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MGI worksheet answers .pdf

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Introduction Module
1. On which mouse chromosome would you find the
vang-like 2 gene (Vangl2)
a) Chr 1
b) Chr 4
c) Chr 10
d) Chr 19
e) Chr X
Gene positional coordinates can be found in several
places in MGI, but notably within the “Sequence Map”
row on Gene Detail pages. Gene detail pages can be
accessed via the Quick Search.

2. How many phenotypic alleles have been described for
a) 1
b) 3
c) 7
d) 14
e) 22
Phenotypic alleles are described on Gene Detail pages
in the “Alleles and Phenotypes” row. For Vangl2, the
hyperlinked number next to “All alleles” is 22. The
hyperlinks reading 12, 6, 1 and 3 correspond to specific
allele category subsets.

Has a mouse mutant of this gene been used to model
a human disease? If yes, which one?
a) No
b) Yes, Neural Tube Defects
c) Yes, Cancer
d) Yes, Alzheimer Disease
e) Yes, polydactyly
At the bottom ot the Alleles and phenotypes row is
an annotation for “Human Diseases Modeled Using
Mouse Vangl2 (1)”. Clicking the hyperlinked number
in brackets will generate a pop-up for Human Disease
Models Associates with Alleles of Mutant Vangl2
which indicates the specific disease associations(s) - in
this case, Neural Tube Defects - along with hyperlinks
to MGI’s corresponding Human Disease and Mouse
Model page(s) and OMIM page(s).

4. What category of allele is Vangl2Lp-m1Jus?
a) Reporter
b) Gene trap
c) Spontaneous
d) Chemically induced (ENU)
e) Targeted (null/knockout)
Go to the Phenotypic alleles summary by clicking the
hyperlinked (22) next to All Alleles. Locate the allele
symbol Vangl2Lp-m1Jus in the first column, then look to
the corresponding information found in the Category
column. Allele generation type and attributes are also
located in the Mutation details section of Allele Detail
5. What are the mutation details for Vangl2Lp-m1Jus?
a) Exon 1 is floxed
b) Exon 4 was targeted and replaced by a neomycin
c) A transversion mutation changing Asp255 to Glu
d) A stop codon mutation truncating the protien at
amino acid 410
e) The entire gene was deleted
Specific information about an allele’s construction can
be found in the Mutation details row of Allele Detail
pages. Click on the triangle toggle ( ) next to
Mutation description to expand this section and reveal
specifics, in this case, an Asp255Glu substitution. A
J# will aslo appear indicating the original publication
which describes the generation or characterization of
the allele. Click on an allele symbol to go to the Allele
Detail page.
6. Which of the following nervous system phenotypes
have been observed in mice homozygous for
a) craniorachischisis
b) abnormal synapse morphology
c) abnormal kidney morphology
d) decreased Purkinje cell number
e) no observed nervous system phenotypes
In MGI, phenotypes are annotated to genotypes, rather
than alleles (which can have background dependence),
or genes (where different alleles may have varied impacts). Find the hm1 genotype which indicates homozygosity in the Allele composition column, click the
triangle ( ) next to nervous system in the Affected
Systems table to expand sub-terms and locate check
marks in the column which corresponds to genotype
hm1. Click on checks or column headers for a free text
popup and references for each observation.


Using the Phenotypes, Alleles & Diseases Query
form, how many targeted alleles have been annotated
to craniorachischisis?
Hint: prior to May 22nd “Categories: targeted (all)”,
after May 22nd, “Categories: Generation Method:
a) 1
b) 3
c) 13
d) 15
e) 35
The Phenotypes, Alleles and Diseases Query form can
be accessed through the options on the Search drop
down menu, or from the Phenoypes (see tab) home
page (partially hidden).

On this query form, type “craniorachischisis”
into the Phenotype/Disease box. Leave the second
section (“Nomenclature & genome location”)
blank in this case, but selecting options here can
be used to restrict your list, either by genes/alleles
which share text similarity (e.g. certain gene families, or lab codes for alleles), or to markers within a
defined genomic region.
In the Categories section, you can apply filters to select Generation Method(s), Allele
attribute(s) and mutant Collections. A link in
the help documentation at the top of the page (see
question mark icon) provides definitions for each
of these terms. Multiple selections can be made
if desired, but to answer question 6 above, simply
select “Targeted” in “Generation Method”. Click
Search to execute the query.
The Phenotypes, Alleles and Disease Models
Search returns a table listing the alleles that match
your selected parameters. Look to the count in the
top-right corner of the page, or tally the number of
rows, which should come to 15.
For any questions, please contact:



