Allele Frequencies Research Articles

Association of histidine-rich glycoprotein C633T single nucleotide polymorphism and recurrent miscarriage in Iranian women.

Recurrent miscarriage (RM) is defined as the occurrence of at least two or three subsequent miscarriages within the 20th -24th weeks of pregnancy. The primary objective of this study was to investigate whether histidine-rich glycoprotein C633T single nucleotide polymorphism (HRG C633T SNP) statistically correlates with the occurrence of RM among Iranian women. Blood samples from 200 women were taken at the outset of the study. Then, the blood samples of 100 women who had a record of RM (case group) were compared with the other 100 women's blood samples who had no record of RM (control group). Following DNA extraction, the polymorphism of histidine-rich glycoprotein C633T (HRG C633T) for every case was specified and all women were genotyped by the amplification-refractory mutation system (ARMS) method. The results of the study revealed that there was a statistically significant difference between T/T genotype (OR = 3.5, CI (1.39-8.77), p = 0.007), and C/T genotype (OR = 1.83, CI (0.99-3.37), p = 0.05) in the case and control groups. Also, a statistically significant association was observed in T allelic frequency in the RM participants compared to the control group (OR = 2.01, CI (1.31-3.09), p = 0.01). The present study determined that there was a statistically significant relationship between HRG C633T SNP and increased RM regarding allelic and genotypical aspects. Moreover, it became apparent that women with homozygous T/T genotype were more susceptible to the risk of RM.

Genome-wide association study on meningioma risk in Japan: a multicenter prospective study.

Although meningiomas are the most common primary intracranial tumors, their genetic etiologies have not been fully elucidated. To date, only two genome-wide association studies (GWASs) have focused on European ancestries, despite ethnic differences in the incidence of meningiomas. The aim of this study was to conduct the first GWAS of Japanese patients with meningiomas to identify the SNPs associated with meningioma susceptibility. In this multicenter prospective case-control study, we studied 401 Japanese patients with meningioma admitted in five institutions in Japan, and 50,876 control participants of Japanese ancestry enrolled in Biobank Japan. The quality control process yielded 536,319 variants and imputation resulted in 8,224,735 variants on the autosomes and 224,820 variants on the X chromosomes. This GWAS eventually revealed no genetic variants with genome-wide significance (P < 5 × 10 - 8) and observed no significant association in the previously reported risk variants rs11012732 and rs2686876 due to low minor allele frequency in the Japanese population. This is the first GWAS of meningiomas in East Asian populations and is expected to contribute to the development of GWAS research for meningiomas.

Resistance of Lepidopteran Pests to Bacillus thuringiensis Toxins: Evidence of Field and Laboratory Evolved Resistance and Cross-Resistance, Mode of Resistance Inheritance, Fitness Costs, Mechanisms Involved and Management Options.

Bacillus thuringiensis (Bt) toxins are potential alternatives to synthetic insecticides for the control of lepidopteran pests. However, the evolution of resistance in some insect pest populations is a threat and can reduce the effectiveness of Bt toxins. In this review, we summarize the results of 161 studies from 20 countries reporting field and laboratory-evolved resistance, cross-resistance, and inheritance, mechanisms, and fitness costs of resistance to different Bt toxins. The studies refer mainly to insects from the United States of America (70), followed by China (31), Brazil (19), India (12), Malaysia (9), Spain (3), and Australia (3). The majority of the studies revealed that most of the pest populations showed susceptibility and a lack of cross-resistance to Bt toxins. Factors that delay resistance include recessive inheritance of resistance, the low initial frequency of resistant alleles, increased fitness costs, abundant refuges of non-Bt, and pyramided Bt crops. The results of field and laboratory resistance, cross-resistance, and inheritance, mechanisms, and fitness cost of resistance are advantageous for predicting the threat of future resistance and making effective strategies to sustain the effectiveness of Bt crops.

HINT1 Gene Polymorphisms, Smoking Behaviour, and Personality Traits: A Haplotype Case-Control Study.

