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The walleye pollock, Gadus chalcogrammus (Pallas, 1814), is one of the most commercially and ecologically valuable species in the Northwestern Pacific. However, combined pressures of overfishing and environmental changes have led to a substantial decline in its production in Japan and Russia since the 1990s, and a collapse in Korea since the 2000s. The objective of this study was to comprehensively examine its genetic diversity and population structure with an extensive sampling effort of 16 populations across the Northwestern Pacific including South Korea, Japan, and Russia. A multiplex PCR assay composed of seven microsatellite markers revealed a moderate level of observed heterozygosity (Ho = 0.369–0.599), which is lower than that reported in previous studies of this species. All loci were highly polymorphic, with the mean PIC ranging from 0.608 to 0.793. The structure of the 16 populations was characterized by heterozygote deficiency, a modest effective allele number (Ne = 4.551–7.969), low genetic differentiation (FST = 0.000–0.054), a weak population structure, a genetic admixture, and no significant correlation between the genetic and geographic distance. These characteristics are typical of pelagic marine species with large population sizes due to a consistent gene flow among populations when there are no physical boundaries in the open ocean. The seasonal and country-specific genetic structure indicated that G. chalcogrammus populations in the Northwestern Pacific region should be managed as a single management unit. The findings from this study provide critical information for future genetic monitoring, conservation management, and the development of strategies aimed at restoring the populations of this species. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is an inherited disorder that causes progressive loss of vision. This study aimed to describe the possible causative variants of the USH2A gene in Korean RP families and their associated phenotypes. We recruited 94 RP families (220 subjects, including 94 probands and 126 family members) in a Korean cohort, and analyzed USH2A gene variants through whole-exome sequencing. The pathogenicity of the variants was classified according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. We found 14 USH2A disease-causing variants, including 5 novel variants. Disease causing variants were identified in 10 probands with RP, accounting for 10.6% (10/94) of the Korean RPs in the cohort. To visually represent the structural changes induced by novel variants, we modeled the three-dimensional structures of the wild-type and mutant proteins. This study expands the spectrum of USH2A variants and provides information for future therapeutic strategies for RP. [ABSTRACT FROM AUTHOR]

Background and Aims: Elevated serum ferritin is associated with incident Type 2 diabetes (T2D), but the interactions between serum ferritin and genetic factors which may improve understanding underlying mechanism in the development of T2D are still unclear. We determined the gene-ferritin interactions on the development of T2D by genome-wide gene-ferritin interaction analyses.Methods and Results: A total of 3405 participants from two prospective cohorts of community living residents were included, and the median follow-time was 3.99 years. Genome-wide gene-ferritin interactions were analyzed using the joint test with two degrees of freedom and the interaction test with one degree of freedom. There were 18 SNPs selected in the joint test. Finally, four independent variants [rs355140 (LINC00312), rs4075576 (nearby PDGFA), rs1332202 (PTPRD), and rs713157 (nearby LINC00900)] with low pairwise linkage disequilibrium (r2<0.2) and located at least 1000 kb from the index SNP showed interactions with serum ferritin level. In the association analyses between serum ferritin levels (tertiles of ferritin and ferritin status) and the incidence of T2D according to genotype, the Incidence Rate Ratios (IRRs) in the highest tertile of ferritin level (vs. the lowest tertile) were greater for participants with heterozygotes of risk alleles of each of the four SNP than IRRs for those with wild type. Compared with the normal group, the elevated ferritin group also had a higher risk of T2D for all genetic variants of risk alleles, particularly its homozygotes.Conclusion: Serum ferritin level interacts with genetic variants (rs355140, rs4075576, rs1332202, and rs713157) in the development of T2D. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is one of the most complex diseases and is characterized by neuropathological features, including accumulation of beta‐amyloid plaques and tau neurofibrillary tangles. These neuropathological features exhibit heterogeneity across brain regions in different patients, leading to different symptoms. Dysregulation of alternative splicing (AS) has been observed to contribute to neuropathological features in AD; however, their molecular mechanisms via AS remain unclear. Therefore, we aimed to systemically investigate the impact of AS (i.e., exon skipping) on AD‐related neuropathological features (i.e., Braak stage and plaque density) and the functional connections of alternately spliced genes across multiple brain regions in AD patients. Method: We analyzed RNA‐seq data generated by the MSBB project representing two brain regions: the frontal region (frontal pole; FP, n = 175, inferior frontal gyrus; IF, n = 87) and the temporal (parahippocampal gyrus; PH, n = 93 and superior temporal gyrus; ST, n = 101). The data were mapped to the hg19 reference genome with the STAR aligner and exon skipping rates were estimated as percent spliced in (PSI) by rMATs. Then, we performed a linear regression to evaluate clinical or pathogenic associations between exon PSI levels and the Braak stage and plaque density mean for each brain region, considering sex as a covariate. Result: We identified 192 and 158 exon skipping (ES) associated with Braak stages in the frontal and temporal regions, respectively. In addition, 863 and 845 events were associated with plaque density. Notably, while the two regions shared only 20% (60 events) of Braak‐associated ES, they coincided in 90% (808 events) of plaque‐associated ES. Enrichment analysis of functional annotations found that frontal‐specific ES associated with Braak stage was enriched in interleukin signaling and the neurodegenerative‐related CDK5 pathway, while temporal‐specific ES was enriched in lipoprotein clearance functional pathways. For plaque density‐associated ES shared between regions, the most significantly enriched pathway was Notch4 signaling, represented for example by SOD2, in which skipping of the functional domain‐encoding exon 4 was associated with plaque mean in both regions. Conclusion: This study provides a landscape of brain region‐dependent AS events and of AD risk genes that contribute to neuropathological features in AD patients. [ABSTRACT FROM AUTHOR]