Homozygous variants in CDC23 cause female infertility characterized by oocyte maturation defects
In this study, we identified two homozygous missense variants (c.986A > G, p.Y329C and c.988C > T, p.R330C) inCDC23 that are responsible for female infertility characterized by oocyte maturation defects in three infertile individuals. CDC23 (cell division cycle 23) is one of the core subunits of the APC/C. In vitro experiments showed that the variant c.986A > G (p.Y329C) led to a decrease in CDC23 protein level and the variant c.988C > T (p.R330C) changed the localization of CDC23 in HeLa cells and mouse oocytes. In vivo studies showed thatCdc23Y329C/Y329C mice successfully mimicked the pa...
Source: Human Genetics - September 28, 2023 Category: Genetics & Stem Cells Source Type: research
Understanding the pathogenesis of brain arteriovenous malformation: genetic variations, epigenetics, signaling pathways, and immune inflammation
AbstractBrain arteriovenous malformation (BAVM) is a rare but serious cerebrovascular disease whose pathogenesis has not been fully elucidated. Studies have found that epigenetic regulation, genetic variation and their signaling pathways, immune inflammation, may be the cause of BAVM the main reason. This review comprehensively analyzes the key pathways and inflammatory factors related to BAVMs, and explores their interplay with epigenetic regulation and genetics. Studies have found that epigenetic regulation such as DNA methylation, non-coding RNAs and m6A RNA modification can regulate endothelial cell proliferation, apop...
Source: Human Genetics - September 28, 2023 Category: Genetics & Stem Cells Source Type: research
Homozygous variants in CDC23 cause female infertility characterized by oocyte maturation defects
In this study, we identified two homozygous missense variants (c.986A > G, p.Y329C and c.988C > T, p.R330C) inCDC23 that are responsible for female infertility characterized by oocyte maturation defects in three infertile individuals. CDC23 (cell division cycle 23) is one of the core subunits of the APC/C. In vitro experiments showed that the variant c.986A > G (p.Y329C) led to a decrease in CDC23 protein level and the variant c.988C > T (p.R330C) changed the localization of CDC23 in HeLa cells and mouse oocytes. In vivo studies showed thatCdc23Y329C/Y329C mice successfully mimicked the pa...
Source: Human Genetics - September 28, 2023 Category: Genetics & Stem Cells Source Type: research
Understanding the pathogenesis of brain arteriovenous malformation: genetic variations, epigenetics, signaling pathways, and immune inflammation
AbstractBrain arteriovenous malformation (BAVM) is a rare but serious cerebrovascular disease whose pathogenesis has not been fully elucidated. Studies have found that epigenetic regulation, genetic variation and their signaling pathways, immune inflammation, may be the cause of BAVM the main reason. This review comprehensively analyzes the key pathways and inflammatory factors related to BAVMs, and explores their interplay with epigenetic regulation and genetics. Studies have found that epigenetic regulation such as DNA methylation, non-coding RNAs and m6A RNA modification can regulate endothelial cell proliferation, apop...
Source: Human Genetics - September 28, 2023 Category: Genetics & Stem Cells Source Type: research
N6-methyladenosine modified lncRNAs signature for stratification of biochemical recurrence in prostate cancer
In this study, methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted on primary and metastatic PCa samples, leading to the identification of 21 lncRNAs exhibiting differential methylation and expression patterns. We further established a PCa prognostic signature, named m6A-modified lncRNA score (mLs), based on 9 differential methylated lncRNAs in 4 multicenter cohorts. The high mLs score cohort exhibited a tendency for earlier biochemical recurrence (BCR) compared to the low mLs score cohort. Remarkably, the predictive performance of the mLs score surpassed that of five previously reported lncRNA-based si...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
A SACS deletion variant in Great Pyrenees dogs causes autosomal recessive neuronal degeneration
AbstractARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is a human neurological disorder characterized by progressive cerebellar ataxia and peripheral neuropathy. A recently recognized disorder in Great Pyrenees dogs is similarly characterized by widespread central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. Onset of clinical signs occurred in puppies as young as 4 months of age, with slow progression over several years. A multi-generation pedigree suggested an autosomal recessive mode of inheritance. Histopathology revealed co...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
Leveraging molecular quantitative trait loci to comprehend complex diseases/traits from the omics perspective
