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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. Genome structure Mendelian genetics Linkage and recombination. Chromosome Painting. Chromosome structure. Short arm: p. long arm: q. - PowerPoint PPT Presentation
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EECS 730Introduction to Bioinformatics
Genome and Gene
Luke HuanElectrical Engineering and Computer Science
http://people.eecs.ku.edu/~jhuan/
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Overview
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
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 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 Mendel started genetics research before we know
chromosome and gene Phenotype-- observable difference among members in a
population For example: hair color, eye color, blood type
What controls a phenotype? 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. 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 He bred green peas with yellow peas
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
F0 F0
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Mendel’s Results Mendel collected results for F1 and F2
generations F1 generation-- offspring of the F0 generation
(parents)
F1 generation 227 0green yellow ratio
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Mendel’s Explanation: Gene Model
Model postulated that there are something called “genes” that controls the phenotype 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 F2 generation-- offspring of F1 generation crossed
to itself What should we expect to see in F2?
Green seed: ¾ Yellow seed: ¼
His experimental results:
F1 generation 227 0F2 generation 593 193 3.07
green yellow ratio
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Continuing the experiments
If we pick up yellow seed from the F2 generation and breed from them, what should we expect: All yellow (since yellow are recessive and hence we
have both genes that contribute to yellow)
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Continuing the experiments
If we pick up green seed from the F2 generation and cross these organisms, what should we expect: 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: 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
193 crosses 193 yellow offspring only 0 green pea pods
593 crosses 201 green offspring only 392 green and yellow F3
2:1 ratio green: yellow
overall
1/4 F2 matings green, 1/2 F2 matings mixed, 1/4 F2 matings yellow1:2:1 ratio for all F2 crosses
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Genetics by Diagram
More terminology:
Gamete -- reproductive cell
Zygote-- fertilized egg
Adult F0:
gamete
Zygote F1:
X
X
gamete
Zygote F2:
Mendel's Principle of Segregation: In the formation of gametes, thepaired gene separate such that each gamete is equallylikely to contain either one.
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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
The two chromatids belong to the same chromosome separated randomly during a cell division
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Gene linkage Experiments: white eyed female flies cross with
wild type males (red eye, dominant) What should we expect:
All red eyed flies in F1 No! We have 50% red eyed and 50% white eyed
Why? A further study show that all red eyed are female and
all white eyed are male
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Gene Linkage:
Morgan’s explanation:
w w
+Y
X
w+
Female, red eye
w Y
Male, while eye
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Recombination
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: female: 50% wm, 50% normal male: 50% wm, 50% normal
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Recombination
What we have: F2 generation (ie. heterozygous female crossed to a wm male: 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
chromtides exchange their DNA components.
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Modern Genetics
Forward genetics: given a phenotype, how do we identify the genes that contribute to the phenotype? Cancer, Parkinson's Disease,…
Reverse genetics: given a gene, how could we know what are the phenotype that the gene might control? Diagnostics
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How are Phenotypes Caused?
Through a biochemical pathways:
Genes, mRNA, and proteins
A B C D EW X Y Z
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Chromosome structure
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Chromosome StructureChromosomes 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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heterochromatin: dense, compact structure during interphasegenerally near the centromere and telomeres (chromosome ends)composed of long tracks of fairly short base pair repeatsfew genes compared to euchromatin
euchromatin: less dense DNA that only becomes visible after condensingtypically has genes being actively transcribed
Chromosome Structure
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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 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• 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
Signal sequences target proteins
Secretory Pathway
Secretion(export)
Other
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