A genome can be metaphorically described as the blueprint or instruction manual for life. This genetic ‘blueprint’ comprises all the genes, including the inter-gene spaces forming our chromosomes. Chromosomes are structures made up of DNA (Deoxyribonucleic Acid), a long string composed of four building blocks called nucleotides or bases – Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). The different combinations and sequences of these four elements across 23 chromosome pairs make up the genome, providing essential information about our genetic makeup.
Genome sequencing is the process of determining the explicit order of these bases in the chromosomes. Through individual genome sequencing, scientists can delve into human genetic diversity and comprehend how diseases may impact us differently.
Constituents of a Reference Genome
A reference genome, also referred to as a reference map, functions like a standard map that aids scientists in studying and sequencing new genomes. It provides a benchmark for comparing and understanding the differences between the newly sequenced genome and the standard genome.
The first reference genome created in 2001 achieved significant scientific breakthroughs, such as discovering genes connected to diseases, comprehending the genetic aspects of diseases like cancer, and developing new diagnostic testing methods. However, this reference genome had limitations; it was primarily based on the genome of one individual from mixed African and European ancestry and contained some errors and gaps. Although more comprehensive and error-free than previous efforts, the existing pangenome still doesn’t entirely represent the full diversity of human genetics.
Pangenome Map: A New Approach
The Pangenome map introduces a unique representation of genetic information. Unlike the previous linear reference genome, the pangenome is visualized as a graph with each chromosome imagined as a bamboo stem with nodes. These nodes represent sequences shared among all individuals in the study, while the variances between the nodes denote the genetic variations among individuals from different ancestries. A technology called long-read DNA sequencing has been used by researchers to create these complete and continuous chromosome maps.
Significance and Drawbacks of the Pangenome Map
The pangenome map is a crucial tool for understanding human genetic diversity. While two humans share over 99% of their DNA, the remaining 0.4% difference equates to around 12.8 million nucleotides considering the vast size of the human genome (3.2 billion nucleotides). An accurate pangenome map can aid in making sense of these differences and revealing the diversity among individuals. Besides, it can assist in studying genetic variations contributing to underlying health conditions.
However, the current pangenome map lacks representation from different population groups, including communities from Africa, Indian subcontinent, indigenous groups in Asia and Oceania, and West Asian regions.
Genome Mapping Initiatives in India
In April 2023, the Indian government announced the Genome India Project (GIP), an ambitious initiative aiming to sequence 10,000 genomes by the end of the year. This program intends to create an extensive database of Indian genomes, allowing researchers to learn about unique genetic variants and develop personalized drugs and therapies. However, the efforts fall short when compared to countries like the United Kingdom, China, and the United States, where programs aim to sequence at least 100,000 genomes.
The Role of Genome Sequencing in Agriculture
Genome sequencing holds significant potential for agriculture, particularly in identifying disease resistance and drought tolerance in crops. This technique reduces the time required to develop new crop varieties and helps analyze host-pathogen relationships in plants. For instance, Chinese scientists decoded the rice genome in 2002. The Indian Agricultural Research Institute (IARI) has since used genome sequencing to develop improved rice varieties like Pusa Basmati-1 and Pusa Basmati-1121. Genome sequencing has also enabled the development of transgenic crops that are resistant to pests, herbicides, or viruses.
Problem-Solving through Genome Sequencing
Genome sequencing serves as a reliable method for studying host-pathogen interactions at the molecular, cellular, organism, or population levels. It helps understand how microbes or viruses survive within host organisms and provides insights into pathogens’ survival or breeding zones. Therefore, genome sequencing stands as a potent tool, not only for understanding genetic diversity and disease resistance but also for developing strategies for crop protection and improvement.
