The human genome contains a staggering 3 billion DNA base pairs aligned in specific sequences. A sequence alteration by just one base pair can have dramatic effects, from the normal and common (think eye and hair color) to devastating genetic disorders with profound impacts on health.1
Mutations can range from the mis-ordering of bases within one gene to the damage or deletion of part of a chromosome, involving many genes. Today, more than 10,000 human diseases are caused by just one error in one gene. Some of these so-called monogenic diseases include thalassaemia, sickle cell anemia, hemophilia, cystic fibrosis, Tay-Sachs disease, Fragile X syndrome and Huntington's disease.2 Diseases caused by missing chromosome sections include rare disease such as cri du chat syndrome (chromosome 5); Prader-Willi syndrome (chromosome 15); and Wolf-Hirschhorn syndrome (chromosome 4).3
Mutations are either inherited or acquired, such as from exposure to a toxin. Inherited mutations last a lifetime and are carried in every cell. Genetic diseases caused by mutations have several classifications based on whether one parental copy or both cause illness, or if the X or Y chromosome is involved.4 Some mutations are dominant, in that if only one parent has the mutation, its effects, such as a disease like Huntington's disease or neurofibromatosis type 1, will manifest in a child.5 Other mutations are recessive and require a copy from each parent for illness to result, such as cystic fibrosis, sickle cell disease6 and Gaucher disease.7 Some mutations nearly always result in the development of diseases, while others merely predispose a person to a health problem.
In contrast, acquired, or somatic, mutations can occur at any time due to spontaneous mutations. Some de novo mutations have known causes, like smoking leading to genetic changes in lungs and causing cancer, but many of these mutations have no known cause other than an error in DNA replication.8 If these mutations occur in eggs or sperm, they can be become inheritable. Such mutations in other cells cannot be passed to children. Somatic mutations are known to cause rare diseases including McCune-Albright, Proteus syndrome, Klippel-Trenaunay and Maffuci.9
Research into the role of mutations in causing disease reveals targets for treatment. For example, the genetic mutations of Hunter Syndrome, a rare X-linked recessive disease, cause a deficiency or absence of a protein that acts as an enzyme to break down certain types of complex sugars in the body. Current research by Shire is looking into how a replacement enzyme therapy might help people with Hunter Syndrome manage their illness. A future goal for development of treatments of many genetic diseases could be gene therapies that might deliver healthy genes to counter the effects of mutations.
Although scientists' understanding of the genetic underpinning of disease has advanced dramatically in the last century, much more work remains to first better understand the role of mutations acting alone or together to cause disease as well as how an individual’s genetic make-up may impact treatment. This medical frontier holds tremendous promise to advance human health.