Genetics 320EEB320MCB320S1 - PowerPoint PPT Presentation

Title: Genetics 320EEB320MCB320S1


1
Genetics 320/EEB320/MCB320 S1 Lecture
1 August 23, 2004. Teds Introduction Style
Comments Overheads- right-hand screen Copies
of figures used Web page booklet at
bookstore NOT COMPLETE!! NOR SELF-EXPLANATORY C
halkboard- 1/5 of the presentation Informal.
Ask Questions. Stories Book-Genetics From Genes
to Genomes Hartwell et al (former
colleague) 2nd edition (take your chances and
responsibility with 1st edition) Problem
Sets-Weekly- out Friday, due Friday By 11AM in
box in front. Period. Thanks for being on
time. Exams -3 of them. Practice problems
available (Ted)
2

• Todays Lecture S2
• Big Picture
• Transmission genetics, Experimental genetics,
  Genomics
• Wed, Fri
• Review of basic molecular biology
• Preview of Experimental Genetics
• Chapter 1. Pages 1-12
• Homework PS1 Due August 31, Friday- 10 points.
  Typed ONLY.
• Describe ONE an interesting thing in science that
  youve heard, or that youd like to hear more
  about, or that inspires you, or that puzzles you
  or that scares you?
• What are your career aspirations?
• Name one thing youd like to learn in genetics.

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Transmission vs. Experimental Genetics
S3 Example Genes involved in eye development in
flies
Mutant fly with no eyes !
Normal fly with eyes
??
Wildtype- Gene 1
Gene 1- (Gene 1-/Gene 1-)
Transmission Genetics
Question Where are the genes?
Fly cell
-

-
Gene 1

Fly cell
-


(2 sets of homologs shown)
4
Transmission Genetics vs. Experimental Genetics
S4 Example Genes involved in eye
development in flies
Normal fly with eyes
Mutant fly with no eyes
Nothin
Wildtype- Gene 1
Gene 1- (Gene 1-/Gene 1-)
Experimental Genetics Ultimate
Goal Define what genes (proteins) do. Genetics
Goal Identify Genes Define order of
function Define positive negative
regulators
Example of Genetics Goal Define A Pathway of Eye
Development
Signal Gene 1 Gene 3 Gene
2 eyes
And Test specific biochemical models
5
S5
Use of Model Organisms in Experimental Genetics
Phage
Diversity in size, in genomes .. in what they
tell us about biology.
Flies
Yeast
Bacteria
10uM
Mice
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S6
Genome Comparisons- Synteny of mammalian genomes
Human-Ape comparisons
Humans/ great apes
Chr 1
Chr 2
Very similar
banding pattern
Human- Mouse
Human chromosomes
Wildly Sequence content
Wildly mixed!
Mouse chromosomes
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S7
Genomics and Technology brings potential for
diagnosis Example BRCA1, breast cancer
susceptibility gene. Synthetic DNA molecules
and tricks lead to the sequence of a gene
Brca1/Brca1
Brca1/Brca1-

• DNA sequencing of human genome
• Took several years and millions
• In1000!!!!
• (says Lee Hood, Seattle, Wa)
• Implications for diseasepriceless

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Some basic molecular biology Example eye genes
in flies
S8
Normal fly with eyes
Eye1 mutant
no eyes
Eye2 mutant
multiple eyes!

• Genetics make mutants, identifies genes.
• A few basics about genes.
• Molecular biology of a gene
• Genotype/phenotype/recessive/dominant
• Order of Function (bars and arrows)

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S9
Molecular biology of a gene
Eye1
Diploid cell
centromere
telomere
mRNA transcript
P
E
ATG..TGA
Transcriptional regulatory sites
Elements of typical gene

• ORF- Open Reading Frame- ORF
• 3 nucleotides code for amino acid.
• sense TTT, TAT, ATG, etc
  (61)
• nonsense TGA. TAA, TAG stop codons (3)

• P -promoter, RNA polymerase binding site
• E- Enhancer binding site helps RNA polymerase
• 5 and 3untranslated regions of transcript
• (No introns here to simplify the discussion)

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S10

• Chapter 1 Genetics The Study of Biological
  Information
• Key Points
• Bioinformation is in DNA
• Biological function emerges mostly from proteins
• Complexity in biological systems
• All life is closely related
• Modular construction, gene families and rapid
  evolution of
• GENOMES
• Model organisms allow us to figure out Life
• Focus on human genetics

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S11
Bioinformation Resides first in DNA
chromosomes
DNA
10 base pairs
100 million base pairs
Base-pairing
Gene density

• DNA- A-T, C-G base pairing
• Gene density (50 in bacteria, 3 in humans
• Chromosomes have wildly different sizes-
• 108bp/chromosome in humans
• 4x106bp/chromosome in bacteria

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S12
Central Dogma
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S13

• Bioinformation function in proteins (mostly)
• Numbers argument
• 20 amino acids in proteins
• 4 bases in nucleic
  acids,
• (and other candidate molecules -
  carbohydrate?)
• Some enzymatic functions in RNA
• (life may have begun with RNA, in fact)

Bioinformation proteins-proteins, proteins-RNA,
proteins-DNA
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S14
Complexity. Why the study of
biology will continue for many decades.
1. Mind-boggling range of scale..
2. More Practically most proteins have more
than one function with many functions
(cytochrome C in energy and cell death)
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S15

• 3rd Level of Complexity
• 1 protein effects multiple complexes
• (A way to understand why different alleles might
  have
• different affects in different
  people)

If protein 1 is less active, then protein 1
might form less protein1-protein5 complex, which
means that protein-5 dependent function is
reduced, which means that.
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All life is closely related
S16
Conservation of Cytochrome C between organisms..
Yeast PlantsWormsFlys Mice Human
Pax6 controls eye development in flies and
humans!!!
17
S17
Modular construction and gene families allows
for rapid evolution of genomes
What is a gene family structurally-related
proteins
How they arose during evolution gene duplication
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S18
Gene Family Immunoglobulin fold
Proteins with similar structures evolved from
single geneand now have different functions
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S19
Model organisms and genetic techniques allow us
to figure out Life
(we hope)
Wildtype mutant
Model Organisms
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S20
Ultimate focus on human genetics
(.. technology provides a great assist)