Titre :

Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases.

Auteur(s) :

Hitti-Malin, Rebekkah J. [Auteur]
Donders Institute for Brain, Cognition and Behaviour
Dhaenens, Claire-Marie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Panneman, D. M. [Auteur]
Corradi, Z. [Auteur]
Khan, M. [Auteur]
Hollander, A. I. D. [Auteur]
Farrar, G. J. [Auteur]
Gilissen, C. [Auteur]
Hoischen, A. [Auteur]
Van De Vorst, M. [Auteur]
Bults, F. [Auteur]
Boonen, E. G. M. [Auteur]
Saunders, P. [Auteur]
Roosing, S. [Auteur]
Cremers, F. P. M. [Auteur]

Titre de la revue :

Human Mutation

Numéro :

43

Pagination :

2234–2250

Éditeur :

Wiley Online Library

Date de publication :

2022-10-26

ISSN :

1098-1004

Mot(s)-clé(s) :

cost-effective
high-throughput
macular diseases
smMIPs
targeted gene sequencing

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related ...
Lire la suite >Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 iMD and AMD-associated genes and noncoding or regulatory loci, known pseudo-exons, and the mitochondrial genome in two test cohorts that were previously screened for variants in ABCA4. Following detailed sequencing analysis of 110 probands, a diagnostic yield of 38% was observed. This established an ‘‘MD-smMIPs panel,” enabling a genotype-first approach in a high-throughput and cost-effective manner, whilst achieving uniform and high coverage across targets. Further analysis will identify known and novel variants in MD-associated genes to offer an accurate clinical diagnosis to patients. Furthermore, this will reveal new genetic associations for MD and potential genetic overlaps between iMD and AMD.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-01-16T00:30:41Z
2025-02-26T08:46:56Z