Publication highlights: November 2022 to January 2023
By Research Management team on
Below are some of the notable papers published by researchers from our research community in the last few months. These publications use data from the National Genomics Research Library.
Whole genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
Robbe et al., Nature Genetics, Nov 2022
Chronic lymphocytic leukemia (CLL) is the most common adult haematological cancer and accounts for about 1/4 of new leukemia cases. Treatment outcomes are highly variable and difficult to predict, in part due our limited understanding of the genomic landscape that influences CLL and the lack of established genomic prognostic markers.
Here, the authors used whole genome sequencing data from 485 participants in the 100,000 Genomes Project to explore the genomic landscape of CLL and investigate its relationship to clinical outcome. They produced a detailed map of diverse variants and genomic features associated with the condition and then used this information to define 5 genomic subgroups of CLL which predict treatment outcome.
Their findings greatly increase our understanding of the genomics underlying CLL and may improve our ability to predict and optimise treatment outcomes for individual patients.
Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing
Macken et al., Nature Communications, Nov 2022
Whole genome sequencing (WGS) has revolutionised our ability to diagnose rare diseases and is now commonly used in clinical practice and research. However, interpretation of WGS for complex disorders can be challenging and standard semi-automated analyses often fail to return a diagnosis.
Here, Macken et al. examine WGS data from 102 adults with mitochondrial disease phenotypes. They demonstrate that in cases where a genomic diagnosis is not provided by initial standard analyses, a tailored multidisciplinary re-examination – including bespoke bioinformatic approaches, expanded variant analysis, phenotypic validation, and functional work – can greatly improve the diagnostic rate (16.7% to 31.4%).
They argue that providing such personalised scrutiny to complex cases is critical to maximising diagnostic gains and clinical benefit for patients.
The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision
Chrystal et al., Nature Communications, Nov 2022
Cilia are hair-like cellular projections that play crucial roles in human reproduction, development, health and disease. Motile cilia generate force to propel sperm and extracellular fluids, while non-motile cilia act as antennae for the reception and transduction of critical extracellular signals. Defects in motile and non-motile cilia produce distinct clinical phenotypes (ciliopathies) and are largely assumed to have exclusive genetic causes.
Here, the authors identify 8 human patients with inherited retinal dystrophy, a condition often caused by non-motile cilia defects, and uncover causative biallelic missense and canonical splice-site variants in CFAP20. Using a combination of zebrafish, C. elegans, and mammalian cell culture model systems they then demonstrate critical molecular functions for CFAP20 in both motile and non-motile cilia.
Together, their work sheds new light on the genetics of ciliopathies and challenges the common assumption that motile and non-motile ciliopathies are caused by mutations in distinct groups of proteins.
For more publications being produced by our research community, visit our publications page.
