Genes最新文献

Background/Objectives:MYO3A belongs to the unconventional myosin superfamily, and the myosin IIIa protein localizes on the tip of the stereocilia of vestibular and cochlear hair cells. Deficiencies in MYO3A have been reported to cause the deformation of hair cells into abnormally long stereocilia with an increase in spacing. MYO3A is a rare causative gene of autosomal recessive sensorineural hearing loss (DFNB30), with only 13 cases reported to date. In this study, we aimed to elucidate the phenotypes caused by MYO3A variations. Methods: Massively parallel DNA sequencing was performed on 15,684 Japanese hearing loss patients (mean age 27.5 ± 23.1 years old, 6574 male, 8612 female and 498 patients for whom information was unavailable), identifying nine candidate patients with MYO3A variants. Results: We identified eight causative MYO3A variants by massively parallel DNA sequencing, including six novel variants, and reported nine individuals possessing MYO3A gene variants, which is the largest group of non-related patients yet to be detected. Our findings confirmed that MYO3A variants cause progressive hearing loss, with its onset varying from birth to the second decade, eventually leading to severe-to-profound hearing loss. Conclusions: We clarified that patients with MYO3A gene variants present with late-onset, progressive hearing loss. Our findings have enabled us to predict the outcomes of hearing loss in patients with candidate MYO3A gene variants and to provide intervention in a timely manner.

Background/objectives: A striking feature of the karyotypes of stingless bees is the large amount of heterochromatin present in most species. Cytogenomic studies performed in some Meliponini species have suggested that evolutionary events related to the diversification and amplification of satellite DNA families in the heterochromatin may reflect the structuring of phylogenetic clades in this tribe. In this study, we performed a genomic analysis in Frieseomelitta varia to characterize different satDNA families in its genome. We also investigated the presence of the most abundant satDNA family of F. varia in its own chromosomes, in two other Frieseomelitta species, and in other Meliponini genera encompassing the three main clades of Neotropical Meliponini, according to the available molecular phylogeny.

Methods: Genomic analyses were performed using RepeatExplorer2 on the Galaxy platform, and chromosomal investigations were conducted using fluorescent in situ hybridization.

Results: Seven satDNA families were recovered, which together totaled an abundance of 11.223% of the analyzed F. varia genomic fraction. The most abundant satDNA family, FvarSat01-306, predominates in the analyzed repetitive fraction (representing around 89%) and was recently amplified and homogenized in almost all the heterochromatin of F. varia. In addition, the data revealed an unprecedented sharing of this satDNA family in the centromeric/pericentromeric heterochromatin among different Meliponini genera, with independent amplifications and loss of this sequence in some taxa.

Conclusions: One family of satellite DNA makes up most of the heterochromatin in this species and is shared with other Meliponini.

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced SASP factors specifically secreted by renal cortical epithelial (RCE) cells and their role in promoting renal cell carcinoma (RCC) progression.

Methods: Proteomic data from the SASP Atlas were analyzed to identify IR-induced factors unique to RCE cells, with subsequent evaluations performed at both the gene and protein levels. Thirty-seven proteins were identified as exclusively upregulated and secreted by senescent RCE cells. Gene expression analysis of these RCE-specific SASP factors was conducted using the Gene Expression database of Normal and Tumor tissues (GENT2) and The Cancer Genome Atlas (TCGA). To assess their prognostic relevance in RCC, the corresponding proteins were further analyzed using the Human Protein Atlas (HPA), emphasizing the relationship between SASP factor expression and RCC progression.

Results: ALDH18A1 and ASPH emerged as key RCE-specific SASP factors with significant upregulation at both the gene and protein levels (Log2 ratio > 1.15, p < 0.05). These proteins are implicated in pro-cancer activities and are strongly associated with poor prognostic outcomes in RCC. Their critical roles in RCC progression underscore their potential as promising therapeutic targets for the prevention and treatment of the disease.

Conclusions: This study provides novel insights into the role of IR-induced SASP in renal carcinogenesis, marking the first identification of ALDH18A1 and ASPH as specific secreted proteins associated with tumor progression in RCC. This study suggests that ALDH18A1 and ASPH hold promise as early biomarkers for RCC and as therapeutic targets for disease prevention and treatment.

Background: Polydactylus macrochir (Günther; 1867) is a member of the family Polynemidae. The placement of Polynemidae among teleosts has varied over the years.

