Splice site variants in the canonical donor site ofMED13Lexon 7 lead to intron retention in patients withMED13Lsyndrome DOI

Jade Fauqueux,

Simon Boussion,

C. Thuillier

et al.

Journal of Medical Genetics, Journal Year: 2024, Volume and Issue: 61(11), P. 1040 - 1044

Published: Aug. 24, 2024

Pathogenic variants in the MED13L gene are associated with autosomal dominant syndrome, which is characterised by global developmental delay and cardiac malformations. We investigated two heterozygous located at canonical donor splice site motif of exon 7: c.1009+1G>C c.1009+5G>C. report that silico predictions suggested possible outcomes: 7 skipping, resulting loss phosphodegron essential for regulation, or activation a cryptic intron 7, leading to retention. RNA analysis confirmed both affected site, retention 73 bp 7. This caused frameshift premature translation termination, consistent haploinsufficiency. Our results highlight importance combining predictive experimental approaches understand functional impact variants. These insights into molecular consequences provide deeper understanding genetic basis syndrome.

Language: Английский

GENA-LM: a family of open-source foundational DNA language models for long sequences DOI Creative Commons
Veniamin Fishman, Yuri Kuratov, Aleksei Shmelev

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(2)

Published: Jan. 11, 2025

Abstract Recent advancements in genomics, propelled by artificial intelligence, have unlocked unprecedented capabilities interpreting genomic sequences, mitigating the need for exhaustive experimental analysis of complex, intertwined molecular processes inherent DNA function. A significant challenge, however, resides accurately decoding which inherently involves comprehending rich contextual information dispersed across thousands nucleotides. To address this need, we introduce GENA language model (GENA-LM), a suite transformer-based foundational models capable handling input lengths up to 36 000 base pairs. Notably, integrating newly developed recurrent memory mechanism allows these process even larger segments. We provide pre-trained versions GENA-LM, including multispecies and taxon-specific models, demonstrating their capability fine-tuning addressing spectrum complex biological tasks with modest computational demands. While already achieved breakthroughs protein biology, GENA-LM showcases similarly promising potential reshaping landscape genomics multi-omics data analysis. All are publicly available on GitHub (https://github.com/AIRI-Institute/GENA_LM) HuggingFace (https://huggingface.co/AIRI-Institute). In addition, web service (https://dnalm.airi.net/) allowing user-friendly annotation models.

Language: Английский

Citations

3
Genome Annotation and Analysis DOI

Harsharan Singh,

Mannatpreet Khaira,

Karan Sharma

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

1
Splice site variants in the canonical donor site ofMED13Lexon 7 lead to intron retention in patients withMED13Lsyndrome DOI

Jade Fauqueux,

Simon Boussion,

C. Thuillier

et al.

Journal of Medical Genetics, Journal Year: 2024, Volume and Issue: 61(11), P. 1040 - 1044

Published: Aug. 24, 2024

Pathogenic variants in the MED13L gene are associated with autosomal dominant syndrome, which is characterised by global developmental delay and cardiac malformations. We investigated two heterozygous located at canonical donor splice site motif of exon 7: c.1009+1G>C c.1009+5G>C. report that silico predictions suggested possible outcomes: 7 skipping, resulting loss phosphodegron essential for regulation, or activation a cryptic intron 7, leading to retention. RNA analysis confirmed both affected site, retention 73 bp 7. This caused frameshift premature translation termination, consistent haploinsufficiency. Our results highlight importance combining predictive experimental approaches understand functional impact variants. These insights into molecular consequences provide deeper understanding genetic basis syndrome.

Language: Английский

Citations

0