Canis lupus familiaris
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ABSTRACT:
PROVIDER: PRJNA357240 | ENA |
REPOSITORIES: ENA
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Project description:In a rare subtype of XX Disorder of Sex Development (DSD), individuals are negative for SRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both of these phenotypes occur in the same family. This is a naturally occurring disorder in humans (Homo sapiens) and dogs (C. familiaris), and phenotypes in the canine XX DSD model are strikingly similar to those in this type of human XX DSD. The purposes of this study were to identify 1) a variant associated with XX DSD in the canine model and 2) gene expression alterations in canine embryonic gonads that could be informative to causation. Using a genome wide association study (GWAS) and whole genome sequencing (WGS), we identified a variant on C. familiaris autosome 9 (CFA9) that is significantly associated with XX DSD in the canine model and in affected purebred dogs. This is the first marker and candidate causative variant identified for inherited canine XX DSD. It lies within the canine ortholog for the human disorder (OMIM 278850), which resides on 17q24, upstream of SOX9. Gene expression studies (RNA-seq and PRO-seq) in embryonic gonads at risk of XX DSD from the canine model identified significant RSPO1 downregulation in comparison to XX controls, without significant upregulation of SOX9 or other known testis pathway genes. A novel mechanism is proposed in which the canine XX DSD variant acts upstream of RSPO1 to induce epigenomic gonadal mosaicism.
2017-10-25 | GSE92283 | GEO
Project description:Remarkable progress has been achieved in understanding the mechanisms controlling sex determination, yet the cause for many Disorders of Sexual Development remains unknown. Of particular interest is a rare XX DSD subtype in which individuals are negative for SRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both phenotypes occur in the same family. This is a naturally occurring disorder in humans and dogs (Canis lupus familiaris), and phenotypes in the canine XX DSD model are strikingly similar to those in this type of human XX DSD. The purposes of this study were to identify 1) a variant associated with XX DSD in the canine model and 2) gene expression alterations in canine embryonic gonads that could be informative to causation. Using a genome wide association study (GWAS) and whole genome sequencing (WGS), we identified a variant on Canis familiaris autosome 9 (CFA9) that is significantly associated with XX DSD in the canine model and in affected purebred dogs. This is the first marker and candidate mutation identified for inherited canine XX DSD, and it lies within the canine ortholog for the human disorder (OMIM 278850). Inheritance of the variant indicates that XX DSD is a complex trait in which breed genetic background affects penetrance. Furthermore, the homozygous variant genotype is associated with embryonic lethality in at least one breed. Gene expression studies (RNA-seq and PRO-seq) in embryonic gonads at risk of XX DSD from the canine model identified significant RSPO1 downregulation without significant upregulation of SOX9 or other known testis pathway genes. A novel mechanism is proposed in which the canine XX DSD mutation acts upstream of RSPO1 to induce epigenomic gonadal mosaicism.
2017-10-02 | GSE92318 | GEO
Project description:Comparative oncology is a developing research discipline that is being used to assist our understanding of human neoplastic diseases. Companion canines are a preferred animal oncology model due to spontaneous tumor development and similarity to human disease at the pathophysiological level. We use a paired RNA sequencing (RNA-Seq)/microarray analysis of a set of four normal canine lymph nodes and ten canine lymphoma fine needle aspirates to identify technical biases and variation between the technologies and convergence on biological disease pathways. Surrogate Variable Analysis (SVA) provides a formal multivariate analysis of the combined RNA-Seq/microarray data set. Applying SVA to the data allows us to decompose variation into contributions associated with transcript abundance, differences between the technology, and latent variation within each technology. A substantial and highly statistically significant component of the variation reflects transcript abundance, and RNA-Seq proved more sensitive for detection of transcripts expressed at low levels. Latent random variation among RNA-Seq samples is also distinct in character from that impacting microarray samples. In particular, we observed variation between RNA-Seq samples that reflects transcript GC content. Platform-independent variable decomposition without a priori knowledge of the sources of variation using SVA represents a generalizable method for accomplishing cross-platform data analysis. We identified genes differentially expressed between normal lymph nodes of disease free dogs and a subset of the diseased dogs diagnosed with B-cell lymphoma using each technology. There is statistically significant overlap between the RNA-Seq and microarray sets of differentially expressed genes. Analysis of overlapping genes in the context of biological systems suggests elevated expression and activity of PI3K signaling in B-cell lymphoma biopsies compared with normal biopsies, consistent with literature describing successful use of drugs targeting this pathway in lymphomas.
2012-12-15 | GSE41917 | GEO
Project description:Comparison of gene expression by RNA-seq in canine gonads from embryos at risk of XX Disorder of Sex Development (XX), male (XY) littermate controls, and age-matched female (XX) and male (XY) controls.
| PRJNA357092 | ENA
Project description:Comparative oncology is a developing research discipline that is being used to assist our understanding of human neoplastic diseases. Companion canines are a preferred animal oncology model due to spontaneous tumor development and similarity to human disease at the pathophysiological level. We use a paired RNA sequencing (RNA-Seq)/microarray analysis of a set of four normal canine lymph nodes and ten canine lymphoma fine needle aspirates to identify technical biases and variation between the technologies and convergence on biological disease pathways. Surrogate Variable Analysis (SVA) provides a formal multivariate analysis of the combined RNA-Seq/microarray data set. Applying SVA to the data allows us to decompose variation into contributions associated with transcript abundance, differences between the technology, and latent variation within each technology. A substantial and highly statistically significant component of the variation reflects transcript abundance, and RNA-Seq proved more sensitive for detection of transcripts expressed at low levels. Latent random variation among RNA-Seq samples is also distinct in character from that impacting microarray samples. In particular, we observed variation between RNA-Seq samples that reflects transcript GC content. Platform-independent variable decomposition without a priori knowledge of the sources of variation using SVA represents a generalizable method for accomplishing cross-platform data analysis. We identified genes differentially expressed between normal lymph nodes of disease free dogs and a subset of the diseased dogs diagnosed with B-cell lymphoma using each technology. There is statistically significant overlap between the RNA-Seq and microarray sets of differentially expressed genes. Analysis of overlapping genes in the context of biological systems suggests elevated expression and activity of PI3K signaling in B-cell lymphoma biopsies compared with normal biopsies, consistent with literature describing successful use of drugs targeting this pathway in lymphomas. RNA was extracted from 10 lymphoma fine needle aspirates attained from companion canines. 4 normal lymph node samples were obtained from a Beagle breeding colony at Pfizer, including two samples that were taken from the same dog but different lymph nodes. This Series represents the Affymetrix gene expression only, not RNA-Seq referenced above. RNA-Seq data have been submitted to SRA as SRA059558.
2012-12-15 | E-GEOD-41917 | biostudies-arrayexpress
Project description:Sox9 duplications cause Sry-negative XX sex-reversal in dogs
| PRJNA245545 | ENA
Project description:Expression data from canine osteosarcoma primary tumors (Affymetrix Canine 2.0 array)
| PRJNA133055 | ENA
Project description:Mizzou Comparative Canine Resequencing
| PRJNA263947 | ENA