Centre for Human Genetics

MicroRNA 517a-3p suppresses α-synuclein fibril accumulation in human glioblastoma cells

Abstract Background Synucleinopathies are a group of neurodegenerative disorders characterized by the misfolding, aggregation, and accumulation of α-synuclein (α-syn) into oligomeric assemblies and amyloid inclusions. Alongside neurons, glial cells can internalize pathological α-...

Spike antibody Fc is associated with protection from SARS-CoV-2 challenge in macaques

A definitive correlate of protection (CoP) for SARS-CoV-2 has yet to be formally established. We previously reported that neutralising antibodies (NAbs) are the strongest candidate CoP for clinical protection against COVID-19 and that spike binding antibody is the strongest candi...

Lithium chloride in vitro treatment shows potential to rescue the neuronal phenotype caused by WDFY3 haploinsufficiency

We provide a comprehensive phenotypic characterization of loss-of-function (LoF) variants in WDFY3 based on the largest cohort reported to date (n = 32). Our findings define a monogenic disorder marked by neuropsychiatric features (including autism and ADHD), mild to moderate neu...

Modulating splicing in 5ʹ untranslated regions to treat rare haploinsufficient disease

Abstract Background Rare genetic disorders collectively impact over 300 million people worldwide, yet around 95% have no specific treatments. For the many rare disorders caused by haploinsufficiency, effective therapies need to upregulate protein expression. However, therapeutic...

Association for Clinical Genomic Science (ACGS) Best Practice Guidelines for Variant Classification in Rare Disease

Revised ACGS variant classification guidelines 2026.

Accurately modeling RNase H-mediated antisense oligonucleotide efficacy.

, achieving a 5.72-fold reduction in screening effort compared to random selection. ASO Atlas provides the first systematic resource to rigorously evaluate hypotheses regarding key parameters in ASO design, including sequence composition, chemical modifications, and target region...

Longitudinal dynamics of gene expression and metabolomics in an aging population cohort

Multiomic profiling provides a comprehensive physiological overview at the molecular level, but understanding of its spatiotemporal dynamics remains limited in human populations. We profiled longitudinal whole-blood gene expression and metabolite levels in 335 females over 8 year...

Deviations from genetic additivity driven by rare variants at biobank scale

Abstract Additive genetic models are the default for genome-wide association studies, but deviations from additivity are crucial for understanding disease mechanisms and therapeutic responses. Yet existing methods for testing nonadditivity are computationally infeasible for large...

Conserved dimerization architecture in C‐type lectins from virus‐vector mosquitoes

Abstract C-type lectins (CTLs) play key roles in innate immunity and microbial carbohydrate recognition. In the disease vector mosquito Aedes aegypti , the CTLD-S family comprises 34 soluble CTLs whose members are implicated in flavivirus dissemination and microbial homeostasis,...

Neurodevelopmental and neurological features in children with hypochondroplasia

Abstract Aim To assess neurodevelopmental and neurological features, including neuroimaging abnormalities, in children with molecularly confirmed hypochondroplasia. Method A retrospective cohort study of children with molecularly confirmed hypochondroplasia seen at Evelina London...