Tom Laver

Senior Lecturer in Diabetes at the University of Exeter Medical School. Interested in rare disease genetics, bioinformatics, DNA sequencing.

[European Journal of Human Genetics @ejhg_journal]

A novel mechanism for congenital hyperinsulinism.
https://t.co/yJjpOsJs3v

[Sarah E. Flanagan @flanagan_se]

@TomLaver is flying the flag for #congenitalhyperinsulinism #SGGDExeter2024. Great to see him showcase the team’s work on low level mosaic variants in CHI. A study made possible through generous @MDBRide4Rare grant funding @congenitalhi

[Tom Laver @TomLaver]

Only 5 days left to apply for this bioinformatics post-doc position in Exeter. Deadline April 10th https://t.co/mB1OFYGuVJ

[Tom Laver @TomLaver]

We're hiring a Postdoctoral Research Fellow in Bioinformatics and Genetics - https://t.co/mB1OFYGuVJ. Come join our team in Exeter researching the genetic causes of monogenic diabetes and hyperinsulinism.

[Exeter Uni Jobs @UoE_Jobs]

Recruiting now for a Postdoctoral #Research Fellow in #Bioinformatics and Genetics to join a world-leading team of researchers studying the genetic basis of diabetes and related conditions. To find out more: https://t.co/WW8LB4Vlct

[Tom Laver @TomLaver]

We're hiring a Postdoctoral Research Fellow in Bioinformatics and Genetics - https://t.co/mB1OFYGuVJ. Come join our team in Exeter researching the genetic causes of monogenic diabetes and hyperinsulinism.

[Veera Rajagopal  @doctorveera]

A fascinating gene detective work by @flanagan_se and team uncovers large deletions disrupting FOXA2 as the genetic cause of congenital hyperinsulinism (HI).

Here the authors identify five HI patients with overlapping heterozygous large deletion CNVs. Interestingly, the causal gene turned out to be the one that lay outside the critical region deleted in all the patients.

Mapping the genes within large CNVs to their phenotypes is extremely difficult as I have mentioned in a previous post about CNVs (https://t.co/WdLdBCyR02). To identify the causal gene underlying a particular phenotype (e.g. a disease) observed among CNV carriers, the scientists overlay all the CNVs, say, deletions of different sizes and triangulate the critical region that is deleted in all the individuals with the disease and then, study genes that fall within that critical region. This common approach ignores the non-coding genome. The current paper emphasizes the importance of looking at the noncoding genome as well when mapping causal genes.

Overlaying the deletions identified in the five HI patients, the authors found five genes whose entire coding regions fell within the critical region. However, none of these genes couldn't be linked to the disease phenotype. So, the authors started looking outside the critical region and noticed FOXA2 which was previously linked to HI via heterozygous pathogenic variants (https://t.co/VwcDh6VjTd).

In two of the five patients, the FOXA2 coding region was deleted. Makes sense. But then, what about the ones who had intact FOXA2 sequences? It turned out that in those individuals the regulatory regions critical for FOXA2 expression were instead disrupted causing an effect similar to deleting the FOXA2 gene itself.

The current discovery is a new addition to the list of genetic discoveries that the authors have been uncovering over the years in their clinical cohort of unsolved cases of congenital hyperinsulinism. Refer to this thread (https://t.co/BQi2wlvvBw) to learn about a previous discovery by the authors (https://t.co/VApffYaNAO).

The current preprint:
https://t.co/AkTv1hr9Ha

[Tom Laver @TomLaver]

Great opportunity to become part of our team at Exeter

[Dr Adam Rutherford @AdamRutherford]

h this is a good idea; like anti-particles, the predicted result will be annihilation, with a puff of guff? https://t.co/heDziKtEop

[Sarah E. Flanagan @flanagan_se]

The @HIgenes teams inaugural bioRxiv'ed paper. Syndromic causes of #hyperinsulinism are a rare but important cause of disease in individuals presenting with isolated hyperinsulinism @TomLaver https://t.co/q9RhDPfkTL

[Exeter Med School @ExeterMed]

Huge congratulations to @flanagan_se, who has been awarded the G.B. #Morgagni Silver Young Investigator Award, which celebrates exceptional research in the field of metabolic diseases! #ExeterDiabetes

Find out more about Dr Flanagan's achievement here: https://t.co/XtlG2aDmGh

[Sarah E. Flanagan @flanagan_se]

CACNA1D mutations cause #hyperinsulinaemic #hypoglycaemia, it's great to see this work published https://t.co/xPQplIcUX3 @HIgenes