Professor Jane Farrar School of Genetics & Microbiology, TCD.

Transcription

1 Lecture 1 Genetics An Overview Professor Jane Farrar School of Genetics & Microbiology, TCD. CAMPBELL BIOLOGY Campbell, Reece and Mitchell CONCEPTS OF GENTICS Klug and Cummings A Whistle-Stop Tour of 150 years of Genetics - History 1860s Mendel published his research on inheritance of unit factors. Cytologists describe chromosomes and their behaviour during mitosis and meiosis. 1900s Rediscovery of Mendel s work. Chromosomes behave like unit factors. The term Gene proposed to replace unit factors Genetics becomes a discipline in itself 1940s Confirmation that the genetic material is DNA not protein 1950s Watson and Crick describe double-helical structure of DNA The structure reveals how it functions one strand is the template of the other Molecular Biology Era Begins 1960s Cracking the triplet code and defining the pathway of information flow: DNA makes RNA makes protein 1

2 1970s Discovery of restriction enzymes: Recombinant DNA technology becomes possible Expression of human growth hormone gene in E. coli Discovery of split genes in eukaryotes: introns and exons Methods for sequencing DNA 1980s Commercialization of Recombinant DNA technology Methods for making transgenic plants and animals 1990s Genome sequencing: Human, Plant, Drosophila, nematode and many microbial genomes completely sequenced by Working draft of the human genome sequence. Complete sequence Cost approx. $3 billion! 2001 Technology for expression profiling of the entire gene complement in a genome 2012 Whole exome sequencing and diagnosing disease Cost approx.$1,000 (price reduction!) 3 x 10 9 bp of DNA in the human genome 3 billion bases. If there were 3,000 letters on a typed page that would be 1 million pages of text in our genomes the same 1 million pages of text in every nucleus of every cell in the human body. Chromatin Humans have trillions of cells, each cell with approx. 2 meters of DNA packaged into the nucleus of the cell. There are over 3,000 genetic diseases in humans which are termed mendelian due to a mutation in a single gene 2

3 So humans have trillion cells. Humans are comprised of hundreds of different cell types... 3

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10 The same 3 billion base pairs of DNA are present in every cell of your body. Approximately 25,000 genes present in 23 pairs of human chromosomes in the 3 billion DNBA base pairs How does each cell function so differently? Not all genes are active in all cell types. Genes make RNA which is translated into proteins, the building blocks required for each cell to function. Different cell types need different proteins to function. Mutations in the DNA sequence can result in no protein or incorrect proteins being formed giving rise to genetic disorders. Mutations in a single gene that give rise to a disease are called single gene defects (or Mendelian disorders after Gregor Mendel) e.g. Cystic fibrosis etc 10

11 Mendelian disorders On average 50% of children are affected with the disease and 50% are unaffected gig.org.uk/education2.htm Mendelian disorders gig.org.uk/education2.htm On average 25% of children are normal, 50% are carriers and 25% are affected with the disease 11

12 XY XX XY XX Mendelian disorders All female children from an affected male will be carriers of the disease On average 50% of male children from a carrier female will have the disease and 50% of female children will themselves be carrier health.allrefer.com/pictures-images/x-linked-recessive-genetic-defects.html 12

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15 Valuable technology for developing therapies for dominant diseases RNA Interference: Craig Mello + Andrew Fire Noble prize 2006 Davidson & Paulson

16 Genetics and Human Health/Welfare 1. Production of safer vaccines: recombinant single subunit vaccines e.g. hepatitis B vaccine 2. Production of recombinant human therapeutic proteins e.g. insulin, growth hormone, clot dissolving proteins 3. Inherited disorders can be diagnosed prenatally 4. Prenatal genotyping in vitro fertilisation & pre implantation diagnosis 16

17 5. Populations and individuals could be genotyped for Quantitative disease alleles e.g. predisposition to mental health problems, heart disease, high blood pressure, cancer, Alzheimer s disease etc. Issues of privacy: who owns the information and who has access Implications for health insurance and employment 6. Pharmacogenomics: using genomics to genotype populations and individuals for alleles that determine responsiveness to drug therapies. Aim: individualization of drug therapies 7. Gene therapy for inherited diseases (What about other traits?) designer babies 17

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