AbstractComprehending the molecular basis of quantitative genetic variation is a principal goal for complex diseases or traits. Molecular quantitative trait loci (molQTLs) have made it possible to investigate the effects of genetic variants hiding behind large-scale omics data. A deeper understanding of molQTL is urgently required in light of the multi-dimensionalization of omics data to more fully elucidate the pertinent biological mechanisms. Herein, we reviewed molQTLs with the corresponding resource from the omics perspective and further discussed the integrative strategy of GWAS-molQTL to infer their causal effects. S...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
CYP26B1-related disorder: expanding the ends of the spectrum through clinical and molecular evidence
AbstractCYP26B1 metabolizes retinoic acid in the developing embryo to regulate its levels. A limited number of individuals with pathogenic variants inCYP26B1 have been documented with a varied phenotypic spectrum, spanning from a severe manifestation involving skull anomalies, craniosynostosis, encephalocele, radio-humeral fusion, oligodactyly, and a narrow thorax, to a milder presentation characterized by craniosynostosis, restricted radio-humeral joint mobility, hearing loss, and intellectual disability. Here, we report two families withCYP26B1-related phenotypes and describe the data obtained from functional studies of ...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
N6-methyladenosine modified lncRNAs signature for stratification of biochemical recurrence in prostate cancer
In this study, methylated RNA immunoprecipitation sequencing (MeRIP-seq) was conducted on primary and metastatic PCa samples, leading to the identification of 21 lncRNAs exhibiting differential methylation and expression patterns. We further established a PCa prognostic signature, named m6A-modified lncRNA score (mLs), based on 9 differential methylated lncRNAs in 4 multicenter cohorts. The high mLs score cohort exhibited a tendency for earlier biochemical recurrence (BCR) compared to the low mLs score cohort. Remarkably, the predictive performance of the mLs score surpassed that of five previously reported lncRNA-based si...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
A SACS deletion variant in Great Pyrenees dogs causes autosomal recessive neuronal degeneration
AbstractARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is a human neurological disorder characterized by progressive cerebellar ataxia and peripheral neuropathy. A recently recognized disorder in Great Pyrenees dogs is similarly characterized by widespread central nervous system degeneration leading to progressive cerebellar ataxia and spasticity, combined with peripheral neuropathy. Onset of clinical signs occurred in puppies as young as 4 months of age, with slow progression over several years. A multi-generation pedigree suggested an autosomal recessive mode of inheritance. Histopathology revealed co...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
Leveraging molecular quantitative trait loci to comprehend complex diseases/traits from the omics perspective
AbstractComprehending the molecular basis of quantitative genetic variation is a principal goal for complex diseases or traits. Molecular quantitative trait loci (molQTLs) have made it possible to investigate the effects of genetic variants hiding behind large-scale omics data. A deeper understanding of molQTL is urgently required in light of the multi-dimensionalization of omics data to more fully elucidate the pertinent biological mechanisms. Herein, we reviewed molQTLs with the corresponding resource from the omics perspective and further discussed the integrative strategy of GWAS-molQTL to infer their causal effects. S...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
CYP26B1-related disorder: expanding the ends of the spectrum through clinical and molecular evidence
AbstractCYP26B1 metabolizes retinoic acid in the developing embryo to regulate its levels. A limited number of individuals with pathogenic variants inCYP26B1 have been documented with a varied phenotypic spectrum, spanning from a severe manifestation involving skull anomalies, craniosynostosis, encephalocele, radio-humeral fusion, oligodactyly, and a narrow thorax, to a milder presentation characterized by craniosynostosis, restricted radio-humeral joint mobility, hearing loss, and intellectual disability. Here, we report two families withCYP26B1-related phenotypes and describe the data obtained from functional studies of ...
Source: Human Genetics - September 27, 2023 Category: Genetics & Stem Cells Source Type: research
Circulating DNA reveals a specific and higher fragmentation of the Y chromosome
In this study, we employed shallow whole genome sequencing (sWGS) to comprehensively assess the total cirDNA and the individual chromosome fragment size profiles in the plasma of healthy male individuals. Here, we show that (i) the fragment size profiles of total circulating DNA (cirDNA) and DNA fragments originating from autosomes and the X chromosome in blood plasma are homogeneous, and have a remarkably low variability (mean CV = 7%) among healthy individuals, (ii) the Y chromosome has a distinct fragment size profile with the accumulation of the fragment < 145 bp and depletion of the dinucleosome-associate...
Source: Human Genetics - September 25, 2023 Category: Genetics & Stem Cells Source Type: research
