HGP, the human genome project

RIZWANABBAS3 6,875 views 35 slides Oct 24, 2017
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About This Presentation

HGP, the human genome project


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HISTORY OF HUMAN GENOME PROJECT The project had its ideological origins in the mid-1980s , but its intellectual roots stretch back further In the mid-1970s, Frederick Sanger developed techniques to sequence DNA he received his second Nobel Prize in chemistry in 1980.

The Human Genome Project, The First Five Years, FY 1991-1995 ." The HGP began as a joint effort between the Department of Energy (DOE ) and the United States National Institutes of Health (NIH). This initial research plan set out specific goals for the first five years of what was then projected to be a 15-year research effort.

The Human Genome Project (HGP) is an international research effort to determine the DNA sequence of the entire human genome The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life science What is human genome project..????

Cost of HGP

Two groups tied in first sequencing a human genome The Human Genome Project Celera genome sequencing project The Human Genome Project Funded by the US Department of Energy, and Celera Genomics, a private company. The Human Genome Project took 10 years and cost $3 billion USD (US Dollars), Celera genome sequencing project took two years and cost just $300 million USD. Both projects concluded in 2000 or 2001, depending on what is considered a "complete" human genome sequencing.

DNA SEQUENCING

DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. The advent of rapid DNA sequencing methods has greatly accelerated biological and medical research and discovery. It includes any method or technology that is used to determine the order of the four bases in a strand of DNA which are Adenine Guanine Cytosine, Thymin DNA SEQUENCING

DNA Sequencing Methods

Maxam-Gilbert sequencing is performed by chain breakage at specific nucleotides. DMS G G G G FA G A G G A G A A H C T T C T C C T H+S C C C C Maxam -Gilbert Sequencing

Sequencing gels are read from bottom to top (5′ to 3′). G G+A T+C C 3′ A A G C A A C G T G C A G 5′ Longer fragments Shortest fragments G A Maxam -Gilbert Sequencing

Chain Termination (Sanger) Sequencing In this method, the DNA is used as a template to generate a set of fragments that differ in length from each other by a single base. The fragments are then separated by size, and the bases at the end are identified, recreating the original sequence of the DNA.

Chain terminates at ddG Chain Termination (Sanger) Sequencing The 3′-OH group necessary for formation of the phosphodiester bond is missing in ddNTPs .

Template area to be sequenced - 3 ′ OH TCGACGGGC… 5 ′ OP - Primer Template A sequencing reaction mix includes labeled primer and template . Dideoxynucleotides are added separately to each of the four tubes.

ddATP + ddA four dNTPs dAdGdCdTdGdCdCdCdG ddCTP + dAdG ddC four dNTPs dAdGdCdTdG ddC dAdGdCdTdGdC ddC dAdGdCdTdGdCdC ddC ddGTP + dA ddG four dNTPs dAdGdCdT ddG dAdGdCdTdGdCdCdC ddG ddTTP + dAdGdC ddT four dNTPs dAdGdCdTdGdCdCdCdG A C G T

The collection of fragments is a sequencing ladder. The resulting terminated chains are resolved by electrophoresis. Fragments from each of the four tubes are placed in four separate gel lanes.

Sequencing gels are read from bottom to top (5′ to 3′). G A T C 3′ G G T A A A T C A T G 5′ Longer fragments Shorter fragments ddG ddG

GOALS OF DNA sequencing Large insert clones YACs (Yeast Artificial Chromosomes Useful for mapping ~1mb inserts Unstable during construction and propagation Not useful for sequencing BACs (Bacterial Artificial Chromosomes) ~150kb insert Extremely stable and easy to propagate Gold standard for sequencing targets and chromosome-scale maps Cosmids ~50kb insert Extremely stable and easy to propagate Useful for sequencing but too small for chromosome

Messenger RNA sequencing

Messenger RNAs (mRNA) describes cytoplasmic product Pre-mRNA (part of hnRNA ) in nucleus is processed and exported Describe by gene/protein, including isoform spliced or NCBI sequence (NM, natural; XM, in silico ) New methods for describing mRNAs ( Sammeth 2008)

The genes in DNA encode protein molecules, which are the "workhorses" of the cell, carrying out all the functions necessary for life. For example, enzymes, including those that metabolize nutrients and synthesize new cellular constituents, as well as DNA polymerases and other enzymes that make copies of DNA during cell division, are all proteins. In the simplest sense, expressing a gene means manufacturing its corresponding protein, and this multilayered process has two major steps .

