Since the completion of the human genome project in 2001, the field of genomics has advanced exponentially, largely due in part to the introduction of next generation sequencing (NGS); a technique that has revolutionised the ways in which genetic disease is investigated. NGS enables the simultaneous sequencing of multiple reads in parallel, which provides researchers with the opportunity to interrogate vast numbers of candidate genes in order to establish the genetic eitiology and key components of disease. Exome sequencing in particular offers an efficient method to investigate disease, as the exomic regions make up 1% of the whole genome, but can contain up to 85% of functional variants responsible for disease. Next generation sequencing has been employed to investigate and identify the genetic cause of Acrocallosal syndrome (a rare autosomal recessive disorder). Exome sequencing was then also applied to investigate the genetic associations with both familial and sporadic pheochromocytomas and paragangliomas (neuroendocrine tumours). This study describes the various applications, challenges and potential benefits that can be achieved by using exome sequencing as a tool to investigate rare autosomal recessive disorders in addition to more complex disorders including familial and sporadic cancer. This study aims to employ cutting edge technology to investigate human disease, in order to enhance current understandings of disease biology and pathogenesis. Through this, it is hoped that these findings may help to contribute to on-going efforts to develop novel therapeutic strategies and improve the clinical management of these disorders
