Middletonrobbins7793

Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China. Methods A total of 99,546 newborns were screened by modified fluorescent spot test at the Women and Children's Hospital, Xiamen University. High-risk neonates were recalled for diagnosis by either a measurement of G6PD activity or genetic testing for the presence of pathogenic G6PD variants using a quantitative G6PD enzymatic assay or the MeltPro® G6PD assay, respectively. Results In the first-tier screening, 1,256 newborns were categorized as high risk. Of these, 1,051 were diagnosed with G6PD deficiency, indicating a prevalence of 1.39% in Xiamen, China. Among the 1,013 neonates who underwent genotyping, 851 carried hemizygous, heterozygous, homozygous, or compound heterozygous variants, for a positive predictive value (PPV) of 84.01%. In total, 12 variants and 32 genotypes were identified, and the six most common variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.871G>A, and c.392G>T, which accounted for approximately 94% of the identified alleles. Different variants showed characteristic enzymatic activities, although high phenotypic heterogeneity was observed for each variant. The use of cold-chain transportation significantly improved the PPV of NBS. Conclusions We determined the profile of G6PD deficiency in Xiamen, including the prevalence, variant spectrum, and genotype-phenotype correlations and confirmed that maintaining a low temperature during sample transport is essential to ensure the high screening accuracy of NBS. Our data provides epidemiological, genotypic, phenotypic, and clinical practice references to standardize future interventions for G6PD deficiency.Multiple sclerosis (MS) is an early onset chronic neurological condition in adults characterized by inflammation, demyelination, gliosis, and axonal loss in the central nervous system. The pathological cause of MS is complex and includes both genetic and environmental factors. Non-protein-coding RNAs (ncRNAs), specifically miRNAs and lncRNAs, are important regulators of various biological processes. Over the past decade, many studies have investigated both miRNAs and lncRNAs in patients with MS. Since then, insightful knowledge has been gained in this field. Here, we review the role of miRNAs and lncRNAs in MS pathogenesis and discuss their implications for diagnosis and treatment.Background Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility. PPIB pathogenic variants cause a perinatal lethal form of OI type IX. A limited number of pathogenic variants have been reported so far worldwide. Methods We identified a rare pedigree whose phenotype was highly consistent with OI-IX. Exome sequencing was performed to uncover the causal variants. The variant pathogenicity was classified following the ACMG/AMP guidelines. The founder effect and the age of the variant were assessed. Results We identified a homozygous missense variant c.509G > A/p.G170D in PPIB in an affected fetus. This variant is a Chinese-specific allele and can now be classified as pathogenic. We estimated the allele frequency (AF) of this variant to be 0.0000427 in a Chinese cohort involving 128,781 individuals. All patients and carriers shared a common haplotype, indicative of a founder effect. The estimated age of variant was 65,160 years. We further identified pathogenic variants of PPIB in gnomAD and ClinVar databases, the conserved estimation of OI type IX incidence to be 1/1,000,000 in Chinese population. Conclusion We reported a founder pathogenic variant in PPIB specific to the Chinese population. We further provided our initial estimation of OI-IX disease incidence in China.Uncovering the genetic basis and optimizing the late blight tolerance trait in potatoes (Solanum tuberosum L.) are crucial for potato breeding. Late blight disease is one of the most significant diseases hindering potato production. The traits of late blight tolerance were evaluated for 284 potato cultivars to identify loci significantly associated with the late blight tolerance trait. Of all, 37 and 15 were the most tolerant to disease, and 107 and 30 were the most susceptible. A total of 22,489 high-quality single-nucleotide polymorphisms and indels were identified in 284 potato cultivars. All the potato cultivars were clustered into eight subgroups using population structure analysis and principal component analysis, which were consistent with the results of the phylogenetic tree analysis. The average genetic diversity for all 284 potato cultivars was 0.216, and the differentiation index of each subgroup was 0.025-0.149. Genome-wide linkage disequilibrium (LD) analysis demonstrated that the average LD was about 0.9 kb. A genome-wide association study using a mixed linear model identified 964 loci significantly associated with the late blight tolerance trait. Fourteen candidate genes for late blight tolerance traits were identified, including genes encoding late blight tolerance protein, chitinase 1, cytosolic nucleotide-binding site-leucine-rich repeat tolerance protein, protein kinase, ethylene-responsive transcription factor, and other potential plant tolerance-related proteins. This study provides novel insights into the genetic architecture of late blight tolerance traits and will be helpful for late blight tolerance in potato breeding.Since their inception, genome-wide association studies (GWAS) have identified more than a hundred thousand single nucleotide polymorphism (SNP) loci that are associated with various complex human diseases or traits. The majority of GWAS discoveries are located in non-coding regions of the human genome and