“…Transcriptomic studies in the brains of homozygous and heterozygous HNRNPU-de cient mouse models demonstrated widespread effects on gene expression, particularly in the homozygote mice affecting multiple signalling pathways including synaptogenesis, neuroin ammation and (cell cycle control (33)). Evidence for disordered RNA splicing (a known role of HNRNPU) was detected in HNRNPU mutant mice brain cortex (29). Though RNA splicing is critical for brain development, our ndings suggest that that the pathogenesis of HNRNPU-NDD might also be related to disordered epigenetic regulation of gene expression.…”
Section: Discussionmentioning
confidence: 57%
“…Genes associated with hypomethylated CpGs are NAV1, LRFN1, FOCAD and those related to hypermethylated DMBs are ADGRA2, LRRC14, LRRC24, RXRA, WFDC1, TPGS1, LINC02245, SLC1A4, PPFIA1, PRDM10. Two of these genes have been linked with human disaese previously, biallelic germline pathogenic variants in SLC1A4 were reported to cause an autosomal recessively inherited disorder charactrised by spastic tetraplegia, thin corpus collosum and progressive microcephaly (MIM 616657) (26-28) and compound heterozygous or homozygous mutations in FOCAD were associated with severe congenital liver disease (MIM 619991) (29).…”
HNRNPU encodes a multifunctional RNA-binding protein that plays critical roles in regulating pre-mRNA splicing, mRNA stability, and translation. Aberrant expression and dysregulation of HNRNPU have been implicated in various human diseases, including cancers and neurological disorders. We applied a next generation sequencing based assay (EPIC-NGS) to investigate genome-wide methylation profiling for > 2M CpGs for 7 individuals with a neurodevelopmental disorder associated with HNRNPU germline pathogenic loss-of-function variants. Compared to healthy individuals, 227 HNRNPU-associated differentially methylated positions were detected. Both hyper- and hypomethylation alterations were identified but the former predominated. The identification of a methylation episignature for HNRNPU-associated neurodevelopmental disorder (NDD) implicates HNPRNPU-related chromatin alterations in the aetiopathogenesis of this disorder and suggests that episignature profiling should have clinical utility as a predictor for the pathogenicity of HNRNPU variants of uncertain significance. The detection of a methylation episignaure for HNRNPU-associated NDD is consistent with a recent report of a methylation episignature for HNRNPK-associated NDD.
“…Transcriptomic studies in the brains of homozygous and heterozygous HNRNPU-de cient mouse models demonstrated widespread effects on gene expression, particularly in the homozygote mice affecting multiple signalling pathways including synaptogenesis, neuroin ammation and (cell cycle control (33)). Evidence for disordered RNA splicing (a known role of HNRNPU) was detected in HNRNPU mutant mice brain cortex (29). Though RNA splicing is critical for brain development, our ndings suggest that that the pathogenesis of HNRNPU-NDD might also be related to disordered epigenetic regulation of gene expression.…”
Section: Discussionmentioning
confidence: 57%
“…Genes associated with hypomethylated CpGs are NAV1, LRFN1, FOCAD and those related to hypermethylated DMBs are ADGRA2, LRRC14, LRRC24, RXRA, WFDC1, TPGS1, LINC02245, SLC1A4, PPFIA1, PRDM10. Two of these genes have been linked with human disaese previously, biallelic germline pathogenic variants in SLC1A4 were reported to cause an autosomal recessively inherited disorder charactrised by spastic tetraplegia, thin corpus collosum and progressive microcephaly (MIM 616657) (26-28) and compound heterozygous or homozygous mutations in FOCAD were associated with severe congenital liver disease (MIM 619991) (29).…”
HNRNPU encodes a multifunctional RNA-binding protein that plays critical roles in regulating pre-mRNA splicing, mRNA stability, and translation. Aberrant expression and dysregulation of HNRNPU have been implicated in various human diseases, including cancers and neurological disorders. We applied a next generation sequencing based assay (EPIC-NGS) to investigate genome-wide methylation profiling for > 2M CpGs for 7 individuals with a neurodevelopmental disorder associated with HNRNPU germline pathogenic loss-of-function variants. Compared to healthy individuals, 227 HNRNPU-associated differentially methylated positions were detected. Both hyper- and hypomethylation alterations were identified but the former predominated. The identification of a methylation episignature for HNRNPU-associated neurodevelopmental disorder (NDD) implicates HNPRNPU-related chromatin alterations in the aetiopathogenesis of this disorder and suggests that episignature profiling should have clinical utility as a predictor for the pathogenicity of HNRNPU variants of uncertain significance. The detection of a methylation episignaure for HNRNPU-associated NDD is consistent with a recent report of a methylation episignature for HNRNPK-associated NDD.
