On May 27, a preprint titled “The complete sequence of the human genome” was posted in the online repository bioRxiv . In this preprint, scientists from the Telomere-to-Telomere (T2T) Consortium, an international collaboration of around 30 institutions, reported the most complete sequencing of the human genome until now.
- What is Genome Sequencing?
- T2T Consortium Project and the Technology used (Sequencing Technology)
- History of Genome Sequencing Projects
- Importance of the project
- Potential uses of Genome Sequencing in general
What is Genome Sequencing?
- The genome, or genetic material, of an organism (bacteria, virus, potato, human) is made up of DNA. This resides in the nucleus of every cell of the organism.
- The DNA consists of a double-stranded molecule, each of which is built up by four bases – adenine (A), cytosine (C), guanine (G) and thymine (T).
- Every base on one strand pairs with a complementary base on the other strand (A pairs only with T, and C only with G).
- Each organism has a unique DNA sequence which is composed of bases. Each genome contains all of the information needed to build and maintain that organism.
- In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus.
- Genome Sequencing is a laboratory procedure that determines the order of DNA nucleotides, or bases (the order of As, Cs, Gs, and Ts) that make up an organism’s DNA
- If you know the sequence of the bases in an organism, you have identified its unique DNA fingerprint, or pattern.
T2T Consortium Project and the Technology used:
- The Telomere-to-Telomere (T2T) consortium is led by researchers at the National Institutes of Health and the University of California, Santa Cruz
- It is an international collaboration of around 30 institutions
- The T2T is an open consortium and all are welcome to join the effort to generate the first truly complete assembly of a human genome
- It focuses on the first gapless assembly of a human genome, finishing each chromosome from one end to the other
- The Telomere-to-Telomere (T2T) consortium announced our v1.0 assembly that includes more than 150 Mbp of novel sequence compared to GRCh38, achieves near-perfect sequence accuracy, and unlocks the most complex regions of the genome to functional study.
- protein-coding sequences or protein-coding genes are DNA sequences that get transcribed on ribonucleic acid (RNA) as an intermediate step.
- These in turn make the proteins responsible for various functions such as keeping the body healthy or determining the colour of the eye — proteins carry out the instructions encoded in the genes.
- The DNA used did not belong to any person.
- According to a report in Nature , it was a cell line derived from a tissue known as a complete hydatidiform mole.
- This is the tissue that forms when a sperm inseminates an egg that has no nucleus. Hence, this tissue has the chromosomes of just the father.
History of Genome Sequencing Projects:
- The Human Genome Project that began in 1990 gave the first results of the complete human genome sequence in 2003.
- For the first time, we were able to read the blueprint of human life.
- However, though it was announced as the complete human genome, about 15% of it was incomplete.
- Due to limitations of technology, scientists were not able to piece together some repetitive parts of the human genome.
- Solving some of the problems, an updated “complete” version was released in 2013, which still missed out on 8% of the genome.
Importance of the project:
One step Closer to Whole Human Genome Mapping:
- The researchers have nearly completed the job, adding 200 million base pairs and 115 new protein-coding genes to the list.
- They have, in the process, discovered over a hundred new genes that code for proteins. The total size of the genome they have sequenced is close to 3.05 billion base pairs.
- This adds 200 million base pairs to the last draft of the human genome that was published in 2013.
- With this, we are a step closer to mapping the whole human genome.
Standard of Reference:
- One of the most important uses of this release will be that it forms a standard for comparison in future sequencing attempts
- This sequence of the human genome will be a gold standard of reference for future attempts.
Unprecedented Level of Accuracy:
- The level of accuracy is unprecedented.
- Earlier, Researchers were trying to piece together strands of DNA that were a few hundred base pairs long.
- The technology used by the Telomere-to-Telomere Consortium used sequencing technology that could scan 20,000 base pairs at one go. This is a significant technological feat.
Missing Y- Chromosome Data:
- The present release has no information about the Y chromosome.
- All chromosomes in an arbitrary cell’s nucleus are found in pairs – we have 23 pairs of chromosomes in each cell.
- However, the sex cells such as sperm and egg cells contain only one of each pair of chromosomes (haploid cells).
- So, while egg cells always carry a copy of the X chromosome, sperms can carry either an X chromosome or a Y chromosome.
- The cell line that the researchers studied had an X chromosome only and no Y chromosome. Therefore, information about the Y chromosome is missing in this release.
Chances of Errors:
- It is also not 100% complete. The researchers say that about 0.3% of the genome may have errors.
Potential uses of Genome Sequencing in general:
- The primary purpose of sequencing one’s genome is to obtain information of medical value for future care.
- genome sequencing has the potential to increase the ability to act preemptively prior to disease development or commence treatment for a disease that has not yet been diagnosed.
Drug Efficacy Studies (pharmacogenomics):
- Another advantage of genome sequencing is that information regarding drug efficacy or adverse effects of drug use can be obtained.
- The relationship between drugs and the genome is called pharmacogenomics.
Discovering Gene Mutations:
- genome sequence does not change unless influenced by environmental factors, for example, in the development of many cancers
- Genome sequencing can help discovery of rare or novel variants.
- This point can be illustrated by considering BRCA gene mutations, which confer a high risk of breast and ovarian cancer development in women.
- Early discovery of these mutations provides options for prophylactic action.
Mould your thought: What is genome sequencing? With reference to the recent efforts, discuss the importance of Human Genome Sequencing.
Approach to the answer:
- Define Genome Sequencing
- Discuss the T2T consortium results
- Discuss the potential uses of genome sequencing