HUMAN GENOME PROJECT DECODE THE CODES OF

LIFE

Arjunaa Prabhakar

• The Human Genome Project was an international research effort to determine the sequence of the human genome and identify the genes that it contains.

• The US Human Genome Project is a 13 year effort, which is coordinated by the – Department of Energy (DOE) and– National Institutes of Health (NIH).

WHAT IS HUMAN GENOME?- THE STUFF THAT MAKE WHO WE ARE

• A genome is an organism’s complete set of genetic instructions. Each genome contains all of the information needed to build that organism and allow it to grow and develop.

• Our bodies are made up of millions of cells? (100,000,000,000,000), each with their own complete set of instructions for making us, like a recipe book for the body. This set of instructions is known as our genome and is made up of DNA. Each cell in the body, for example, a skin cell or a liver cell, contains this same set of instructions.

• DNA is packed in chromosomes in the nucleus of cell. We have 23 pairs of chromosomes.

DNA- Deoxyribo nucleic acid

DNA is a long molecule, made up of lots of smaller units called nucleotides. To make a DNA molecule you need:• nitrogenous bases—there are four of these: adenine (A),

thymine (T), cytosine (C), guanine (C)• Pentose sugar molecules• phosphate moleculesIf you take one of the four nitrogenous bases, and put it together with a sugar molecule and a phosphate molecule, you get a nucleotide base. The sugar and phosphate molecules connect the nucleotide bases together to form a single strand of DNA. Two of these strands then wind around each other, making the twisted ladder shape of the DNA double helix. The nucleotide bases pair up to make rungs of the ladder, and the sugar and phosphate molecules make the sides. The bases pair up together in specific combinations: A always pairs with T, and C always pairs with G to make base pairs.There are distinct sections of DNA that affect a particular characteristic or condition is known as genes. These genes used to create the amino acids that joins together to make protein and this how the gene expression occurs. Their is certain sequences in DNA which are not genes they are known as junk DNA.

HISTORY OF HGP- IN TIMELINE1970’s – Fred Sanger invented the DNA sequencing technique.1985 - Robert Sinsheimer, chancellor of the University of California, Santa Cruz (UCSC), holds first meetings to propose sequencing the human genome? with potential funders, the US Department of Energy, the US National Institutes of Health (NIH) and the UK Medical Research Council (MRC).1986 – US Dept. of Energy and National Institute of Health come to fund the project1988 – Human Genome Organization (HUGO) was founded1889 – Medical Research Council sponsored1990 – HGP was initiated- directed by James Watson1993 – Welcome Trust Institute joins1994 – Genetic privacy act1997 – NHGRI was established1998 – Celera Genomics founded , other group to do HGP independently.1999 – Human chromosome 22 was sequenced firstly2000 – Working draft was completed2001 – Published the analysis of working draft 2003 – Human Genome Project was completed

GOALS OF HUMAN GENOME PROJECT• To identify all the genes in human DNA.• To develop a genetic linkage map of human genome.• To obtain a physical map of human genome.• To develop technology for the management of human genome

information.• To know the function of genes.• Determine the sequences of the 3 billion chemical base pairs

that make up human DNA.• Store this information in public databases.• Develop tools for data analysis.• Transfer related technologies to the private sectors.

ETHICAL, LEGAL AND SOCIAL IMPLICATIONS

• Fairness in the use of genetic information.• Privacy and confidentiality of genetic information. • Psychological impact, stigmatization, and discrimination.• Reproductive issues.• Clinical issues. • Uncertainties associated with gene tests for susceptibilities and complex

conditions.• Fairness in access to advanced genomic technologies. • Conceptual and philosophical implications.• Health and environmental issues.• Commercialization of products.• Education, Standards, and Quality control.• Patent issues.

SEQUENCING STRATEGIESMapping of human genomeMapping is dividing each chromosome into small segments, characterizing them and arranging them sequentially on the chromosome.A genome map describes: order of gene, other known fragment, spacing between them on each chromosome.There are 2 types of fragments 1. Genetic Map:- order by which gene are arranged along a chromosome. It is facilitated by known

marker ie, gene or other DNA2. Physical Map:- Shows the actual sites of genes on the genome.

• The sample to be sequenced is taken from blood.

• To sequence of DNA it must be amplified or increase the quantity.2 types of DNA amplification: 1. Cloning 2. PCR

By the amplification techniques many copies of DNA fragment is formed.

Sequencing TechniquesShot Gun Method

Shotgun sequencing, also known as shotgun cloning, is a method used for sequencing long DNA strands. It is named by analogy with the rapidly expanding, quasi-random firing pattern of a shotgun. In shotgun sequencing, DNA is broken up randomly into numerous small segments, which are sequenced using the chain termination method to obtain reads. Multiple overlapping reads for the target DNA are obtained by performing several rounds of this fragmentation and sequencing. Computer programs then use the overlapping ends of different reads to assemble them into a continuous sequence.

