End to End Genome Sequencing : Telomere to Telomere Consortium

Content:

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.

Challenges: 

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:

Predictive medicine:

• 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.