title: Gene inactivation and its implications for annotation in the era of personal genomics.
abstract: The first wave of personal genomes documents how no single individual genome contains the full complement of functional genes. Here, we describe the extent of variation in gene and pseudogene numbers between individuals arising from inactivation events such as premature termination or aberrant splicing due to single-nucleotide polymorphisms. This highlights the inadequacy of the current reference sequence and gene set. We present a proposal to define a reference gene set that will remain stable as more individuals are sequenced. In particular, we recommend that the ancestral allele be used to define the reference sequence from which a core human reference gene annotation set can be derived. In addition, we call for the development of an expanded gene set to include human-specific genes that have arisen recently and are absent from the ancestral set.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Suganthi
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Lukas
authors.initials: L
authors.lastname: Habegger
authors.forename: Adam
authors.initials: A
authors.lastname: Frankish
authors.forename: Daniel G
authors.initials: DG
authors.lastname: MacArthur
authors.forename: Rachel
authors.initials: R
authors.lastname: Harte
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harrow
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
mesh_terms: D020868:Gene Silencing / Q000502:physiology*; D030661:Genetic Privacy / Q000639:trends; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide