Molecular Development

Disorders of sexual development (DSDs) are surprisingly common and often result in genital abnormalities, gender mis-assignment, infertility and psychological trauma. The Molecular Development group aims to pool its expertise in human genetics, molecular and developmental biology, to find genes important for sex development, identify gene defects that cause DSD, and study their function. The team will liaise with clinicians to apply these findings to the accurate diagnosis and medical care of DSD in children.

Group Leaders: 
Dr Katie Ayers
Role: 
Research Officer
Dr Thomas Ohnesorg
Role: 
Postdoctoral Fellow
Dr Elena Tucker
Role: 
Research Officer
Jocelyn van den Bergen
Role: 
Research Assistant
Gorjana Robevska
Role: 
Research Assistant
Katie Griffin
Role: 
Executive Assistant
Chloe Hanna
Role: 
Project Officer
Ingrid Knarston
Role: 
PhD student
Brittany Croft
Role: 
PhD Student
Dr Aurore Bouty
Role: 
Paediatric Surgeon

Disorders of Sex Development: Genetics, Diagnosis, Informing Clinical Care
The cause of Disorders of Sexual Development (DSDs) is often the breakdown of the complex network of gene regulation and expression which is essential for proper development of testes or ovaries in the embryo.
DSDs present a major paediatric concern because they are difficult to diagnose and are associated with complications including gonad cancer and infertility.
Since the discovery of the sex-determining region Y gene (SRY) in 1990, there have been considerable advances in understanding the genetic factors involved in gonad differentiation. Nevertheless, it has been estimated that a molecular diagnosis is made in only about 20 per cent of DSD cases.
Our lab is using Massively Parallel Sequencing (MPS, or Next Generation Sequencing) technologies for the identification of potential novel DSD candidate genes in order to increase the number of patients who can be given an accurate molecular diagnosis.

Identification and analysis of regulatory regions associated with Disorders of Sexual Development
While mutations in several key genes have been identified, the majority of DSD cases still cannot be explained. Preliminary studies undertaken by the group on DSD patients suggest that disruption of the regulatory regions of known and potentially novel genes may explain a significant proportion of DSD cases. Mutations or deletions/duplication of regulatory regions may result in over- or under-expression of key gonad development genes, resulting in a dysfunctional gonad, and DSD.
The group is using state-of-the-art methods to identify the regulatory regions of genes involved in DSD and sex-specific enhancers genome-wide. The function of these regions is further analysed by a variety of different approaches. Regions confirmed in vitro are then used to generate transgenic mice to validate their functionality in vivo.
This research will increase our knowledge of DSD gene regulation, improve diagnosis of these patients and assist in their clinical management.