Download Lecture 1 Genetics – An Overview Professor Jane Farrar School of

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
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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
1980 s 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 2000
2000
Working draft of the human genome sequence. Complete
sequence 2003. 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 109 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 10-100 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
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So humans have 10-100 trillion cells.
Humans are comprised of hundreds of different cell types........
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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
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Mendelian
disorders
On average 50% of children are affected with the disease and 50% are unaffected
gig.org.uk/education2.htm
Mendelian
disorders
On average 25% of children are normal, 50% are
carriers and 25% are affected with the disease
gig.org.uk/education2.htm
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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
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Valuable technology for developing therapies
for dominant diseases
www.nsls.bnl.gov/.../2005/01-Joshua-Torr.htm
RNA Interference:
Craig Mello + Andrew Fire
Noble prize 2006
Davidson & Paulson 2004
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  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
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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
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