Cre Module
You want to design an experiment where you study the effects of removing cadherin 2 (Cdh2) from mouse stomach
glandular epithelium, but NOT the respiratory system.
To do this requires use of a cre-lox strategy, where you
have (1) a mouse with a targeted conditional allele of Cdh2,
with loxP recombinase recognition sites used to flank
some portion of the Cdh2 gene, and (2) a mouse carrying
a cre transgene with recombinase activity detected in the
stomach glandular epithelium along with no activity in the
respiratory system.
8. Of the following, which allele of Cdh2 would be most
a) Cdh2Gt(OST49160)Lex
b) Cdh2tm1Glr
c) Cdh2tm1Hyn
d) Cdh2tm1e(EUCOMM)Wtsi
e) None of the above
Type “Cdh2” into the Quick Search and navigate to the
Gene Detail page for cadherin 2. There, scroll to the
Alleles and phenotypes row which indicates “All alleles
(5)”. Click the hyperlink to view on the Phenotypes,
Alleles and Disease Models Summary page.
Use the Category column to determine the Generation
Method and Allele Attributes.
To do tissue-specific gene manipulation requires a
conditional ready targeted allele. Introduction of the
recombinase recognition sites in the absense of recombinase co-expression is expected to have no functional
impact, and the gene product should be expressed at
normal levels, with normal function.
The Cdh2tm1Glr allele has the Category of “Targeted
(Conditional ready, no functional change)”. Click on
the Allele Symbol to go to the Allele Detail page, which
has more specific and detailed information about the
allele generation and/or characterization, along with a
reference in the Mutation Details row.

Which exon(s) of the Cdh2 gene are flanked by loxP
(floxed) in Cdh2tm1Glr?
a) The entire gene
b) Exon 1 and upstream transcriptional regulatory
c) Exon 3
d) Exons 4&5
e) It is not specified
On the Allele Detail page, click the triangle toggle ( )
next to Mutation details in the Mutation description
row. The text there describes flanking of exon 1.

10. How many cre alleles have recombinase activity
results annotated to “stomach glandular epithelium”?
a) none
b) 6
c) 61
d) 122
e) It is impossible to tell
To search for recombinase alleles, use the Recombinase tab along the top, or click on the “Recombinases
(cre)” button on MGI’s home page.
In the Access Data section, begin typing “stomach
glandular epithelium” in the box beneath “Recombinase activity in:” and select the term when it appears.
Structures in black text have at least one recombinase
activity annotation, while structures in grey text do not
have any activity annotations.
Six rows, corresponding to six transgenes will be returned after running the query.
11. Of the following, which transgene is the best match
for recombinase activity “detected in: alimentary
system” (which contains stomach glandular epithelium) and also has recombinase activity known to be
“not detected in: respiratory system”?
a) Tg(Atp4b-cre)1Jig
b) Mnx1tm4(cre)Tmj
c) Tg(Chst4-cre)1Hkwa
d) Any/all of the above
e) None of the above
The query from question 10 will return all transgenes
that have a recombinase activity result reported in
stomach glandular epithelium (whether examined and
detected, or examined and not detected).
Alimentary system is bolded to indicate that this system contains the structure “stomach glandular epithelium” which was originally searched. It is additionally
underlined with a solid line in the image on the right.
In each case here, the transgene satisfies the “detected
in: alimentary system” requirement.
Examining both columns for respiratory system (underlined with a dashed line on the right) shows three
alleles (Tg(Chst4-cre)1Hkwa, Mnx1tm4(cre)Tmj, and
Tg(Sftpa1-cre)1Xya) where recombinase activity was
detected in some structure of the respiratory system,
two transgenes (Tg(Atp4b-cre)3Xya and
Tg(Cyp1a1-cre)1Dwi) with no information reported
on recombinase activity in the respiratory system, with
only one (Tg(Atp4b-cre)1Jig) where respiratory system
is reported, and classed as not detected.

12. Which is the driver of the cre recombinase transgene
a) cre
b) CMV
c) Thyroglobulin
d) Atp4b
e) There is no driver
Drivers - aka promoters controlling expression of the
cre expressed sequence - are listed in the first column
of the results table. As well, all transgenes follow the
standard naming convention of:
= Tg
(Driver = Atp4b
Expressed sequence)
= cre
Serial or line number = 1
Lab code
= Jig for Jeffrey I Gordon
This information also appears on transgene detail page,
which can be accessed by clicking on the Allele symbol.

13. Which tissues, structures or substructures of the renal
and urinary system were examined for cre recombinase activity in Tg(Atp4b-cre)1Jig? Was recombinase
activity noted as detected (√) or not detected (-)?
a) bladder (-)
b) renal tubule (√) and renal corpuscle (-)
c) kidney (√)
d) kidney (-)
e) metanephros (-)
Click on the triangle toggles ( ) in the Activity table
within the Recombinase activity row to expand more
detailed structures. Columns indicate specimen age,
with E0-19.5 for embryonic developmental ages.
Within the renal and urinary system, adult metanephros is the only tissue with activity data, and recombinase activity was not detected (-).
14. What is the level (present/absent) and pattern of cre
recombinase activity detected in the stomach of mice
aged post-natal week 7 (adult)?
a) Not reported
b) absent, not applicable
c) present, not specified
d) present, strong
e) present, regionally restricted
Click the check mark next to stomach on the
Activity table to access a systems level recombinase
activity detail page. Locate data and more information
in the table.

