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De novo mutations in regulatory elements in neurodevelopmental disorders

Overview of attention for article published in Nature, March 2018
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • Good Attention Score compared to outputs of the same age and source (72nd percentile)

Citations

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229 Dimensions

Readers on

mendeley
491 Mendeley
citeulike
8 CiteULike
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Title
De novo mutations in regulatory elements in neurodevelopmental disorders
Published in
Nature, March 2018
DOI 10.1038/nature25983
Pubmed ID
Authors

Patrick J. Short, Jeremy F. McRae, Giuseppe Gallone, Alejandro Sifrim, Hyejung Won, Daniel H. Geschwind, Caroline F. Wright, Helen V. Firth, David R. FitzPatrick, Jeffrey C. Barrett, Matthew E. Hurles

Abstract

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.

X Demographics

X Demographics

The data shown below were collected from the profiles of 255 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 491 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Unknown 490 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 117 24%
Researcher 107 22%
Student > Master 42 9%
Student > Bachelor 37 8%
Other 27 5%
Other 80 16%
Unknown 81 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 161 33%
Agricultural and Biological Sciences 102 21%
Medicine and Dentistry 47 10%
Neuroscience 37 8%
Computer Science 13 3%
Other 36 7%
Unknown 95 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 214. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 October 2020.
All research outputs
#181,471
of 25,397,764 outputs
Outputs from Nature
#11,053
of 97,875 outputs
Outputs of similar age
#4,293
of 347,654 outputs
Outputs of similar age from Nature
#251
of 914 outputs
Altmetric has tracked 25,397,764 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 97,875 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 102.5. This one has done well, scoring higher than 88% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 347,654 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 914 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.