STEAP3 promotes colon cancer cell proliferation and migration via regulating histone acetylation
AbstractColorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ...
Source: Human Genetics - March 13, 2024 Category: Genetics & Stem Cells Source Type: research
PdmIRD: missense variants pathogenicity prediction for inherited retinal diseases in a disease-specific manner
AbstractAccurate discrimination of pathogenic and nonpathogenic variation remains an enormous challenge in clinical genetic testing of inherited retinal diseases (IRDs) patients. Computational methods for predicting variant pathogenicity are the main solutions for this dilemma. The majority of the state-of-the-art variant pathogenicity prediction tools disregard the differences in characteristics among different genes and treat all types of mutations equally. Since missense variants are the most common type of variation in the coding region of the human genome, we developed a novel missense mutation pathogenicity predictio...
Source: Human Genetics - March 13, 2024 Category: Genetics & Stem Cells Source Type: research
Trisomy silencing by XIST: translational prospects and challenges
This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are key to its translational relevance, and then discuss recent efforts to develop translational utility of XIST for chromosome dosage disorders, particularly Down syndrome (DS). Remarkably, it was shown in vitro that expression of an XIST transgene inserted into one chromosome 21 can comprehensively silence that chromosome and “dosage compensate” Trisomy 21, the cause of DS. Here we summarize recent findings ...
Source: Human Genetics - March 9, 2024 Category: Genetics & Stem Cells Source Type: research
PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss
AbstractIdentification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing.PKHD1L1 was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants inPKHD1L1 also cause hearing loss in humans. Exome sequencing was performed on DNA of four families segregating autosomal recessive nonsyndromic sensorineural hearing loss. Compound heterozygous p.[(Gly129Ser)...
Source: Human Genetics - March 9, 2024 Category: Genetics & Stem Cells Source Type: research
Trisomy silencing by XIST: translational prospects and challenges
This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are key to its translational relevance, and then discuss recent efforts to develop translational utility of XIST for chromosome dosage disorders, particularly Down syndrome (DS). Remarkably, it was shown in vitro that expression of an XIST transgene inserted into one chromosome 21 can comprehensively silence that chromosome and “dosage compensate” Trisomy 21, the cause of DS. Here we summarize recent findings ...
Source: Human Genetics - March 9, 2024 Category: Genetics & Stem Cells Source Type: research
PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss
AbstractIdentification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing.PKHD1L1 was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants inPKHD1L1 also cause hearing loss in humans. Exome sequencing was performed on DNA of four families segregating autosomal recessive nonsyndromic sensorineural hearing loss. Compound heterozygous p.[(Gly129Ser)...
Source: Human Genetics - March 9, 2024 Category: Genetics & Stem Cells Source Type: research
Clinical and genetic architecture of a large cohort with auditory neuropathy
In conclusion, genes distribution of AN, with the most common genes beingOTOF andAIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups. (Source: Human Genetics)
Source: Human Genetics - March 8, 2024 Category: Genetics & Stem Cells Source Type: research
Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies
We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. These individuals exhibit both shared and unique clinical manifestations, highlighting the complexity and variability of the disorder. We propose that the involvement of MAP3K20 in endothelial –mesenchymal transition provides a plausible etiology of these features. Together, these findings characterize a disorder that both expands the phenotypic spectrum associated withMAP3K20 ...
Source: Human Genetics - March 7, 2024 Category: Genetics & Stem Cells Source Type: research
Identification and functional analysis of rare HECTD1 missense variants in human neural tube defects
In this study, we report the identification of five rareHECTD1 missense sequence variants in NTD cases. The variants were found through targeted next-generation sequencing in a Chinese cohort of 352 NTD cases and 224 ethnically matched controls. We present data showing thatHECTD1 is a highly conserved gene, extremely intolerant to loss-of-function mutations and missense changes. To evaluate the functional consequences of NTD-associated missense variants, functional assays in HEK293T cells were performed to examine protein expression and the ability of HECTD1 sequence variants to suppress eHSP90 secretion. One NTD-associate...
Source: Human Genetics - March 7, 2024 Category: Genetics & Stem Cells Source Type: research
Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies
We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. These individuals exhibit both shared and unique clinical manifestations, highlighting the complexity and variability of the disorder. We propose that the involvement of MAP3K20 in endothelial –mesenchymal transition provides a plausible etiology of these features. Together, these findings characterize a disorder that both expands the phenotypic spectrum associated withMAP3K20 ...
Source: Human Genetics - March 7, 2024 Category: Genetics & Stem Cells Source Type: research
Functional categorization of gene regulatory variants that cause Mendelian conditions
AbstractMuch of our current understanding of rare human diseases is driven by coding genetic variants. However, non-coding genetic variants play a pivotal role in numerous rare human diseases, resulting in diverse functional impacts ranging from altered gene regulation, splicing, and/or transcript stability. With the increasing use of genome sequencing in clinical practice, it is paramount to have a clear framework for understanding how non-coding genetic variants cause disease. To this end, we have synthesized the literature on hundreds of non-coding genetic variants that cause rare Mendelian conditions via the disruption...
Source: Human Genetics - March 4, 2024 Category: Genetics & Stem Cells Source Type: research
The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease
AbstractThe differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-...
Source: Human Genetics - February 29, 2024 Category: Genetics & Stem Cells Source Type: research
