HUMAN PANGENOME MAP – SCIE & TECH
News: Explained | Understanding a human pan-genome
map
What's in the news?
● A
new study published in the May 10 issue of the Nature journal describes a
pan-genome 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.
Genome:
● 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.
● In
other words, 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:
● Genome
sequencing is the method used to determine
the precise order of the four letters and how they are arranged in
chromosomes.
● Sequencing
individual genomes helps us understand
human diversity at the genetic level and how prone we are to certain
diseases.
What is a 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.
● It
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
a remarkable feat, the reference genome of 2001 was 92% complete and contained
many gaps and errors.
● Additionally,
it was not representative of all human beings as it was built using mostly the
genome of a single individual of mixed African and European ancestry. Since
then, the reference genome map has been refined and improved to have complete
end-to-end sequences of all the 23 human chromosomes.
● Although complete and
error-free, the finished reference genome map does not represent all of human
diversity.
Pan Genome 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 converges
(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 pan genome project, the researchers used long-read DNA sequencing
technologies, which produce strings of contiguous DNA strands 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 Pan Genome 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 pan genome 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.
India and Genome Sequence:
● Even
though the current map does not contain genome sequences from Indians, it will
help map Indian genomes better against the error-free and complete reference
genomes known so far.
● 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, help discover new genes for rare diseases, design better
diagnostic methods, and help discover novel drugs against those diseases.