Meta Gene最新文献

Developmental and epileptic encephalopathy-38 (DEE38) is an inherited neurodegenerative disorder described by the onset of various type of seizures usually between around 4 and 7 months of age. Mutations in the ARV1 gene have recently been described in association with DEE38. Extracted genomic DNA from blood sample was used to perform whole exome sequencing in an affected member of an Iranian family with Developmental and Epileptic Encephalopathy type 38. The mutational screening revealed a novel homozygote ARV1 gene mutation c.593_594delTT (p.Ile198MetfsTer4) in the proband. We identified a novel homozygous deletion in the ARV1 that associates with the Developmental and epileptic encephalopathy-38.

Objectives

To determine whether the SNPs rs11868035, rs823144 and rs3851179 associate with PD susceptibility significantly.

Methods

A meta-analysis on the effect size of rs11868035, rs823144, rs3851179 on PD risk was conducted. The pooled ORs and 95% CIs with dominant, recessive, and allele models were calculated to examine the association effects.

Results

The meta-analysis involves 7786 patients with 33,581 controls, 1480 patients with 1453 controls, and 1160 patients with 1856 controls for the three SNPs respectively. The overall ORs (95% CI) in allele model for the three SNPs are 1.0073 (0.7170, 1.4152), 1.2957 (1.1539, 1.4549) and 1.0839 (0.8147, 1.4421), respectively. The major allele in rs11868035 polymorphism among Chinese and Western population is completely opposite (G for Western and A for Chinese).

Conclusions

Meta-analysis supports a significant association between RAB7L1 rs823144 and PD risk but indicates no significant association of SREBF1 rs11868035 or PICALM rs3851179 with PD susceptibility.

Background

An important condition for the management of diabetes mellitus is thorough understandings of its pathogenesis and risk factors, of which genetic factors play essential roles. Several variants of the FTO gene were reported as an obesity susceptibility factor. There have been a number of studies conducted in different Asian populations on various variants of the FTO gene with inconsistent results on the association with type 2 diabetes (T2D). The purpose of this study is to undertake a systematic review and meta-analysis to provide updated and comprehensive evidence regarding the associations between FTO gene polymorphisms and T2D risk in the Asian ethnic communities.

Methods

A systematic literature research of PubMed database and Cochrane Library was performed to identify eligible studies for pooled analyses. For each genetic polymorphism, odds ratios and their 95% confidence intervals were estimated under allelic model for each individual study. Pooled odds ratios were estimated using a random-effects model or a fixed-effect model depending on the heterogeneity among studies. Further, subgroup analyses by geographic region was also performed.

Results

Totally 40 studies with 81,727 subjects were included for analyses. The pooled analyses showed that four SNPs of the FTO gene (rs9939609, rs8050136, rs3751812 and rs7193144) were significantly associated with susceptibility to T2D in Asian populations, of which, the rs3751812 and rs7193144 were reported for the first time in a meta-analysis. The evidence strength varied among different geographic regions.

Conclusions

The results supported that certain variants of the FTO gene could be used to identify individuals at high risk of developing T2D in Asians populations.

Tetrasomy 18p is an extremely rare disorder with estimated incidence 1:140,000-180,000. The most common clinical presentations include developmental delay, intellectual disability, and several dysmorphic features such as the triangular face, low-set ears, depressed nasal bridge or smooth philtrum. The disease's hallmark is a small supernumerary isochromosome 18p consisting of two copies of the same arm of chromosome 18. Males and females are affected equally. Here, we present the case of 20 months old girl with tetrasomy 18p, the only affected child out of the dizygotic twins born to healthy parents. Routine cytogenetic testing revealed the presence of the marker chromosome in the girl's sample. Combination of Multicolor Banding fluorescent in situ hybridization and array-based Comparative Genomic Hybridization confirmed the isochromosome 18p in this girl. Quantitative Fluorescence PCR determined the maternal origin of the isochromosome 18p. The presented case of tetrasomy18p in one of the non-identical twins supports the hypothesis that tetrasomy 18p arises de novo and are of maternal origin. We conclude that the formation of isochromosome 18p is a random event that can occur in pregnancies of cytogenetically normal parents and maternal age is probably the main risk factor in etiology of the tetrasomy 18p.

A common mutation has occurred in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), known as D614G (A23403G). There are discrepancies in the impact of this mutation on the virus's infectivity. Also, the whole genome sequencings are expensive and time-consuming. This study aims to develop three fast economical assays for prompt identifications of the D614G mutation including Taqman probe-based real-time reverse transcriptase polymerase chain reaction (rRT PCR), an amplification refractory mutation system (ARMS) RT and restriction fragment length polymorphism (RFLP), in nasopharyngeal swab samples. Both rRT and ARMS data showed G614 mutants indicated by the presence of HEX probe and 176 bp, respectively. Additionally, the results of the RFLP data and DNA sequencings confirmed the prevalence of the G614 mutants. These methods will be important, in epidemiological, reinfections and zoonotic aspects, through detecting the G614 mutant in retro-perspective samples to track its origins and future re-emergence of D614 wild type.

