AN OVERVIEW OF HUMAN GENOME PROJECT, OMIM ANDHAP MAP : AN OVERVIEW OF HUMAN GENOME PROJECT, OMIM ANDHAP MAP GUIDED BY: DR.JYOTI BHOJWANI
PRESENTED BY: ASMITA GAUR Human Genome Project : Human Genome Project Brief history of HGP : Brief history of HGP 1984 to 1986 - first proposed at US DOE meetings
1988 - endorsed by US National Research Council
(Funded by NIH and US DOE $3 billion set aside)
1990 - Human Genome Project started formally.
First draft published in Science and Nature in February, 2001
Finished Human Genome sequence published in Nature 2003. Goals of HGP : Goals of HGP Create a genetic and physical map of the 24 human chromosomes (22 autosomes, X & Y)
Identify the entire set of genes & map them all to their chromosomes
Determine the nucleotide sequence of the estimated 3 billion base pairs
Analyze genetic variation among humans
Map and sequence the genomes of model organisms like bacteria(E.coli),yeast,Drosophila,mouse etc.
Consider and address ‘ELSI’ The Genome is Who We Are on the inside! : The Genome is Who We Are on the inside! What is a genome?
Chromosomes consist of DNA
molecular strings of A, C, G, & T
base pairs, A-T, C-G
DNA sequences that encode proteins Information coded in DNA PRACTICAL BENEFIT TO LEARNING ABOUT DNA : PRACTICAL BENEFIT TO LEARNING ABOUT DNA DNA variations among individuals
Providing clues to understanding human biology, on human organisms DNA sequences
Solving challenges in health care,agriculture,environment remediation ELSI CHALLENGES PRESENTED BY HUMAN GENOME PROJECT : ELSI CHALLENGES PRESENTED BY HUMAN GENOME PROJECT $ 1 Million was spent on ELSI HGP project.
Emphasizes the privacy of genetic information, its safe and effective introduction to clinical setting.
Promoting public understanding
Privacy Two Competing Strategies for Human Genome : Two Competing Strategies for Human Genome Hierarchical shotgun [Public human genome project]
Map First, Sequence Later
Whole-genome Shotgun [Celera project]
Sequence First, Map Last Slide 13: 2 Strategies for Sequencing Human Genome Map First Sequence Later : Map First Sequence Later Sort chromosomes
For each chromosome clone large fragments of DNA
Identify set of clones that span the chromosome
Shotgun sequence each clone
Finish (close gaps) Sequence First Map Last (Whole Genome Shotgun) : Sequence First Map Last (Whole Genome Shotgun) Isolate genomic DNA
Construct clone libraries of varying sizes
Make sure library is random or nearly so
Sequence both ends of each clone
Assemble the sequences computationally
Finish (close gaps) Whole-genome shotgun sequencing : Whole-genome shotgun sequencing Whole genome randomly sheared
Plasmid library constructed with ~ 2kb inserts
Plasmid library with ~10 kb inserts
Computer program assembles sequences into chromosomes
No physical map construction Important features of Human Genome : Important features of Human Genome 20,000 – 25,000 protein-coding genes (2006)
It produced a reference sequence of human genome which is used world wide.
Fewer genes, only about 1.5% coding for proteins
3 Billion chemical bases
The average genes consists of 3000 bases but size vary greatly
The order of almost all 99.9% nucleotide bases is exactly the same in all individuals Impact of Human Genome on Biomedical domain : Impact of Human Genome on Biomedical domain Applications to medicine and biology : Applications to medicine and biology Disease genes
pharmaceutical industry has depended upon a limited set of drug targets to develop new therapies
now can find new target
Gene therapy Genomic Medicine/molecular medicine : Genomic Medicine/molecular medicine Anticipatory, not reactive
Predictive, preventive and personalized
Knowledge from genomics and derivative disciplines
Screening of individuals and populations
New analytical technologies and bioinformatics approaches Genomic Medicine: Consequences : Genomic Medicine: Consequences Improve efficacy and reduce side effects
Reduction of the burden of chronic illness
Decrease in the prevalence of common complex diseases Biology’s Industrial Revolution : Biology’s Industrial Revolution Traditional biology
Data hard to get
Iterative solution Genomics
Large, interdisciplinary teams
Data analysis Other applications : Other applications Energy and environment application
Agriculture, livestock breeding and bioprocessing What is OMIM? : What is OMIM? OMIM stands for “Online Mendelian Inheritance in Man”
It is a system of cataloging human genes and genetic diseases.
It was first created by Dr. Victor McKusick of Johns Hopkins University. History of OMIM : History of OMIM Initiated in the early 1960s by Dr. Victor A. McKusick
Total 12 book editions of MIM were published between 1966-1998
The online version OMIM was created in 1985 by collaboration between the National Library of Medicine and the William H. Welch medical library at Johns Hopkins.
