EECS 730 Introduction to Bioinformatics Genome and Gene Luke Huan Electrical Engineering and Computer Science

EECS 7302 Overview Genome structure Mendelian genetics Linkage and recombination

EECS 7303 Chromosome Painting

EECS 7304 Chromosome structure Short arm: p long arm: q

EECS 7305 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)

EECS 7306 Chromosomes in Cell Division

EECS 7307 Chromosome Structure

EECS 7308 Chromosome structure

EECS 7309 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.

EECS Mendel’s Peas

EECS Mendel’s Peas

EECS 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

EECS Mendel’s Results Mendel collected results for F1 and F2 generations F1 generation-- offspring of the F0 generation (parents) F 1 generation2270 greenyellowratio

EECS 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?

EECS 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: F 1 generation2270 F 2 generation greenyellowratio

EECS 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)

EECS 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

EECS Mendelian Genetics Importantly, Mendel went another step further looking at F 3 plants 193 crosses 193 yellow offspring only 0 green pea pods 593 crosses 201 green offspring only 392 green and yellow F 3 2:1 ratio green: yellow overall 1/4 F 2 matings green, 1/2 F 2 matings mixed, 1/4 F 2 matings yellow 1:2:1 ratio for all F 2 crosses

EECS 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, the paired gene separate such that each gamete is equally likely to contain either one.

EECS Another Rule Principle of Independent Assortment: segregation of any pair of alleles is independent of other pairs in the formation of gametes adult gametes

EECS Our Explanation of Mendelian Genetics The two chromatids belong to the same chromosome separated randomly during a cell division

EECS 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

EECS Gene Linkage: Morgan’s explanation: wwww +Y+Y X w+w+ Female, red eye wYwY Male, while eye

EECS 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

EECS 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!

EECS Recombination chromtides exchange their DNA components.

EECS 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

EECS How are Phenotypes Caused? Through a biochemical pathways: Genes, mRNA, and proteins A B C D E W X Y Z

EECS Chromosome structure

EECS 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

EECS 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 Chromosome Structure

EECS } 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

EECS 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

EECS 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

EECS Ribosomes and Translation

EECS Translation

EECS 73037

EECS Compartments and Sorting Signal sequences target proteins Secretory Pathway Secretion (export) Other