“…Genes associated with hypomethylated CpGs are NAV1 , LRFN1 , FOCAD and those related to hypermethylated DMBs are ADGRA2, LRRC14, LRRC24, RXRA, WFDC1, TPGS1, LINC02245, SLC1A4, PPFIA1, PRDM10 . Two of these genes have been linked with human disease previously, biallelic germline pathogenic variants in SLC1A4 were reported to cause an autosomal recessively inherited disorder characterised by spastic tetraplegia, thin corpus callosum and progressive microcephaly (MIM 616657) [ 28 – 30 ] and compound heterozygous or homozygous mutations in FOCAD were associated with severe congenital liver disease (MIM 619991) [ 31 ]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Transcriptomic studies in the brains of homozygous and heterozygous HNRNPU -deficient mouse models demonstrated widespread effects on gene expression, particularly in the homozygote mice affecting multiple signalling pathways including synaptogenesis, neuroinflammation and (cell cycle control [ 36 ]. Evidence for disordered RNA splicing (a known role of HNRNPU ) was detected in HNRNPU mutant mice brain cortex [ 31 ]. Though RNA splicing is critical for brain development, our findings suggest that the pathogenesis of HNRNPU -NDD might also be related to disordered epigenetic regulation of gene expression.…”
HNRNPU encodes a multifunctional RNA-binding protein that plays critical roles in regulating pre-mRNA splicing, mRNA stability, and translation. Aberrant expression and dysregulation of HNRNPU have been implicated in various human diseases, including cancers and neurological disorders. We applied a next generation sequencing based assay (EPIC-NGS) to investigate genome-wide methylation profiling for >2 M CpGs for 7 individuals with a neurodevelopmental disorder associated with HNRNPU germline pathogenic loss-of-function variants. Compared to healthy individuals, 227 HNRNPU-associated differentially methylated positions were detected. Both hyper- and hypomethylation alterations were identified but the former predominated. The identification of a methylation episignature for HNRNPU-associated neurodevelopmental disorder (NDD) implicates HNPRNPU-related chromatin alterations in the aetiopathogenesis of this disorder and suggests that episignature profiling should have clinical utility as a predictor for the pathogenicity of HNRNPU variants of uncertain significance. The detection of a methylation episignaure for HNRNPU-associated NDD is consistent with a recent report of a methylation episignature for HNRNPK-associated NDD.
Aquaculture supplies the world food market with a significant amount of valuable protein. Highly productive aquaculture fishes can be derived by utilizing genome-editing methods, and the main problem is to choose a target gene to obtain the desirable phenotype. This paper presents a review of the studies of genome editing for genes controlling body development, growth, pigmentation and sex determination in five key aquaculture Salmonidae and Cyprinidae species, such as rainbow trout (Onchorhynchus mykiss), Atlantic salmon (Salmo salar), common carp (Cyprinus carpio), goldfish (Carassius auratus), Gibel carp (Carassius gibelio) and the model fish zebrafish (Danio rerio). Among the genes studied, the most applicable for aquaculture are mstnba, pomc, and acvr2, the knockout of which leads to enhanced muscle growth; runx2b, mutants of which do not form bones in myoseptae; lepr, whose lack of function makes fish fast-growing; fads2, Δ6abc/5Mt, and Δ6bcMt, affecting the composition of fatty acids in fish meat; dnd mettl3, and wnt4a, mutants of which are sterile; and disease-susceptibility genes prmt7, gab3, gcJAM-A, and cxcr3.2. Schemes for obtaining common carp populations consisting of only large females are promising for use in aquaculture. The immobilized and uncolored zebrafish line is of interest for laboratory use.
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