Human genome project by M.Sohail Riaz Hashmi
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The Human Genome Project (HGP), initiated in 1990 and completed in 2003, aimed to determine the nucleotide sequence of the human genome and identify all human genes. This international collaboration involved multiple countries and has significant medical implications, including the potential for gene therapy and the understanding of genetic diseases. Key objectives included improving sequencing technology, studying genetic variations, and addressing social implications arising from the expanded genetic knowledge.
![Single nucleotide polymorphisms
A single-nucleotide polymorphism (SNP,
pronounced snip) is a DNA sequence variation
occurring when a single nucleotide adenine (A),
thymine (T), cytosine (C), or guanine (G]) in the
genome differs between members of a species](https://image.slidesharecdn.com/humangenomeproject-210409063840/85/Human-genome-project-by-M-Sohail-Riaz-Hashmi-49-320.jpg)
Human genome project by M.Sohail Riaz Hashmi
- 2. Presented by: Muhammad Sohail Riaz Presented to: Miss Iqra Munir
- 3. Table of Content Human Genome Project (HGP) Main objectives Human Genome Project (HGP) Goals for the HGP Medical Implications Applications of HGP
- 4. Human Genome Project (HGP) HGP was conceived in 1984 & officially begun in earnest in October 1990 The US side of the Human Genome Project was initially led by James Watson (one half of Crick and Watson, who discovered the structure of DNA), and later by Francis Collins HGP is a large multicentric, international collaboration
- 5. Cont….. The main aim of which is to determine the nucleotide sequence of the entire human nuclear genome In 1997, United States established the National Human Genome Research Institute (NHGRI) The HGP was an international research groups from six countries- USA, UK, France, Germany, Japan and China, & several laboratories and a large no. of scientists and technicians from various disciplines
- 8. Timeline of HGP 1970 – Fredrick Sanger developed a technique for DNA sequencing, known as the Sanger’s method of DNA sequencing 1985 - Robert Sinsheimer at UCSC proposed the idea of sequencing the human genome 1986 - the U.S. Dept of Energy and the National Institute of Health came forward to fund the Human Genome Project 1989 - U.K’s medical research council (MRC) joined the Human Genome Project
- 9. Cont….. 1990 – HGP was officially launched with James Watson as its Project Director The 1st gene to be mapped was BRCA1, which is the gene for breast cancer 1993 - 1st 5 year plan for HGP was published. Sanger Institute(UK) joins HGP 1994 – HGP’s Human genetic mapping goal was achieved
- 11. Cont……. 1995 - Genetic privacy act was passed. 1st bacterial genome was sequenced (Hemophilus influenzae) 1996 – 1st Human Gene map was published. Yeast genome was sequenced. HGP’s mouse genetic mapping goal was achieved 1997 - NIH becomes NHGRI • E.coli genome sequenced • Genoscope, French National Genome Sequencing Centre was established
- 14. Cont…… 1998 - 2nd 5 year plan for HGP was published. Japan’s RIKEN Genomic Services Centre was established. Genome of the roundworm Caenorhabditis elegans was sequenced. SNP sequencing was initiated. The Chinese National Human Genome Centres were established in Beijing and Shanghai 1999 - sequencing of human chromosome 22 was completed and was published in “The Nature.”
- 16. Cont……. 2000 - working draft of human genome completed. US president Clinton & UK’s PM Blair support free access to genome information. Genomes of D.melanogaster and A.thaliana were sequenced & published in “The Nature” 2001 – working draft of human genome sequence was published in “The Nature” & “Science”
- 18. Cont…… 2002 – working draft of mouse genome sequence was completed & published 2003 - finished version of human genome sequence was completed HGP ended with all the goals achieved
- 21. Technical aspects in HGP The process of determining the human genome first involves genome mapping, or characterizing the chromosomes. This is called a genetic map The next step is DNA sequencing ,or determining the order of DNA bases on a chromosome. These are physical maps
- 23. Mapping strategies Genetic markers are invaluable for genome mapping Markers are any inherited physical or molecular characteristics that are different among individuals of a population (polymorphic) A genetic map shows the relative locations of these specific markers on the chromosomes An example of a marker includes restriction fragment length polymorphisms (RFLP)
- 24. Cont…… Used in RFLP markers are restriction enzymes These enzymes recognize short sequences of DNA and cut them at specific sites, therefore, DNA can be cut into many different fragments These fragments are the DNA pieces used in physical maps RFLPs reflect sequence differences in DNA sites which are cleaved by restriction enzymes
- 26. Sequencing strategies To sequence DNA, it must be first be amplified, or increased in quantity Two types of DNA amplifications are cloning and Polymerase Chain Reactions (PCR) Now that the DNA has been amplified, sequencing can begin
- 28. Primer A primer is a short nucleic acid sequence that provides a starting point for DNA synthesis In living organisms, primers are short strands of RNA Polymerases Polymerases are enzymes that catalyze the synthesis of DNA
- 30. Cont……. Sequencing techniques used in HGP are:- 1. Shotgun sequencing method 2. Sanger sequencing method
- 31. Shotgun sequencing method Shotgun sequencing is a laboratory technique for determining the DNA sequence of an organism's genome The method involves breaking the genome into a collection of small DNA fragments that are sequenced individually
- 33. Sanger sequencing method Sanger sequencing, also known as the “chain termination method”, is a method for determining the nucleotide sequence of DNA The method was developed by two time Nobel Laureate Frederick Sanger and his colleagues in 1977, hence the name the Sanger Sequence
- 35. Outcomes of HGP There are approximately 22,300 protein-coding genes in human beings, the same range as in other mammals • Mouse – 23,000 genes (approx) • Drosophila – 17,000 genes (approx) • C.elegans - < 22,000 genes
