Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease

@article{Tufarelli2003TranscriptionOA,
  title={Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease},
  author={Cristina Tufarelli and J. A. Sloane Stanley and David Garrick and Jacqueline A. Sharpe and Helena Ayyub and William G. Wood and Douglas R. Higgs},
  journal={Nature Genetics},
  year={2003},
  volume={34},
  pages={157-165}
}
Nearly all human genetic disorders result from a limited repertoire of mutations in an associated gene or its regulatory elements. We recently described an individual with an inherited form of anemia (α-thalassemia) who has a deletion that results in a truncated, widely expressed gene (LUC7L) becoming juxtaposed to a structurally normal α-globin gene (HBA2). Although it retains all of its local and remote cis-regulatory elements, expression of HBA2 is silenced and its CpG island becomes… 
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It is reported a cancer-affected family showing dominant transmission of soma-wide highly mosaic MLH1 methylation and transcriptional repression linked to a particular genetic haplotype, which was erased in spermatozoa but reinstated in the somatic cells of the next generation.
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TLDR
It is shown that many TSGs have nearby antisense RNAs, and an inverse relation between p15 antisense (p15AS) and p15 sense expression in leukaemia is found, which suggests natural antisense RNA may be a trigger for heterochromatin formation and DNA methylation in TSG silencing in tumorigenesis.
Genomic imprinting: a mammalian epigenetic discovery model.
  • D. Barlow
  • Biology, Medicine
    Annual review of genetics
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TLDR
The progress in understanding how imprinted protein-coding genes are silenced is described and the role of macro ncRNAs that have broad relevance as a potential new layer of regulatory information in the mammalian genome is focused on.
Isolation of cancer-specific chimeric transcripts induced by hypomethylation of the LINE-1 antisense promoter.
TLDR
Findings indicate that loss of L1 methylation in cancer cells is linked to the expression of L 1-chimeric transcripts which may therefore constitute a useful set of markers of malignancy.
Transcriptional gene silencing in humans
TLDR
How non-coding RNA plays a role in regulation of transcription and epigenetic gene silencing in human cells is reviewed by revisiting earlier studies and the mechanistic insights gained to date.
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