The human body is made up of cells, tiny factories that perform much of the action in the body. They make up tissues, which make up organs, which in turn make up the body. The cell is thus the ultimate action site. What cells do is governed by the information packed inside its head office — the nucleus. The information there is packed in the collection of chromosomes, each of which has this information written in the collection of genes. Genes contain this information for what a cell does, and hence the tissues and organs do, and the body itself does. An error in the information contained in one or several of the genes can reflect itself in the form of a malfunction in the tissue, organ or the body.
This information in the genes is written in the form of DNA molecules, each of which is a long sequence of four molecules, known as ‘bases’, strung together in a long polymeric chain. While the English alphabet has 26 letters and punctuation marks, the alphabet of the genes has four bases, called A, G, C and T, as letters. The sequence in which these are arranged makes the genetic words and punctuation marks.
Book of life
The human genome is the collection of information contained in the genes packed into the chromosomes, which in turn are packed inside the nucleus of cells. Our genome is thus our book of life containing chromosomes as chapters, each packed in sentences written in the genes, which in turn are coded in the collection and sequence of the four-letter genetic alphabet.
As the cell reads out the information stored in its chromosomes, it performs its action. The major part of this action is in the form of translating the genetic language into action molecules called proteins. In essence it is the reading out of the codes in the DNA software that leads to action in the cell and the “hardware,” or the body.
It is an interesting fact of biological history that we had already started learning about and identifying genes before we understood the nature and chemical structure of DNA and the genetic code. The Austrian monk Gregor Mendel, experimenting with pea plants, between 1856 and 1863, identified inheritable traits or “factors” (we now call them genes) that form the colour of the flowers. That certain traits such as haemophilia run in families was understood as faults in genes, though how to read them in molecular terms was still far away.
Proteins in the body are made from the message inscribed in the genes. While it became possible to read the sequence of bases in the DNA of genes only in the last 50 years or so, reading the sequence of amino acids in protein chains became popular even by the 1950s. Scientists began studying the properties of proteins associated with diseases. Even one change in the amino acid sequence can sometimes lead to alterations in the properties of a protein and lead to health issues. As Drs Pauling and Ingram showed over 70 years ago, replacement of the amino acid ‘glu’ in the sequence of a haemoglobin molecule by the amino acid ‘val’ changes its properties dramatically, leading to a form of anaemia.
Genetic basis of disease
Errors of this type in protein sequences often arise due to errors in the sequence of the parent genes. Once it became possible to read the sequence of the DNA in genes, it led to an understanding of the genetic basis behind the disease, and the field of medical genetics was born. With the rapid pace in which gene sequencing has developed in the last two decades, medical genetics has flowered fast. Cancer genetics is a busy area, and a study of the genes associated with cancer has become popular. So has the field of understanding the genetic connection to Alzheimer’s and similar neural disorders.
The 23 November issue of the journal Nature lists the “Greatest Hits of the Human Genome.” It points out that out of the 20,000 or so protein-coding genes in the human genome, just 100 account for more than a quarter of scientific papers and reports published! And out of this 100, there are but 10 genes that are most studied and thus on the High Table.
And of this ten, the topper is the gene for the protein named as p53. This protein has a role in suppressing tumours. No wonder it has been studied in 8,479 publications. Next to p53 is the gene for TNF, coding for another molecule called tumour necrosis factor, which plays a role in killing tumour cells; this has been discussed in 5,314 publications. Fifth in the list is the gene termed APOE, studied in 3,977 papers. The coded protein APOE is associated with a risk of Alzheimer’s disease. The reason behind these large citations is the hope that once we understand the molecular basis of a disease, we may devise treatment modes, which focus on the genetic, and hence, the cellular basis behind the disease. Thus the Top 10 hits here do not represent a fashion parade or a Guinness Book entry, but a reflection of the attempts to alleviate human suffering through medical genetics.
dbala@lvpei.org
