HEИндивидуална стипендия2023–2025

STRIPE · Structural variants impacting peripheral neurodegeneration

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-10-01 → 2025-09-30
Финансиране от ЕС: 191 760 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Наследствените невропатии се изследват чрез ново секвениране на ДНК, което открива сложни генетични дефекти, невидими за стандартните тестове. Това помага за по-бързата диагностика на пациентите и предоставя точна генетична консултация за семействата им.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Structural variants impacting peripheral neurodegeneration

Inherited peripheral neuropathies are rare neurological conditions that cause progressive nerve dysfunction, muscle wasting, walking problems, and lifelong disability. Despite advances in genetic testing, many patients still remain without a genetic diagnosis, often for years. This "diagnostic odyssey" delays access to specialist care and prevents families from receiving accurate genetic counselling. One major reason for the low diagnostic rate is that standard short-read DNA sequencing technologies are unable to detect certain types of genetic variation. This project sets out to address this challenge by applying long-read genome sequencing, an emerging technology capable of reading continuous stretches of DNA much longer than conventional methods. This technology provides a more complete view of the genome and has the potential to uncover disease-causing genetic defects that were previously unrecognized. The overall objectives are to apply nanopore genome sequencing to individuals with unsolved inherited neuropathies to identify candidate disease-causing genetic variants, determine how these variants affect gene function, and to establish novel gene-disease relationships.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Many Mendelian diseases have benefited from next-generation sequencing (NGS) technologies for gene discovery and the establishment of molecular diagnosis. However, the technical limitations of NGS pose a challenge for identifying mutational mechanisms in genomic regions impenetrable by these technologies. I hypothesize that complex genomic rearrangements called structural variants in these loci can explain a significant proportion of missing heritability in many monogenic diseases. To this end, I propose to investigate the involvement of structural variants in the pathogenesis of Charcot-Marie-Tooth disease (CMT), the most common genetic affliction of the peripheral nervous system. I will utilize long-read Nanopore sequencing in a unique patient cohort to look for potentially disease-causing structural variants. I will then adopt genetic and functional in vitro and in vivo approaches to characterize the identified genomic variants and ascertain the associated functional genes that most likely underlie molecular pathology. The findings of my pioneering study will highlight the contribution of structural variants in peripheral neurodegeneration, discover non-conventional mutational mechanisms long overlooked by state-of-the-art technologies, and deliver in vivo models that might provide clues for therapeutic approaches for peripheral nerve disorders with common etiology.

Оригинален текст от CORDIS (на английски).

Участници

VIB VZW · ZWIJNAARDE - GENTКоординаторБелгия