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EECS 730
Introduction to Bioinformatics
Genome and Gene
Luke Huan
Electrical Engineering and Computer Science
http://people.eecs.ku.edu/~jhuan/
Overview
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Genome structure
Mendelian genetics
Linkage and recombination
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Chromosome Painting
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Chromosome structure
Short arm: p
long arm: q
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A few terms
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A chromosome contains two (almost) identical
copies of DNA molecules. Each copy is called a
chromatid and two chromatids are joined at their
centromeres.
Chromosomes and regions in a chromosome are
named. For example by notation 6p21.3, we mean
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6 : chromosome number
p : short arm (from petit in French), q for long arm
21.3 : band 21, sub-band 3 (microscope)
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Chromosomes in Cell Division
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Chromosome Structure
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Chromosome structure
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Mendelian Genetics
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Mendel started genetics research before we know
chromosome and gene
Phenotype-- observable difference among members in a
population
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What controls a phenotype?
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For example: hair color, eye color, blood type
This is the question that Mendel tried to answer
Is still the central question of modern genetics
He used pea, a simple organism, and quantitative method
to study phenotypes.
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We call a quantitative study of biology computational biology
now.
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Mendel’s Peas
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Mendel’s Peas
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Mendel’s Experiments
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He bred green peas with yellow peas
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In genetics, we call this practice cross (or mating) -sexual reproduction between 2 organisms
Parental strains (denoted by P0 or F0)-- originally
crossed organisms
X
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F0
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F0
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Mendel’s Results
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Mendel collected results for F1 and F2
generations
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F1 generation-- offspring of the F0 generation
(parents)
F1 generation
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green
227
yellow
0
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ratio
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Mendel’s Explanation: Gene
Model
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Model postulated that there are something called “genes”
that controls the phenotype
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For the time being, let’s assumes that each organism always have
two copies of the same gene. One from “father” and the other
from “mother”.
Some genes are dominant: the associated phenotype is visible in
the F1 generation, e.g. green seed color
Some genes are recessive: the associated phenotype is invisible
in the F1 generation, e.g. yellow seed color
How could we tell whether the gene model is correct or
not?
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Mendel’s New Experiments
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F2 generation-- offspring of F1 generation
crossed to itself
What should we expect to see in F2?
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Green seed: ¾
Yellow seed: ¼
His experimental results:
F1 generation
F2 generation
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green
227
593
yellow
0
193
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ratio
3.07
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Continuing the experiments
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If we pick up yellow seed from the F2 generation
and breed from them, what should we expect:
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All yellow (since yellow are recessive and hence we
have both genes that contribute to yellow)
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Continuing the experiments
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If we pick up green seed from the F2 generation
and cross these organisms, what should we
expect:
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Green seeds: 8/9
Yellow seeds: 1/9
If we pick up green seed from the F2 generation
and cross an organism with itself, what should we
expect:
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Some produce only green seeds: 1/3
Some produces both green seeds and yellow seeds: 2/3
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Mendelian Genetics
Importantly, Mendel went another step further looking at F3 plants
593 crosses
201 green offspring only
392 green and yellow F3
2:1 ratio green: yellow
193 crosses
193 yellow offspring only
0 green pea pods
overall
1/4 F2 matings green, 1/2 F2 matings mixed, 1/4 F2 matings yellow
1:2:1 ratio for
all F2 crosses
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Genetics by Diagram
Adult F0:
X
More terminology:
Gamete -- reproductive cell
Zygote-- fertilized egg
Mendel's Principle of
Segregation: In the
formation of gametes, the
paired gene separate such
that each gamete is equally
likely to contain either one.
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gamete
Zygote F1:
X
gamete
Zygote F2:
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Another Rule
Principle of Independent Assortment: segregation of any pair of
alleles is independent of other pairs in the formation of gametes
adult
gametes
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Our Explanation of Mendelian
Genetics
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The two chromatids belong to the same chromosome
separated randomly
during a cell division
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Gene linkage
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Experiments: white eyed female flies cross with
wild type males (red eye, dominant)
What should we expect:
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All red eyed flies in F1
No! We have 50% red eyed and 50% white eyed
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Why?
A further study show that all red eyed are female and
all white eyed are male
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Gene Linkage:
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Morgan’s explanation:
w
w
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X
+
Y
w
+
Female, red eye
w
Y
Male, while eye
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Recombination
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F1 generation: white eyed, miniature wing female
crossed to wild type male
F2 generation (ie. heterozygous female crossed to
a wm male.
We know that white eye gene and the miniature
gene are in the same chromosome
What should we expect:
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female: 50% wm, 50% normal
male: 50% wm, 50% normal
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Recombination
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What we have: F2 generation (ie. heterozygous
female crossed to a wm male:
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white eyes, normal wings 223
red eyes, miniature wings 247
red eyes, normal wings
395
white eyes, miniature wings 382
We have some combination that does not appear
in parents!
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Recombination
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chromtides exchange their DNA components.
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Modern Genetics
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Forward genetics: given a phenotype, how do we
identify the genes that contribute to the
phenotype?
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Cancer, Parkinson's Disease,…
Reverse genetics: given a gene, how could we
know what are the phenotype that the gene might
control?
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Diagnostics
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How are Phenotypes Caused?
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Through a biochemical pathways:
A
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W
B
X
C
Y
D
Z
E
Genes, mRNA, and proteins
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Chromosome structure
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Chromosome Structure
Chromosomes are made up of a single continuous DNA molecule
can’t be straight-- would be many times length of the cell
Chromatin: ordered aggregate of DNA
and proteins visible in the cell cycle
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Chromosome Structure
heterochromatin: dense, compact structure during interphase
generally near the centromere and telomeres (chromosome ends)
composed of long tracks of fairly short base pair repeats
few genes compared to euchromatin
euchromatin: less dense DNA that only becomes visible after condensing
typically has genes being actively transcribed
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Gene Expression
• genes are located at specific places on the
chromosome (loci)
• regions corresponding to genes are
transcribed
• sequences flanking the coding sequence
control the start and stop of transcription
• not all genes are expressed at the same
rates or at the same times
}
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Regulation of Expression
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gene expression is regulated by proteins binding to
promoter and regulatory regions
regulatory proteins (eg., hormones) can 'turn on' or
'turn off' genes according to other factors
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Steroid Hormone Action
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nuclear receptors are transcription factors
hormone binding exposes DNA binding domain
binding to promoter region turns genes 'on' or 'off'
tend to have a longer lasting effect
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Ribosomes and Translation
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Translation
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Compartments and Sorting
Secretion
(export)
Other
Signal sequences target proteins
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Secretory Pathway
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