Question

Describe the hierarchical approach to determining the DNA sequence of the human genome used by the Human Genome Project (HGP). Your answer should include descriptions of how physical maps were established and how BAC (bacterial artificial chromosome) libraries facilitated sequencing? (Min 2 and a half pages)

Answer 1

• Human Genome Project (HGP) was a very ambitious project of sequencing human genome which was launched in the year 1990.The Human Genome Project was a 13 year project coordinated by the U.S. Department of Energy and the National Institute of Health.Hence this project is commonly known as a mega project.
• The hierarchical approach of HGP involved two major approaches.

1. Expressed Sequence Tags (ESTs)
2. Sequence Annotation

The former approach focused on identifying all the genes that expressed as RNA and the later one is an approach of simply sequencing the whole set of genome that contained all the coding and non-coding sequence.

The cloning results into amplification of each piece of DNA fragment so that it subsequently could be sequenced with ease.The commonly used hosts were bacteria and yeast.The vectors were called as BAC (bacterial artificial chromosomes) and YAC (yeast artificial chromosomes).

The sequences were then arranged based on some overlapping regions present in them,a method developed by Frederick Sanger.Alignment of these sequences was possible with the help of specialised computer based programs.Hence physical maps were established.