The factors influencing the development and maintenance of nicotine dependence are numerous and complex. Recent studies indicate that smokers exhibit distinct genetic predispositions to nicotine dependence. We aimed to analyse (1) the association between rs2551038 and cigarette smoking, (2) the association of between the rs3864236-rs2526303-rs2551038 haplotype and cigarette smoking, and (3) the personality traits measured by the NEO Five-Factor Inventory in cigarette users and never-smokers. No significant differences were present in the frequency of rs2551038 genotypes and alleles in the studied cigarette users compared to the control group. Cigarette users, compared to the control group, had higher scores on the NEO-FFI Extraversion scale (p = 0.0011), and lower scores were obtained by the cigarette users for the NEO-FFI Openness (p = 0.0060), Agreeability (p ≤ 0.000), and Conscientiousness (p ≤ 0.000) scales. There was a significant positive Pearson's linear correlation between the age and the Fagestrom test (r = 0.346; p < 0.0001) and the NEO-FFI Openness scale (r = 0.180; p < 0.0001) in the group of cigarette users. We observed significant linkage disequilibrium between rs2526303 and rs3864236 (D' = 0.3581; p < 2.2204 × 10-16) and between rs2526303 and rs2551038 (D' = 0.9993; p < 2.2204 × 10-16) in the tested sample. The sex-stratified haplotype analysis revealed that in the group of male never-smokers, the GTC haplotype was significantly more frequent than in the group of cigarette users (38% vs. 22%; p = 0.0039). The presented study reveals significant differences in personality trait scores between cases and controls. Moreover, the sex-stratified analysis showed significant differences in haplotype distribution. These results underscore the interplay between genetic predisposition, sex, and personality in nicotine-using individuals.

Monitoring of the nAChRsα6 G275A spinetoram resistance allele in Drosophila melanogaster populations from New York vineyards.

Spinosyns are a group of naturally occurring and semi-synthetic insecticides with widespread utility in agriculture, including organic production systems. One example is spinetoram (Delegate), which is the only registered insecticide in New York State (for control of Drosophila melanogaster in vineyards) to which vinegar flies have not yet evolved high levels of resistance. However, low levels of resistance have been found in vineyard populations of D. melanogaster, and a highly resistant strain was obtained after only five selections (in the laboratory). We identified the nAChR α6 mutation (G275A) responsible for the resistance and developed a rapid, high-throughput assay for resistance. Surveys of collections made in 2023 show low levels of the resistance allele in four populations. A correlation was observed between vineyard use of spinetoram and frequency of the resistance allele, but not between county-wide use of spinosyns and frequency of the resistance allele. One of the sites we monitored was previously surveyed in 2019 and the frequency of the resistance allele detected in 2023 had increased. Implications of these findings to resistance management of D. melanogaster are discussed. © 2024 Society of Chemical Industry.

Allelic frequency of pathogenic α1-antitrypsin variants in the Japanese population: Results from a survey of open Japanese genetic variation databases

α1-antitrypsin deficiency (AATD) is a hereditary disorder with a global prevalence that differs across regions. AATD is highly prevalent in Europe and North America but rarely found in Asian countries, including Japan, possibly because of the founder effect of the pathogenic SERPINA1 variants PI*Z and PI*S. However, AATD remains underdiagnosed even in high-prevalence and low-prevalence regions, possibly because of lack of awareness. In this study, we surveyed open Japanese genetic variation databases to estimate AATD prevalence in Japan. We identified allelic frequencies (AFs) of 5 among the 14 major pathogenic SERPINA1 variants from three datasets, collectively derived from 63,119 Japanese participants. The mean AF was determined to be 8.56 × 10−4 (95% confidence interval [CI]: 6.43 × 10−4 to 1.12 × 10−3). Given that this represents the entire Japanese population, one AATD patient was speculated to be born per 1.37 × 106 births (95% CI: 7.97 × 105 to 2.42 × 106) in Japan. Our results support the prevailing notion that AATD is extremely rare in Japan.

Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.

Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p=0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p=0.015) in the univariate analysis and 0.315 (p=0.023) in the multivariate analysis. In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. UMIN Clinical Trials Registry with the number UMIN000043798.

Liquid biopsy in brain tumors: moving on, slowly.

