title: Missing genetic risk in neural tube defects: can exome sequencing yield an insight?
abstract: BACKGROUND
  Neural tube defects (NTD) have a strong genetic component, with up to 70% of variance in human prevalence determined by heritable factors. Although the identification of causal DNA variants by sequencing candidate genes from functionally relevant pathways and model organisms has provided some success, alternative approaches are demanded.
  
  
  METHODS
  Next generation sequencing platforms are facilitating the production of massive amounts of sequencing data, primarily from the protein coding regions of the genome, at a faster rate and cheaper cost than has previously been possible. These platforms are permitting the identification of variants (de novo, rare, and common) that are drivers of NYTD etiology, and the cost of the approach allows for the screening of increased numbers of affected and unaffected individuals from NTD families and in simplex cases.
  
  
  CONCLUSIONS
  The next generation sequencing platforms represent a powerful tool in the armory of the genetics researcher to identify the causal genetic basis of NTDs.
authors.affiliation: Duke Molecular Physiology Institute, DUMC, 300 North Duke Street, Durham, NC, 27701.
authors.forename: Deidre R
authors.initials: DR
authors.lastname: Krupp
authors.forename: Karen L
authors.initials: KL
authors.lastname: Soldano
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.forename: Heidi
authors.initials: H
authors.lastname: Cope
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
mesh_terms: D001483:Base Sequence; D059472:Exome / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054259:Neural Tube / Q000196:embryology; D009436:Neural Tube Defects / Q000235:genetics*; D017422:Sequence Analysis, DNA
keywords: compound heterozygosity; de novo, rare and common variation; next generation exome sequencing