MARCH 28TH, 2019

The shortest bi-weekly genomics research report in the world. Curated by the Emedgene Research Division.

Hubris meets Humility

This was one of our favorite reads this week, but it could have been the title that hooked us in. How will medical genetics be transformed by clinical genomics? Here are some lessons learned in 6 years of exome/genome sequencing (a partial list):

  • Exome sequencing has better diagnostic yield than gene panels
  • Communication with the ordering clinician is essential
  • Diagnostic yield is quite high (assuming careful patient selection)
  • Insurance coverage has been spotty, much as it was for chromosomal microarrays when they were introduced
  • Most patients and parents decline the opportunity to “opt out” of incidental findings, and those are found in about 2% of cases

Genetics in Medicine

While we’re on the philosophical side of things, should we return VUS to patients? This review argues that the benefits outweigh the potential harm.
Nature Reviews Genetics

The gnomAD SV callset, ready to use

The first large-scale reference map for SVs. Constructed from deep whole-genome sequencing (WGS) of 14,891 individuals across diverse global populations and available via the gnomAD website.


If you’ve been following Breaking Genes for a while, you know this is something we’re particularly interested in.

1st we have prenatal genetic carrier screening in a database of over 100k exomes. The researchers looked at 415 genes associated with severe recessive conditions. Screening for all 415 would identify 0.17–2.52% of couples as being at risk for having a child affected by one of these conditions. An ancestry specific panel with 5-28 genes would have the same yield as a 40 gene panethnic panel.
Genetics in Medicine

2% of patients from a 7k+cohort had multiple potentially relevant genetic findings, particularly when patients from consanguineous families or presented with greater clinical complexity. In these cases,exome testing might be more effective than panel at ending the diagnostic odyssey.
Genetics in Medicine

Cartoon Break !


If you’re flying to Seattle for a quick ACMG meeting, you can find us at:

Booth #403
Visit any time for a live demo

Poster #412
‘Determining the Optimal Familial Composition of Exome Sequencing Samples: Clinical Recommendations Based on Empirical Data’
Friday, April 5, 10:30 am – 12:00 pm

We’re on a transcriptome roll

A large transcriptomic imputation study of schizophrenia identifies 413 genic associations across 13 brain regions. The researchers are hoping to elucidate signals in GWAS loci.
Nature Genetics

The AI Corner

Researchers trained an algorithm to automatically add symptoms to patient charts. The model proved highly sensitive (92%) to clearly mentioned symptoms, but only half the symptoms met that criteria.
JAMA Internal Medicine

We have our own model for automatically importing phenotypes from clinical notes. Although the sensitivity is high, from a design standpoint the geneticist on the case has the ability to review and modify entities the algorithm selects.

Significant singles:
  • New Emedgene contributed publication: Novel WWOX deleterious variants cause early infantile epileptic encephalopathy European Journal of Paediatric Neurology
  • De novo SMARCD1 mutations in a syndromic neurodevelopmental disorder AJHG

Ada Reports

(Ada is our AI engine, she likes to add an interesting new factoid she discovered in every issue)

By identifying a novel variant in FOXP3, researchers show the variable nature of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.
Frontiers in Pediatrics

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The shortest bi-weekly genomics research report in the world

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