Methods: Therefore, in this study, we sequenced the complete mitochondrial genome of P. macrochir, analyzed the characterization of the mitochondrial genome, and investigated the phylogenetic relationships of Polynemidae.

Results: The length of the P. macrochir mitogenome was 16,738 bp, with a typical order. Nucleotide composition analysis showed that the P. macrochir mitogenome was AT-biased (54.15%), and the PCGs tended to use A and C rather than T and G at the third codon. All the PCGs started with the regular codon ATG, except for cox1, which started with GTG. The termination codon varied across the PCGs. It was shown that the ka/ks ratios of all the PCGs were less than one. Phylogenetic analysis, based on the maximum likelihood (ML) and Bayesian inference (BI) methods, indicated that eight threadfins formed a well-supported monophyletic cluster. Polynemidae and Sphyraenidae clustered together as a monophyletic group. According to TimeTree analyses, the most recent common ancestor (MRCA) of Polynemidae was traced back to about 52.81 million years ago (MYA), while six species within Polynemidae diverged from 11.70 MYA to 20.05 MYA.

Conclusions: The present study provides valuable mitochondrial information for the classification of P. macrochir and new insights into the phylogenetic relationships of Polynemidae.

Background: Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci fall in non-coding regions of the genome, and it is unclear how these non-coding variants affect circulating lipid levels. One hypothesis is that genetically mediated variation in transcript abundance, detected via the analysis of expressed quantitative trait loci (eQTLs), is key to the biologic function of causal variants. Here, we investigate the hypothesis that non-coding GWAS risk variants affect the homeostatic expression of a nearby putatively causal gene for serum LDL-C levels. Methods: We establish a set of twenty-one expert-curated and validated genes implicated in hypercholesterolemia via dose-dependent pharmacologic modulation in human adults, for which the relevant tissue type has been established. We show that the expression of these LDL-C genes is impacted by eQTLs in relevant tissues and that there are significant genomic-risk loci in LDL-GWAS near these causal genes. We evaluate, using statistical colocalization, whether a single variant or set of variants in each genetic locus is responsible for the GWAS and eQTL signals. Results: Genome-wide association study results for serum LDL-C levels demonstrate that the 402 identified genomic-risk loci for LDL-C are highly enriched for known causal genes for LDL-C (OR 527, 95% CI 126-5376, p < 2.2 × 10^-16). However, we find limited evidence for colocalization between GWAS signals near validated hypercholesterolemia genes and eQTLs in relevant tissues (colocalization rate of 26% at a locus-level colocalization probability > 50%). Conclusions: Our results highlight the complexity of genetic regulatory effects for causal hypercholesterolemia genes; we suggest that context-responsive eQTLs may explain the effects of non-coding GWAS hits that do not overlap with standard eQTLs.

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and Caribbean countries, resulting in 13,014 confirmed infections. Similarly to other orthobunyaviruses, OROV can undergo genetic reassortment events with itself as well as other viruses. This occurred during this current outbreak, resulting in novel strains with increased pathogenicity and levels of transmission. For the first time, pregnant women with Oropouche fever have sustained poor perinatal outcomes, including miscarriage, fetal demise, stillbirths and malformation syndromes including microcephaly. In July 2024, PAHO issued an Epidemiological Alert warning of the association of OROV with vertical transmission. OROV has now been identified in the fetal blood, cerebrospinal fluid, placenta and umbilical cords, and fetal somatic organs including the liver, kidneys, brain, spleen, heart, and lungs using nucleic acid and antigen testing. Perinatal autopsy pathology has confirmed central nervous system infection from OROV in infants with congenital infection including microcephaly, ventriculomegaly, agenesis of corpus callosum, and neuronal necrosis. The latest data from Brazil show 3 confirmed cases of OROV vertical transmission; 2 cases of fetal death; 1 case of congenital malformation; and ongoing investigations into the role of OROV in 15 cases of fetal death, 3 cases of congenital malformations and 5 spontaneous miscarriages. This Commentary discusses the mechanisms and significance of development of novel reassortant strains of OROV during the current outbreak and their recent recognition as causing vertical infection and adverse perinatal outcomes among pregnant women with Oropouche fever.

