By Dr Ananya Mandal, MD
Several discoveries have made genetic research one of the fastest developing research areas in the world today. With the understanding of genetic basis of disease there is a rapid development of genetic basis for disease risk and diagnosis and treatment. Genetic engineering has also made progress over the last few decades.
Organisms used in genetic research
Certain organisms formed the origins of genetic research experiments. Gregor Mendel for example discovered theories of inheritance from sweet pea plants.
In addition, many genetic studies and experiments have been conducted on what is known as the “Cinderella” of genetics – Drosophilla Melanogaster (Fruit fly). There are over 2,500 species of Drosophila and, of these, D. melanogaster is the one that has been extensively exploited for research.
Drosophila has been used as model organism right from the beginning of the 20th century, in the very early years of the development of the field of genetics. T H Morgan, at Columbia University, pioneered the use of Drosophila for the study of genetics.
Drosophila is one of the most suitable model systems for genetic work due to its short life cycle of about 10 to 11 days at 22 degree C, and high reproductive potential. It produces a large number of progeny, which is required for statistical analysis of the results.
Other models include:
bacterium Escherichia coli
plant Arabidopsis thaliana
baker's yeast Saccharomyces cerevisiae
the nematode Caenorhabditis elegans
the common house mouse Mus musculus
What makes a good model organism?
Organisms thus are chosen based on characteristics like:
short generation time
easy genetic manipulation
large number of progeny
Medical research and genetic engineering
Medical genetics includes studies of populations that look at the effects of genetic changes, mutations and variations on human health and disease. Principles of genetic linkage and genetic pedigree charts may help determine the location on the genome associated with the disease.
Mendelian randomization helps to look for locations in the genome that are associated with diseases. This is a technique useful for multigenic traits not clearly defined by a single gene.
After a gene is identified to be associated with a disease further research is often done on the same gene in the experimental models. Genotypes are established to pinpoint the exact location of the gene.
Certain individuals are prone to certain side effects with some drugs due to their genetic predisposition. Drug efficacy may also vary with the genetic makeup. Pharmacogenetics is the science that helps in understanding the role that an individual’s genetic make-up plays in how well a medicine works, as well as what side effects are likely to occur (personalised or tailor made medicine).
For example, effects of ACE inhibitors (angiotensin converting enzyme inhibitors) that improve symptoms and survival in heart failure have been found to be greater in people of Europe or the UK than African-Americans.
Similarly normally some pain relief medications such as codeine are broken down and metabolized in the liver by a protein called CYP2D6. Variations in the information contained in the CYP2D6 gene may cause changes in codeine handling by the body. People who have low levels of the enzyme that metabolises codeine will eliminate and break it down slowly and so it will be in the body for a longer period of time. Slow metabolizers of codeine are more likely to have respiratory side effects.
Drugs that can target specific genotypes are being used increasingly. For example, women with metastatic breast cancer with over-expression of the protein product of the gene called HER2 may have aggressive disease and a poor prognosis. The drug Herceptin® is an artificially developed antibody against the HER2 gene product and is called a monoclonal antibody. It acts by binding to the receptor sites on the cell surface, thereby limiting cell division and growth of the cancer.
DNA is used for research in the laboratory. Restriction enzymes are a commonly used enzyme that cut DNA at specific sequences. This is then visualized through the use of gel electrophoresis. The DNA can then be amplified, modified or cut into pieces for research using sophisticated technology. DNA can be amplified using a procedure called the polymerase chain reaction (PCR).
DNA may be sequenced and this allows researchers to determine the sequence of nucleotides in fragments of DNA. This is progressively becoming easier and less expensive. This can be used in DNA fingerprinting or RFLP (Restriction Fragment Length Polymerization).
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)