HUMAN GENOME PROJECT (HGP)
❖ Genetic make-up of an organism or an individual lies in the DNA sequences.
The sequence of bases in DNA that determines the genetic information of a given
organism.
❖ If two individuals differ, then their DNA sequences should also be different, at least
at some places.
❖ A very ambitious project of sequencing human genome was launched in the year
1990.
❖ Genetic engineering techniques helped to isolate and clone any piece of DNA and
determine DNA sequences quickly.
Why HGP was called a mega project.
❖ Chemical base pairs in Human genome were 3X109 bp.
Cost of sequencing 1 bp was 3$
Total estimated cost was 9 billion dollars.
❖ Data storage in typed form: 1000 letters in each page with 1000 page in each book
requires 3300 books for one human cell (24 chromosomes= 22 autosomes + XY)
❖ High speed computational devices for data storage and retrieval, and analysis.
❖ HGP was closely associated with the rapid development of a new area in biology
called Bioinformatics.
Goals(AIMS) of HGP
1. Identify all the approximately 20,000-25,000 genes in human DNA;
2. Determine the sequences of the 3 billion chemical base pairs that make up
human DNA;
3. Store this information in databases;
4. Improve tools for data analysis;
5. Transfer related technologies to other sectors, such as industries;
6. Address the ethical, legal, and social issues (ELSI) that may arise from the
project.
The Human Genome Project was a 13-year project and completed
in 2003.
➢ Coordinated by The U.S. Department of Energy and the National Institute of
Health (NIH).
➢ The Wellcome Trust (U.K.) – A major partner.
➢ additional contributions from Japan, France, Germany, China and others.
Advantages of HGP:
➢ Knowledge about DNA variations helps to diagnose, treat and someday
prevent the thousands of disorders that affect human beings.
➢ Provide clues to understanding human biology.
➢ learning about non-human organisms DNA sequences can lead to an
understanding of their natural capabilities that can be applied toward
solving challenges in health care, agriculture, energy production,
environmental remediation.
Dr.K.LAKSHMIANARAYANA
Non-Human organisms
Organism Size of the genome
1. Eschirichia coli (Bacteria) 4.64 Mb (Mega base pair) 4,640,000bp
2. Saccharomyces cervisiae (yeast) 12,067,280bp
3. Caenorhabditis elegans (Free living 100.3Mb (106)
nematode)
4. Drosophila melanogaster (Fruit fly) 118.4Mb (106)
5. Mus musculus (Mammal) 2.6 Gb (Giga base pairs -109) 99% of genes are
direct counterparts of the human.
6. Arabidopsis thaliana (Flowering plant) 120Mb (106) 100 genes are similar to disease
causing genes of human.
7. Oryza sativa (Rice) 430 Mb (106)
METHODOLOGIES:
1. Expressed Sequence Tags (ESTs): Identifying all the genes that are expressed as RNA.
2. 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 (a term
referred to as Sequence Annotation).
3. The total DNA from a cell is isolated and converted into random fragments of relatively
smaller sizes (recall DNA is a very long polymer, and there are technical limitations in
sequencing very long pieces of DNA) and cloned in suitable host using specialised vectors.
4. The commonly used hosts were bacteria and yeast.
5. The vectors were called as BAC (bacterial artificial chromosomes), and YAC (yeast artificial
chromosomes).
6. The cloning resulted into amplification of each piece of DNA fragment. Sequencing can be
done with ease.
7. The fragments were sequenced using automated DNA sequencers that worked on the
principle of a method developed by Frederick Sanger. (Sanger also developed method for
determination of amino acid sequences in proteins Double Nobel Laureate).
8. These sequences were then arranged based on some overlapping regions present in them.
This required generation of overlapping fragments for sequencing.
9. Specialised computer-based programs were developed for the alignment of these sequences
was humanly not possible.
10. These sequences were subsequently annotated and were assigned to each chromosome.
Dr.K.LAKSHMIANARAYANA
11. Another challenging task was assigning the genetic and physical maps on the genome. This
was generated using information on polymorphism of restriction endonuclease recognition
sites, and some repetitive DNA sequences known as microsatellites.
Salient Features of Human Genome
(i) The human genome contains 3164.7 million bp.
(ii) The average gene consists of 3000 bases, but sizes vary greatly, with the largest known
human gene being dystrophin at 2.4 million bases.
(iii) The total number of genes is estimated at 30,000–much lower than previous estimates of
80,000 to 1,40,000 genes. Almost all (99.9 per cent) nucleotide bases are exactly the same in all
people.
(iv) The functions are unknown for over 50 per cent of the discovered genes.
(v) Less than 2 per cent of the genome codes for proteins.
(vi) Repeated sequences make up very large portion of the human genome.
(vii) Repetitive sequences are stretches of DNA sequences that are repeated many times,
sometimes hundred to thousand times. They are thought to have no direct coding functions, but
they shed light on chromosome structure, dynamics and evolution.
(viii) Chromosome 1 has most genes (2968), and the Y has the fewest (231).
(ix) Scientists have identified about 1.4 million locations where single base DNA differences
(SNPs – single nucleotide polymorphism, pronounced as ‘snips’) occur in humans. This
information promises to revolutionise the processes of finding chromosomal locations for
disease-associated sequences and tracing human history.
(x) The sequence of chromosome 1 was completed only in May 2006 (this was the last of the 24
human chromosomes.
Applications and Future Challenges
Meaningful knowledge from the DNA sequences will lead to our understanding of biological
systems.
Deriving meaningful knowledge require the expertise and creativity of tens of thousands of
scientists from varied disciplines in both the public and private sectors worldwide.
HG sequence gives a radically a new approach to biological research. In the past, researchers
studied one or a few genes at a time. With whole-genome sequences and new high-throughput
technologies, we can approach questions systematically and on a much broader scale.
They can study all the genes in a genome, for example, all the transcripts in a particular tissue or
organ or tumor, or how tens of thousands of genes and proteins work together in
interconnected networks to orchestrate the chemistry of life.
Dr.K.LAKSHMIANARAYANA
