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Oguz Kanca

@okanca.bsky.social

710 followers 870 following 23 posts

Assistant professor at Baylor College of Medicine, Drosophila enthusiast, tackling the conserved genome one gene at a time

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Oguz Kanca @okanca.bsky.social · Mar 20

Thank you very much for the kind words, Tim. Just a small correction, it was the GDP and DRSC that got the award.

Reposted by Oguz Kanca

The American Journal of Human Genetics @ajhgnews.bsky.social · Mar 14

📣New from @okanca.bsky.social & co
📄De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms
🧬🪰🧠

De novo variants in CDKL1 and CDKL2 are associated with neurodevelopmental symptoms

This study identifies de novo variants in CDKL1 and CDKL2 in individuals with neurodevelopmental symptoms and seizures. Functional analysis in fruit flies provides compelling evidence that these varia...

Oguz Kanca @okanca.bsky.social · Mar 15

The project was done by a talented postdoc in our lab Ali Bereshneh. The paper can be reached following the link below:
authors.elsevier.com/a/1km46geXDylR

authors.elsevier.com

Oguz Kanca @okanca.bsky.social · Mar 15

We are grateful to families and individuals who participated in the study and our clinical collaborators for an excellent collaboration. We are also grateful for our fly collaborators Jonathan Andrews and Daniel Eberl.

Oguz Kanca @okanca.bsky.social · Mar 15

We noticed that when we co-express the variant CDKL1 or 2 together with reference CDKL5 in Cdkl mutant background,(or CDKL1 or 2) the rescue ability of reference genes was impaired. This indicates that the variants we identified act in a dominant negative manner.

Oguz Kanca @okanca.bsky.social · Mar 15

All the individuals in our cohort are de novo heterozygous individuals, suggesting the variants we tested were unlikely to be loss of function alleles. We tested whether variants in CDKL1 or 2 can impinge on the function of reference CDKL genes.

Oguz Kanca @okanca.bsky.social · Mar 15

Variants in CDKL1 and CDKL2 either failed to rescue the observed phenotypes or rescued partially. CDKL genes with the exception of CDKL5 are tolerant to variation, with many individuals in control populations with one copy loss of CDKL1 or 2.

Oguz Kanca @okanca.bsky.social · Mar 15

We broaden our search to paralogs of CDKL2 to find variants that may be associated with Mendelian Diseases. We identified two variants in CDKL1 presenting with developmental delay in publicly available Deciphering Developmental Delay and GeneDx consortia that we included in our analysis.

Oguz Kanca @okanca.bsky.social · Mar 15

Interestingly, loss of Cdkl caused semi lethality, heat induced seizures and climbing defects. These phenotypes could be rescued by expressing the reference UAS human cDNAs of CDKL1, CDKL2, CDKL4 and CDKL5.

Oguz Kanca @okanca.bsky.social · Mar 15

To our surprise, Cdkl was very sparsely expressed in the central nervous system but we noticed Cdkl expression in every sensory neuron we analyzed (with the exception of photoreceptors). Below is our contribution to fluorescent Friday

Oguz Kanca @okanca.bsky.social · Mar 15

We generated a versatile allele of Cdkl, Cdkll-T2AGAL4 that allow us to determine the expression pattern of the gene and loss of function phenotypes associated with the loss of the gene. More details about the methodology and similar alleles can be found in flypush.research.bcm.edu/pscreen/crim...

GDP Screen Database

The Drosophila Gene Disruption Project (GDP) aims to obtain a transposable element insertion in each gene and is a collaboration among the Bellen, Perrimon and Spradling labs.

flypush.research.bcm.edu

Oguz Kanca @okanca.bsky.social · Mar 15

We used fruit fly model to study the impact of the identified variants. Drosophila has a single gene CG7236 (that we propose to rename Cdkl) which is orthologous to all 5 CDKL family of genes.

Oguz Kanca @okanca.bsky.social · Mar 15

Through gene matching efforts we connected with other clinical collaborators from Harvard Medical School and Belfast City Hospital who identified individuals with CDKL2 variants presenting with neuorodevelopmental symptoms partially overlapping with CDD symptoms.

Oguz Kanca @okanca.bsky.social · Mar 15

Variants in CDKL5 cause CDKL5 Deficiency Disorder (CDD), which is a rare disease with severe symptoms. Individuals with CDKL5 Deficiency disorder typically show symptoms including early onset epilepsy and developmental delay.

Oguz Kanca @okanca.bsky.social · Mar 14

It all started with our clinical collaborators from the Undiagnosed Diseases Network who identified an individual with a de novo variant in CDKL2 gene. CDKL2 is a member of Cyclin Dependent Kinase Like gene family. The only CDKL family member associated with a Mendelian disease was CDKL5.

Oguz Kanca @okanca.bsky.social · Mar 14

We are excited to share our latest paper published today linking specific variants in CDKL2 and CDKL1 to a novel neurodevelopmental disorder.
www.bcm.edu/news/new-cdk...

New CDKL genes linked to neurodevelopmental disorders

CDKL5, one of the five members of the CDKL family of genes, is important for proper neurodevelopment and associated with seizures. However, the role the...

Oguz Kanca @okanca.bsky.social · Nov 21

Look what I made! 🦋 With help from Scholar Goggler scholargoggler.com made by @morinryan.bsky.social.
Thanks @axelvisel.bsky.social for inspiration.

Oguz Kanca @okanca.bsky.social · Nov 20

Admittedly, flies are not as boopworthy but it reminded me of our cover from 2014.

Reposted by Oguz Kanca

Esther Verheyen 🇨🇦 @estherverheyen.bsky.social · Nov 20

Hello Bsky folks - here is a paper that we published earlier this year - great collaboration with the Bellen lab, Hyung-lok Chung, @okanca.bsky.social and others. Have a look if you're interested in Cdk8/19, mitochondria, Parkinsonism and Drosophila!

The Interactive Fly @interactivefly.bsky.social · Nov 14

Liao, J. Z., Chung, H. L., Shih, C., Wong, K. K. L., ...., Sew, K., Bellen, H. J., Verheyen, E. M. (2024). Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila. Nat Commun, 15(1):3326 www.nature.com/articles/s41...

Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila - Nature Communications

Mitochondrial fission, performed by Drp1, is carefully regulated, particularly in neurons. Here, the authors examine Drosophila Cdk8/CDK19 function in mitochondrial fission and uncover a role phosphor...

Oguz Kanca @okanca.bsky.social · Nov 20

Thank you Filip. And thanks for making the starter pack.

Oguz Kanca @okanca.bsky.social · Nov 20

Could you please add me too?

Reposted by Oguz Kanca

Esther Verheyen 🇨🇦 @estherverheyen.bsky.social · Nov 16

All these awesome starter packs are a great way to find folks to invite to conferences or seminars! I've met so many new people in the last few days 🪰🐸🪱🐭🐠
Check out the Animal models of disease one I made!
go.bsky.app/MhUwjSx

Oguz Kanca @okanca.bsky.social · Nov 13

I think when you swipe left you go from discovery mode to following mode where you only see the posts from those you follow. Does that help?

Reposted by Oguz Kanca

Jack Bateman @jbateman01.bsky.social · Nov 12

I thought we could use a Drosophila starter pack, please let me know if you’d like to be added. (I think there is also a more general insect list out there somewhere that i cant find rn..) go.bsky.app/JGggkH3

Oguz Kanca @okanca.bsky.social · Nov 13

I’d love to be added if possible. Thank you for the starter list