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The identification of novel age‐related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage‐based biomarkers of age, mainly due to the lack of precise methods for genome‐wide surveys of different types of DNA damage. Recently, we developed two techniques for genome‐wide mapping of the most prevalent types of DNA damage, single‐strand breaks and abasic sites, with nucleotide‐level resolution. Herein, we explored the potential of genomic patterns of DNA damage identified by these methods as a source of novel age‐related biomarkers using mice as a model system. Strikingly, we found that models based on genomic patterns of either DNA lesion could accurately predict age with higher precision than the commonly used transcriptome analysis. Interestingly, the informative patterns were limited to relatively few genes and the DNA damage levels were positively or negatively correlated with age. These findings show that previously unexplored high‐resolution genomic patterns of DNA damage contain useful information that can contribute significantly to both practical applications and basic science. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify the hub gene in gastric cancer (GC) tumorigenesis. A biomarker prediction model was constructed and analyzed, and protein expression in histopathological samples was verified in a validation cohort. Methods: Differentially expressed genes (DEGs) were identified from GC projects in The Cancer Genome Atlas (TCGA) database. Functional enrichment analysis of DEGs was performed between the high- and low-Ribonuclease P protein subunit p30 (RPP30) expression groups. ROC analysis was performed to assess RPP30 expression to discriminate GC from normal tissues. Functional enrichment pathways and immune infiltration of DEGs were analyzed using GSEA and ssGSEA. Survival analysis and nomogram construction were performed to predict patient survival. Immunohistochemical staining of GC tissues was performed to validate RPP30 expression in GC and paracancerous samples. Results: Gene expression data and clinical information of 380 cases (375 GC samples and 32 para-cancerous tissues) were collected from TCGA database. The AUC for RPP30 expression was found to be 0.785. The G alpha S signaling pathway was the most significantly enriched signaling pathway. Primary therapy outcome (p < 0.001, HR = 0.243, 95% CI = 0.156-0.379), age (p = 0.012, HR = 1.748, 95% CI = 1.133-2.698), and RPP30 expression (p < 0.001, HR = 2.069, 95% CI = 1.346-3.181) were identified as independent prognostic factors. As a quantitative approach, a nomogram constructed based on RPP30 expression, age, and primary therapy outcome performed well in predicting patient survival. Nineteen of the 25 tissue samples from the validation cohort showed positive RPP30 expression in GC tissues, whereas 16 cases showed negative RPP30 staining in normal tissues. The difference between the two was statistically significant. Conclusion: High RPP30 expression was significantly correlated with disease progression and poor survival in GC, promoting tumorigenesis and angiogenesis via tRNA dysregulation. This study provides new and promising insights into the molecular pathogenesis of tRNA in GC. [ABSTRACT FROM AUTHOR]

Tomato yellow leaf curl virus (TYLCV) responsible for tomato yellow leaf curl disease (TYLCD) causes a substantial decrease in tomato (Solanum lycopersicum L.) yield worldwide. The use of resistant variety as a sustainable management strategy has been advocated. Tremendous progress has been made in genetically characterizing the resistance genes (R gene) in tomato. Breeding tomato for TYLCV resistance has been based mostly on Ty-3 as a race-specific resistance gene by introgression originating from wild tomato species relatives. Improvement or development of a cultivar is achievable through the use of marker-assisted selection (MAS). Therefore, precise and easy use of gene-targeted markers would be of significant importance for selection in breeding programs. The present study was undertaken to develop a new marker based on Ty-3 gene sequence that can be used for MAS in TYLCV resistant tomato breeding program. The new developed marker was named ACY. The reliability and accuracy of ACY were evaluated against those of Ty-3 linked marker P6-25 through screening of commercial resistant and susceptible tomato hybrids, and genetic segregation using F2 population derived from a commercial resistant hybrid AG208. With the use of bioinformatics and DNA sequencing analysis tools, deletion of 10 nucleotides was observed in Ty-3 gene sequence for susceptible tomato variety. ACY is a co-dominant indel-based marker that produced clear and strong polymorphic band patterns for resistant plant distinguishing it from its susceptible counterpart. The obtained result correlates with 3:1 segregation ratio of single resistant dominant gene inheritance, which depicted ACY as gene-tag functional marker. This marker is currently in use for screening 968 hybrids varieties and one thousand breeding lines of tomato varieties stocked in Jiangsu Green Port Modern Agriculture Development Company (Green Port). So far, ACY has been used to identify 56 hybrids and 51 breeding lines. These newly detected breeding lines were regarded as potential source of resistance for tomato breeding. This work exploited the sequence of Ty-3 and subsequently contributed to the development of molecular marker ACY to aid phenotypic selection. We thus recommend this marker to breeders, which is suitable for marker-assisted selection in tomato. [ABSTRACT FROM AUTHOR]

Background: Cerebral cavernous malformations (CCMs) are common vascular malformations that predominantly arise in the central nervous system and are mainly characterized by enlarged vascular cavities without intervening brain parenchyma. Familial CCMs (FCCMs) is inherited in an autosomal dominant pattern with incomplete penetrance and variable symptoms. Methods: Mutations of three pathogenic genes, CCM1, CCM2, and CCM3, were investigated by direct DNA sequencing in a Chinese family with multiple CCM lesions. Results: Four heterozygous variants in the CCM2 gene, including one deletion (c.95delC), a missense mutation (c.358G>A, p.V120I), one silent mutation (c.915G>A, p.T305T), and a substitution (c. *1452 T>C), were identified in the subjects with multiple CCM lesions, but not in a healthy sibling. Among these variants, the c.95delC deletion is a novel mutation which is expected to cause a premature termination codon. It is predicted to produce a truncated CCM2 protein lacking the PTB and C-terminal domains, thus disrupting the molecular functions of CCM2. Conclusions: The novel truncating mutation in the CCM2 gene, c.95delC, may be responsible for multiple CCM lesions in a part of FCCM. In addition, it may represent a potential genetic biomarker for early diagnosis of FCCM. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the allelic frequency of 4 short terminal repeats (STRs) in Han and She populations from eastern China. Methods: DNA samples from Han (N = 110) and She (N = 110) healthy subjects were amplified using PCR and primers specific for the STRs. D21S11 and D21S1446 (chromosome 21) and D18S865 and D18S535 (chromosome 18). The frequency and homozygocity of different STRs were evaluated. Results: For both populations, D21S11 and D18S535 were more polymorphic than D21S1446 and D18S865, and the D21S1446 1 allele was very common (48.6% and 55.0% for the Han and She groups, respectively).The Han and She groups significantly differed from one another in respect to the distribution of D21S11, D18S865, and D18S535 allelic frequency (all P -values ≤ 0.48) but had a similar allelic distribution for D21S1446 ( P = 0.106). D21S1446 was found to be homozygous about 50% of the time which was significantly greater compared to the other STRs analyzed. Conclusion: This study found that the Han and She differ genetically at 3 autosomal STRs located on chromosome 18 and 21. The STR D21S1146 was often homozygous within these groups, indicating it would be poor marker for analyzing trisomy within these populations. [ABSTRACT FROM AUTHOR]