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