Mouse as a Model Worksheet-TylerNelson
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Transcript of Mouse as a Model Worksheet-TylerNelson
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1) What did the 1937 Life magazine article suggest?
The similar physiological structure of mice and humans
2) Why is the mouse such a good model for studying human diseases?
The mouse is really as Life magazine noted, a mans life cycle in miniature. The
mouse has an extremely small gestation period and shares roughly 99% of the genesthat humans do.
3) What are some of the diseases that we can study using mouse models?
Diabetes, atherosclerosis, heart disease, cancer, glaucoma, anaemia, hypertension,
obesity, osteoporosis, bleeding disorders, asthma and neurological disorders.
4) What is a QTL? What is your understanding of what it is and how it is used
in mouse genetics?
A QTL is a quantitative trait locus, which is a stretch of DNA that makes op or relates
to the gene that codes for a trait or phenotype. Discovering the location and makeup
of QTLs can help in our understandings of inherited and genetic diseases.
5) What's the difference between a discrete trait and a quantitative trait? Give
some examples
Discrete traits are traits that are influenced by one gene and the presence or
absence of the gene represents a phenotype. Examples include eye color, or the
presence or absence of disease. Quantitative traits are much more difficult to
pinpoint and vary continuously over a range of distribution in a population. These
traits are influenced by multiple genes as well as genegene and geneenvironment
interactions. Examples include blood pressure, high density lipoprotein (HDL)
levels, weight and so on.
6) The article describes three major stages of the use of mice in genetics
studies, and states that we're in the third historical stage. What are these
three stages?
Stage 1: Establishment of the first inbred mouse strain
Stage 2: analysis of single-gene defects arising by spontaneous mutations in inbred
strains
Stage 3: Quantitative Trait Analysis
7) What is meant by a "strain"? Give some examples of different strains, and
perhaps how they are used.
A strain is a final generation that has a genotypic variable that makes it useful inmouse genetics. An example of a strain is an inbred strain. In this strain the end
result or genotypic variable is that the final generation of mice are genetically
identical.
8) How are inbred mouse strains created? What is the end product of creating
inbred strains?
Two parent mice (brother and sister mice) give birth to a generation of mice, and for
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20 consecutive generations only brother and sister mice are able to mate with each
other. The end result is that the final generations of mice are genetically identical
and homozygous at all loci.9) What is a recombinant inbred strain? How is it developed, and what might
be the result of breeding?The recombinant inbred strain is created when you have two different mating pairs
of mice and the offspring of one mice pair is crossed with offspring for the other
pair. Then for 20 consecutive generations, like the inbred strain, the brother and
sisters are bred. The result of the breeding is the recombinant inbred strain has a
unique, fixed combination of the original parental genomes.
10) What is the Collaborative Cross? Who runs it, and what is its purpose?
The collaborative cross is an effort to provide a common, genetically defined and
reproducible panel of strains that are available at a reasonable cost. It will start with
eight genetically diverse inbred strains and end with 1,000 recombinant inbred
strains. The Complex Trait Consortium is leading this effort to make the strainsmore readily available so that in the future more work can be done in studying
complex diseases.
11) The article talks to the analysis of spontaneous mutations. What does the
article say about mutation frequencies and how they are generated?
The spontaneous mutation rate is relatively low and mutation frequency can be
accelerated using chemical mutagens.
12) What's a congenic strain? What is a coisogenic strain? What are some
variations on the congenic-strain concept?
Congenic Strain: A strain that is produced by repeated backcrossing (ten
generations) to an inbred strain, with selection for heterozygosity at each
generation for a specific locus in the donor strain.
Coisogenic Strain: Strains of mice that differ at a single locus. When a spontaneous
mutation occurs in an inbred strain, the mutant and the non-mutant mice are
coisogenic.
Variations on the congenic-strain concept are chromosome substitution strains
(CSS) and genome tagged mice (GTM).
13) What's a "knockout" mouse? What's a "knockout line?" Who creates these
kinds of mice?
A knockout mouse is a laboratory mouse that has had one of its genes knocked out
or disabled by an artificial piece of DNA. This most often changes the phenotype of
the mouse. A knockout line is a line in which every gene in the mouse genome has
been knocked out and the data is collected.
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The knockout mice are being created by the International Gene Trap Consortium,
the private efforts of Lexicon Genetics and Deltagen, and outside the Unites States
by the North American Conditional Mouse Mutagenesis Project and European
Conditional Mouse Mutagenesis Program.
14) The article gives a "cautionary" note about the use of online mousegenome resources. What is that cautionary note?
Mouse genome-sequence reference assembly, computational gene predictions and
biological knowledge about mouse genes and gene products change over time.
15) What's the Mouse Phenome Project? Who created it, and what does it do?
A group who met at the Jackson Laboratory realized the need for and strived to
make, a publicly available, systematic survey of phenotypic and genotypic
information on a standard set of inbred mouse strains. The result was the Mouse
Phenome Database.
16) What is a genetic marker? How is it used?A genetic marker is a known location on a chromosome that can be used to identify
the type of species or another allele closely located on the same chromosome. An
example is noting that a person with red hair usually has freckles. The red hair gene
would be a genetic marker for the freckles gene. A genetic marker is used to help
locate which chromosome may carry a gene for a specific phenotype.
17) Describe some of the practical considerations of identifying QTLs.
One of the most important practical considerations is the parent strain. The greater
the statistical difference between strains is, the greater the chances of finding
significant QTLs. One of the parental strains should carry a disease-causing allele.
18) What are some of the categories for online mouse genome resources?
What are examples of these? What ones have you had some exposure to?
Some categories include: sequence/phenotype, pathways analysis and knockout and
transgenic mice. I have had exposure to sequence/phenotype databases, pathways
analysis and SNP databases.
19) What is MGI?
An acronym for Mouse Genome Informatics.
20) What is meant by "gene ontology"?
Gene ontology is an initiative to standardize the representation of genes and geneproducts across species and databases.
21) Take a look at Figure 3. What do you think this graphic means? What do
you think it is telling you? Be careful to NOT just copy the captionI can read
too!
Figure 3 represents the varying ways to narrow QTL intervals. The top bar
represents a first pass genome scan which though it narrows the results, the interval
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is still too large. The other bars represent better techniques that can be used to
narrow the interval considerably more.
22) What is haplotype analysis? What is a haplotype?
A haplotype is a combination of alleles located close together on a chromosome and
tend to be inherited together. A haplotype analysis is the best technique fornarrowing QTL intervals and uses bioinformatics tools to identify a set of closely
linked segments of DNA.
23) What is an "eQTL"? (Hint: something related to microarrays). eQTLs (and
microarrays) are particularly useful in facilitating the identification of what?
Expression QTLs are genomic loci that regulate expression levels of mRNAs or
proteins and are useful in identifying pathways.
24) At the very end of the article, they talk about a new software package.
What is this software? Do a little background exploration of this tool!
The software is J/qtl. This is a Java graphical user interface that is an add-on to thestatistical program R. This is a program for someone like me who has no
programming experience. It helps people like me analyze their data by operating
with a point and click interface and translates the data into R format. J/qtl is mostly
just a user-friendly interface that masks R and R/qtl that do the work.
25) What did you find the most interesting or the most useful about this
article?
I knew that mice were genetically similar to humans, but I did not know that we
share 99% of the same genes. I also did not know about knockout mice and think
that would be a fascinating field of research with enormous possibilities for future
discoveries in disease.