title: Identification of novel variants in colorectal cancer families by high-throughput exome sequencing.
abstract: BACKGROUND
  Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results; the use of exome sequencing in coding regions may identify novel segregating variants.
  
  
  METHODS
  We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci. Variants shared among all sequenced cases within each family were identified and filtered to exclude common variants and single-nucleotide variants (SNV) predicted to be benign.
  
  
  RESULTS
  We identified 32 nonsense or splice-site SNVs, 375 missense SNVs, 1,394 synonymous or noncoding SNVs, and 50 indels in the 16 families. Of particular interest are two validated and replicated missense variants in CENPE and KIF23, which are both located within previously reported CRC linkage regions, on chromosomes 1 and 15, respectively.
  
  
  CONCLUSIONS
  Whole-exome sequencing identified DNA variants in multiple genes. Additional sequencing of these genes in additional samples will further elucidate the role of variants in these regions in CRC susceptibility.
  
  
  CONCLUSIONS
  Exome sequencing of familial CRC cases can identify novel rare variants that may influence disease risk.
authors: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors: Melissa S
authors: MS
authors: DeRycke
authors: Shanaka R
authors: SR
authors: Gunawardena
authors: Sumit
authors: S
authors: Middha
authors: Yan W
authors: YW
authors: Asmann
authors: Daniel J
authors: DJ
authors: Schaid
authors: Shannon K
authors: SK
authors: McDonnell
authors: Shaun M
authors: SM
authors: Riska
authors: Bruce W
authors: BW
authors: Eckloff
authors: Julie M
authors: JM
authors: Cunningham
authors: Brooke L
authors: BL
authors: Fridley
authors: Daniel J
authors: DJ
authors: Serie
authors: William R
authors: WR
authors: Bamlet
authors: Mine S
authors: MS
authors: Cicek
authors: Mark A
authors: MA
authors: Jenkins
authors: David J
authors: DJ
authors: Duggan
authors: Daniel
authors: D
authors: Buchanan
authors: Mark
authors: M
authors: Clendenning
authors: Robert W
authors: RW
authors: Haile
authors: Michael O
authors: MO
authors: Woods
authors: Steven N
authors: SN
authors: Gallinger
authors: Graham
authors: G
authors: Casey
authors: John D
authors: JD
authors: Potter
authors: Polly A
authors: PA
authors: Newcomb
authors: Loïc
authors: L
authors: Le Marchand
authors: Noralane M
authors: NM
authors: Lindor
authors: Stephen N
authors: SN
authors: Thibodeau
authors: Ellen L
authors: EL
authors: Goode
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D059472:Exome; D005260:Female; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012042:Registries
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