Benefit from the human pangenome map

(MainsGS3:Science and Technology- developments and their applications and effects in everyday life.)

Context:

• Recently, a new study describes a pangenome reference map, built using genomes from 47 anonymous individuals (19 men and 28 women), mainly from Africa but also from the Caribbean, Americas, East Asia, and Europe.

Blueprint of life:

• The genome is the blueprint of life, a collection of all the genes and the regions between the genes contained in our 23 pairs of chromosomes. 
• Each chromosome is a contiguous stretch of DNA string or our genome consists of 23 different strings, each composed of millions of individual building blocks called nucleotides or bases. 
• The four types of building blocks (A, T, G and C) are arranged and repeated millions of times in different combinations to make all of our 23 chromosomes.

Genome sequencing:

• While the sequence or order of base pairs is identical in all humans, compared to that of a mouse or another species, there are differences in the genome of every human being that makes them unique. 
• The process of deciphering the order of base pairs, to decode the genetic fingerprint of a human is called genome sequencing.
• In other words, genome sequencing is the method used to determine the precise order of the four letters and how they are arranged in chromosomes. 
• Thus, sequencing individual genomes helps us understand human diversity at the genetic level and how prone we are to certain diseases.

About reference genome:

• When genomes are newly sequenced, they are compared to a reference map called a reference genome. 
• This helps us to understand the regions of differences between the newly sequenced genome and the reference genome. 
• One of this century’s scientific breakthroughs was the making of the first reference genome in 2001 which helped scientists discover thousands of genes linked to various diseases; better understand diseases like cancer at the genetic level; and design novel diagnostic tests.
• Although complete and error-free, the finished reference genome map does not represent all of human diversity. 
• But the new study published in Nature changes describe the making of the pangenome map, the genetic diversity among the 47 individuals, and the computational methods developed to build the map and represent differences in those genomes.

Pangenome map:

• Unlike the earlier reference genome, which is a linear sequence, the pangenome is a graph. 
• The graph of each chromosome is like a bamboo stem with nodes where a stretch of sequences of all 47 individuals converge (similar).
• And with internodes of varying lengths representing genetic variations among those individuals from different ancestries. 
• To create complete and contiguous chromosome maps in the pangenome project, the researchers used long-read DNA sequencing technologies, which produce strings of contiguous DNA strands of tens of thousands of nucleotides long. 
• Using longer reads helps assemble the sequences with minimum errors and read through the repetitive regions of the chromosomes which are hard to sequence with short-read technologies used earlier.

Importance of pangenome map:

• Although any two humans are more than 99% similar in their DNA, there is still about a 0.4% difference between any two individuals. 
• This may be a small percentage, but considering that the human genome consists of 3.2 billion individual nucleotides, the difference between any two individuals is a whopping 12.8 million nucleotides. 
• A complete and error-free human pangenome map will help us understand those differences and explain human diversity better. 
• It will also help us understand genetic variants in some populations, which result in underlying health conditions. 
• The pangenome reference map has added nearly 119 million new letters to the existing genome map and has already aided the discovery of 150 new genes linked to autism.

Conclusion:

• Future pangenome maps that include high-quality genomes from Indians, including from many endogamous and isolated populations within the country, will shed light on disease prevalence.
• They also help in discovering new genes for rare diseases, design better diagnostic methods, and help discover novel drugs against those diseases.