Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A genotype-first approach identifies variants for orofacial clefts and other phenotypes in dogs

ABSTRACT: A genotype-first approach identifies variants for orofacial clefts and other phenotypes in dogs

PROVIDER: PRJNA1168062 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

A genotype-first approach identifies variants for orofacial clefts and other phenotypes in dogs

Project description:Dog breeding promotes within-group homogeneity through conformation to strict breed standards and also drives between-group heterogeneity in pursuit of distinct morphological forms and characteristic breed traits. In this study, the genotype-first approach was adapted to the dog genome to investigate coding variation from over 2000 dogs, leading to discoveries of new mutations related to craniofacial morphology and stature. Breed enriched variants were prioritized according to gene constraint, which was calculated using a mutation model derived from trinucleotide substitution probabilities in the dog. Most priority variants were not associated with genomic signatures for breed differentiation, as these regions were enriched for constrained genes intolerant to nonsynonymous variation, suggesting a model of breed phenotype diversification based on regulatory changes to essential genes. Identification of trait-associated variants in dogs informs new biological roles of genes. Improved collection of breed disease risk data, along with increased breed representation, will drive further discoveries.

2024-10-02 | GSE278600 | GEO

Genetic modifiers of Syndromic Orofacial Clefts

Project description:Genetic modifiers of Syndromic Orofacial Clefts

| PRJNA671479 | ENA

Genetic modifiers of Syndromic Orofacial Clefts

Project description:Genetic modifiers of Syndromic Orofacial Clefts

| PRJNA671480 | ENA

Kids First: Genomics of Orofacial Clefts in the Philippines

Project description:Kids First: Genomics of Orofacial Clefts in the Philippines

| PRJNA760581 | ENA

Kids First: Genomics of Orofacial Clefts in the Philippines

Project description:Kids First: Genomics of Orofacial Clefts in the Philippines

| PRJNA760635 | ENA

Identification of human orofacial enhancers and their role in orofacial clefts

Project description:Identification of human orofacial enhancers and their role in orofacial clefts

| PRJNA624190 | ENA

Identification of human orofacial enhancers and their role in orofacial clefts

Project description:Identification of human orofacial enhancers and their role in orofacial clefts

| PRJNA624191 | ENA

Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice

Project description:Orofacial clefts of the lip and palate are widely recognized to result from complex gene–environment interactions, but inadequate understanding of environmental risk factors has stymied development of prevention strategies. We interrogated the role of DNA methylation, an environmentally malleable epigenetic mechanism, in orofacial development. Expression of the key DNA methyltransferase enzyme DNMT1 was detected throughout palate morphogenesis in the epithelium and underlying cranial neural crest cell (cNCC) mesenchyme, a highly proliferative multipotent stem cell population that forms orofacial connective tissue. Genetic and pharmacologic manipulations of DNMT activity were then applied to define the tissue- and timing-dependent requirement of DNA methylation in orofacial development. cNCC-specific Dnmt1 inactivation targeting initial palate outgrowth resulted in OFCs, while later targeting during palatal shelf elevation and elongation did not. Conditional Dnmt1 deletion reduced cNCC proliferation and subsequent differentiation trajectory, resulting in attenuated outgrowth of the palatal shelves and altered development of cNCC-derived skeletal elements. Finally, we found that the cellular mechanisms of cleft pathogenesis observed in vivo can be recapitulated by pharmacologically reducing DNA methylation in multipotent cNCCs cultured in vitro. These findings demonstrate that DNA methylation is a crucial epigenetic regulator of cNCC biology, define a critical period of development in which its disruption directly causes OFCs, and provide opportunities to identify environmental influences that contribute to OFC risk.

2023-12-20 | GSE250370 | GEO

Kids First: Whole Genome Sequencing of African and Asian Orofacial Clefts Case-Parent Triads

Project description:Kids First: Whole Genome Sequencing of African and Asian Orofacial Clefts Case-Parent Triads

| PRJNA613740 | ENA

Kids First: Whole Genome Sequencing of African and Asian Orofacial Clefts Case-Parent Triads

Project description:Kids First: Whole Genome Sequencing of African and Asian Orofacial Clefts Case-Parent Triads

| PRJNA613741 | ENA