Genomics Explained

An individual’s genome is a person's genes (the genome) carried in their cells. These genes can be positioned in the cell’s nucleus or the mitochondria. In genomic studies we examine how an individual’s genes vary from the population, and how those genes interact with each other and with the person's environment.

Deoxyribonucleic acid (DNA) is the building block for genes and carries all the instructions required for the development and functioning of an individual. DNA strands are made of chemical units called nucleotides. There are four types of nucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C). The order of the As, Ts, Cs and Gs determines the meaning of the information encoded in that part of the DNA molecule just as the order of letters determines the meaning of a word. Virtually every single cell in the body contains a complete copy of the approximately 3 billion DNA base pairs, or letters, that make up the human genome.

Whole genome sequencing

Whole genome sequencing (WGS) means determining the exact order of the nucleotide bases in a strand of DNA. In research WGS is used to search for genetic variations that may play a role in the development or progression of a disease. The disease-causing change may be as small as the substitution, deletion, or addition of a single nucleotide base pair or as large as a deletion of thousands of bases along the DNA strand.

The Human Genome Project

The Human Genome Project, which was led at the National Institutes of Health (NIH) by the National Human Genome Research Institute, with extensive international collaboration over 13 years, which was completed in 2003 and produced a very high-quality version of the human genome sequence that is freely available in public databases (1). This sequence is not that of one person but is a composite derived from several individuals. Therefore, it is a "representative" or generic human sequence.

One main resource the Human Genome Project provides is the ability to look at individual genetic variations that differ from the reference sequence and possibly align them to disease causation including autoimmune diseases. However, every human genome contains around 3–5 million genetic variants compared with the reference sequence. Therefore, expert interpretation paired with research and literature aligned with the patient’s clinical information preferably in a multi-disciplinary setting is required. In addition, further experimental studies on these gene variants allow researchers to fully understand how the genome functions and to discover the genetic basis for health and disease (2).

Personalised medicine and genomics

Many diseases have some basis in our genes. The study of genetic variants in disease until recently was limited to severe birth defects or haematological diseases. However, with the increasing amount of data generated by the Human Genome Project and other genomic researchers it has been possible to study the role of multiple genetic factors acting together and with the environment in the causation of more complex diseases.

Personalized medicine is an emerging practice of medicine that uses an individual's genetic profile to guide decisions made about the prevention, diagnosis, and treatment of disease. Knowledge of a patient's genetic profile can help researchers and clinicians develop improved diagnostics and select tailormade therapy with evidence-based approaches for demonstrating clinical efficacy, and better decision-making tools for patients and providers. Ultimately, it appears inevitable that treatments will be tailored to a patient's particular genomic makeup.

Genomics in personalised medicine explained

References

1.      Lander ES. Linton LM. Birren B, et al. Initial sequencing and ­analysis of the human genome. Nature. 2001;409:860–921. 

2.      Brittain HK, Scott R, Thomas E. The rise of the genome and personalised medicine. Clin Med (Lond). 2017 Dec;17(6):545-551. doi: 10.7861/clinmedicine.17-6-545. PMID: 29196356; PMCID: PMC6297695.