The association between DNA methylation and human height and a prospective model of DNA methylation-based height prediction
AbstractAs a vital anthropometric characteristic, human height information not only helps to understand overall developmental status and genetic risk factors, but is also important for forensic DNA phenotyping. We utilized linear regression analysis to test the association between each CpG probe and the height phenotype. Next, we designed a methylation sequencing panel targeting 959 CpGs and subsequent height inference models were constructed for the Chinese population. A total of 11,730 height-associated sites were identified. By employing KPCA and deep neural networks, a prediction model was developed, of which the cross...
Source: Human Genetics - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
STRAS:a snakemake pipeline for genome-wide short tandem repeats annotation and score
AbstractHigh-throughput whole genome sequencing (WGS) is clinically used in finding single nucleotide variants and small indels. Several bioinformatics tools are developed to call short tandem repeats (STRs) copy numbers from WGS data, such as ExpansionHunter denovo, GangSTR and HipSTR. However, expansion disorders are rare and it is hard to find candidate expansions in single patient sequencing data with ~ 800,000 STRs calls. In this paper I describe a snakemake pipeline for genome-wide STRs Annotation and Score (STRAS) using a Random Forest (RF) model to predict pathogenicity. The predictor was validated by benchmark ...
Source: Human Genetics - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
Genetic evidence for T-wave area from 12-lead electrocardiograms to monitor cardiovascular diseases in patients taking diabetes medications
ConclusionPatients taking diabetes medications are prone to have decreased aVR_T-area and an increased risk of IHD and CA. The aVR_T-area is therefore a potential ECG marker for pre-clinical prediction of IHD and CA in patients taking diabetes medications. (Source: Human Genetics)
Source: Human Genetics - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
The association between DNA methylation and human height and a prospective model of DNA methylation-based height prediction
AbstractAs a vital anthropometric characteristic, human height information not only helps to understand overall developmental status and genetic risk factors, but is also important for forensic DNA phenotyping. We utilized linear regression analysis to test the association between each CpG probe and the height phenotype. Next, we designed a methylation sequencing panel targeting 959 CpGs and subsequent height inference models were constructed for the Chinese population. A total of 11,730 height-associated sites were identified. By employing KPCA and deep neural networks, a prediction model was developed, of which the cross...
Source: Human Genetics - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
STRAS:a snakemake pipeline for genome-wide short tandem repeats annotation and score
AbstractHigh-throughput whole genome sequencing (WGS) is clinically used in finding single nucleotide variants and small indels. Several bioinformatics tools are developed to call short tandem repeats (STRs) copy numbers from WGS data, such as ExpansionHunter denovo, GangSTR and HipSTR. However, expansion disorders are rare and it is hard to find candidate expansions in single patient sequencing data with ~ 800,000 STRs calls. In this paper I describe a snakemake pipeline for genome-wide STRs Annotation and Score (STRAS) using a Random Forest (RF) model to predict pathogenicity. The predictor was validated by benchmark ...
Source: Human Genetics - March 20, 2024 Category: Genetics & Stem Cells Source Type: research
Genome-wide analyses reveal the regulatory roles of DNA methylation-regulated alternative promoter transcripts in breast cancer
AbstractA certain proportion of genes are regulated by multiple, distinct promoters, revealing a dynamic landscape of the cancer transcriptome. However, the contribution of alternative promoters (APs) in breast cancer (BRCA) remains largely unexplored. Here, we identified 3654 genes with multiple promoters in BRCA patients, and 53 of them could generate distinct AP transcripts that are dysregulated and prognosis-related in BRCA, namely prognosis-related dysregulated AP (prdeAP) transcripts. Interestingly, when we searched for the genomic signatures of these prdeAP genes, we found that the promoter regions of 92% of the prd...
Source: Human Genetics - March 19, 2024 Category: Genetics & Stem Cells Source Type: research
A novel 193-plex MPS panel integrating STRs and SNPs highlights the application value of forensic genetics in individual identification and paternity testing
AbstractMassively parallel sequencing (MPS) has emerged as a promising technology for targeting multiple genetic loci simultaneously in forensic genetics. Here, a novel 193-plex panel was designed to target 28 A-STRs, 41 Y-STRs, 21 X-STRs, 3 sex-identified loci, and 100 A-SNPs by employing a single-end 400 bp sequencing strategy on the MGISEQ-2000™ platform. In the present study, a series of validations and sequencing of 1642 population samples were performed to evaluate the overall performance of the MPS-based panel and its practicality in forensic application according to the SWGDAM guidelines. In general, the 193-pl...
Source: Human Genetics - March 18, 2024 Category: Genetics & Stem Cells Source Type: research
Integrative regulation of hLMR1 by dietary and genetic factors in nonalcoholic fatty liver disease and hyperlipidemia
In this study, we first screened for nutritional/hormonal factors and found that hLMR1 was robustly induced by insulin/glucose in cultured human hepatocytes, and this induction is dependent on the transcription factor SREBP1. We then tested if GWAS SNPs genetically linked to hLMR1 could regulate hLMR1 expression. We found that DNA sequences flanking rs9653945, a SNP from the last exon of the hLMR1 gene, functions as an enhancer that can be robustly activated by SREBP1c depending on the presence of rs9653945 major allele (G). We further performed CRISPR base editing in human HepG2 cells and found that rs9653945 major (G) to...
Source: Human Genetics - March 17, 2024 Category: Genetics & Stem Cells Source Type: research
Novel compound heterozygous variants in FANCI cause premature ovarian insufficiency
This study first links replication stress response defects with the pathogenesis of human POI, providing a new insight into the essential roles of the FA genes in ovarian function. (Source: Human Genetics)
Source: Human Genetics - March 14, 2024 Category: Genetics & Stem Cells Source Type: research
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