- 38. Cont….. we share many homologous genes (called "orthologs") with both these animals. But:- • Many of our protein-encoding genes produce more than one protein product (e.g., by alternative splicing of the primary transcript of the gene) • On average, each of our ORFs produces 2 to 3 different proteins So the human "proteome" (our total number of proteins) may be 10 or more times larger than that of the fruit fly and roundworm
- 39. CONT…… A larger proportion of our genome :- • Encodes transcription factors is dedicated to control elements to which these transcription factors bind • The combinatorial use of these elements provides much greater flexibility of gene expression than is found in Drosophila and C.elegans
- 40. Cont…… Gene density :- • 23 genes per million base pairs on chromosome 19(Chromosome 19 spans more than 58.6 million base pairs, the building material of DNA) • 5 genes per million base pairs on chromosome 13(Chromosome 13 spans about 114 million base pairs, the building material of DNA)
- 41. Cont…… Humans, and presumably most vertebrates, have genes not found in invertebrate animals like Drosophila and C. elegans. Few of those genes are :- • Antibodies and T cell receptors for antigen (TCRs) the transplantation antigens of the Major Histocompatibility Complex (MHC) & Human Leucocyte Antigen (HLA) • Cell-signaling molecules including the many types of cytokines the molecules that participate in blood clotting
- 42. Cont….. Human genome comprises of 2% of exons (coding regions) and 98% of introns (non-coding regions)
- 43. Main objectives Human Genome Project (HGP) This collaboration was named as International Human Genome Sequencing Consortium (IHGSC) The main objectives set out early in history of the project include: 1. To obtain complete sequence of pooled DNA extracted from cells donated by several anonymous donors, so as to determine the sequence of DNA in each chromosome
- 44. Cont…… 2. To construct genetic map for studies 3. To discover all human genes to allow further study of human genetic diseases 4. To develop simplified and automated technology for DNA sequencing process
- 45. Cont…… The HGP results attracted worldwide attention This achievement was hailed with many description in the media • The mystery of life unraveled • The library of life • The periodic table of life • The Holy grail of human genetics
- 46. Cont…… The total no. of genes in the human genome is in the range of 33,000 to 44,000 Approximately 75% of these genes have the same DNA sequence in all individuals, except for those with rare mutations
- 47. Cont…….. Any two human genomes are approximately 99.9% identical in sequence The apparently insignificant difference of 0.1% has a highly significant effect on personality, behaviour, intelligence, disease susceptibility and other traits
- 48. Goals for the HGP 1. Establish the complete human genome sequence and to make it freely accessible 2. Improve the sequencing technology by developing new and more effective methods 3. Analyze sequence variations in the human genome, such as single nucleotide polymorphisms (SNPs) and other DNA sequence variations
- 49. Single nucleotide polymorphisms A single-nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotide adenine (A), thymine (T), cytosine (C), or guanine (G]) in the genome differs between members of a species
- 50. Cont……. 4. Develop technology for functional genomics. It includes • Development of additional cDNA resources and technology for detailed analysis of gene expression • Comprehensive study of functions of non-protein coding sequences • Encourage development of technology for global protein analysis
- 51. Cont……. 5. Study comparative genomics by completing the genome sequence of some model organism (e.g. Mouse etc) which would enhance our understanding of the human genome 6. Develop bioinformatics and computational biology, to impart advanced training to young scientists and encourage establishment of academic careers in genomic research
- 52. Cont……. 7. Consider social implications of the vastly expanding knowledge base It is anticipated that clash of this new and advanced knowledge with the pre-existing philosophical perspectives may result in undesirable consequences, which have to be taken care of
- 53. Medical Implications The medical implications of the huge amount of genetic information obtained from the HGP are tremendous It would serve as resource for identification of the human disease gene For example the oncogenic sequence changes in cancer cells can be directly identified by comparing cancer genome sequences against draft genome
- 54. Oncogenic gene Sequence of deoxyribonucleic acid (DNA) that has been altered or mutated from its original form Oncogenes may cause the growth of cancer cells
- 55. Draft genomes Draft genomes can have segments of contiguous base pairs interspersed with gaps for which the sequence is unknown When two or more contigs are joined by overlapping sequences but there is a gap between them
- 56. Contig A contig--from the word "contiguous"--is a series of overlapping DNA sequences used to make a physical map that reconstructs the original DNA sequence
- 57. Cont……. Advancement in biotechnology with regard to development of useful genes would expand the scope of gene therapy and open new ways of combating disease It may even initiate new fields such as pharmacogenomics which would individualized therapies depending on genetic make up of the patient
- 58. Applications of HGP 1. Identification of human genes and their functions 2. Understanding of polygenic disorders e.g. cancer, hypertension, diabetes 3. Improvements in gene therapy 4. Improved diagnosis of diseases 5. Development of pharmacogenesis: study of how people respond differently to drug therapy based upon their genetic makeup or genes
- 59. Cont…… 6. Genetic basis of psychiatric disorders 7. Understanding of complex social trait 8. Improved knowledge on mutations 9. Better understanding of developmental biology 10. Development of biotechnology