WGS to ascertain if the gain identified affects gene functionality
Research type
Research Study
Full title
Follow up studies on patients with known copy number gains in OMIM/DDG2P genes to ascertain if the gain affects the functionality of the gene and contributes to the phenotype.
IRAS ID
240481
Contact name
Karen Marks
Contact email
Sponsor organisation
St George's University Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Copy Number Variants (CNVs) are gains or losses of sections of the genome. Array Comparative Genome Hybridisation (CGH) is a technique used to detect these CNVs in the genome, by comparing the quantity of patient DNA to reference DNA. The reference and patient genomes are labelled with different fluorescent tags. Both sets of tagged DNA are applied to a slide and compete to attach to the corresponding 60 base pair (bp) segments of DNA attached to the slide.
Array CGH however, is unable to tell positional information about the gain/duplication. Most are assumed to be arranged one in front of the other, in tandem. However in some cases where they do not, their location and/or orientation can disrupt genes or form fusion genes. A fusion gene is where two previously separate genes are joined together. This can have consequences on gene function, regulation and expression in the body, and in turn have an effect on the patient’s characteristics (phenotype).
Whole genome sequencing (WGS) is a molecular technique which allows you to be able to sequence the full genetic code of an individual. This technique gives us additional information about the duplication including positional information as well as information on the orientation of the duplication.
This study will be looking at copy number gains, previously identified by array CGH, in a cohort of patients, and using the extra information available from WGS to evaluate how these CNV duplications are arranged in their genome. Following this, specialist bioinformatics and interpretation software will be utilised to judge how the gain/genomic rearrangement is likely to affect an individual’s overall phenotype. Combining this information with information from clinical notes for our cohort of patients, we will be able to establish if there is a correlation with the observed unusual phenotype in our patients, and the genomic rearrangements identified by WGS.
REC name
London - Bloomsbury Research Ethics Committee
REC reference
18/LO/0748
Date of REC Opinion
14 May 2018
REC opinion
Favourable Opinion