Our lives would have been better if diseases likely to occur in the future can be anticipated and taken care of before the moment slips out of our hands. This far-fetched scenario is now possible with the completion of the sequencing of the human genome. A single gene or a set of genes may appear to predispose a degenerative disease, alter sensitivity to environmental pollutants and toxins, and even an infectious disease. Understanding an individual's genetic make-up may help avoid situations that are likely to cause disease leading to preventive medical treatment. Early disease of identification of disease and prevention thereof may help susceptible individuals in recovery as well as may save time and cost associated for treatment.

 

 

 

 

All genes of a species collectively are referred to as their genome. The gene is the most fundamental unit of inheritance. Genes provide the information needed to specify physical and biological features and are passed down from parents to offspring. The process of creating an RNA copy of a gene sequence is known as transcription. This copy, known as a messenger RNA (mRNA) molecule, exits the nucleus and travels to the cytoplasm, where it controls the creation of the protein it encodes. During protein synthesis, translation is the process of converting the sequence of a messenger RNA (mRNA) molecule into a sequence of amino acids. The genetic code describes the link between the base pair sequence of a gene and the amino acid sequence that it encodes.

 

 

The human genome project (HGP) was a big exploration of sequencing and mapping the complete human genome. The HGP, which ran between October 1, 1990 and April 2003, provided humans the ability to read nature's whole genetic blueprint of a body.The main objective of the Human Genome Project was first enunciated in 1988 by a special committee of the U.S. National Academy of Sciences, which was later adopted by the National Institutes of Health (NIH) and the Department of Energy (DOE). The researchers decoded the HGP in three ways i.e. by determining the sequence of the genome, to make maps showing the location of genes in chromosomes, and to produce a linkage map to determine inherited traits that could be tracked over generations. The first draft of the entire genome sequence, 3 billion of them, was published in Nature in February 2001. After two years of its publication by the Human Genome Project and Celera Genomics, a high-quality human genome sequence was delivered that was almost complete, accounting for more than 90% of the human genome.

 

 

Further studies aimed to identify functional elements of the human genome, especially targeting junk DNA, was carried out by ENCODE, funded by the National Human Genome Research Institute (NHGRI) in 2002. The Encyclopaedia of DNA Element (ENCODE) is a public research project which aims to identify functional elements in the human genome. Around 151 million base pairs of sequence data was dispersed throughout the genome as "junk DNA" with no evident function. ENCODE is the first systematic attempt to figure out what the DNA outside the protein-coding genes accomplishes, and it is the largest single update to the data from the human genome since its final draft was published in 2003. The researchers discovered over 10,000 additional "genes" within these regions that code for components influencing how the more familiar protein-coding genes function. Up to 18% of DNA sequence is responsible for managing less than 2% of DNA actively coding for proteins. According to ENCODE scientists, around 80% of the DNA sequences can be ascribed a biological purpose. The findings of the five-year ENCODE research were published in 30 of high impact papers including Nature, Science, Genome Biology, and Genome Research. The researchers discovered 4 million switches in what was originally assumed to be junk DNA, many of which may help them better comprehend a variety of prevalent human diseases such as diabetes and heart disease involving the complicated interaction of numerous genes and their regulatory components.

 

 

 

 

Nearly two decades after the Human Genome Project was published the first (almost complete) human genome sequence; scientists in the Telomere-to-Telomere (T2T) Consortium have reported the first genuinely complete human genome sequence. Initially, the Human Genome Project that ended in the year 2003 covered mainly the euchromatic portion of the genome, overlooking almost 10% due to technological limitations. Euchromatin is a region of the chromosome that is densely packed with genes and actively participates in the transcription process. The T2T Consortium presents a complete 3 billion base pair sequence of the human genome including gapless assemblies for all the chromosomes except the Y chromosome. In May 2021, the level of "full genome" was achieved and published on March, 2022, with only 0.3% of nucleotides remaining with potential concerns.

 

 

The overlooked fractions of the genome were mainly consisted of repeating regions. These repeat-rich regions are crucial in the expression and transmission of genes, and abnormalities in them have been linked to cancer and aging. The consortium took advantage of new devices capable of reading DNA segments of tens of thousands of bases. The researchers also devised methods for determining the location of particularly perplexing repeating sequences in a genome. Nearly 2,000 additional genes has been uncovered inside those novel DNA strands, majority of which appeared to be handicapped by mutations, with only 115 appeared to be capable of producing proteins.

