Human Genome Project

Salient features of the Human Genome Project:

• The human genome contains 3 billion nucleotide bases.
• An average gene consists of 3000 bases, the largest known human gene being 'dystrophin' with 2.4 million bases.
• Genes are distributed over 24 chromosomes. Chromosome 19 has the highest gene density. Chromosome 13 and Y chromosomes have the lowest gene densities.
• The chromosomal organization of human genes shows diversity.
• There may be 35000-40000 genes in the genome and almost 99.9% of nucleotide bases are exactly the same in all people.
• Functions for over 50% of the discovered genes are unknown.
• Less than 2% of the genome codes for proteins.
• Repeated sequences make up a very large portion of the human genome.
• Repetitive Sequences: These are stretches of DNA sequences that are repeated many times (a hundred to a thousand times) in a genome.
  These have no coding function but provide, information about chromosome structure, dynamics, and evolution.
• The highest number of genes (2968) are present in Chromosome 1. The least number of genes (231) are present in chromosome 'Y'.
• Scientists have identified about 1.4 million locations where single-base DNA differences (SNPs – Single nucleotide polymorphism – pronounce as ‘snips’) occur in humans. Identification of ‘SNIPS’ is helpful in finding chromosomal locations for disease-associated sequences and tracing human history.

Goals of Human Genome Project:

Some of the important goals of HGP were as follows:

• Determining the sequence and number of all the base pairs (three billion) in the human genome.  
• Identifying all the genes present in human genome.
• Determining the functions of all the genes and identifying the various genes that cause genetic disorders.
• Storing the information in databases. 
• Improving tools for data analysis. 
• Finding out possibilities of transfer of technology developed during HGP to industry.  
• Address ethical, legal, and social issues (ELSI) that may arise from the project. 
• To have greater understanding of the process of human evolution. 
• To understand more about genetic structure, functions, gene mutation, expression, and methods to control them.

Methods of Human Genome Project:

The Human Genome Project involves two methods that play a significant role in this HGP.

1. The first method was focused on identifying all the genes that are expressed as RNAs. These are referred to as 'Expressed Sequence Tags (ESTs)'.
2. The second approach was the sequencing of the genome, which contains all the coding and non-coding sequences, and later assigning different regions in the sequences with functions. This is known as 'Sequence Annotation'.

Human Genome Project:

• The total genetic content in a haploid set of chromosomes in eukaryotes, in a single chromosome in bacteria, or in the DNA or RNA viruses is called genome.
• When two individuals differ, their DNA sequence should also differ.
• These assumptions led to the quest of finding out the complete DNA sequence of human genome, i.e. the mapping of whole genome on a nucleotide level. 
• The establishment of genetic engineering made it possible to isolate and clone any segment of DNA.  
• Furthermore, easier and faster techniques of DNA sequencing helped the project.  
• The international human genome project was launched in the year 1990.
• Human Genome Project (HGP) was called a mega project.
• The human genome is about 25 times larger than the genome of any organism sequenced to date and is the first vertebrate genome to be completed.
• The human genome is said to have approximately 3 × 10⁹ bp.
• As a huge amount of data was sequenced, storage of the enormous data was troublesome.  
• This led to the development of a new area in biology named 'Bioinformatics', which included the use of computational techniques. It provided the necessary high speed, sufficient storage, and ease of data analysis and retrieval.
• The Human Genome Project was a 13-year project coordinated by the U.S. Department of Energy and the National Institute of Health.
• The project was completed in 2003. 
• During the early years of the HGP, the 'Wellcome Trust (U.K.)' became a major partner; additional contributions came from Japan, France, Germany, China, and others.

Process of Human Genome Project:

• The complete DNA was isolated from a cell.
• The DNA was then divided into small fragments using restriction enzymes.
• These fragments were then amplified with the help of a commonly used vector which is usually known as BAC (Bacterial artificial chromosomes) and YAC (Yeast artificial chromosomes).
• The fragments were sequenced using automated DNA sequencers that worked on the principle of a method developed by Frederick Sanger. 
• These sequences were then arranged based on some overlapping regions present in them. 
• This required generation of overlapping fragments for sequencing.
• All the information of this genome sequence was then stored in a computer-based program.
• These sequences were subsequently annotated and were assigned to each chromosome.
• In this way, the entire genome was sequenced and stored as a genome database in computers. 
• The last of human chromosome to be sequenced was chromosome 1. Its sequencing was completed in May 2006.
• HGP also generated two types of maps:
  (a) Genetic Linkage Map
  (b) Physical Map
• The maps were based on polymorphism (variation seen at the genetic level) of restriction endonuclease recognition sites, and some repetitive DNA sequences are known as Micro Satellites i.e., the repetitive DNA sequences.