Due to limited access to the tumor, there is an obvious clinical potential for liquid biopsy in patients with primary brain tumors. Here, we review current approaches, present limitations to be dealt with, and new promising data that may impact the field. The value of circulating tumor cell-free DNA (ctDNA) in the cerebrospinal fluid (CSF) for the noninvasive diagnosis of primary brain tumors has been confirmed in several reports. The detection of ctDNA in the peripheral blood is desirable for patient follow-up but requires ultrasensitive methods to identify low mutant allelic frequencies. Digital PCR approaches and targeted gene panels have been used to identify recurrent hotspot mutations and copy number variations (CNVs) from CSF or plasma. Tumor classification from circulating methylomes in plasma has been actively pursued, although the need of advanced bioinformatics currently hampers clinical application. The use of focused ultrasounds to open the blood-brain barrier may represent a way to enrich of ctDNA the peripheral blood and enhance plasma-based liquid biopsy. Monitoring CNVs and hotspot mutations by liquid biopsy is a promising tool to detect minimal residual disease and strengthen response assessment in patients with primary brain tumors. Novel methods to increase the relative and/or absolute amount of ctDNA can improve the clinical potential of plasma-based liquid biopsies.

Characterization of a missense variant in COG5 in a Tunisian patient with COG5-CDG syndrome and insights into the effect of non-synonymous variants on COG5 protein.

The clinical diagnosis of patients with multisystem involvement including a pronounced neurologic damage is challenging. High-throughput sequencing methods remains crucial to provide an accurate diagnosis. In this study, we reported a Tunisian patient manifesting hypotonia and global developmental delay with visual and skin abnormalities. Exome sequencing was conducted followed by segregation analysis and, subsequently additional investigations. In silico analysis of non-synonymous variants (nsSNPs) described in COG5 in conserved positions was made. Results revealed a homozygous missense variant c.298 C > T (p.Leu100Phe) in the COG5 inherited from both parents. This variant altered both protein solubility and stability, in addition to a putative disruption of the COG5-COG7 interaction. This disruption has been confirmed using patient-derived cells in vitro in a COG5 co-immuno-precipitation, where interaction with binding partner COG7 was abrogated. Hence, we established the COG5-CDG diagnosis. Clinically, the patient shared common features with the already described cases with the report of the ichtyosis as a new manifestation. Conversely, the CADD scoring revealed 19 putatively pathogenic nsSNPs (Minor Allele Frequency MAF < 0.001, CADD > 30), 11 of which had a significant impact on the solubility and/or stability of COG5. These properties seem to be disrupted by six of the seven missense COG5-CDG variants. In conclusion, our study expands the genetic and phenotypic spectrum of COG5-CDG disease and highlight the utility of the next generation sequencing as a powerful tool in accurate diagnosis. Our results shed light on a likely molecular mechanism underlying the pathogenic effect of missense COG5 variants, which is the alteration of COG5 stability and solubility.

Clinical characteristics and HLA associations of azithromycin-induced liver injury.

Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.

Investigation of hereditary cholesterol deficiency (CD) in Holstein Cattle at the state farms in Türkiye

Türkiye is exposed to international animal and semen movements. For this reason, Türkiye is very affected by diseases and hereditary disorders. State Farms is a state organization that raises and distributes breeding cattle. This study was aimed at investigating the presence and distribution of mutant alleles causing cholesterol deficiency (CD) disorder in Holstein cattle on state farms. For this purpose, blood and sperm samples were collected from 466 Holstein cattle. The real-time PCR method was used for genotyping. A total of seven cattle were found to be heterozygous. The frequency of the mutant allele was determined to be 0.75%. The kinship of four cattle carrying the mutant allele with Mauglin Storm, the bull in which this disease was first detected, was determined. The presence of cattle carrying the mutant allele in Türkiye is quite low compared to other countries. The Apolipoprotein-B (APOB) mutant allele was found at low frequencies and detected for the first time at the State Farms in Türkiye. Therefore, it is necessary to develop control programs by screening other Holstein herds.

Distribution of Major Histocompatibility Complex Alleles in Cohorts of Patients with Different Levels of Post-­Vaccination Antibodies against Hepatitis B

