Epigenomic engineering for Down syndrome

@article{Mentis2016EpigenomicEF,
  title={Epigenomic engineering for Down syndrome},
  author={Alexios‐Fotios A. Mentis},
  journal={Neuroscience \& Biobehavioral Reviews},
  year={2016},
  volume={71},
  pages={323-327}
}
  • A. Mentis
  • Published 1 December 2016
  • Biology
  • Neuroscience & Biobehavioral Reviews

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References

SHOWING 1-10 OF 65 REFERENCES

Down syndrome—recent progress and future prospects

TLDR
Recent research progress in DS is reviewed, highlighting exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21.

Translating Dosage Compensation to Trisomy 21

Down’s syndrome is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21. We tested the concept that gene imbalance across an extra chromosome can be de facto

Domains of genome-wide gene expression dysregulation in Down’s syndrome

TLDR
The results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.

Understanding the Basis for Down Syndrome Phenotypes

TLDR
This work considers genotype–phenotype interactions with the goal of producing working concepts that will be useful for approaches to ameliorate the effects of trisomy.

Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in down syndrome

TLDR
Examination of whole-genome DNA methylation in buccal epithelial cells of 10 adults with DS and 10 controls indicated that both Trisomy 21 and cognitive impairment were associated with distinct patterns ofDNA methylation.

Identification of a DNA methylation signature in blood cells from persons with Down Syndrome

TLDR
An epigenetic signature of DS is identified that sustains a link between developmental defects and disease phenotype, including segmental premature aging of central nervous and immune systems.

Classification of human chromosome 21 gene-expression variations in Down syndrome: impact on disease phenotypes.

TLDR
It is shown that alternative transcripts belonging to the same gene are similarly regulated in Down syndrome but sense and antisense transcripts are not, and most of the chromosome 21 transcripts are compensated for the gene-dosage effect.

Can Down syndrome be treated?

TLDR
Several clinical trials of drugs to improve memory and learning in adults with Down syndrome are now under way, and labs are attempting to steer brain development onto a more typical path early on, for example, by inactivating the extra chromosome.
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