Prospective Study to Assess Medical Performance of Optical Mapping and Long Read Sequencing in Detecting Numerical and Structural Chromosome Abnormalities

Summary

Chromosomal aberrations are major causes of developmental disorders (Intellectual disability (ID), multiple congenital anomalies (MCA), autism spectrum disorders (ASD)) as well as reproductive disorders (RD) in particular gametogenesis defects and recurrent miscarriages. Current first tier genetic investigations for chromosome analysis in clinical settings include karyotyping in case of RD (5 \~ 10% diagnosis rate) and chromosomal microarrays (CMA) in case of ID/MM (10 \~ 20% diagnosis rate). However, both assays show significant drawbacks, e.g. low resolution for karyotyping and inability to detect balanced structural rearrangement for CMA.

Optical genome mapping and long read genome sequencing are emerging technologies that offer new opportunities to overcome these limitations and allow for a higher resolution chromosome analysis.

This project aims at assessing the performance of optical mapping and long read whole genome sequencing compared to current gold standard cytogenetics methods in a prospective study. The investigator will evaluate their ability to become the all-in-one methodology for genomic analysis that could replace both karyotype and CMA and their added-value compared to these latter by uncovering new diagnoses.

Conditions

• Infertility
• Intellectual Disability
• Malformation
• Miscarriage

Interventions

GENETIC

Optical Genome Mapping (Bionano®)

Search for chromosome abnormalities through alteration of the optical map of the genome compared to reference genome using the Bionano® 's pipeline.

GENETIC

Longread sequencing (Nanopore®)

Search for chromosome abnormalities from the sequencing data obtain from high molecular weight DNA molecules using dedicated analysis pipeline.

Sponsors & Collaborators

• CHU Rennes - Hopital Pontchaillou

  collaborator OTHER

• APHP

  collaborator OTHER

• CHU de Rouen - Accueil

  collaborator OTHER

• University Hospital, Strasbourg

  collaborator OTHER

• Université Montpellier

  collaborator OTHER

• University Hospital, Clermont-Ferrand

  collaborator OTHER

• CHU de Reims

  collaborator OTHER

• APHM

  collaborator UNKNOWN

• Hospices Civils de Lyon

  collaborator OTHER

• Institut National de la Santé Et de la Recherche Médicale, France

  lead OTHER_GOV

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-09-26

Primary Completion

2025-03-26

Completion

2026-06-26

Countries

• France

Study Locations