Genome projects

Learning Objectives

  • Describe genome projects and their applications:

    • Disease Diagnosis

    • Personalized Medicine

    • Agriculture

  • Discuss social and ethical implications of genome projects (e.g., Human Genome Project)

Smallest and Biggest Genomes

  • Smallest Genome:

    • Organism: Rous sarcoma virus

    • Contains 4 genes or 3,500 base pairs

    • Needs a host to multiply

  • Simplest Free-Living Organism:

    • Organism: Mycoplasma genitalium

    • Contains 482 genes or 580,000 base pairs

  • Largest Genome:

    • Organism: Paris japonica

    • Contains 149 billion base pairs (>100 meters DNA per cell)

Genome Size vs. Complexity

  • Increased DNA does not necessarily equate to higher complexity:

    • Homo sapiens: 3.3 × 10^9 bps (21,000 genes)

    • Mus musculus: 3.4 × 10^9 bps (23,000 genes)

    • Amphibians: 10^9 – 10^11 bps

    • Paris japonica: 1.5 × 10^{12} bps (80% of which is extragenic)

Human Genome Project (HGP)

  • Definition:

    • A massive collaborative effort to determine the sequence of DNA in all human chromosomes and identify/map genes

  • Objectives:

    • Sequence the full human genome

    • Identify disease-causing genes for specific treatments

HGP Timeline and Participants

  • Involved Nations: 18 countries including the US, UK, Japan, France, and Germany.

  • Start Year: 1990

  • Completion Year: 2003

  • Major Contributors: Universities and research centers, privately funded by Celera Genomics

  • Methodology: Highly automated shotgun sequencing technology

    • Utilized 300 machines and 50 people along with supercomputers

    • Draft sequence completed in 9 months

Genome Sequencing Samples

  • Donor Collection: Blood/sperm from several diverse, anonymous donors

    • Libraries included two males and three females from varied ethnic backgrounds

    • Celera’s HGP utilized 5 libraries for genome sequencing

Findings of the HGP

  • Genome Size: 3.3 billion bps (haploid)

  • Gene Count: Actual gene count found to be 20,000 – 25,000 genes (less than earlier estimates)

    • Genes account for only 1.2% of total DNA, remainder is extragenic

  • Next Steps: Data interpretation to enhance understanding

Spinoff Projects from HGP

  • Genomic Science Program (GSP):

    • Studying microbes and plants at cellular/molecular levels for insights into biological processes

  • 1000 Genomes Project:

    • Aim to sequence genomes of at least 1,000 people to establish detailed human genetic variation catalogue

  • International HapMap Project:

    • Developing a haplotype map of the human genome linking DNA variations with health/disease responses

  • Cancer Genome Anatomy Project:

    • Focusing on gene expression profiles to improve diagnosis and treatment

  • Environmental Genome Project:

    • Investigating how human genetic variations influence disease susceptibility from environmental exposures

Cost of Genome Sequencing Over Time

  • 1990 cost per base = $10

  • 2001 cost per base = $0.10; draft of first human genome (> $3 billion incurred)

  • Current costs < $300 per individual genome

  • Historical cost reductions shown in graphical data

Applications of Genomics

  • In Agriculture:

    • Using genomic data to enhance crop and livestock quality, yield, and resistance to pests

  • In Disease Diagnosis:

    • Genetic tests predicting risk of conditions (e.g., breast cancer)

  • In Personalized Medicine:

    • Tailoring treatments based on individual genomic profiles and responses to drugs

Ethical and Social Implications

  • Psychological impacts and stigmas attached to genetic differences

  • Concerns regarding the fairness and privacy of genetic information usage

  • Questions about how genetic data influences individual identities and societal perceptions

  • Issues around genetic determinism vs. free will and moral/ethical treatment choices

Contemporary Issues in Genomics

  • Case Study: Angelina Jolie's double mastectomy due to genetic risk for breast and ovarian cancers demonstrates proactive personalized medicine based on genetic testing

  • Growing concern about the implications of gene editing (e.g., CRISPR technology scandals) and regulation of genetic research

Feel free to expand upon specific areas of interest or add additional details as you study!