In 1985,OMIM was developed for the World Wide Web by NCBI
It was made available on the internet starting in 1987 VERSION : VERSION It is available as a book named after the project, and it is currently in its 12th edition. The online version is called Online Mendelian Inheritance in Man (OMIM), which can be accessed with the Entrez database searcher of the National Library of Medicine and is part of the NCBI Education project. COLLECTION PROCESS : COLLECTION PROCESS The information in this database was collected and processed under the leadership of Dr. Victor A. McKusick at Johns Hopkins University, assisted by a team of science writers and editors. Relevant articles are identified, discussed and written up in the relevant entries in the MIM database. How do I find OMIM? : How do I find OMIM? Start this tutorial by going to the National Center for Biotechnology Information (NCBI) homepage
https://www.ncbi.nlm.nih.gov Finding OMIM on NCBI : Finding OMIM on NCBI On the NCBI homepage there is a link for OMIM at the top. Now I’m at OMIM…What next? : Now I’m at OMIM…What next? OMIM gives you an introduction to what it is on the main page. There is also a toolbar along the side. What is available to me on the toolbar? : What is available to me on the toolbar? The options available allow you to include:
A help function
Search gene or morbid maps
A FAQ section
There are links to other well known sources of genetic information
The current number of genes and which inheritance pattern it belongs to under the Statistics tab Can I search for something specific? : Can I search for something specific? You may use the search field at the top to look for any disease or gene location. What the Search bar does for you : What the Search bar does for you Once you enter in the item you want to look for a list of matches will appear. Choose from the list which one is closest to your intended choice.
This is an example
of PKU You found your topic…What next? : You found your topic…What next? Once you have clicked on your topic of interest you will be given
the location on the chromosome
the alternative names for the disease
A complete description that includes the clinical features, the mapping, the inheritance, the epidemiology, the pathogenesis, and often many other important facts regarding the topic of interest THE MIM CODE : THE MIM CODE Every disease and gene is assigned a six digit number of which the first number classifies the method of inheritance.
If the initial digit is 1, the trait is deemed autosomal dominant; if 2, autosomal recessive; if 3, X-linked.
e.g., Pelizaeus-Merzbacher disease [MIM*169500] SEARCHING OMIM : SEARCHING OMIM There are 3 different interfaces available for accessing records in OMIM:
1.Gene Map - Lists genes in OMIM by cytogenetic location
2.Morbid Map - Alphabetically lists the genetic disorders in OMIM
3.Search - Provides options for searching by keyword(s) Using OMIM's Gene Map : Using OMIM's Gene Map What is Gene Map?
With Gene Map, users can browse a table of genes organized by cytogenetic map location
How do I search Gene Map?
At the OMIM home page select Search Gene Map from the blue navigation menu on the left. Fields of each entry in Gene Map: : Fields of each entry in Gene Map: Location - For the location 6p21.3, 6 is the chromosome number, p indicates the short arm of the chromosome, and 21.3 is the number assigned to a particular band on a chromosome. Slide 45: Symbol - The official symbol approved by the HUGO Gene Nomenclature Committee.
Title - The complete name of a gene.
MIM# - The unique six-digit number.
Disorder - Names of disorders that have been linked to a particular gene.
Comments - Additional gene information.
Method - Symbols that represent the different methods used to map a particular gene. This field would be most meaningful to scientists.
Mouse - The cytogenetic location of the mouse ortholog Using OMIM's Morbid Map : Using OMIM's Morbid Map What is Morbid Map ?
Morbid Map is a table of all the genetic disorders featured in OMIM.
Why would I use OMIM's Morbid Map?
Use Morbid Map to browse an alphabetical listing of human disorders. What’s with all the paper references? : What’s with all the paper references? The most common form you will see is peer-reviewed journal articles.
If you click on a highlighted author name it will take you to the full reference which will allow you to easily find the article of interest through another search engine The advantages of OMIM : The advantages of OMIM An excellent resource
All entries are written for readability.
There is easy access to the appropriate references. Cautions when using OMIM : Cautions when using OMIM OMIM is a compilation (a review).
Some topics are more inclusive than others.
All information is the most current knowledge for the revision date….it doesn’t not necessarily imply that everything is accurate. Enjoy your trial run : Enjoy your trial run Try it out. By clicking on any toolbar on the side panel you will be given description of what it is designed to help you search for. Slide 53: The International HapMap Project What Is the HapMap? : What Is the HapMap? The HapMap is a catalog of common genetic variants that occur in human beings. It describes what these variants are, where they occur in our DNA, and how they are distributed among people within populations. What is it? : “The International HapMap Project is a multi-country effort to identify and catalog genetic similarities and differences in human beings.” What is it? Why? : Why? “Using the information in the HapMap, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors.” The Hypothesis : The Hypothesis “According to an idea known as the common disease-common variant hypothesis, the risk of contracting common diseases is influenced by genetic variants that are relatively common in populations.” Samples used : Samples used Four populations were selected for inclusion in the HapMap: Nigeria ,European ancestry , Tokyo, Japan , Beijing, China (CHB). Scientific strategy : Scientific strategy Using SNPs
Acts as Markers
SNPs can be a pointer to locate gene involved in disease http://www.hapmap.org : http://www.hapmap.org Finding SNPs : Finding SNPs Enter the gene name : Enter the gene name Haplotypes : Haplotypes Genetic variants
A sequence of consecutive alleles on a particular chromosome Background : Background Unlike with the rarer Mendelian diseases, combinations of different genes and the environment play a role in the development and progression of common diseases (such as diabetes, cancer, heart disease, stroke, depression and asthma), or in the individual response to pharmacological agents How Will the HapMap Benefit Human Health? : How Will the HapMap Benefit Human Health? Extensive resource
Origin of illness
By identifying haplotypes, the HapMap provides a tool that can be used in what are called association studies Slide 66: “MAN IS A NUISANCE
MAN IS A CRACKPOT
BUT ONLY MAN CAN
HIT THE JACKPOT”