Background: Lamb health is crucial for producers; however, the percentage of lambs that die before weaning is still 15-20%. One factor that can contribute to lamb deaths is congenital diseases. A novel semi-lethal disease has been identified in newborn Polypay lambs and termed dozer lamb syndrome. This study aims to determine if there is a genetic predisposition to dozer lamb syndrome. These lambs are weak and unable to lift their heads, suckle, and swallow, resulting in nasal reflux.

Methods: Genetic analyses, including a genome-wide association, runs of homozygosity, and fine mapping to determine haploblock within regions of interest, were utilized in determining genetic predispositions to dozer lamb syndrome.

Results: The genome-wide association study identified a region of chromosome 15 with three significant SNPs (p-values of 6.81 × 10^-6, 5.71 × 10^-6, and 8.52 × 10^-6). Genetic analysis identified a run of homozygosity on the same region of chromosome 15 with an odds ratio of 236.7. Fine mapping of this region identified three haploblocks associated with the dozer lamb syndrome (p-value = 2.41 × 10^-5).

Conclusions: The most significant and promising gene in this region is CELF1, which is known to play an important role in muscle development. Abnormal CELF1 abundance and cellular location are reported to result in abnormal muscle development. Identification of genetic aberrations associated with dozer lamb syndrome provides a tool for decreasing or eliminating the genotype and, thus, the associated phenotype(s) from Polypay sheep.

Background/objectives: Chrysanthemum (Chrysanthemum morifolium), a key ornamental and medicinal plant, presents challenges in cultivar identification due to high phenotypic similarity and environmental influences. This study assessed the genetic diversity and discrimination of 126 spray-type chrysanthemum cultivars.

Methods: About twenty-three simple sequence repeat (SSR) markers were screened for the discrimination of 126 cultivars, among which six SSR markers showed polymorphic fragments.

Results: Results showed high polymorphism across six markers, with an average of 3.8 alleles per locus and a mean polymorphism information content (PIC) of 0.52, indicating strong discriminatory efficiency. The average observed heterozygosity (Ho) was 0.72, reflecting significant genetic diversity within the cultivars. Cluster analysis using the unweighted pair group method with arithmetic mean (UPGMA) grouped the cultivars into seven clusters, correlating well with the PCA. Bayesian population structure analysis suggested two primary genetic subpopulations.

Conclusions: These findings confirm SSR markers as an effective tool for the genetic characterization and precise discrimination of spray type chrysanthemum cultivars, offering significant applications in breeding, cultivar registration, and germplasm conservation. The SSR marker-based approach thus provides a reliable and efficient strategy to enhance the management and commercialization of diverse chrysanthemum germplasm collections.

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease. However, there are gaps in translating how individual genomic variation affects phenotypic presentation. The expansion of criteria for genetic testing and the increasing utilization of comprehensive genetic panels may enhance the identification of individuals carrying P/LP variants linked to hereditary breast cancer. Individualized risk assessment could facilitate the implementation of personalized risk-reduction strategies for these individuals. Preventive interventions encompass lifestyle modifications, chemoprevention, enhanced surveillance through breast imaging, and risk-reducing surgeries. This review addresses the current literature's inconsistencies and limitations, particularly regarding risk factors and the intensity of preventive strategies for women with P/LP variants in moderate- and high-penetrance genes. In addition, it synthesizes the latest evidence on risk assessment and primary and secondary prevention in women at high risk of breast cancer.

Flowers, serving as the reproductive structures of angiosperms, perform an integral role in plant biology and are fundamental to understanding plant evolution and taxonomy. The growth and organogenesis of flowers are driven by numerous factors, such as external environmental conditions and internal physiological processes, resulting in diverse traits across species or even within the same species. Among these factors, genes play a central role, governing the entire developmental process. The regulation of floral genesis by these genes has become a significant focus of research. In the AE model of floral development, the five structural whorls (calyx, corolla, stamens, pistils, and ovules) are controlled by five groups of genes: A, B, C, D, and E. These genes interact to give rise to a complex control system that governs the floral organsgenesis. The activation or suppression of specific gene categories results in structural modifications to floral organs, with variations observed across different species. The present article examines the regulatory roles of key genes, including genes within the MADS-box and AP2/ERF gene clusters, such as AP1, AP2, AP3, AG, STK, SHP, SEP, PI, and AGL6, as well as other genes, like NAP, SPL, TGA, PAN, and WOX, in shaping floral organ genesis. In addition, it analyzes the molecular-level effects of these genes on floral organ formation. The findings offer a deeper understanding of the genetic governance of floral organ genesis across plant species.