 

 

 

 

The total amount of genome data is vast. The real challenge lies in identifying the “driver” gene. The driver gene is the one that once mutated can raise the risk of a person developing diseases such as cancer or Alzheimer’s. The discovery of the muted gene may lead to a more effective and personalized treatment. This is especially important for diseases like Alzheimer’s disease, where researchers don't fully understand how the disease progresses and hence can't create effective treatments.

 

 

Several approaches are currently being used to screen hundreds of compounds in order to get promising result. Through the human genome data, targets can be specifically pinpointed, around which treatments can be built. Researchers may mine the genome data to figure out the genetic variation associated with a particular disease. Then the biomarker is investigated and associated with a particular variant that leads to the disease.

 

 

For example, Cystic fibrosis (CF) a common inherited disorder, wherein a mutation occurs in the gene coding for a protein known as the cystic fibrosis transmembrane regulator (CFTR). CFTR is a controlled chloride channel that must work properly in the epithelia of the lung, pancreas, and other organs to maintain proper ion and water balance. If a child inherits two silenced genes, he or she will get CF, resulting in building up thick mucus in the bronchopulmonary tree, making it more susceptible to infection, particularly from Pseudomonas species. The exact mutations that cause CF have now been found through simple testing. This allows for precise identification of CF carriers among people who desire to know their vulnerability . If both members of a couple are carriers, families may select prenatal diagnostics to determine the presence of a homozygous CFTR mutation in the foetus. Gene therapy may directly correct the genetic defect and completely prevents the development of the disease.

 

 

A study released recently discovered that treatments with genomic evidence are more than twice as likely to avail an approval from the US Food and Drug Administration (USFDA) and corresponding success in clinical trial.

 

 

Patentability Aspects The discussion about the genome project will not be complete without little discourse over the patentability of any invention claiming a gene. A patent is granted by a country's sovereign for an invention claimed by the inventor(s) or an applicant to whom said invention is assigned by the inventor(s), and granting territorial rights to prevent others from creating, using, selling, proposing to sell, or importing the invention. Coming to this aspect of discussion, individuals may be able to profit commercially as well as companies could theoretically get ownership of specific DNA sequences or genes the patenting process. However, owning part of nature-made physiological system by any third individual or a company may be counterproductive, contrary to ethical and moral values, as well as against the prima facie essential criterion of patenting i.e. Novelty. Anything that already exists in nature can’t be claimed as man-made. Even a liberal jurisdiction like USA held, “anything under the Sun, made by men, is patentable”, therefore, in order to obtain a patent, an invention must be made by men, not already created by nature. This principle, however, could be tweaked when it comes particularly to a diagnostic method, wherein the target is a naturally occurring genome, to be tagged by a man-made probe, something which is acceptable, at least till the final decision in the “Myriad” case back in 2015. Myriad Genetics, a molecular diagnostic company based in Utah, USA, patented two genes linked to breast cancer, BRCA1 and BRCA2, for the anticipatory diagnosis of mitigating a potential patient’s probability of suffering from breast cancer. This effectively barred other scientists or practitioners from accessing the gene or testing for it. The patenting of the gene disturbed the mood of scientists involved in the Human Genome Project. In 1992, James Watson resigned as Director of the Human Genome Project and passed on the role to Francis Collins. James Watson was concerned that patenting parts of the DNA before the understanding of its function(s), could jeopardise healthcare. The scientists who wanted to patent the DNA sequences, on the other hand, feared that without patents, potential licensees from the US industry would be unwilling to pursue commercial development of the discoveries. These debates lasted the duration of the project. The US Supreme Court only prohibited the patenting of the human genome in 2013 on the grounds that human DNA is a "product of nature." This verdict invalidated Myriad Genetics' patents on the two genes linked to the risk of breast and ovarian cancer. Coming to India, no naturally existing genetic material is patentable and engineering at least in one point i.e. at least with a single base is essential to obtain a patent. Although, in absence of a set case law, it is argued that a genetic material made in laboratory conditions by copying a naturally existing sequence, should be patentable if and only if, it may show a clear human hand, at least the process for doing so is. In addition, to obtain a patent, a general criterion is that genetic material must show its existence in free-floating form i.e. without being part of a gene or without being impregnated in a gene.

 

 

 

 

Many genes that are directly responsible for human inherited disorders have already been identified. Molecular methods utilized in the Human Genome Project may allow for the identification of more genes that predispose to most human diseases. This ability to predict disease can be utilized to pinpoint the need for lifestyle and medicinal changes that can help prevent or slow the onset of a hereditary condition. Early diagnosis and more cost-effective preventive actions and treatments may result from DNA-based diagnostic processes targeted at certain sensitive populations. The on-going debate thus is, whether patents should be granted to protect this molecular engineering.