Regulatory mutations in the PAX6 locus as pathogenic lesions in aniridia

Advances in human genetics have greatly contributed to recognition of the fact that the proper control of gene activity in time and space is controlled by DNA sequences located outside of the gene itself – regulatory elements. Whilst we are quite good at understanding how mutations within genes cause disease, identifying DNA sequence changes that disrupt regulatory elements and cause developmental defects remains a major problem. This project is designed to systematically investigate the role of mutations in regulatory elements that control the expression of PAX6 – a gene important in eye development and whose mutation results in Aniridia and blindness. The data generated will be vital in assigning pathogenicity to these regulatory element mutations, enabling confident diagnosis and genetic counselling for Aniridia patients.