• IHGSC used Hierarchichal Shot Gun Sequencing Method• Celera genomics used Whole genome sequencing shot gun method

KEY FINDINGS• Human Genome ic composed at 3200

Mbp. • 1.1 to 1.5% genome codes for protein. • Approximately 24% of the total genome

is composed of introns that split the coding regions (exons). And appear as repeating sequence with no specific functions.

• The number of protein coding gene is in the range of 30000-40000.

• An average gene consist of 3000 bases/ the sizes however vary greatly. Dystrophin gene is the largest human gene with 2.4 billion bases.

• Chromosome 1 contains highest number of gene 2968. While the Y chromosome has the lowest.

• Genes and DNA sequences associated with many diseases such as breast cancer, muscle diseases, deafness and blindness have been identified.

• About 100 coding regions appear to have been copied and moved by RNA based transposition.

• Repeated sequence constitute 50% of the human genome.

• A vast majority of the genome has no known function.

• Between the humans the DNA differs only by 0.2% as one in 500 bases.

• More than 3 million SNPs identified. • 98% of Human Genome similar to chimpanzee.

APPLICATIONS1. DNA Identification (Forensics)• identify potential suspects whose DNA may match evidence left at crime scenes• exonerate persons wrongly accused of crimes• identify crime and catastrophe victims• establish paternity and other family relationships• identify endangered and protected species as an aid to wildlife officials (could be used for prosecuting poachers)• detect bacteria and other organisms that may pollute air, water, soil, and food• match organ donors with recipients in transplant programs• determine pedigree for seed or livestock breeds• authenticate consumables such as caviar and wine2. Molecular Medicine • improve diagnosis of disease• detect genetic predispositions to disease• create drugs based on molecular information• use gene therapy and control systems as drugs• design “custom drugs” (pharmacogenomics) based on individual genetic profiles

3. Microbial Genomics• rapidly detect and treat pathogens (disease-causing microbes) in clinical practice• develop new energy sources (biofuels)• monitor environments to detect pollutants• protect citizenry from biological and chemical warfare• clean up toxic waste safely and efficiently4. Waste Control and Environmental Cleanup In 1994, through advances gained by the HGP, the DOE formulated the Microbial Genome Initiative to sequence the genomes of bacteria useful in the areas of energy production, environmental remediation, toxic waste reduction, and industrial processing. Resulting from that project, six microbes that live under extreme temperature and pressure conditions have been sequenced. By learning the unique protein structure of these microbes, researchers may be able to use the organisms and their enzymes for such practical purposes as waste control and environmental cleanup. 5. Agriculture, Livestock Breeding, and Bioprocessing (Biotechnology)• grow disease-, insect-, and drought-resistant crops• breed healthier, more productive, disease-resistant farm animals• grow more nutritious produce• develop biopesticides• incorporate edible vaccines incorporated into food products• develop new environmental cleanup uses for plants like tobacco

6. Bioarchaeology, Anthropology, Evolution, and Human Migration• study evolution through germline mutations in lineages• study migration of different population groups based on maternal inheritance• study mutations on the Y chromosome to trace lineage and migration of males• compare breakpoints in the evolution of mutations with ages of populations and historical events7. Energy Sources Biotechnology, strengthened by the HGP, will be important in improving the use of fossilbased resources. Increased energy demands require strategies to circumvent the many problems with today's dominant energy technologies. Biotechnology will help address these needs by providing a cleaner means for the bioconversion of raw materials to refined products. Additionally, there is the possibility of developing entirely new biomass-based energy sources. Having the genomic sequence of the methane-producing microorganism Methanococcus jannaschii, for example, will allow researchers to explore the process of methanogenesis in more detail and could lead to cheaper production of fuel-grade methane.8. Risk Assessment Understanding the human genome will have an enormous impact on the ability to assess risks posed to individuals by environmental exposure to toxic agents. Scientists know that genetic differences cause some people to be more susceptible than others to such agents. More work must be done to determine the genetic basis of such variability, but this knowledge will directly address the DOE's long-term mission to understand the effects of low-level exposures to radiation and other energy-related agents, especially in terms of cancer risk (3). Additional positive spin-offs from this research include a better understanding of biology, increased taxonomic understanding, increased development of pest-resistant and productive crops and livestock, and other commercially useful microorganisms.

DISADVANTAGES • It may lead to parents attempting to determine which character their off spring shall inherit. This

will lead to the development of designer baby. • This may restrict the human gene pool and interface with natural selection and loss of diversity

among the human population. • Misuse of genetic information may violate genetic privacy Also health or life insurance policies

may be deemed to an individual on the basis of his genetic information. • It can be misused for developing weapon of mass destruction. • It could also develop racial discrimination.

• The success of HGP may widen the gap between developed and developing, as only the rich

countries alone would be able to enjoying the advance medical treatment.