Week 3 Flashcards by Sara Richmond

_________ the analysis and comparison of genomes from different species.
Purpose:
-how species evolved
-function of genes and non coding regions

comparative genomics

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___________ is a measure of relatedness

homology

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____________ derived from a common ancestor

homology • Homology can also refer to evolutionarily related structures

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IS Sequence similarity alone is homology?

No, sequence similarity does not mean common ancestor

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_________ type of homologs, different species

orthologs

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________: type of homologs. within the same species

paralogs

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Why does it matter if two sequences are homologous/ similar?

similar sequences typically code of a common function. This allow us to construct phylogenetic trees

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sequence conservation implies ________________

functional conservation. 
Sequence alignment is key to: 
-finding important regions 
-determining function 
-uncovering the evolutionary forces

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Genes aren’t the only conserved sequence:

lots of non coding regulatory elements

- mutational drift

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The greater the conservation, _______________

the more relevant the residue/ region is to function

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conserved noncoding sequences probably represent _______________________

functional elements

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__________ is reconstructing history of changes, the goal is to infer past history that produce a set of Morden sequences

phylogeny

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What is the law of parsimony

the most simplistic is the most likely outcome.

ex: the smallest number of mutations

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____________ one base is replaced by another

pont mutations (substitution)

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_________ one or more bases are inserted. Caused by copying errors

insertions

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____________ one or more bases are removed. Caused by copying errors

deletions

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What is polymerase slipping

The slipping of DNA polymerase II from the DNA template strand at the report region and the subsequent reattachment to a more distant site

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________ a directed acyclic graph

a tree

there exists a single unique path between any pair of nodes
the lengths of the path corresponds to the evolutionary distance (extend of sequence similarity) for some types of trees

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Phylogeny standard assumptions:

-sequences diverge by speciation represented usually as _______________

bifurcation events

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Phylogeny standard assumptions:

sequences are essentially ___________ once they diverge from their common ancestor

independent

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Phylogeny standard assumptions:

The probability of observing one nucleotide at the same site in the ______________

future depends only on the current nucleotide at the site

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Phylogeny standard assumptions: different sites (character within a sequence) evolve __________

independently

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phylogenetic trees can be _________________

between or within species

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Phylogenetcis applied to the 1990 HIV dentist case

compared to viral sequences from the dentist three of his HIV+ patient and two HIV+ local controls. It showed that 2 of 3 HIV patients were closer to the dentist than other local controls

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Human to human genetic variation is estimated to b around __________________

0.5% of the genome

Human genetic variation: | -Every human has essentially the __________

same set of genes

But there are different forms of each gene known as ______________

alleles ex: blue vs brown eyes genetic diseases such as cystic fibrosis or Huntingtons disease

___________ single nucleotide polymorphisms

SNPs

___________ are the most simple form and most common source of genetic polymorphism in the human genome

SNPs single nucleotide polymorphisms

There are two types of nucleotide base substitution results from SNPs:

- transition | - transversion

_________ substitution between purine (A,G) or between pyrimidines (C,T). Constitutes two thirds of all SNPs

Transition

__________ substitution between purine and a pyrimidine

transversion

To be defined as a single nucleotide polymorphism it has to ___________

have a population frequency >1%

SNPs occur every

-200 bases on average and most have no phenotypic effect

What are synonymous with SNPs

signal that doesn't cause changes in the amino acid | non synonymous does cause changes in amino acid

_________ SNP that is an amino acid change

missense mutation

_______________ SNP that is an amino acid change

nonsense mutation

If 4% of the human SNPs that have been found fall within a coding region yet only about 3% of all DNA is coding does this mean genes are "mutation magnets"

No because this is based on research that focuses primarily on coding regions so there might proportionally be more SNPs discovered here than in non coding regions

What is the primary difference between a polymorphism and a mutation?

polymorphism and mutation occur in different prevalence in a population. Polymorphisms myst occur in at least 1% of population

What are the similarities between polymorphism and mutations?

polymorphisms start as mutations during evolution. There exists both heterozygous and homozygous polymorphisms or mutations

________ can occur anywhere in the genome. The longer the repeat, the more polymorphic it is. Are the basis for DNA fingerprinting, forensic testing and paternity testing.

polymorphic repeats

___________ DNA finger printing uses repetitive sequences that are highly variable called variable numbers tandem pets VNTR. VNTR loci are very similar between closely related humans, but so variable that unrelated individuals extremely

polymorphic repeats

polymorphic repeats are found less frequently in ___________

genes | -this is because they have been implicated in several inherited genetic disorders such as myotonic dystrophy.

