The astonishing story of Human Genome
Dr. Mehnaz Mazumdar
“What more powerful form of study of mankind could there be than to read our own instruction book?” was proudly said by the famous physician-geneticist, Francis S. Collins on the landmark accomplishment of deciphering and mapping Human genome in the year 2003. Scientists all over the globe with major contributors like U.S.A, U.K, Japan, China, Germany, France and many others were extensively involved in a tedious 13 year research project from 1990 to 2003 with an estimated cost of around $ 3.8 billions to unravel the mystery of human genome. It is the contribution of this project that we humans now exactly know that we have around 20,000-25,000 genes in each of our body cells which are actually composition of 3.2 billion chemical bases and “dystrophin” is the biggest gene present in our body and abnormality in the sequence of these chemical bases may be responsible for various human physical and functional anomalies.
Once a biology teacher asked one of his student “why are girls pretty?” while taking class on genetical material of life. The student replied quickly, “Because girls are made up of sugar and candy”. The teacher couldn’t help but laughed and said, “Actually the answer is not sugar and candy but the genes which are responsible for creating a good looking or average looking person”. Infact it now known to all that genes are reasons behind our skin color, hair color, eye color, height, intelligence, reasoning, immunity, strength and everything that possibly physically and functionally makes us. It is very common to hear from elders that “he or she looks like his or her father or mother.” The obvious reason behind such comparison is again attributed to the genes which are inherited by children from their parents and hence they look similar to one of their parents or a combination of both or sometimes improvised version of both their parents. It is nothing but the beautiful working and manifestations of the genes.
To define and understand “Genome”, we can simulate it to be just like a “library”. The books in the “genome library” are the “genes”. The genes are contained in the cells which make up the human body. Every gene is different in size and the information they contain, just like the different books in the library. Like the different sections in the library, our genes are also compartmentalized into different chromosomes. We humans have 23 pairs of chromosomes. One pair contains the information from our father and the other one from our mother. Therefore, unlike libraries, where you may find more than one copy of a book, our genome has two copies of each gene (except the genes on the X and Y chromosomes which carry only one set of genes). The chromosomes which contain the genes are made up of Deoxyribonucleic acids (DNA). A mere small word “Deoxyribonucleic acid” responsible for designing the man and other organisms appears unbelievable and somewhat astonishing. Chemically, DNA is one of the simplest molecules in the cell. It is comprised of just three building blocks, nitrogenous base (which are of four types, adenine, guanine, cytosine and thymine), sugar (deoxyribose) and phosphate group strung together in enormously long strings. The residues combine to make our genes, and our genes string together to make our chromosomes. When talking about the working and expression of these genes it is more then a marvel to a common man. It is infact difficult for a commoner to understand and perceive how genes work and make something so intricate and beautiful like “Life”.
Since the onset of the discovery of human genome, innumerable interesting facts regarding human health, ancestry, disease etc are continuously emerging. Knowledge of human genome is proving to be a boon or curse is a never ending debate. Scientists at the very onset of the project believed that people will see the Human Genome Project as a tool to offer humans a better standard of life and not just a multi billion dollar project with little reward. But critics considered such enthusiastic thinking as overoptimistic and emphasized on ethical, legal and social implications associated with such undertakings. But amidst all opposition the project continued and got completed with amazing facts and findings of human genome for unquestionably a better life to posterity.
Speaking about the most obvious contribution of human genome in today’s scenario, it is the finding of the causes of various diseases and providing options for genetic medical intervention and lead to cure of such disease. It is now possible to locate genes which are responsible for causing human genetical diseases. Investigation of the DNA has helped in establishing what is currently considered to be incurable are actually caused by genetic disorders (e.g., Alzheimer’s disease) and which can only be prevented by development of revolutionary DNA medicine. Moreover, study of the genome has created new opportunities for early diagnostics and making of useful drugs with directional effect. Secondly development of gene therapy is the major outcome of human genome project. Successful gene therapy trial for Leber's congenital amaurosis (eye disease) and the development of Gleevec for chronic myelogenous leukemia (bone marrow cancer), gastrointestinal stromal tumors (GISTs) and a number of other malignancies are examples of stunning successes in these areas. Recently it was generated from the scientific desk that a "small molecule" has recently been discovered that appears to be highly effective against schistosomiasis, a debilitating parasitic disease that affects tens of millions of people around the world.
