Aim: In forensic science, the authentication of biological samples is critical for accurate analysis and evidence validation. To evaluate the authenticity and genetic stability of 91 long-term preserved human cell line samples under cryogenic conditions over 34 years, and to explore the applicability of forensic-grade short tandem repeat (STR) profiling for long-term cell line authentication.
Methods: We conducted STR-based authentication using 23 forensic STR markers. STR profiles were analyzed using the Tanabe and Masters algorithms for authentication. The study also examined the effects of prolonged passaging and genetic modification on STR stability, and investigated potential contamination events by comparing profiles with public databases.
Results: All uniquely labeled human cell lines were successfully revived and yielded complete STR profiles, confirming the efficacy of long-term cryopreservation. One male cell line showed the Y-indel in the absence of a
Conclusion: This study represented one of the most extensive single-laboratory investigations into cell line preservation using forensic-grade tools, providing new reference alleles and valuable insights into cell line authentication. The findings supported the application of forensic STR kits beyond traditional forensic samples, offering a new perspective on their utility in genetic research and laboratory management.
Aim: Multi-InDel marker, which exhibits greater genetic diversity than a single InDel locus, hold significant potential for forensic applications. To enhance the detection rate in degraded DNA samples, our laboratory developed a novel Multi-InDel panel comprising 41 Multi-InDel markers. This study aims to verify the forensic efficacy of this Multi-InDel panel in two Chinese minority groups.
Methods: In this study, we assessed the forensic performance of this Multi-InDel panel by genotyping 92 Yunnan Yi (YNY) and 173 Qinghai Tibetan (QHT) individuals, both belonging to Chinese ethnic minorities. We also explored the genetic relationships between these two groups and 28 global reference populations.
Results: The results showed that 40 of the Multi-InDel markers (excluding MI38) exhibited high polymorphism in the YNY and QHT groups, with cumulative probabilities of matching of 2.28 × 10-26 (YNY) and 5.64 × 10-26 (QHT), and cumulative probabilities of exclusion of 0.9999995429 (YNY) and 0.9999984549 (QHT), respectively. Full sibling identification accuracies in the YNY and QHT groups, along with seven East Asian reference populations, averaged 98.89%, 96.48%, 90.47%, 78.82%, and 61.83% at likelihood ratio (LR) thresholds of 1, 10, 100, 1,000, and 10,000, respectively. Genetic analyses revealed close affinities between the studied groups and other East Asian populations. Additionally, the Multi-InDel panel effectively distinguished African, East Asian, and European populations.
Conclusion: The Multi-InDel panel demonstrated strong performance in various forensic applications, including individual identification, paternity testing, and full sibling identification in the YNY and QHT groups. Moreover, these two groups exhibited closer genetic relationships with East Asian populations than with other global populations.
Aim: There is no definitive evidence to establish a causal relationship between elevated serum alkaline phosphatase (ALP) levels and sepsis susceptibility. This study employed observational and Mendelian randomization (MR) studies to investigate their potential correlation.
Methods: This observational study used data from the eICU Collaborative Research Database (eICU-CRD) and included adult patients who were admitted to the ICU for a single episode, with an ICU stay of ≥ 24 h, and serum ALP records obtained within 24 hours of admission. Based on three quantiles of ALP, participants were divided into three groups (Units/L): ALP ≤ 59, 60 ≤ ALP ≤ 86, and ALP ≥ 87. Multivariate logistic regression (MLR) explored the association between serum ALP levels and sepsis susceptibility in the general population and subgroups categorized by sex, age, blood lactate, and APACHE IV scores. Meanwhile, this study utilized genome-wide association studies (GWAS) data of serum ALP levels (Neale lab, n = 13,586,006) and sepsis (UK Biobank, n = 12,243,539) to conduct MR analysis to validate their causal relationship by the inverse variance weighted (IVW) method.
Results: The observational study comprised 4,458 patients. The sepsis susceptibility of the three groups was 11.1%, 12.5%, and 17.4%, respectively. MLR analysis revealed that sepsis susceptibility of the ALP ≥ 87 group was 1.748 times higher than the ALP ≤ 59 group (OR = 1.748, 95%CI: 1.399-2.183). There was a consistent correlation between them in sex, age, blood lactate, and the APACHE IV scores subgroup. MR study demonstrated a causal association between them (OR = 1.005, 95%CI: 1.002-1.008).
Conclusions: Elevated serum ALP levels are significantly associated with sepsis susceptibility, and there is a causal relationship between them.