have unknown functions. The valley between non-coding GWAS discoveries and downstream affected genes hinders the investigation of complex disease mechanism and the utilization of human genetics for the improvement of clinical care. Meanwhile, advances in high-throughput sequencing technologies reveal important genomic regulatory roles that non-coding regions play in the transcriptional activities of genes. In this review, we focus on data integrative bioinformatics methods that combine GWAS with functional genomics knowledge to identify genetically regulated genes. We categorize and describe two types of data integrative methods. First, we describe fine-mapping methods. Fine-mapping is an exploratory approacd the challenges that different TWAS methods face. Overall, TWAS is a powerful tool for identifying complex trait-associated genes. With the advent of single-cell sequencing, chromosome conformation capture, gene editing technologies, and multiplexing reporter assays, we are expecting a more comprehensive understanding of genomic regulation and genetically regulated genes underlying complex human diseases and traits in the future.Background Statin intolerance impacts approximately 10% of statin users, with side effects ranging from mild myalgia to extreme intolerance resulting in myopathy and rhabdomyolysis. Statin intolerance results in poor adherence to therapy and can impact statin efficacy. Many genetic variants are associated with statin intolerance. The effect of these variants on statin efficacy has not been systematically explored. Methods Using longitudinal electronic health records and genetic biobank data from Tayside, Scotland, we examined the effect of seven genetic variants with previously reported associations with simvastatin or atorvastatin intolerance on the outcome of statin response. Statin response was measured by the reduction achieved when comparing pre- and post-statin non-high-density lipoprotein-cholesterol (non-HDL-C). Post-treatment statin response was limited to non-HDL-C measured within 6months of therapy initiation. Univariate and multivariable linear regression models were used to assess the main and ad non-HDL-cholesterol compared to those with rs1045642-TC or TT genotype and the rs12975366-TT genotype (95% CI 0.05, 0.16; p less then 0.001). Conclusion We report two genetic variants for statin adverse drug reactions (ADRs) that are associated with statin efficacy. While the ABCB1 variant has been shown to have an association with statin pharmacokinetics, no similar evidence for LILRB5 has been reported. These findings highlight the value of genetic testing to deliver precision therapeutics to statin users.On average, half of the animal's estimated breeding value (EBV) is passed on to their progeny. However, it is not known how the performance of beef-cross-dairy cattle relates to the EBV of their beef sire. Such information is required to determine the genetic potential of beef sires selected based on existing EBV to be used on dairy cows in New Zealand. This study evaluated the relationship between the EBV of 30 Angus and 34 Hereford sires and the performance of their progeny for birth, growth, and carcass traits, via progeny testing of 975 beef-cross-dairy offspring born to dairy cows and grown on hill country pasture. Overall, BREEDPLAN EBV did predict progeny performance of the beef-cross-dairy cattle from this study. Gestation length and birthweight increased with increasing sire EBV (mean 0.37-0.62days and 0.52-0.64kg, respectively, p0.05). Liveweight increased with sire EBV for liveweight at 400, 600, and 800days, by a similar amount for both breeds (between 0.23 and 0.42kg increase in progeny liveweight per extra kilo of sire EBV, p less then 0.05). The relationships were more inconsistent for carcass traits. For Hereford, carcass weight and eye muscle area increased with increasing sire EBV (0.27kg and 0.70cm2, respectively, p less then 0.05). For Angus, marble score increased by 0.10 with 1% extra in sire EBV for intramuscular fat (p less then 0.05). Rib fat depth tended to increase with sire EBV for both breeds (p less then 0.1). learn more EBV derived from beef-breed data work in dairy-beef systems but maybe slightly less than the expected 0.5units of performance per unit of EBV. New Zealand farmers should consider BREEDPLAN EBV when selecting sires to mate dairy cows or when buying beef-cross-dairy calves for beef production, to ensure the resulting calves are born safely and on time and then grow well to produce carcasses of suitable meat and fat composition.Background Hepatocellular carcinoma (HCC) is considered the most common type of liver cancer and the fourth leading cause of cancer-related deaths in the world. Since the disease is usually diagnosed at advanced stages, it has poor prognosis. Therefore, reliable biomarkers are urgently needed for early diagnosis and prognostic assessment. Methods We used genome-wide gene expression profiling datasets from human and rat early HCC (eHCC) samples to perform integrated genomic and network-based analyses, and discovered gene markers that are expressed in blood and conserved in both species. We then used independent gene expression profiling datasets for peripheral blood mononuclear cells (PBMCs) for eHCC patients and from The Cancer Genome Atlas (TCGA) database to estimate the diagnostic and prognostic performance of the identified gene signature. Furthermore, we performed functional enrichment, interaction networks and pathway analyses. Results We identified 41 significant genes that are expressed in blood and conserved across species in eHCC.