Weibel-Palade bodies and Golgi apparatus

This project is now closed

Determining the role of regulatory mutations in developmental disorders and anomalies

Project supervisor: Greg Elgar (Systems Biology)

This project combines both experimental and computational approaches to start to identify and characterise (largely de novo) regulatory variations/mutations that are associated with, or responsible for, human developmental disorders and anomalies.

The student will use a targeted enrichment capture approach to specifically sequence conserved regulatory regions from large clinical cohorts. This approach permits the sequencing of hundreds of individual samples per run on our Illumina sequencing platform, rendering it manageable at both the cost and data analysis level.

The chosen regulatory regions are well studied in the Elgar group and consist of a large set (about 7000) of conserved noncoding elements (CNEs) that reside adjacent to transcription factor and signalling genes that orchestrate early developmental patterning in the embryo. In particular these genes are implicated in CNS and brain development, as well as in the emergence of other key features of the vertebrate head, including jaw, skull and sensory organs. Thus these putative regulatory regions, some of which have been shown in vivo to act as tissue specific enhancers, are likely to play a role in a number of developmental disorders and cranio-facial anomalies (e.g. Kleinjan et al, 2009; Benko et al, 2009; Epstein, 2009). The project will involve:

This project is novel, fits very well alongside extremely successful ‘exome’ strategies and is timely, given that it uses state-of-the-art sequencing technologies and exploits emerging data from the 1000 genomes project, and the Wellcome UK10K project data, which I have been granted early access to.

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