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Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse

BACKGROUND: The current study focused on the extent genetic diversity within a species (Mus musculus) affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS) formed from the same eight inbred strains that have been used to...

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Autores principales: Iancu, Ovidiu D, Darakjian, Priscila, Walter, Nicole AR, Malmanger, Barry, Oberbeck, Denesa, Belknap, John, McWeeney, Shannon, Hitzemann, Robert
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091732/
https://www.ncbi.nlm.nih.gov/pubmed/20959017
http://dx.doi.org/10.1186/1471-2164-11-585
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author Iancu, Ovidiu D
Darakjian, Priscila
Walter, Nicole AR
Malmanger, Barry
Oberbeck, Denesa
Belknap, John
McWeeney, Shannon
Hitzemann, Robert
author_facet Iancu, Ovidiu D
Darakjian, Priscila
Walter, Nicole AR
Malmanger, Barry
Oberbeck, Denesa
Belknap, John
McWeeney, Shannon
Hitzemann, Robert
author_sort Iancu, Ovidiu D
collection PubMed
description BACKGROUND: The current study focused on the extent genetic diversity within a species (Mus musculus) affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS) formed from the same eight inbred strains that have been used to create the collaborative cross (CC). The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6) × DBA/2J (D2) F(2 )intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum) gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA). RESULTS: Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F(2 )modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes). Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. CONCLUSIONS: Despite the marked differences in genetic diversity, the transcriptome structure was remarkably similar for the F(2), HS4 and HS-CC. These data suggest that it should be possible to integrate network data from simple and complex crosses. A careful examination of the HS-CC transcriptome revealed the expected structure for striatal gene expression. Importantly, we demonstrate the integration of anatomical and network expression data.
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spelling pubmed-30917322011-05-12 Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse Iancu, Ovidiu D Darakjian, Priscila Walter, Nicole AR Malmanger, Barry Oberbeck, Denesa Belknap, John McWeeney, Shannon Hitzemann, Robert BMC Genomics Research Article BACKGROUND: The current study focused on the extent genetic diversity within a species (Mus musculus) affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS) formed from the same eight inbred strains that have been used to create the collaborative cross (CC). The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6) × DBA/2J (D2) F(2 )intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum) gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA). RESULTS: Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F(2 )modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes). Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. CONCLUSIONS: Despite the marked differences in genetic diversity, the transcriptome structure was remarkably similar for the F(2), HS4 and HS-CC. These data suggest that it should be possible to integrate network data from simple and complex crosses. A careful examination of the HS-CC transcriptome revealed the expected structure for striatal gene expression. Importantly, we demonstrate the integration of anatomical and network expression data. BioMed Central 2010-10-19 /pmc/articles/PMC3091732/ /pubmed/20959017 http://dx.doi.org/10.1186/1471-2164-11-585 Text en Copyright ©2010 Iancu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Iancu, Ovidiu D
Darakjian, Priscila
Walter, Nicole AR
Malmanger, Barry
Oberbeck, Denesa
Belknap, John
McWeeney, Shannon
Hitzemann, Robert
Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse
title Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse
title_full Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse
title_fullStr Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse
title_full_unstemmed Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse
title_short Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse
title_sort genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (hs-cc) mouse
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091732/
https://www.ncbi.nlm.nih.gov/pubmed/20959017
http://dx.doi.org/10.1186/1471-2164-11-585
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