Human Genome Project

The human genome is the total genetic material in the cells of a human being. It contains billions of nucleotide base pairs. The genetic material is present in the chromosomes.  Human Genome Project involves sequencing of all the DNA base pairs and mapping of several genes. The project started in 1991 in the USA. It was the largest project in human genetics. It was completed by April 14, 2003. The National Institutes of Health-funded primarily for this project. The project covered 99% euchromatic genome with 99.99% accuracy. Human genome sequencing benefitted a lot. It helped in understanding the diseases, genotyping of specific microbes, identification of mutations, cancer genetics, drug designing, and biotechnology. Specific databases were designed to store the sequences of the DNA. The National Center for Biotechnology Information (NCBI) consists of all the database information in GenBank. It is a hub for gene sequence information, protein sequences, and related information.

Image: Human Genome Project

Objectives of the Human Genome Project:

1.     Human Genome Sequencing:

It is used to figure out the order of nucleotides or bases such as adenine, guanine, cytosine or thymine.

2.     Human Gene Mapping:

It is used to identify a locus of a gene and the distance between the genes. Human gene mapping places a collection of molecular markers on their respective genome positions.

3.     Mapping of human inherited Diseases:

It helps to identify genes and biological processes. It is used to understand the molecular basis of inheritance.

4.     Development of new DNA technologies:

Human genome project developed new DNA technologies. They consisted of recombinant techniques for studying diseases and drug designing.

5.     Development of bioinformatics:

It helped in assembling DNA sequences, finding genetic landscape features, genome mining, the study of genetic variation and disease.

6.     Comparative genomics:

A computer-based analysis is used to compare the entire genome sequence. Comparative genomics is used to study similarity and difference regions.

Techniques used in the Human Genome Project:

Genome annotation technique used in the human genome project identified boundaries between genes and other features in a DNA. The bioinformatics domain stores the genome annotated sequences. RNA-Seq is a new technology introduced to sequence a messenger RNA in the cells. RNA-Seq was more accurate than annotation.

Highlights of the findings:

·        The Human genome project identified approximately 22,300 protein-coding genes.

·        Human genome sequencing identified 3.2 billion base pairs.

·        A human body consists of 26,000 to 35,000 genes.

·     Genes constitute only 5% of the human genome. Over 95% of the human genome is known as junk DNA. The non-coding DNA is known as junk DNA.

·        The junk DNA constitutes repeating DNA segments.

·        Only 7% of protein families were vertebrate specific.

·        Genes function as complex networks.

The Mapping Phase of Human Genome Project:

The gene mapping involved restriction fragment length polymorphisms (RFLPs). These RFLPs are highly polymorphic DNA markers. It comprised of 393 RFLPs. It also consisted of ten polymorphic markers. The marker density was 10 Mb. The RFLP map consisted of single strand length polymorphisms (SSLPs). Clone contigs were primarily used to develop physical mapping. Methods used were STS screening and clone fingerprinting.

A clone contig map consisted of 33,000 Yeast Artificial Chromosomes (YACs). However, there was a limitation of YAC. It contained few pieces of non-contiguous DNA. STS markers were mapped using radiation hybrid mapping. STS maps included 7000 polymorphic SSLPs.

Human Genome Sequencing:

Since YACs consisted of non-contiguous DNA, the entire focus switched over to BACs. The scientists cloned and mapped the Bacterial artificial chromosomes (BACs). A library of three lakh BAC clones was generated and mapped into the genome. The ready map of BAC was a primary foundation for the sequencing project. The shotgun sequencing method was used to replace the clone contig method.

There are many advantages to the human genome project. It helps to study the genes and mutations associated with them. It is easier to diagnose, predict and prevent the disease using HGP principles. Medicines can be developed based on the individual’s response to treatment. There is a wide scope for personalized medicine and drug designing. Using the databases generated during HGP, it is easy to carry out research activities. The gene databases help the molecular and cytogeneticists to study specific gene mutations, chromosomal abnormalities, and sequencing strategies. DNA fingerprinting techniques are useful in forensic medicine and crime investigation. With the help of gene mapping, it becomes easier to study inherited diseases and conduct efficient genetic counseling and prenatal diagnosis. However, there are very few disadvantages to the human genome project. Knowing one’s genome and possible risks that could result in a disease in the future may create an environment for genetic discrimination. However certain laws have been implemented such as GINA act to prevent genetic discrimination.

Cancer genomics:

With approximately millions of cancer cases worldwide, the survival rates of cancer patients are decreasing every year. The response of patients to the current treatment methodologies is not satisfactory. Moreover, the drugs and radiations given to the patients have been fraught with severe toxicity and side effects thereby limiting their applications in the cancer therapeutics. The human genome project had an objective of genome sequencing and mapping. Thus the research can be directed toward the development of new anti-cancer products. These products might target the signaling pathways, apoptosis, metastasis or migration of cancer cells. An increasingly rapid DNA analysis with the help of the human genome project may establish new therapeutic targets and facilitate effectiveness.

Enable Technologies:

An evolutionary improvement in the existing genome sequencing technologies through Human genome project may have a revolutionary impact on the genetic research. The human genome project would be helpful in designing treatment strategies for various diseases. The past, present and the future are genome based. Overcoming those few disadvantages of HGP might equip the human population to adopt the changes in the future. Though the human genome project is a well-established one, we know that studying the entire genome would never be complete. As the environment changes, the conditions may change and so the genes. Thus human genome would always be a topic for study. Chances of new mutations would be high. Thus, studying a human genome is a coordinated effort of the researchers to carry out the mapping and sequencing. High-throughput revolutionary technologies developed with the synergy of advanced computerization, automated machines, and robotics work excellent with microarrays, modern screening, and imaging techniques.

References:
[1] Genomes, T.A. Brown
[2] Human Genome Project- Wikipedia
[3] Genetics Home Reference

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