We all know cancer is a disease of the genome and in fact, the commonest genetic disease. The Cancer Genome Project, which is funded by NHGRI and the National Cancer Institute, is using data from the Human genome project and employing high throughput techniques for detecting variants/mutations in the genomes of cancer cells to identify genes critical in the development of human cancers. The plan is to build an atlas of genomic changes that will provide new insights into the biological basis of cancer, which in turn will lead to new tests to detect cancer in its early, most treatable stage, new therapies to target cancer at its most vulnerable points and, ultimately, new strategies to prevent cancer. For example, breast cancer is one disease that is being treated based on genetic information. More than a dozen genes have been associated with breast cancer, and patients can make their treatment decisions based on the knowledge this genetic testing reveals. For instance, women who have inherited the BRCA1 or BRCA2 genes in their chromosomes, have a high risk of developing breast cancer, ovarian cancer or other female cancers. Therefore, it is possible to have surgical intervention before cancers are developed.
The Human Genome Project lead to development of other projects like the International HapMap Project under which DNA samples from various ethnic groups were studied and Single Nucleotide polymorphisms (SNPs) was charted. SNPs are the change in which a single base in the DNA differs from the usual base at that position in the DNA. SNPs study confirmed that genetic code differs from person to person at around 10 million points (out of 3.2 billion DNA base pairs). But despite these SNPs, human beings only differ from one another by about 0.1 percent, enough to ensure that no two human beings are genetically identical, even, sometimes, identical twins. Understanding SNPs has help understand genetic variation better among individuals and ethnic groups.
Scientists now know the minimum number of genes required for life to emerge and makes it easier to determine what actually life is. The genome knowledge gives insight to interaction in biological systems, which can be useful to predict environmental change. It also provides a profound understanding of common genetic basis of all living creatures and humans, explaining the evolution of man and showing our place in the natural systems.
Study of comparative genomics which is the study of relationships between the genomes of different species or strains of the same species is creating grounds for study of human genome by analogy with the animal genome. Researchers have learned a great deal about the function of human genes by examining their counterparts in simpler model organisms such as the mouse. According to Dr. Collins, almost 30 mammalian genomes have been sequenced to date and many more are on the way. As the result of a revolution in DNA sequencing technology, particularly in the last several years, he said that sequencing genomes is becoming increasingly faster and easier, so much so that the amount of data being generated is almost overwhelming.
Genetic investigations are also highly applicable in the forensic science, for example for identification of individuals and using of their genetic material as evidence. Even small pieces of skin, drops of blood or other material allow to create a DNA profile (or DNA fingerprint), which can be used for identification of both criminals and their victims. Among other advantages one should not forget the gain in energy technologies, agriculture and food production. Genome research is contributing to development of new types of fuels (biofuels), genetically modified foods as well as reduction of environment pollution. Understanding of plants and animals genetic structure, combined with knowledge of human genome is allowing producing new types of nutritious food with preprogrammed features. Scientists are manipulating genes and producing crops and cattle’s of better productivity and nutrition.
Despite all the exciting discoveries and those that await us, it will be inappropriate to conclude that we can fully understand the inner workings of the Genome. Human biology is "highly complex". We humans can do and understand remarkable things but completely understanding 3.2 billion chemical pieces of DNA may be too much for our minds to fully comprehend it. The journey continues and the road is never ending. We are constantly bumping into new amazing findings. Those new findings we are tapping into are not toys to be played with but knowledge to be utilized judiciously for our improvement and benefit. As long as we remember it knowledge of the Human Genome will give us rewards in medicine and science forever.