TY  - JOUR
A1  - Neville, Matthew D.C.
A1  - Kohze, Robin
A1  - Erady, Chaitanya
A1  - Meena, Narendra
A1  - Hayden, Matthew
A1  - Cooper, David N.
A1  - Mort, Matthew
A1  - Prabakaran, Sudhakaran
T1  - A platform for curated products from novel open reading frames prompts reinterpretation of disease variants
Y1  - 2021/02/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 327 
EP  - 336 
DO  - 10.1101/gr.263202.120 
VL  - 31 
IS  - 2 
UR  - http://genome.cshlp.org/content/31/2/327.abstract 
N2  - Recent evidence from proteomics and deep massively parallel sequencing studies have revealed that eukaryotic genomes contain substantial numbers of as-yet-uncharacterized open reading frames (ORFs). We define these uncharacterized ORFs as novel ORFs (nORFs). nORFs in humans are mostly under 100 codons and are found in diverse regions of the genome, including in long noncoding RNAs, pseudogenes, 3′ UTRs, 5′ UTRs, and alternative reading frames of canonical protein coding exons. There is therefore a pressing need to evaluate the potential functional importance of these unannotated transcripts and proteins in biological pathways and human disease on a larger scale, rather than one at a time. In this study, we outline the creation of a valuable nORFs data set with experimental evidence of translation for the community, use measures of heritability and selection that reveal signals for functional importance, and show the potential implications for functional interpretation of genetic variants in nORFs. Our results indicate that some variants that were previously classified as being benign or of uncertain significance may have to be reinterpreted. 
ER  -