A haploid human genome comprises of 23 chromosomes, roughly 20,000 genes and is encoded by approximately 3 million base pairs (the building blocks of DNA – A, T, C and G). The full code for life’s blueprint for making a human, was revealed back in 2003 through an international collaboration known as The Human Genome Project (HGP). Considered as one of the greatest scientific achievements of the century, the HGP gave scientists never-before-seen insight into human genetics and sparked a wider interest in the study of human genomics.
Taken alone, a single human genome provides limited diagnostic information for a disease of unknown cause: the power of human genomic studies lies in being able to make comparisons. In 2012, another international effort known as the 1000 Genomes Project was completed, this time with many more genomes to study, and the project gave scientists a fresh look at the extent of human genetic variation (Nature, 2012). The 1000 Genomes project greatly benefited from faster and cheaper DNA sequencing technology (Mardis, 2011), a field that is still advancing today (Scott, 2016). Whereas the HGP took 13 years and nearly $2.7 billion to obtain the sequence of one mosaiced human genome (samples were provided by multiple donors), today a person’s genome can be sequenced for around $1,000 and in about a day (Scott, 2016). The same year the 1000 Genomes Project announced it had completed 1092 genome sequences, another exciting and ambitious genomics initiative was launched, this time entirely in the UK; the 100,000 Genomes Project.
The 100,000 Genome Project is funded by the Department of Health and it aims to annex a genomic medicine program to the NHS while also providing a platform for UK genomic scientific investigation. At this point, you may be wondering what the 100,000 genomes project has to do with BHD? Well, the 100,000 genomes project largely focuses on two areas, cancer and rare diseases, two fields that are relevant to the BHD community. In fact, one of the criteria for rare disease patients wanting to volunteer is familial (family-history associated) primary spontaneous pneumothorax. Recurrent pneumothorax can be suggestive of BHD especially if it runs in the family, and BHD patients are believed to be 50 times more likely to experience a pneumothorax than the general population (Zbar et al. 2002).
Unfortunately, anyone who is known to have folliculin (FLCN) mutations will not be able to sign up to the 100,000 Genome Project because it is only recruiting patients with primary pneumothorax, (whereas BHD patients suffer from secondary pneumothorax associated with an underlying pulmonary cause). There is a requirement that prospective volunteers with suspected familial pulmonary primary pneumothorax be screened for FLCN mutations prior to entering the study, to rule out BHD as the potential cause. The BHD Foundation thinks that there are some positive messages to be taken away from this. Firstly, BHD awareness has clearly infiltrated the study of rare diseases well, which is important given that it is so rare, even by rare disease standards. Currently there are roughly 600 families worldwide with a BHD diagnosis (published BHD families) but BHD is certainly underdiagnosed, perhaps significantly. Secondly, the requirement of FLCN screening before entering the study will hopefully increase the diagnosis rate of people with a FLCN mutation: quicker and earlier diagnosis of BHD is important because it allows for better management and surveillance for all possible BHD symptoms, including renal cell carcinoma.