Whole genomic sequencing for diagnosis of rare disorders

Should Scotland provide whole genomic sequencing for diagnosis of rare disorders? A health economic analysis

Taken together, rare disorders are common and affect 6-8% of the Scottish population. Most are severe and life-threatening with a profound impact upon the quality of life and wellbeing of the individual and their family. The typical journey to diagnosis, or ‘diagnostic odyssey’, can take many years, with numerous hospital visits, costly and invasive tests, several misdiagnoses, and shattered hopes and expectations; many families never receive a diagnosis. As 80% of rare disorders have a genetic origin, increasing access to genetic diagnosis is a key component of UK and Scottish Rare Disease policy. Standard genetic testing is limited to examination of DNA from single gene variants to smaller gene panels (typically <100 genes) and is triggered by specialist clinical suspicion. More recently, comprehensive sequence analysis of a person’s entire DNA (Whole Genome Sequencing/WGS) or all the protein coding parts of their DNA (Whole Exome Sequencing/WES) increases diagnostic yield (% of cases receiving a positive diagnosis) and is expected to enable quicker diagnosis. Potential benefits to patients and families of comprehensive sequence analysis include improved diagnostic yield, reduced length and scope of the diagnostic odyssey, reduced need for clinical attendance and investigative tests, and information for family planning and clinical management. However, little is known about how patients and families value such aspects of comprehensive DNA sequencing. The financial implications are also unclear.

This study will address the evidence gap around the benefits to service users (patients and families) and assess the resource implications of different genomic testing pathways.

HERU researchers involved in this research project: Mandy Ryan, Lynda McKenzie, Rodolfo Hernández and Michael Abbott

External collaborators: Z. Miedzybrodzka, L. Mennie, C. Clark (Medical Genetics, University of Aberdeen) and S. Heidenreich (Evidera)


Abbott, M. (2020) 'What can health economics do for genetics?', Research and Rare Conditions Conference, Royal College of Physicians of Edinburgh, Edinburgh, 9 March 2020.

Abbott, M. (2020) 'It might be of value, but is it worth it? Assessing the costs and benefits of whole genome sequencing for the diagnosis of rare conditions', Scottish Genomes Partnership Forum, Ballathie House, Perth, 4 February 2020.