qin

doi:10.1186/1471-2164-15-255

Abstract

BackgroundIncreasing genetic and phenotypic differences found among natural isolates of C. elegans have encouraged researchers to explore the natural variation of this nematode species.ResultsHere we report on the identification of genomic differences between the reference strain N2 and the Hawaiian strain CB4856, one of the most genetically distant strains from N2. To identify both small- and large-scale genomic variations (GVs), we have sequenced the CB4856 genome using both Roche 454 (~400 bps single reads) and Illumina GA DNA sequencing methods (101 bps paired-end reads). Compared to previously described variants (available in WormBase), our effort uncovered twice as many single nucleotide variants (SNVs) and increased the number of small InDels almost 20-fold. Moreover, we identified and validated large insertions, most of which range from 150 bps to 1.2 kb in length in the CB4856 strain. Identified GVs had a widespread impact on protein-coding sequences, including 585 single-copy genes that have associated severe phenotypes of reduced viability in RNAi and genetics studies. Sixty of these genes are homologs of human genes associated with diseases. Furthermore, our work confirms previously identified GVs associated with differences in behavioural and biological traits between the N2 and CB4856 strains.ConclusionsThe identified GVs provide a rich resource for future studies that aim to explain the genetic basis for other trait differences between the N2 and CB4856 strains.

Highlights

Increasing genetic and phenotypic differences found among natural isolates of C. elegans have encouraged researchers to explore the natural variation of this nematode species
We show that the combined approach in which the strengths of both sequencing methods are used for the detection of Genomic variation (GV) provides an accurate way of detecting single nucleotide variants (SNVs) and small insertions and deletions in highly variable and homopolymeric regions, as well as a basepair-level resolution of the detection of large deletions, insertions and compound variations
To identify genomic variations (GVs) between the genome of the N2 strain of C. elegans and the Hawaiian strain (CB4856), we have sequenced the CB4856 genome using the Roche 454 genome sequencer FLX system [52] and Illumina GA

Summary

Introduction

Increasing genetic and phenotypic differences found among natural isolates of C. elegans have encouraged researchers to explore the natural variation of this nematode species. C. elegans is a model organism that has been widely used for biomedical research, shedding light on diseases such as Alzheimer [1] and cancer [2]. The genome of this hermaphrodite nematode species was the first one published of a multicellular animal [3] and its assembly and annotation is arguably one of the best of the multicellular organisms available today. N2 and CB4856 backgrounds have been used for the generation of genetic tools such as Recombinant Inbred Lines (or RILs) [24,25], Recombinant Inbred Advanced Intercrossed Lines (RIAILs) [26] and Nearly Isogenic Lines (or NILs, known as introgression lines) [27]

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