Human Genome Project:
- The human genome project (HGP) is a project to map and sequence the 3 billion nucleotides contained in the human genome and to identify all the genes present in it.
- It is under the control of an international body, the Human Genome Organization (HUGO). This project was started in 1988 by the US Department of Energy (DOE). The DOE and National Institute of Health (NIH) hand in hand started this project in 1990.
- 250 laboratories from 8 countries were involved in this project James D. Watson was the leader of the project and it was started under the leadership of Francis Collins. This is also called Mega Project & it was completed in 2003.
Aims of the Human Genome Project:
- To identify one lakh genes in human DNA.
- To determine the base sequence of 3 billion chemical base pairs that make up human DNA.
- To store this information in the database.
- To improve tools for data analysis.
- To address the ethical, legal and social issues that may arise from the project.
- To determine the sequence of several modal organisms like E. coli, yeast, Drosophila, rat (Mus musculus)
The technique used in the Human Genome Project:
There are two types of approaches for analyzing the genome.
- Identify all the genes that are expressed as RNA Expressed sequence tags or ESTs.
- Sequencing the whole genome (both coding and non-coding regions) and later assigning the different regions with functions – Sequence annotation.
The second methodology was used in the HGP which involves the following steps:
- The whole DNA of the cell is isolated and broken randomly into fragments.
- They are inserted into specialised vectors like BAC (bacterial artificial chromosomes) and YAC (yeast artificial chromosome).
- The fragments are cloned in suitable hosts like bacteria and yeast. PCR (polymerase chain reaction) can also be used for cloning or making copies of DNA fragments.
- The fragments are sequenced as annotated DNA sequences (an offshoot of the methodology developed by double Nobel laureate, Frederick Sanger), Sanger used Di-deoxy Chain Termination method through advanced DNA sequences.
- The sequences were then arranged on the basis of some overlapping regions. It necessitated the generation of overlapping fragments for sequencing.
- For physical and genetic mapping of sequence recognition sites of restriction endonuclease are used which are located on microsatellite of the chromosomes. Sequencing of the overlapping end is done through a special sequence program through the computer.
Salient Features of Human Genome:
- The human genome has 3.1657 Billions of nucleotide base pairs.
- According to a presumption of the human gene from 80,000 – 140000 but HGP revealed the Number of genes has 30,000.
- The average gene size is 3000 base pairs. Dystrophin is the biggest gene, contains 2.4 crores base pairs.
- Human Genome project revealed Single Nucleotide polymorphism (SNP). At 104 million places this SNP is found. It helps in identifying sequence for disease on the chromosome.
- The function of 50% of genes has been identified.
- Less than 2% of genes are involved in protein synthesis.
- Chromosome Number 1 has the highest gene number which is 2968 genes and the lowest number of genes are present in the Y chromosome which only 231 genes.
- 99.9% of the nucleotide bases are exactly similar in all human beings.
- Only 0.1% of the human genome with some 3.2 million nucleotides represents the variability observed in human beings.
- Repeated or repetitive sequences make up a large portion of the human genome. There are some 30,000 minisatellite loci, each having 11 – 60 bp repeated randomly up to a thousand times. These are about 2,00,000 microsatellites, each with up to 10 basic pair repeated 10 – 100 times.
- Repetitive sequences are nucleotide sequences that are repeated many times, sometimes hundred to thousand times. They do not have direct coding function but provide information as to chromosome structure, dynamics and evolution.