 In the first step, the information in DNA is transferred to a messenger RNA (mRNA) molecule by way of a process called transcription. During transcription, \ the DNA of a gene serves as a template for  complementarybase -pairing, and an  enzyme called RNA polymerase II catalyzes the formation of a pre-mRNA molecule, which is then processed to form mature mRNA. . The resulting mRNA is a single-stranded copy of the gene, which next must be translated into a protein molecule.

During translation, which is the second major step in gene expression, the mRNA is "read" according to the genetic code, which relates the DNA sequence to the amino acidsequence in proteins. Each group of three base pairs in mRNA constitutes acodon , and each codon specifies a particular amino acid (hence, it is a triplet code). The mRNA sequence is thus used as a template to assemble—in order—the chain of amino acids that form a protein.

Human genome maps   g enetic map of the human genome and determine the entire nucleotide  sequence of humandeoxyribonucleic acid (DNA). A nucleotide is the basic unit of nucleic acid, which is found in the 23 pairs ofchromosomes  in the human body. According to the Human Genome Project, there are between 26,000 and 40,000 genes in the human body. Each of these genes is composed of a unique sequence of pairs, each with four bases, called base pairs.

A Whole Genome Map is a high-resolution, ordered, whole genome map generated from single DNA molecules extracted from bacteria, yeast, or other fungi. Whole Genome Mapping is a novel technology with unique capabilities in the field of microbiology, with specific applications in the areas of Comparative Genomics, Strain Typing, and Whole Genome Sequence Assembly.   Whole Genome Maps are generated  de novo , independent of sequence information, require no amplification or PCR steps, and provide a comprehensive view of whole genome architecture. A Whole Genome Map is displayed in the MapCode pattern where the vertical lines indicate the locations of restriction sites, and the distance between the lines represent the restriction fragment size .

Benefits of HGM   to investigate microbial structure, function, diversity and genetics— without the need for amplification, PCR, cloning, paired-end libraries, pure isolates , or genomic specific reagents. Using OpGen’s unique  de novo  Whole Genome Mapping Technology, the Argus Whole Genome Mapping System, BGI delivers high resolution, ordered whole genome restriction maps from single microbial DNA molecules.

there are two mathods of maping Genetic linkage map Physical map Methods of gene maping Physical map Low resolution map Use moliculer biological te chniques to examin the dna directly And position of sequence ,features and including the genes Separate by the electrophrosis

Gene linkage map In the gene linkage Map gentic techniques includes Like crossing breed,or some natural prosses or in the csase of humans the experimental of family history or such traits that’s coming from past Gene map is the anatomy of human genom its easy to understand the function of human genom Help in analysing the heterogenecity and segregationof human genetic And also dividing the chromosoms in the smaller fregments Show the location of gene

Gene linkage map Physical map

uses of human genom project.. identify potential suspects at crime scenes exonerate wrongly accused persons identify crime and catastrophe victims establish paternity and other family relations identify endangered and protected species as an aid to wildlife officials (prosecution of poachers)

assess health damage and risks caused by radiation exposure, including low-dose exposures assess health damage and risks caused by exposure to mutagenic chemicals and cancer-causing toxins reduce the likelihood of heritable mutations

Ethecal issues on HGP fairness in the use of genetic information privacy and confidentiality psychological impact and stigmatization genetic testing reproductive issues education, standards, and quality control Commercialization conceptual and philosophical implications