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.

3
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
6
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
7
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

8
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)

9
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)

10
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

12
S12
Central Dogma
13
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)
15
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.
16
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
18
S18
Gene Family Immunoglobulin fold
Proteins with similar structures evolved from
single geneand now have different functions
19
S19
Model organisms and genetic techniques allow us
to figure out Life
(we hope)
Wildtype mutant
Model Organisms
20
S20
Ultimate focus on human genetics
(.. technology provides a great assist)