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Comparison of sequence variants in transcriptomic control regions across 17 mouse genomes.

Nguyen C, Baten A, Morahan G - Database (Oxford) (2014)

Bottom Line: We also developed an online tool to visualize the genome around each predicted cis-regulatory element in each tissue context and which allows efficient comparison of variation between any two sets of strains.This will be particularly useful in the context of the Collaborative Cross (CC), which was conceived as a powerful new systems genetics resource to accelerate gene discovery.Database URL: www.sysgen.org/ecco.

View Article: PubMed Central - PubMed

Affiliation: Centre for Diabetes Research, The Western Australian Institute for Medical Research, Western Australia, Australia, Centre of Medical Research, University of Western Australia, Perth, Western Australia, Australia and Southern Cross Plant Science, Southern Cross University, Lismore, New South Wales, Australia.

ABSTRACT
The laboratory mouse is the most widely used mammalian model organism in biomedical research, so a thorough annotation of functional variation in the mouse genome would be of significant value. In this study, we compared sequence variation in a comprehensive list of functional elements (e.g. promoters, enhancers and CTCF binding sites) across 17 inbred mouse strains. Sequences were derived for ∼300,000 functional elements experimentally identified by the mouse ENCODE project as regulating gene expression in 19 different tissue sources. We aligned sequences for each predicted cis-regulatory element to genomes of 17 mouse strains. This yielded a database comprising ∼5 million aligned sequences, allowing interrogation of sequence variation of functional elements for each of the 19 tissues/cell types in commonly used mouse strains. We also developed an online tool to visualize the genome around each predicted cis-regulatory element in each tissue context and which allows efficient comparison of variation between any two sets of strains. This will be particularly useful in the context of the Collaborative Cross (CC), which was conceived as a powerful new systems genetics resource to accelerate gene discovery. Comprising a large number of inbred strains derived from eight genetically diverse founders, the CC offers rapid mapping and identification of genes that mediate complex traits. We show that, among the 17 sequenced strains, the set of CC founder strains captures the most variability in the ENCODE elements, further emphasizing the value of this resource. Database URL: www.sysgen.org/ecco.

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Visualization of cis-regulatory elements with sequence variations between the CC founder strains and the set of nine nonfounder strains. (A) Users can select a region of interest by four different methods: (i) selecting a region on a chromosome band, (ii) entering chromosome positions, (iii) inputting a gene name in the search box or (iv) highlighting a region in the zoom area; (B) Users can select any one or more of the cis-regulatory element types and tissue/cell lines for visualization; and (C) Strains' genomic sequences are aligned, showing SNPs and statistics.
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bau020-F2: Visualization of cis-regulatory elements with sequence variations between the CC founder strains and the set of nine nonfounder strains. (A) Users can select a region of interest by four different methods: (i) selecting a region on a chromosome band, (ii) entering chromosome positions, (iii) inputting a gene name in the search box or (iv) highlighting a region in the zoom area; (B) Users can select any one or more of the cis-regulatory element types and tissue/cell lines for visualization; and (C) Strains' genomic sequences are aligned, showing SNPs and statistics.

Mentions: The SNPs and sequence variations in k base pair windows around any of the predicted cis-regulatory elements between the CC founder strains or between any of the 17 sequenced strains can be efficiently compared and visualized, as shown in Figure 2. Users can visualize sequence variations in a location of interest either by searching by gene name or by selecting a specific chromosome region. Users can also select the aligned database based on tissue/cell lines and/or cis-regulatory elements. The default k base pair window is set at 50, but users can specify other values ranging from 1 to 50 for this parameter.Figure 2.


Comparison of sequence variants in transcriptomic control regions across 17 mouse genomes.

Nguyen C, Baten A, Morahan G - Database (Oxford) (2014)

Visualization of cis-regulatory elements with sequence variations between the CC founder strains and the set of nine nonfounder strains. (A) Users can select a region of interest by four different methods: (i) selecting a region on a chromosome band, (ii) entering chromosome positions, (iii) inputting a gene name in the search box or (iv) highlighting a region in the zoom area; (B) Users can select any one or more of the cis-regulatory element types and tissue/cell lines for visualization; and (C) Strains' genomic sequences are aligned, showing SNPs and statistics.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3958616&req=5

bau020-F2: Visualization of cis-regulatory elements with sequence variations between the CC founder strains and the set of nine nonfounder strains. (A) Users can select a region of interest by four different methods: (i) selecting a region on a chromosome band, (ii) entering chromosome positions, (iii) inputting a gene name in the search box or (iv) highlighting a region in the zoom area; (B) Users can select any one or more of the cis-regulatory element types and tissue/cell lines for visualization; and (C) Strains' genomic sequences are aligned, showing SNPs and statistics.
Mentions: The SNPs and sequence variations in k base pair windows around any of the predicted cis-regulatory elements between the CC founder strains or between any of the 17 sequenced strains can be efficiently compared and visualized, as shown in Figure 2. Users can visualize sequence variations in a location of interest either by searching by gene name or by selecting a specific chromosome region. Users can also select the aligned database based on tissue/cell lines and/or cis-regulatory elements. The default k base pair window is set at 50, but users can specify other values ranging from 1 to 50 for this parameter.Figure 2.

Bottom Line: We also developed an online tool to visualize the genome around each predicted cis-regulatory element in each tissue context and which allows efficient comparison of variation between any two sets of strains.This will be particularly useful in the context of the Collaborative Cross (CC), which was conceived as a powerful new systems genetics resource to accelerate gene discovery.Database URL: www.sysgen.org/ecco.

View Article: PubMed Central - PubMed

Affiliation: Centre for Diabetes Research, The Western Australian Institute for Medical Research, Western Australia, Australia, Centre of Medical Research, University of Western Australia, Perth, Western Australia, Australia and Southern Cross Plant Science, Southern Cross University, Lismore, New South Wales, Australia.

ABSTRACT
The laboratory mouse is the most widely used mammalian model organism in biomedical research, so a thorough annotation of functional variation in the mouse genome would be of significant value. In this study, we compared sequence variation in a comprehensive list of functional elements (e.g. promoters, enhancers and CTCF binding sites) across 17 inbred mouse strains. Sequences were derived for ∼300,000 functional elements experimentally identified by the mouse ENCODE project as regulating gene expression in 19 different tissue sources. We aligned sequences for each predicted cis-regulatory element to genomes of 17 mouse strains. This yielded a database comprising ∼5 million aligned sequences, allowing interrogation of sequence variation of functional elements for each of the 19 tissues/cell types in commonly used mouse strains. We also developed an online tool to visualize the genome around each predicted cis-regulatory element in each tissue context and which allows efficient comparison of variation between any two sets of strains. This will be particularly useful in the context of the Collaborative Cross (CC), which was conceived as a powerful new systems genetics resource to accelerate gene discovery. Comprising a large number of inbred strains derived from eight genetically diverse founders, the CC offers rapid mapping and identification of genes that mediate complex traits. We show that, among the 17 sequenced strains, the set of CC founder strains captures the most variability in the ENCODE elements, further emphasizing the value of this resource. Database URL: www.sysgen.org/ecco.

Show MeSH
Related in: MedlinePlus