In what could be the biggest achievement of recent times, researchers from Telomere-to-Telomere (T2T) consortium, an international collaboration of around 30 institutions have sequenced the “first truly complete human reference genome”.
Twenty years from its inception, researchers have finally filled in missing sections, assembling a full genome sequence of 3.055 billion base pairs.
Until now, around 8% of the human genome had been missing from reference genomes. The consortium has been working to fill in the gaps, largely highly repeating sections that don’t encode proteins but rather regulate biochemical processes via other mechanisms including transcription into regulatory RNA sequences or their physical conformation.
One reason that human genomes have remained incomplete has been because of technological constraints. Conventional DNA sequencers sequence relatively short fragments of a few hundred base pairs at a time and then use computer programs to put the fragments in order, constructing the full sequence. That means certain sequences, particularly stretches of DNA with repeating patterns, are challenging to read.
The consortium used two competing new sequencing technologies that avoid this problem by allowing researchers to sequence much longer stretches of the genome with high accuracy.
Two key factors made the completion of the human genome possible this time :
1. Choosing a very special cell type
The newly published genome sequence was created using human cells derived from a very rare type of tissue called a complete hydatidiform mole, which occurs when a fertilized egg loses all the genetic material contributed to it by the mother.
Most cells contain two copies of each chromosome, one from each parent and each parent’s chromosome contributing a different DNA sequence. A cell from a complete hydatidiform mole has two copies of the father’s chromosomes only, and the genetic sequence of each pair of chromosomes is identical. This makes the full genome sequence much easier to piece together.
2. Advances in sequencing technology
After decades of glacial progress, the Human Genome Project achieved its 2001 breakthrough by pioneering a method called “shotgun sequencing,” which involved breaking the genome into very small fragments of about 200 base pairs, cloning them inside bacteria, deciphering their sequences, and then piecing them back together like a giant jigsaw.
This was the main reason the original draft covered only the euchromatic regions of the genome—only these regions could be reliably sequenced using this method.
The project was also aided by software from Chirag Jain, Assistant Professor, Department of Computational and Data Science, the Indian Institute of Science (IISc).
Why it matters?
Areas with repeating DNA bases — like those missing from the HGP genome — have since been linked to many health issues, from ALS and Huntington’s disease to cancer and autism. By sequencing them, we might be better equipped to study and treat those conditions.
What is Human Genome Project ?
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint.
It remains the world’s largest collaborative biological project.
The project was not able to sequence all the DNA found in human cells. It sequenced only euchromatic regions of the genome, which make up 92.1% of the human genome. The other regions, called heterochromatic, are found in centromeres and telomeres, and were not sequenced under the project.
The Human Genome Project (HGP) was declared complete in April 2003.
John Craig Venter is an American biotechnologist who is known for leading the first draft sequence of the human genome and assembled the first team to transfect a cell with a synthetic chromosome
Read more about Human Genome Project .