title: Global analysis of disease-related DNA sequence variation in 10 healthy individuals: implications for whole genome-based clinical diagnostics.
abstract: BACKGROUND
  Understanding how sequence variants within healthy genomes are distributed with respect to ethnicity and disease-implicated genes is an essential first step toward establishing baselines for personalized genomic medicine.
  
  
  METHODS
  In this study, we present an analysis of 10 genomes from healthy individuals of various ethnicities, produced using six different sequencing technologies. In total, these genomes contain more than 34 million single-nucleotide variants.
  
  
  RESULTS
  We have analyzed these variants from a clinical perspective, assaying the influence of sequencing technology and ethnicity on prognosis. We have also examined the utility of OMIM and the disease-gene literature for determining the impact of rare, personal variants on an individual's health.
  
  
  CONCLUSIONS
  Our analyses demonstrate that clinical prognoses are complicated by sequencing platform-specific errors and ethnicity. We show that disease-causing alleles are globally distributed along ethnic lines, with alleles known to be disease causing in Eurasians being significantly more likely to be homozygous in Africans.
authors.affiliation: Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Moore
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Marc
authors.initials: M
authors.lastname: Singleton
authors.forename: Francisco M
authors.initials: FM
authors.lastname: De La Vega
authors.forename: Martin G
authors.initials: MG
authors.lastname: Reese
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
mesh_terms: D000483:Alleles; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D005826:Genetics, Medical; D016678:Genome; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D044469:Racial Groups / Q000235:genetics; D017422:Sequence Analysis, DNA