Why are most repetitive elements within genes found in factor of 3?

They occur in the coding regions. Codons occur in 3s.

SNPs can be found that are linked to any ________

disease alleles

SNPs can be found as markers for __________

genetic diseases and diagnosis

__________ is the global study of gene expression at the RNA level

transcriptomics

Gene expression. distinguishes:

- gender and age - physiological status - tissue and cell type - response to stimuli - health and disease

Gene expression is often measure as the

amount of RNA that is exported out of the nucleus

mRNA s often used as a proxy to study ____________

protein levels

highly. expressed mRNA's correlated well with ________________

protein levels

Evolution of technology: | Northern Blot: ____________

single genes

Evolution of technology: | RT-PCR: ______________

multiple genes

Evolution of technology: | Microarrays: _______________

whole transcriptome

Northern plot is a laboratory technology that is sued to detect a specific RNA sequence in a blood or tissue sample using ______________

radioactive labeling

Evolution of technology: | Next generation sequencing _______________

whole transcriptome

What. are the two types of microarrays

- spotted or cDNA arrays | - oligonucleotiide array

What are the microarray principles?

- array design - hybridization - imaging

What are the basics of microarrays: What are the essential components

- probes | - targets

What are the 4 steps of Microarray analysis

- experiment and data acquisition - data normalization - data analysis - biological interpretation

What is the main application of cDNA microarrays?

compare gene expression in two samples of cells

cDNA Microarrays

1. Array Printing 2. Sample Preparation 3. Analysis (hybridize and scan)

What is the purpose of dye shaping in Microarray analysis

controls for dye bias. For example sometimes the green dye is just brighter than the red

Why do we have hundreds of copies of a single probe in microarray analysis

It Allows for the cDNA to hybridize in a dynamic range and between quantify gene expression levels

Miccrodsarrays __________ to show the presence of one, both, or none of the genes being tests

color mix

oligonucleotide arrays: | ______________ indicates only hybridization intension, high density, multiple probes per gene/mRNA

single color

In Affymetrix exon arrays: | Several probes for each exon allow for the detection of ____________

alternative splicing

sports are fried with software and _______________

normalized vs background

__________ represents the amount of hybridization. pixel intensity

spot intensity

_______ of two dyes are often used to compare two samples

ratios between Cy5 and Cy3

to find the red intensity:

=R foreground - R background

to find the green intensity

=G foreground - G background

Relative expression. of intensity

Log_2 (Red intensity/ Green intensity)

___________: is the non specific hybridization and the other chemical

background intensity

_________ focuses on small regions around the spot to determine the median/ mean pixel values in this regions. Most common approaches

local background detection

What are three possible reasons for experimental noise?

- non uniform spotting - efficency of dye incorporation into CDNA - Efficency of hybridization - dirt/dust - vibration - differences

Image processing noise if the image is __________ i.e. spot locations are not properly satisfied

incorrectly processed

_______ is correlation between duplicate spot intensities. Percentage of spots with negative signals, Distribution

array

_________ is the signal or noise ration

Spot

_______ is a statistical measurement of a relationship between two variables. Values range from +1 to -1

correlation

_________ accounts for experimental noise, Lab to Lab variation, scanner to scanner variation, accounts for all variation

normalization

Normalization allows comparison of __________________________ __________________________

expression levels across experiments (arrays) | -a major goal of microarray experiments

There are several methods of normalization

- global mean method - linear regression method - intensity dependent methods - variance model methods

Normalization using mean global intensity assumes that the total number of mRNA copies for all genes should one the same in _______________

the experiment and the controls

Normalization assumptions:

1. the tool number of mRNA copies per cell is constant | 2. Changes in gene expression are roughly symmetric at all average intensities

What are the procedures of normalization

1. Draw the M-A plot to check data distribution 2. Fit the M-A plot with lowest curve (locally weighted scatterplot smoothing) 3. Transform data using the formula (m'=M-c(A)

what are the advantages of normalized data

works well for normalizing skewed or nonlinear data

what are the disadvantages of normalizing data

more complex and difficult to calculate

What do the outliers represent in the lowest curve

These genes are often what we are going after. They are the genes that are differentially expressed. Meaning they are heavily expressed in one sample and not another

__________ is a curve that follows the trends of the data

lowest curve