No abstract

Ser326Cys polymorphism in the hOGG1 gene, which is involved in the repair of 8‐hydroxyguanine in oxidatively damaged DNA, has been identified and the variant genotype appears to be related to susceptibility to certain cancers. We investigated the association between Ser326Cys polymorphism and squamous‐cell carcinoma of the esophagus among a Chinese population. hOGG1 gene polymorphism was detected by PCR‐based single‐strand conformation polymorphism and DNA sequencing among 201 normal controls and 196 patients with esophageal cancer from Linxian, China, a high‐risk area for the disease. The association between this genetic polymorphism and risk of the cancer was examined by a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 33.8%; Ser/Cys, 52.8%; and Cys/Cys, 13.4%) was significantly different from that among esophageal cancer cases (39.8%, 38.8% and 21.4%, respectively) (p < 0.05). Homozygosity for the Cys/Cys genotype significantly increased the risk of developing esophageal squamous‐cell carcinoma, with the odds ratio (OR) adjusted for age, sex and smoking being 1.9 (95% confidence interval [CI] = 1.3–2.6). Although smoking alone also significantly increased esophageal cancer risk in this case‐control study (adjusted OR = 2.6; 95% CI = 1.7–3.9), no significant interaction between smoking and the Cys/Cys genotype was observed in terms of risk. Our results suggest that the hOGG1 326Cys allele might play a role in the carcinogenesis of the esophagus. © 2001 Wiley‐Liss, Inc.

CRISPR/Cas9-based gene knockout in animal cells, particularly in teleosts, has proven to be very efficient with regards to mutation rates, but the precise insertion of exogenous DNA or gene knock-in via the homology-directed repair (HDR) pathway has seldom been achieved outside of the model organisms. Here, we succeeded in integrating with high efficiency an exogenous alligator cathelicidin gene into a targeted non-coding region of channel catfish (Ictalurus punctatus) chromosome 1 using two different donor templates (synthesized linear dsDNA and cloned plasmid DNA constructs). We also tested two different promoters for driving the gene, zebrafish ubiquitin promoter and common carp β-actin promoter, harboring a 250-bp homologous region flanking both sides of the genomic target locus. Integration rates were found higher in dead fry than in live fingerlings, indicating either off-target effects or pleiotropic effects. Furthermore, low levels of mosaicism were detected in the tissues of P1 individuals harboring the transgene, and high transgene expression was observed in the blood of some P1 fish. This can be an indication of the localization of cathelicidin in neutrophils and macrophage granules as also observed in most antimicrobial peptides. This study marks the first use of CRISPR/Cas9 HDR for gene integration in channel catfish and may contribute to the generation of a more efficient system for precise gene integration in catfish and other aquaculture species, and the development of gene-edited, disease-resistant fish.

No abstract

No abstract