This review critically examines the question posed by Brault JF, Simon J, and Conway SJ in Journal of Translational Genetics and Genomics earlier this year: “What can ATP content tell us about Barth syndrome muscle phenotypes?”. It also offers an alternative perspective on the topic. Our answer is straightforward but warrants a detailed explanation. In the early stages of Barth syndrome, measuring adenosine triphosphate (ATP) content alone is insufficient to accurately characterize the bioenergetic profile of cells or tissues. Nevertheless, such measurements continue to attract interest - even from researchers equipped with advanced techniques - including adenosine diphosphate (ADP) and ATP assays, adenosine monophosphate (AMP) quantification, and assessments of nicotinamide adenine dinucleotide phosphate (NADPH) and nicotinamide Adenine dinucleotide (NADH) [i.e., nicotinamide adenine dinucleotide phosphate oxidized (NADP+) or nicotinamide adenine dinucleotide oxidized (NAD+)]. Assessing the rate of ATP production is a more informative and complementary approach, offering greater insight than ATP measurements alone. However, adopting a bioenergetic framework for studying Barth syndrome remains challenging. This difficulty arises largely from the profound structural and functional changes occurring within the mitochondrial compartment, which affect not only transmembrane ion transport but also the import and maturation of cytoplasmic precursors of mitochondrial proteins. Future research on Barth syndrome (BTHS) is expected to shift focus toward the central role of immature cardiolipin and monolysocardiolipin in mitochondrial membranes and their complex interactions, rather than concentrating solely on disruptions in cellular bioenergetics.
Aim: This study aimed to elucidate the population genetic structure of seven ethnic groups in Guizhou Province, China - namely the Bouyei, Dong, Gelao, Miao, Han, Tujia, and Yi - by employing microhaplotypes as highly informative genetic markers.
Methods: Thirty-three microhaplotype loci were genotyped using multiplex PCR amplification combined with next-generation sequencing. Based on the genotype data, a phylogenetic tree was constructed, and multidimensional scaling, principal component analysis, and population structure analysis were performed to comprehensively assess genetic diversity, population differentiation, and interpopulation relationships.
Results: The analyses revealed a high degree of genetic affinity and frequent gene flow among the Guizhou populations. However, the Miao group exhibited relatively greater genetic differentiation compared with the other groups (pairwise Fst values ranging from 0.0023 to 0.0054), although the extent of this differentiation was modest.
Conclusion: This study provides new insights into the complex population genetic architecture of ethnic minorities in Guizhou and further contributes to the regional microhaplotype genetic database.
Aim: Genetic factors play a critical role in the development and progression of type 2 diabetes (T2DM) and diabetic kidney disease (DKD). Recent studies have reported associations between single nucleotide polymorphisms (SNPs) in the farnesoid X receptor (FXR) gene and the risk of T2DM and DKD. Dyslipidemia is increasingly recognized as a risk factor for DKD in patients with T2DM. This study aimed to investigate the potential genetic contribution of FXR gene SNPs rs11110390 and rs4764980 to susceptibility to T2DM and DKD in a Chinese population.
Methods: This cross-sectional study included 168 patients with dyslipidemia and diabetes, comprising 90 T2DM patients and 78 DKD patients, along with 159 healthy controls. Genotyping of FXR SNPs rs11110390 and rs4764980 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Associations between FXR polymorphisms and disease risk were evaluated using odds ratios (ORs) and 95% confidence intervals (CIs).
Results: Regression analysis revealed that neither the genotypes nor the alleles of FXR rs11110390 and rs4764980 were significantly associated with T2DM risk. In contrast, the rs4764980 GA genotype was significantly associated with an increased risk of DKD (OR = 2.985; 95%CI = 1.412-6.312; P = 0.004).
Conclusion: The FXR rs4764980 GA genotype may confer increased susceptibility to DKD in the Chinese population. However, no significant associations were observed between rs11110390 or rs4764980 and T2DM risk or overall DKD risk.
Aim: Recent advances in brain-imaging techniques have enabled the identification of brain imaging-derived phenotypes (IDPs), representing physiological brain structure. Observational studies have suggested a correlation between these IDPs and stroke, which is confounded and based on limited samples. To investigate the causal relationship between IDPs and stroke and its subtypes for an in-depth mechanistic comprehension of their interplay, we conducted a bidirectional two-sample Mendelian Randomization (MR) study leveraging the
Methods: We utilized GWAS summary statistics from the BIG40 dataset, which included nearly 3,935 IDPs among 33,224 individuals, and GIGASTROKE, which included three etiological ischemia subtypes, as well as cerebral ischemia, intracerebral hemorrhage stroke, and overall stroke among 73,652 stroke cases and 1,234,808 controls.
Results: In the forward MR analysis, we identified eight significant IDPs influencing the risk of stroke and its subtypes after Bonferroni correction. Notably, the volume of the lateral posterior thalamus in the right hemisphere exhibited a significant negative association with all ischemic stroke (OR = 0.79; 95%CI: 0.74 to 0.84; P = 1.21e-13), all stroke (OR = 0.84; 95%CI: 0.79 to 0.89; P = 2.45e-9), and large vessel stroke (OR = 0.54; 95%CI: 0.43 to 0.69; P = 3.01e-7). Conversely, no significant causal association was observed in the reverse MR analysis.
Conclusion: This study enhances our understanding of causality between IDPs and stroke by pinpointing specific causal associations. These findings provide valuable insights into the etiology of stroke, offering potential strategies for predicting and intervening in stroke risk at the level of brain imaging.