Genome Sequencing | Science & Technology for UPSC CSE PDF Download

Genome

• A genome is the DNA, or sequence of genes, in a cell.
• Most of the DNA is in the nucleus and intricately coiled into a structure called the chromosome.
• The rest is in the mitochondria, the cell’s powerhouse, and some is chloroplast DNA.
• Every human cell contains a pair of chromosomes, each of which has three billion base pairs or one of four molecules – adenine (A), thymine (T), guanine (G), and cytosine (C) – that pair in precise ways.

RNA-DNA

• The order of base pairs & varying lengths of these sequences constitutes the “genes”.
• Genes are responsible for making amino acids, proteins and, thereby, everything that is necessary for the body to function.

Gene Magnitude in Body

• When these proteins do not function as intended, it leads to disease.

Genome Sequencing

• Sequencing a genome means deciphering the exact order of base pairs in an individual.
• This “deciphering” or reading of the genome is what sequencing is all about.
• In this particular piece of DNA, an adenine (A) is followed by a guanine (G), which is followed by a thymine (T), which in turn is followed by a cytosine (C), another cytosine (C), and so on.

How do you sequence a genome?

• Almost any biological sample containing a full copy of the DNA — even a very small amount of DNA or ancient DNA — can provide the genetic material necessary for full genome sequencing.
  • Such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, plant leaves, etc.
  • The whole genome cannot be sequenced all at once because available methods of DNA sequencing can only handle short stretches of DNA at a time.
  • Scientists must break the genome into small pieces, sequence the pieces & then reassemble them in the proper order to arrive at the sequence of the whole genome.
  • One strategy, known as the “clone-by-clone” approach, involves first breaking the genome up into relatively large chunks.
  • The other strategy, called “whole-genome” method, involves breaking the genome up into small pieces, sequencing the pieces, & reassembling the pieces into the full genome sequence.

Whole Genome Sequencing

• Exome, the portion of the genes responsible for making proteins occupies just about 1% of the actual gene. Rather than sequence the whole gene, many geneticists rely on “exome maps”.
• However, the non-exome portions also affect the functioning of the genes.
• Hence to know which genes of a person’s DNA are “mutated” the whole genome sequencing is required.
• Whole genome sequencing is the process of determining the complete DNA sequence of an organism’s genome at a single time.
• This entails sequencing all of an organism’s chromosomal DNA as well as DNA contained in the mitochondria and, for plants, in the chloroplast.
• In practice, genome sequences that are nearly complete are also called whole genome sequences.
• The whole genome sequencing relies on new technologies that allow rapid sequencing of the entire genome in a matter of a few days.

Advantages of Whole Genome Sequencing

• It provides a high-resolution, base-by-base view of the genome.
• Captures both large & small variants that might be missed with targeted approaches.
• Identifies potential causative variants for further follow-up studies of gene expression & regulation.
• Delivers large volumes of data in a short amount of time to support the assembly of novel genomes.
• Whole genome sequencing data of a person can be analysed to determine if they carry genes for particular single genetic disorders (caused due to mutation). This will help usher in a new era of personalized medicine.