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Expanding the Transcriptomes at Unstable Tandem Repeat Loci
Author(s) -
Ladd Paula Dianne,
Dubinsky Amy N,
Lomas Nicole S,
Ko Hyeon A,
La Spada Albert R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.778.1
Subject(s) - biology , genetics , tandem repeat , transcriptome , gene , locus (genetics) , genome , chromatin , computational biology , gene expression
Unstable tandem repeats are responsible for at least 30 inherited neurodegenerative diseases, developmental disorders, and muscular dystrophies, where the causative factor is dynamic repeat instability with subsequent expansion beyond a threshold repeat size. Genome‐wide transcriptome studies reveal that antisense transcripts are present at most, if not all, non‐expanded tandem repeat gene loci, indicating that repeat expansions impact both sense and antisense transcripts. Since only a handful of tandem repeat loci have been fully characterized, the functional significance of antisense transcription is not yet known. We hypothesize that the activity of bidirectional transcription is directed by genomic context, thus the consequence of repeat expansion on the antisense transcript varies for each locus. Here we provide uniform characterization of multiple additional tandem repeat gene loci, using single molecule real time sequencing. We demonstrate that for many human tandem repeat genes, the local transcriptome is conserved in the mouse locus, suggesting functional significance. Furthermore, we distinguish gene loci that produce functionally independent bidirectional genes from loci that generate multiple transcriptional units to regulate the local chromatin structure, transcript stability, and/or translation. These distinctions enhance our understanding of disease pathogenesis.