Genetic research on motile ciliopathies
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Zhiping Tan
PROVIDER: PXD070799 | iProX | Fri Nov 14 00:00:00 GMT 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Human cancers result from a complex series of genetic alterations resulting in heterogeneous disease states. Dissecting this heterogeneity is critical for understanding underlying mechanisms and providing opportunities for therapeutics matching the complexity. Mouse models of cancer have generally been employed to reduce this complexity and focus on the role of single genes. Nevertheless, our analysis of tumors arising in the MMTV-Myc model of mammary carcinogenesis reveals substantial heterogeneity, seen in both histological and expression phenotypes. One contribution to this heterogeneity is the substantial frequency of activating Ras mutations, the frequency of which can be changed by alterations in Myc. Additionally, we show that these Myc-induced mammary tumors exhibit even greater heterogeneity, revealed by distinct histological subtypes as well as distinct patterns of gene expression, than many other mouse models of tumorigenesis. Two of the major histological subtypes are characterized by differential patterns of cellular signaling pathways, including B-Catenin and Stat3 activities. We also demonstrate the predictive nature of this approach though examining metastatic potential. Together, these data reveal that a combination of histological and genomic analyses can uncover substantial heterogeneity in mammary tumor formation and therefore highlight aspects of tumor phenotype not evident in the population as a whole. Keywords: Transcription factor expression analysis 20 MMTV-Neu Tumors, 25 Papillary MMTV-Myc T58A and 81 MMTV-Myc tumors of various histological subtypes were arrayed.
2010-03-03 | E-GEOD-15904 | biostudies-arrayexpress
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149464 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149463 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149462 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149459 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149469 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149465 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149461 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149460 | GEO
Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.
2021-03-17 | GSE149467 | GEO