Human genome project is a comprehensive mega project ,international research effort dedicated to map the entire human genome bydetermining the sequence of nucleotides in the DNA of each 22+X and Ychromosomes and to study the function of human genes. It has been also called AsINTERNATIONAL GENOME SEQUENCINGCONSORTIUM.HGP is considered to be the most ambitious project everundertaken due to the following points:1. it deals with 3*10^9 base pairs, to determine their exactsequences in different genes and in different chromosomes and to determine the relationship of different genestovarious characteristics.
2.It deals with storage of huge data.imagine if 3*10^9base pairs and their sequences to be stored in books with more than 1000letters per page and 1000 pages per book just from one single human cell.3. The cost of sequencing this was estimated to be 9billion in the year 1990s .( $3 per base pair).
HISTORY: Human genome project was initially a 13 years project. UKwas the major contributor of this project. The project was funded by NATIONALINSTITUTE OF HEALTH AND US DEPARTMENT OF ENERGY. The project officially beganon October 1,1990. Advances in technology computational devices for dataprocessing , data sorting and data retrieval, the first working draft of entirehuman genome was announced in june ,2000and first detailed analysis appeared inFebruary 2001 on NATURE AND SCIENCEjournel.the project completed in april 2003.GOALS OF HUMAN GENOME PROJECT: 1: To sequence entire above 3 billionbase pairs genomes.2: to storethis information in databases , easily accessible to scientists across theworld.
3.toidentify 20,000-25,000 genes in human DNA.4.to obtaina physical map of human genome by cloning DNA into yeast artificial chromosomes(YACs)and bacterial artificial chromosomes(BACs).5: to developtechnological advances in genetic methodologies like gene cloning , sequencecostigs and sequencing genomes.6.
totransfer related technologies to other sectors (eg:industries)SALIENT FEATURES:A few salient features are:1.size of genes vary greatly. Hence the largest guamn gnenamed DYSTROPHIN considered to have 2.4 billion bases.2:more than 50% genes discovered are not known.3: less than 2% of genes code for proteins.
4:repetitive sequences do not code for proteins are 50%ofhuman genome.( repetitive sequences are stretches of DNA repeated upto thousandtimes)5: 1 billion copies of 5-8 bp repeated sequences areclustered around centromeres and telomeres. They are junk DNA.6: In HGP, as manyas 1.4 million single base difference are found. These are called as SINGLE NUCLEOTIDE POLYMORPHISM(SNP).SNP promises accurate identification and localization of disease associated sequnces and tracing human evolutionary history. STRATEGY AND METHODOLOGY:It includes following stages:1.
Mapping2.Sequencing3.Funtional analysis1: MAPPING:The genetic and physical maps of human genome areprepared by using MOLECULAR MARKERS, SIMPLE SEQUENCE REPEATS OR SEQUENCE TARGETSITES, MICROSATELLITES and PCRamplification of particular microsatellites.
2:SEQUENCING:The methodsused for sequencing the entire genomic DNA of human have two basic approach.EXPRESSED SEQUENCE TAGGING METHOD and SEQUENCE ANNOTATION.1:Expressedsequence tagging method:This methodinvolves identifying all genes that are expressed as RNA.they are representedas ESTs.2: SEQUENCEANNOTATION METHOD:It involvesdetermining all coding and noncoding sequences and assigning functions todifferent regions in the sequence.following steps are used:a)total DNAfrom cell was isolated.broken into fragments randomly by sonication.
( atechnique uses high frequency sound waves to make random fragments of DNA)b)fragmentsare then separated by agarose gel electrophoresis or pluse field gelelectrophoresis.c) separatedfragments are then clone din suitable host by using special vectors.these hostsare yeast and bacteria.
Vectors are YACs and BACs.e)cloningwill result in the amplification of inserted DNA fragments.f)fragmentsare then sequenced by automated DNA sequence.
these sequence costigs arearranged on the basis of overlapping regions present in them. On this basis,acontinuous sequence of nucleotides could be established for a chromosome region.g)specialised computers are developed for alignment of sequences.h)with thehelp of these computer based programs these sequences were annoted and were assigned to each chromosome.
3:GENERATION OF PHYSICALAND GENETIC MAPS:The geneticand physical maps are generated by using information on-1>polymorphismof restriction endonuclease recognition sites2>somerepetitive sequences called microsatellites.APPLICATIONS:1. theknowledge of DNA base sequence can be used for –a)describinga human geneticallyb)diagnosisand treatment of diseases by detecting genetic predisposition to diseases,creating drugs based on molecular information., using gene therapy and controlsystem of drug delivery.c)determininggenetic hereditary of individuals or groupsd)establishingpaternitye)matchingorgans with donors with recipients in organ transplant programsf)DNA FINGERPRINTINGcan help in identifying potential suspectg)establishment of evolutionary relationship of an individual with other animalsof same or different species.