title: A whole-genome analysis of premature termination codons.
abstract: We sequenced the genomes of ten unrelated individuals and identified heterozygous stop codon-gain variants in protein-coding genes: we then sequenced their transcriptomes and assessed the expression levels of the stop codon-gain alleles. An ANOVA showed statistically significant differences between their expression levels (p=4×10(-16)). This difference was almost entirely accounted for by whether the stop codon-gain variant had a second, non-protein-truncating function in or near an alternate transcript: stop codon-gains without alternate functions were generally not found in the cDNA (p=3×10(-5)). Additionally, stop codon-gain variants in two intronless genes were not expressed, an unexpected outcome given previous studies. In this study, stop codon-gain variants were either well expressed in all individuals or were never expressed. Our finding that stop codon-gain variants were generally expressed only when they had an alternate function suggests that most naturally occurring stop codon-gain variants in protein-coding genes are either not transcribed or have their transcripts destroyed.
authors.affiliation: Center for Human Genome Variation, Duke University School of Medicine, Durham, NC 27708, USA.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Cirulli
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heinzen
authors.forename: Fred S
authors.initials: FS
authors.lastname: Dietrich
authors.forename: Kevin V
authors.initials: KV
authors.lastname: Shianna
authors.forename: Abanish
authors.initials: A
authors.lastname: Singh
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Maia
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D022981:Allelic Imbalance; D000704:Analysis of Variance; D018389:Codon, Nonsense / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D011110:Polymorphism, Genetic; D016415:Sequence Alignment; D059467:Transcriptome
chemical_list: D018389:Codon, Nonsense; D018076:DNA, Complementary