title: Whole-genome sequencing and variant discovery in C. elegans.
abstract: Massively parallel sequencing instruments enable rapid and inexpensive DNA sequence data production. Because these instruments are new, their data require characterization with respect to accuracy and utility. To address this, we sequenced a Caernohabditis elegans N2 Bristol strain isolate using the Solexa Sequence Analyzer, and compared the reads to the reference genome to characterize the data and to evaluate coverage and representation. Massively parallel sequencing facilitates strain-to-reference comparison for genome-wide sequence variant discovery. Owing to the short-read-length sequences produced, we developed a revised approach to determine the regions of the genome to which short reads could be uniquely mapped. We then aligned Solexa reads from C. elegans strain CB4858 to the reference, and screened for single-nucleotide polymorphisms (SNPs) and small indels. This study demonstrates the utility of massively parallel short read sequencing for whole genome resequencing and for accurate discovery of genome-wide polymorphisms.
authors.affiliation: Washington University School of Medicine, Department of Genetics and Genome Sequencing Center, 4444 Forest Park Blvd., St. Louis, Missouri 63108, USA.
authors.forename: LaDeana W
authors.initials: LW
authors.lastname: Hillier
authors.forename: Gabor T
authors.initials: GT
authors.lastname: Marth
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Quinlan
authors.forename: David
authors.initials: D
authors.lastname: Dooling
authors.forename: Ginger
authors.initials: G
authors.lastname: Fewell
authors.forename: Derek
authors.initials: D
authors.lastname: Barnett
authors.forename: Paul
authors.initials: P
authors.lastname: Fox
authors.forename: Jarret I
authors.initials: JI
authors.lastname: Glasscock
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickenbotham
authors.forename: Weichun
authors.initials: W
authors.lastname: Huang
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Magrini
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Richt
authors.forename: Sacha N
authors.initials: SN
authors.lastname: Sander
authors.forename: Donald A
authors.initials: DA
authors.lastname: Stewart
authors.forename: Michael
authors.initials: M
authors.lastname: Stromberg
authors.forename: Eric F
authors.initials: EF
authors.lastname: Tsung
authors.forename: Todd
authors.initials: T
authors.lastname: Wylie
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D004252:DNA Mutational Analysis / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*