title: Incidental medical information in whole-exome sequencing.
abstract: Genomic technologies, such as whole-exome sequencing, are a powerful tool in genetic research. Such testing yields a great deal of incidental medical information, or medical information not related to the primary research target. We describe the management of incidental medical information derived from whole-exome sequencing in the research context. We performed whole-exome sequencing on a monozygotic twin pair in which only 1 child was affected with congenital anomalies and applied an institutional review board-approved algorithm to determine what genetic information would be returned. Whole-exome sequencing identified 79525 genetic variants in the twins. Here, we focus on novel variants. After filtering artifacts and excluding known single nucleotide polymorphisms and variants not predicted to be pathogenic, the twins had 32 novel variants in 32 genes that were felt to be likely to be associated with human disease. Eighteen of these novel variants were associated with recessive disease and 18 were associated with dominantly manifesting conditions (variants in some genes were potentially associated with both recessive and dominant conditions), but only 1 variant ultimately met our institutional review board-approved criteria for return of information to the research participants.
authors.affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. solomonb@mail.nih.gov
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Solomon
authors.forename: Donald W
authors.initials: DW
authors.lastname: Hadley
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Pineda-Alvarez
authors.forename: Aparna
authors.initials: A
authors.lastname: Kamat
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Teer
authors.forename: Praveen F
authors.initials: PF
authors.lastname: Cherukuri
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Hansen
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.forename: Alice C
authors.initials: AC
authors.lastname: Young
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Berkman
authors.forename: Settara C
authors.initials: SC
authors.lastname: Chandrasekharappa
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
mesh_terms: D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D028744:Ethics Committees, Research / Q000941:ethics / Q000592:standards*; D059472:Exome / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D033162:Incidental Findings; D007231:Infant, Newborn; D017422:Sequence Analysis, DNA / Q000941:ethics / Q000592:standards*; D014430:Twins, Monozygotic / Q000235:genetics*