Uncovering the burden of hidden ciliopathies in the 100 000 Genomes Project: a reverse phenotyping approach.

ABSTRACT:

Background

The 100 000 Genomes Project (100K) recruited National Health Service patients with eligible rare diseases and cancer between 2016 and 2018. PanelApp virtual gene panels were applied to whole genome sequencing data according to Human Phenotyping Ontology (HPO) terms entered by recruiting clinicians to guide focused analysis.

Methods

We developed a reverse phenotyping strategy to identify 100K participants with pathogenic variants in nine prioritised disease genes (BBS1, BBS10, ALMS1, OFD1, DYNC2H1, WDR34, NPHP1, TMEM67, CEP290), representative of the full phenotypic spectrum of multisystemic primary ciliopathies. We mapped genotype data 'backwards' onto available clinical data to assess potential matches against phenotypes. Participants with novel molecular

SUBMITTER: Best S 

PROVIDER: S-EPMC9691823 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature