Structural Variants Create New Topological-Associated Domains and Ectopic Retinal Enhancer-Gene Contact in Dominant Retinitis Pigmentosa.

Journal:
American Journal of Human Genetics
Published:
DOI:
10.1016/j.ajhg.2020.09.002
Affiliations:
27
Authors:
37

Research Highlight

A complex cause of heritable blindness

© Nastasic/DigitalVision Vectors/Getty Images

A new genetic cause of retinitis pigmentosa, an inherited disorder that causes vision loss, has been uncovered.

Dozens of genes have been linked to the degenerative eye condition, but many afflicted families still lack a molecular diagnosis because they don’t carry mutations in any of these genes.

Now, a team that included scientists from the University of Cape Town has identified a region on chromosome 17 of the human genome where various complex structural variants accounted for the disease.

To better understand how the variants affected cellular function, the team created stem cells from afflicted individuals and turned them into retinal tissue. They found that the genetic changes in chromosome 17 altered the three-dimensional organization of the genome in ways that led to gene misexpression.

This new mechanism provides a new genetic alteration to test for in patients with unexplained retinitis pigmentosa.

Supported content

References

  1. The American Journal of Human Genetics 107, 802-814 (2020). doi: 10.1016/j.ajhg.2020.09.002
Institutions Authors Share
Radboud University Medical Centre (Radboudumc), RU, Netherlands
7.366667
0.20
UCL, United Kingdom (UK)
5.500000
0.15
University of Cape Town (UCT), South Africa
5.200000
0.14
UK Inherited Retinal Dystrophy Consortium (UKIRDC), United Kingdom (UK)
4.333333
0.12
Donders Institute for Brain, Cognition and Behaviour, Netherlands
2.833333
0.08
Leeds Institute of Medical Research at St James's (LIMR), University of Leeds, United Kingdom (UK)
1.500000
0.04
Moorfields Eye Hospital, Moorfields Eye Hospital NHS Foundation Trust, United Kingdom (UK)
1.500000
0.04
Rotterdam Eye Hospital, Netherlands
1.000000
0.03
Max Planck Institute for Molecular Genetics (MPI-MG), Germany
1.000000
0.03
Charité - University Medicine Berlin, Germany
1.000000
0.03
UCL/MRC Prion Unit, United Kingdom (UK)
1.000000
0.03
McGill University, Canada
1.000000
0.03
University of Cambridge, United Kingdom (UK)
0.666667
0.02
Manchester Centre for Genomic Medicine (MCGM), United Kingdom (UK)
0.500000
0.01
Institute of Molecular and Clinical Ophthalmology Basel (IOB), Switzerland
0.333333
0.01
Oxford University Hospitals NHS Trust (OUH), United Kingdom (UK)
0.333333
0.01
University of Oxford, United Kingdom (UK)
0.333333
0.01
NIHR Cambridge Biomedical Research Centre (Cambridge BRC), United Kingdom (UK)
0.333333
0.01
University of Leicester, United Kingdom (UK)
0.333333
0.01
University Hospital Basel (USB), UB, Switzerland
0.333333
0.01
Radboud Institute for Molecular Life Sciences (RIMLS), RU, Netherlands
0.200000
0.01
University of Lisbon (ULISBOA), Portugal
0.200000
0.01
Institute of Molecular Medicine (IMM), Portugal
0.200000
0.01