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Genetics 320/EEB320/MCB320 S1 Lecture 1 August 23, 2004. Ted’s Introduction Style Comments Overheads - right-hand screen Copies of figures used: Web page booklet at bookstore NOT COMPLETE!! NOR SELF-EXPLANATORY Chalkboard - ~1/5 of the presentation

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slide1

Genetics 320/EEB320/MCB320 S1

Lecture 1 August 23, 2004. Ted’s Introduction

Style Comments

Overheads- right-hand screen

Copies of figures used:

Web page

booklet at bookstore

NOT COMPLETE!! NOR SELF-EXPLANATORY

Chalkboard- ~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)

slide2

Today’s 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 you’ve heard, or that you’d 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 you’d like to learn in genetics.
slide3

Transmission vs. Experimental GeneticsS3

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)

slide4

Transmission Genetics vs. Experimental GeneticsS4

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

slide5

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

slide6

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

slide7

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
  • In<10years, your genome sequenced in 1hr for $1000!!!!
  • (says Lee Hood, Seattle, Wa)
  • Implications for disease…”priceless”
slide8

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)

slide9

S9

Molecular biology of a gene

Eye1+

Diploid cell

centromere

telomere

mRNA transcript

E

P

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 3’untranslated regions of transcript
  • (No introns here to simplify the discussion)
slide10

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
slide11

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
slide12

S12

Central Dogma

slide13

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

slide14

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)

slide15

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….”

slide16

All life is closely related

S16

Conservation of Cytochrome C between organisms..

Yeast PlantsWormsFlys Mice Human

Pax6 controls eye development

…in flies and humans…!!!

slide17

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

slide18

Gene Family: Immunoglobulin fold

S18

Proteins with similar structures evolved from single gene…and now have different functions

slide19

S19

Model organisms and genetic techniques allow us to

figure out “Life”

(we hope)

Wildtype mutant

Model Organisms

slide20

S20

Ultimate focus on human genetics

(.. technology provides a great assist…)

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