Taking and sequencing a genomic sample

Last updated: Tuesday, March 12, 2024

The first step in genomic testing for any individual is acquiring a biological sample, typically blood, saliva or tissue biopsy (the latter particularly for cancer). The sample has the genomic material extracted for testing either for single nucleotide polymorphisms (SNPs) or longer stretches of DNA (for exome or genome sequencing). RNA sequencing is also possible, along with other measurements of cell function (protein synthesis, metabolic activity), although these are less common clinically. 

An understanding of the different types of sequencing, when or why they might be used and what they can and can’t be used to identify is helpful when presented with genomic data. 

• Only looks at specific genes or SNPs that are known to be associated with a particular disease, phenotype or symptoms (e.g. monogenic diabetes).

• Looking for something you already suspect. Won’t pick up novel causative genes. 

• Can’t reanalyse data if new genes are found. A new panel has to be created and retested. 

• Exome represents ~2% of human genome, but captures all protein coding regions. 

• Majority of disease causing variants are thought to be found in the exome. 

• Misses copy number variants or variants outside the exome. 

• Can be reanalysed if new genes are identified without need for further sequencing. 

• Can be used for ‘virtual targeted panels’ looking for specific gene variants. 

• The genome includes the whole DNA: exons, introns and all bits in between. 

• Large amount of data requiring costly analysis / storage. 

• Can be used for diagnosis, prediction, prevention or treatment of disease. 

• WGS can also be used to sequence the genome of tumours and infectious agents to allow effective diagnosis and treatment. 

• An example of WGS in practice is the Newborn Genome Programme.

You can read further information on sequencing on the Genomics Education Programme website.

Familial hypercholesterolaemia (FH) is a common autosomal dominant genetic disease that increases the likelihood of coronary artery disease, heart attacks and sudden cardiac death at a young age. Early detection and genetic diagnosis can enable early intervention with effective treatments (e.g. statins) and decrease the risk of cardiovascular disease (CVD), leading to better outcomes and reduced morbidity for patients. It can also allow identification and treatment of affected family members.

A small targeted panel test is used to identify known gene variants. Patients usually have a functional mutation of one of 3 genes; 

All impair LDL receptor-mediated catabolism resulting in higher LDL-C levels. 

Heterozygous FH (person has one copy of a pathogenic variant out of their two copies of the gene) is a common disorder, with an incidence of ~ 1 in 250 individuals in the UK. In England, it is estimated that >150,000 people are affected by FH. Around 7% of those with FH in England have been identified and the aim has been to improve this to 25% by 2024/5. Genetic testing for FH is part of the NHS Long Term Plan (2019).

FH is also currently part of a primary care initiative incentivised by PCN DES IIF 22/23 (CVD-04). This rewards the identification of patients aged 29 and under with a total cholesterol greater than 7.5 mmol/L OR aged 30 and over with a total cholesterol greater than 9.0 mmol/L who have been: