Somatic variation in healthy organisms

Quantifying variation in repetitive DNA

Repetitive DNA sequences are an important source of somatic variation.

Repeat variability within genes and promoters are associated with important traits, such as circadian clock variation, skeletal development, microbial drug resistance, and gene expression variation in humans and plants.

These sequences and their variation are therefore of primary interest in linking cellular heterogeneity to organismal phenotype. However, repetitive DNA is especially challenging to quantify in high-throughput sequence datasets and is frequently discarded.

We aim to develop and validate technologies to assess both functional long DNA repeats and short tandem repetitive sequences. These technologies will enable the identification and accurate genotyping of these difficult to characterise hypermutable sequences.

This will provide greater insight into the types and frequency of variability found within repetitive DNA sequences.

Functional implications of variation in plant and animal cell systems

The genomes of most multicellular organisms are typically contained in a strictly fixed number of chromosomes per cell. 

Gains or losses of chromosomes occur in individual cells, and can directly impact gene expression, cell phenotype and function, and, ultimately, the health of the organism.

Yet little is known of the impact or molecular function and phenotypic implications of such chromosomal number change in normal conditions. To understand the impact, we will study this  in cell culture systems where conditions can be controlled, prior to investigating more complex in vivo systems, such as mammalian or plant cells.

This research will lead to technical advances in single-cell sequencing from plant and animal cells of variable ploidy and size.

This research not only advances single-cell sequencing techniques but also unveils how cells respond to altered chromosome numbers. For example, these insights could shed light on how megakaryocytes produce platelets and lead to potential interventions for platelet production.

Somatic and epigenetic variation in clonally propagated crops

Over 60 essential crops - including bananas, potatoes, and strawberries - are clonally propagated.

The loss of sexual fertility during domestication, limited seeding, or management practices in elite crops leads to genetic erosion and accumulation of somatic variants.

We are developing approaches to efficiently identify somatic and epigenetic variation and characterise its functional consequences in clonal sets of crop species. This will enable future crop improvements through developing new ways to remove deleterious variants and incorporate beneficial genetic diversity in clonal lines, improving resilience and productivity in clonally propagated crops.

Working with leading agritech firm Tropic, we are characterising the functional implications of somatic variants and associating those to quantified phenotypic variation.

We are focusing on fruit-related and fungal resistance phenotypes, applying Oxford Nanopore Technologies to characterise DNA methylation and structural variants, along with reconstructing pangenome graphs for the discovery and functional characterisation of structural variants.

This will determine the functional consequences of epigenetic and somatic variation in agricultural traits for clonal crops, facilitating the incorporation of beneficial genetic diversity in clonal lines to improve resilience and productivity in clonally propagated crops.