"/>Research area

Rare Disease Genomics

Finding answers for the undiagnosed — prioritising causal variants in rare and Mendelian disease with phenotype-driven analysis.

0
genomes per trio
0
ACMG criteria
0
+ repeat disorders
Overview

What this area is.

For families on a diagnostic odyssey, the causal variant is usually rare, often de novo or recessive, and hidden among thousands of benign ones. We use trio and family WGS/WES with phenotype-aware prioritisation to surface it.

Variants are classified against ACMG/AMP criteria and matched to phenotype with HPO terms, turning a vast variant table into a short, defensible candidate list.

Tools & technologies

GATKDeepVariantExomiserHPOClinVarACMG/AMPExpansionHunterVEP
Variant lollipopCandidate variants along the gene of interest.
Genome browserRead-level evidence at the candidate locus.
Capabilities

What we do.

Core methods we apply in rare disease genomics.

Trio & family analysis

Joint analysis of probands and relatives to find de novo and inherited causes.

ACMG/AMP classification

Systematic, criterion-based variant interpretation.

Phenotype-driven ranking

HPO-based prioritisation that matches genotype to clinical features.

De novo & compound-het

Inheritance-aware models for dominant and recessive disease.

Repeat-expansion analysis

Detecting the expansions behind ~60 known disorders.

Predisposition genes

Identifying germline risk in familial cancer and beyond.

Workflow

From data to insight.

How a rare disease genomics project flows end to end.

01

Family WGS/WES

proband + relatives

02

Joint calling

trio genotypes

03

Inheritance

de novo · recessive

04

Phenotype

HPO matching

05

Classify

ACMG / AMP

06

Diagnose

ranked candidates

Visual analytics

Publication-grade figures.

Interactive, live-rendered visualisations used in rare disease genomics.

Variant lollipopCandidate variants along the gene of interest.
Genome browserRead-level evidence at the candidate locus.
Gene networkLinking the gene to known disease modules.
Circos plotStructural events across the family genome.
Focus

Where we go deep.

The undiagnosed

Re-analysis pipelines that revisit negative cases as knowledge grows.

Familial cancer predisposition

Prioritising germline risk genes by whole-genome sequencing.

Repeat-expansion disorders

Detection workflows for an under-served variant class.

Insights

Questions we answer.

A few of the things people ask about rare disease genomics — and our short answers. Ask CGB-AI for more.

Why analyse the whole family?

Trio data reveals de novo events and resolves inheritance, dramatically narrowing the candidate list.

What if the case is unsolved?

Periodic re-analysis against updated databases and gene–disease knowledge solves many initially negative cases.

Selected research

Publications in Rare Disease Genomics.

Drawn from our full record of 173 papers, filtered to this area.

Browse all publications →

Start a rare disease genomics project.

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