MOLECULAR GENETICS 13

 Human genome project

• The scientific project which deal with the study of base sequences of DNA molecules of complete set of chromosomes is called human genome project.
• DNA -decides all property, so curiosity of knowing whole sequence.
• Genetic engineering techniques- DNA piece - isolate - sequencing. (Simple & fast)
• Launched in 1990

Initial problems-

1. 3×10`9 base pairs × initial estimated cost 3$ per base pair. = 9 billion $

2. Storage of info- 1000 latters in one page, 1000 pages per notebook, then it will require 3300 books..

• HGP was closely associated with the rapid development of a new area in biology- Bioinformatics.
• Goals of Human Genome project
• Identify all the approximately 20,000-25,000 genes in human DNA.
• Determine the sequences of the 3 billion chemical base pairs that make up human DNA.
• Store this information in databases;
• Improve tools for data analysis;
• Transfer related technologies to other sectors, such as industries;
• Address the ethical, legal, and social issues (ELSI) that may arise from the project.

Methodologies

• To identifying all the genes that expressed as RNA referred to as Expressed Sequence Tags (ESTs).
• Simply sequencing the whole set of genome that contained all the coding and non-coding sequence, and later assigning different regions in the sequence with functions is called as Sequence Annotation.
• The total DNA from a cell is isolated and converted into random fragments of relatively smaller sizes and cloned in suitable host using specialised vectors.
• The cloning resulted into amplification of each piece of DNA fragment.
• The commonly used vectors are BAC (bacterial artificial chromosomes), and YAC (yeast artificial chromosomes).
• The fragments were sequenced using automated DNA sequencers.
• Specialized computer based programmes were developed for the alignment of the sequences.
• The sequences were subsequently annotated and were assigned to each chromosome.
• The sequence of chromosome 1 was completed only in May 2006.

Automated DNA sequencer 

Salient Features of Human Genome

• The human genome contains 3164.7 million nucleotide bases.
• The average gene consists of 3000 bases with the largest known human gene being dystrophin at 2.4 million bases.

The largest known human gene- dystrophin 

• The total number of genes is estimated at 30,000.
• 9 per cent nucleotide bases are exactly the same in all people.
• The functions are unknown for over 50 per cent of discovered genes.
• Less than 2 per cent of the genome codes for proteins.
• Repeated sequences make up very large portion of the human genome.
• Repetitive sequences are stretches of DNA sequences that are repeated many times.
• Chromosome 1 has most genes (2968), and the Y has the fewest (231).
• Scientists have identified about 1.4 million locations where single base DNA differences (SNPs – single nucleotide polymorphism) occur in humans.

Single nucleotide polymorphism (self-drawn )

Applications of HGP

• All the genes in a genome can be studied together.
• Helps to understand how tens of thousands of genes and proteins work together in interconnected networks.
• Helps to diagnose and treat genetic diseases.