Human-Mouse: Disease Connection Module
You have an exome sequencing result come back for a
patient who as a familial susceptibility to glomerulonephritis (renal/urinary system phenotype), vasuculitis
(cardiovascular system phenotype), and leukemia (tumorigenesis phenotype), which appears to be inherited as
a monogenic trait. The genes with predicted pathogenic
variants are: ACOX1, CHAT, SH2D3C, TUSC2 and ZYX.
For the following problems, use the Human-Mouse: Disease Connection, which has a link from MGI’s homepage,
or can be accessed directly at:
15. Based on mouse phenotypic annotations, which of
these genes is the most likely candidate for your observations?
a) ACOX1
c) SH2D3C
d) TUSC2
e) ZYX
Enter the list of 5 genes into the “Search by genes” box
on the HMDC home page and press “GO”.
On the Gene Homologs x Phenotypes/Diseases grid
that appears, locate the “renal/urinary system”,
“cardiovascular system”, and “tumorigenesis” columns
in the Mammalian Phenotype portion of the grid. You
can place a check mark in boxes above each column in
order to highlight (as shown), or, for a larger list, you
may want to apply these as filters. This will restrict the
table to retain only those columns/rows which have
data in within the selected.
Blue shading in the cells indicate that at least one
mouse mutant genotype has a phenotypic annotation
within the system, and from this list, Tusc2 is the only
gene annotated to all three systems. Clicking on the individual cells at the intersection of Tusc2-cardiovascular
system, Tusc2-renal/urinary system or Tusc2tumorigenesis opens a pop-up windown where the
alleles and more specific phenotypes are displayed.
Glomerulonephritis, vasculitis and leukemia all appear
in these pop-ups.
You can drill down further to locate a mutation description for the allele, it’s complete phenotypic profile
(as reported), associated references, and to locate mice
by clicking on the hyperlinked Allele Symbol to go to
the corresponding MGI Allele Detail page.


16. Which of these genes would be expected to be associated with infertility (a reproductive system phenotype)?
a) Acox1
b) Chat
c) Sh2d3c
d) Tusc2
e) Zyx
Remove any filters that were applied in the previous
question. Examining the Gene Homologs x Phenotypes/
Dieseases grid for reproductive system, shows that three
of the genes (Acox1, Chat, Sh2d3c) have some annotated
data from mouse mutants.
Clicking on the intersectionof Acox1-reproductive
system generates a pop-up with both male and female
infertility annotations reported, making this a good
candidate gene for an infertility effect.
The Chat-reproductive system intersection is marked
by an “N” which indicates that some aspects of the
reproductive system have been examined in mutants
and reported as “normal”, with no abnormal phenotypes
reported within the system.
The Sh2d3c-reproductive system pop-up shows an
annotation to “small testis” which can be associated with
reduced fertility, but is not as promising a candidate as
the Acox1.

17. Which of these genes has variants associated with
Myasthenic Syndrome, Congenital, Associated with
Episodic Apnea in human patients?
a) ACOX1
c) SH2D3C
d) TUSC2
e) ZYX
The CHAT gene has an orange fill at the intersection
of CHAT-Myasthemic Syndrome indicating a human
gene-disease annotation from OMIM.
You can also use the Diseases tab to locate this information. On this tab, click the hyperlinked disease name
to go the a Human Disease and Mouse Model detail
page in MGI.

18. What is the Disease Relevant publication that describes the association of mouse Acox1 in
Peroxisomal Acyl-Coa Oxidase Deficiency?
a) Abbott BD et al. (2012) Reprod. Toxicol.
b) Huang J et al. (2011) Am. J. Pathol.
c) Fan CY et al. (1996) J. Biol. Chem.
d) Suzuki et al. (1994) J. Pediat.
e) This association was made by Mouse Genome
Informatics curators.
This information can be accessed off of the Diseases or
Genes tabs.
On the Diseases tab, only disease-relevant mouse
publications are reported, in the column titled:
“References using Mouse Models”.
On the Genes tab, all mouse references in MGI for
the gene are linked in the References in MGI column,
with a subset pulled out for “Disease Relevant:”.
Click on the hyperlinked number to see the citation
and link to the original article, in this case, the Fan et
al. (1996) paper.
MGI curators never make gene-disease associations
without a peer-reviewed author statement as a reference.
For any questions, please contact:


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