A whole-genome analysis of premature termination codons

作者：Cirulli Elizabeth T; Heinzen Erin L; Dietrich Fred S; Shianna Kevin V; Singh Abanish; Maia Jessica M; Goedert James J; Goldstein David B^*

来源：Genomics, 2011, 98(5): 337-342.

DOI：10.1016/j.ygeno.2011.07.001

• Nonsense-mediated decay
• Whole-genome sequencing
• RNA-Seq
• Premature termination codons

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 x 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 tran stop codon-gains without alternate functions were generally not found in the cDNA (p = 3 x 10(-5)). Additionally, stop colon-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.

• 出版日期2011-11