Background

The etiologic factors of polycystic ovary syndrome (PCOS) are not well understood, however, several studies reported that genetics and environmental factors might be involved in the appearance of PCOS. Therefore understanding some molecular pathways can provide more information about PCOS. The imbalance of pro-inflammatory and anti-inflammatory cytokines could be associated with its pathophysiology. There are huge numbers of polymorphisms within cytokine genes that may affect their production and bring in the women more susceptible for PCOS. The aim of the present study was for evaluation the correlation of single nucleotide polymorphism (−308 G/A) in tumor necrosis factor-alpha (TNF-α) gene and (−1082 A/G) in interleukin-10 (IL-10) gene with PCOS.

Methods

Patients group included 80 women who had a history of PCOS diagnosed using transvaginal or transabdominal ultrasound and don't have any of the inherited disorders such as androgen-secreting neoplasms, congenital adrenal hyperplasia, thyroid dysfunction, and hyperprolactinemia with a mean age (27.23 year). The control group included 70 women with a mean age (26.89 year). Levels of serum IL-10 and TNF-α in woman with PCOS and healthy control have been measured by Enzyme linked immunosorbent assay (ELISA). Single nucleotide polymorphism (SNP) in TNF-α (−308 G/A) and IL-10 (−1082 A/G) genes and the frequency of mutations in patient and control group were evaluated using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).

Results

Showed that serum IL-10 concentration was significantly decreased (p < 0.01) while TNF-α level was significantly increased (p < 0.01) in patients compared to control group. While the genotype prevalence of TNF-α (−308 G/A) and IL-10 (−1082 A/G) and the allele frequency show non-significant difference (p > 0.05) between women with PCOS and healthy controls.

Conclusion

It is concluded that the level of TNF–α and IL-10 could be considered as possible biomarkers for PCOS while polymorphisms in IL-10 gene and TNF-α gene are not considered as risk factors of PCOS in Iraqi women, this suggests that further studies on other loci or other cytokines are required.

Chronic kidney disease (CKD) is a worldwide public health problem that affects a huge number of individuals and documented as a global public health problem. This study was conducted to uncover the association of gene polymorphism of Glutathione S -transferase M1 (GSTM1, rs366631), Glutathione S -transferase T1 (GSTT1, rs17856199), Angiotensin converting enzyme- Insertion/Deletion (ACE-I/D, rs4646994), and Cytochrome P450 Family 11 Subfamily B Member 2 − 344 T/C (CYP11B2 − 344 T/C, rs1799998) with the risk of development of CKD in Bangladeshi population. Blood samples were drawn from 355 participants (175 CKD patients and 180 healthy controls) by an expert phlebotomist. Different techniques like allele-specific multiplex PCR (Polymerase chain reaction), allele-specific PCR, and PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) were used for the genetic polymorphism analysis. Significant associations were evident for GSTT1 null genotype (OR = 2.45; 95% CI = 1.56–3.82; p < 0.001), combined GSTM1-GSTT1 null genotype (OR = 4.16; 95% CI = 1.99–8.64; p < 0.001) and homozygous mutant variant (DD) of ACE- I/D gene (OR = 4.60; 95% CI = 1.77–12.00; p < 0.01). Homozygous mutant variant (DD) of ACE- I/D polymorphism was found to be more prevalent in the male CKD subjects. It is apparent from our findings that the null genotype of GSTT1, combined GSTM1-GSTT1 null genotype, and homozygous mutant variant (DD) of ACE- I/D could be associated with CKD susceptibility.

Language impairment (LI) is highly heritable and aggregates in families. Genetic investigation of LI has revealed many chromosomal regions and genes of interest, though very few studies have focused on rare variant analysis in non-English speaking or non-European samples. We selected four candidate genes (TM4SF20, NFXL1, CNTNAP2 and ATP2C2) strongly suggested for specific language impairment (SLI), a subtype of LI, and investigated rare protein coding variants through Sanger sequencing of probands with LI ascertained from Pakistan. The probands and their family members completed a speech and language family history questionnaire and a vocabulary measure, the Peabody Picture Vocabulary Test-fourth edition (PPVT-4), translated to Urdu, the national language of Pakistan. Our study aimed to determine the significance of rare variants in these SLI candidate genes through segregation analysis in a novel population with a high rate of consanguinity. In total, we identified 16 rare variants (according to the rare MAF in the global population in gnomAD v2.1.1 database exomes), including eight variants with a MAF <0.5% in the South Asian population. Most of the identified rare variants aggregated in proband's families, one rare variant (c.*9 T > C in CNTNAP2) co-segregated in a small family (PKSLI-64) and another (c.2465C > T in ATP2C2) co-segregated in the proband branch (PKSLI-27). The lack of complete co-segregation of most of the identified rare variants indicates that while these genes could be involved in the overall risk for LI, other genes are likely involved in LI in this population. Future investigation of these consanguineous families has the potential to expand our understanding of gene function related to language acquisition and impairment.

Phylogenicity of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 surface glycoproteins reported from Europe to the National Center for Biotechnology Information (NCBI) virus database by the mid of April 2021 is analyzed. Novel function for computing phylogenetic distance is proposed for that purpose. Proposed distance function resulted in better-fitted clusters than Jaccard and Sorensen-Dice and accurate evolutionary links were predicted for B.1.1.7 spike variants. Most B.1.1.7 spike variants were linked to their likely direct predecessors at single amino acid change, that in many cases resulted in loss of the key mutations that are associated to the higher B.1.1.7 SARS-CoV-2 infectivity. There were also cases where second mutation was introduced to compensate for the missing mutation. Unreported V90T SARS-CoV-2 surface glycoprotein mutation was also identified, that contributes towards escaping 2–51 neutralizing antibody.