Relevance. It is known that the immune response to the administration of immunobiological drugs is variable and depends on the individual characteristics of the organism. Host immunogenetic factors have a significant impact on the effectiveness of vaccination. In this study, the frequencies of alleles of the HLA class I (HLA-A, B, C) and class II genes (HLA-DRB1, DPB1, DQB1) were studied in groups of participants with different levels of antibodies (anti-HBs) after vaccination against viral hepatitis B. Aims of the work was to determine the possible relationship between alleles of HLA genes and the intensity of post-vaccination immunity against hepatitis B. Materials and methods. The study included 271 apparently healthy adults who were divided into 3 groups depending on the specific concentration of post-vaccination antibodies (anti-HBs) using ELISA. All calculations were made relative to the groups anti-HBs &gt;100 mIU/ml (n=82), 10-100 mIU/ml (n=98) (protective antibody level) and anti-HBs &lt;10 mIU/ml (n = 91). To type alleles of the HLA class I (HLA-A, B, C) and class II (HLA-DRB1, DPB1, DQB1) genes, we used a panel we developed for whole-genome next-generation sequencing (NGS). Statistical analysis was performed using Pearson's χ2 goodness-of-fit test using the FDR multiple correction method with an initial target of p &lt; 0.05. Results. When typing the six genes studied, the total number of alleles identified at least once was 189 variants that were distinct from each other. We identified 3 alleles (B*38:01:01, DQB1*06:03:01 and DRB1*13:01:01), which were significantly more common (FDR p &lt; 0.05) in the group with a protective level of anti-HBsS. Also in this group there was an increased frequency of occurrence of alleles A*26:01:01, A*32:01:01, C*12:03:01, DPB1*04:01:01 and haplotypes DQB1*06:03:01 -DRB1*13:01:01 and B*38:01:01-C*12:03:01. In the group of seronegative patients, alleles A*02:01:01, A*03:01:01, B*44:02:01, B*44:27:01, C*07:04:01, DPB1*04 were more common :01:01, DQB1*05:01:01, DRB1*01:01:01 and DRB1*16:01:01. It was shown that the identified associations were more significant in the group of individuals with a concentration of post-vaccination anti-HBs above 100 mIU/ml. Conclusion. The results obtained indicate that the HLA alleles we identified may influence the level of anti-HBsS production, and that the genetic factor may, to a greater extent, determine whether the antibody level exceeds 100 mIU/ml. defined as an anti-HBS level of 10 mIU/ ml. The development of an integrated approach to the organization of vaccine prevention, including the determination of genetic markers, will improve the quality of immunization of the population. Information about the association of HLA gene alleles can be used to develop predictive scenarios for the development of the hepatitis B epidemic process.

INDELpred: Improving the prediction and interpretation of indel pathogenicity within the clinical genome

Small insertions and deletions (InDels) are critical yet challenging genetic variations with significant clinical implications. However, the identification of pathogenic InDels from neutral variants in clinical contexts remains an understudied problem. Here, we developed INDELpred, a machine learning-based predictive model for discerning pathogenic from benign InDels. INDELpred was established based on key features, including allele frequency, InDel length, function-based features, and gene-based features. A set of comprehensive evaluation analyses demonstrated that INDELpred exhibited superior performance over competing methods in terms of computational efficiency and prediction accuracy. Importantly, INDELpred highlighted the crucial role of function-based features in identifying pathogenic InDels, with a clear interpretability of the features in understanding the disease-causing variants. We envisage INDELpred as a desirable tool for the detection of pathogenic InDels within large-scale genomic datasets, and thereby enhancing the precision of genetic diagnoses in clinical settings.

Association of the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene with preeclampsia among Chinese women

To assess the association of -c.108C>T and c.192Q>R polymorphisms of paraoxonase 1 (PON1) gene with preeclampsia (PE) and the influence of genotypes on the metabolic and oxidative stress indexes among Chinese women. This case-control study has included 334 patients with PE and 1337 healthy pregnant women. The -c.108C>T and c.192Q>R genotypes were determined by PCR and restriction fragment length polymorphism method. Metabolic and oxidative stress parameters were also analyzed. No statistical difference in the genotypic and allelic frequencies for the -c.108C>T and c.192Q>R polymorphisms of the PON1 gene was found between the PE patients and the healthy controls (P > 0.05). Nevertheless, the 192Q-108T haplotype of these polymorphisms was associated with an increased risk of PE (P = 0.007). Total antioxidant capacity (TAC) and atherosderosis index were higher in patients with the -108TT genotype compared with those with a CT genotype (P < 0.05); whilst total oxidant status was lower in patients with a CT genotype compared with those with a CC genotype (P = 0.036). Malondialdehyde level was higher in patients with a 192RR genotype compared with those with a QQ genotype (P = 0.019). TAC level was higher in patients with a RR genotype compared with those with a QR genotype (P = 0.015). The 192Q-108T haplotype of the PON1 gene is associated with the risk for PE. These polymorphisms may be associated with abnormal lipid metabolism and oxidative stress among Chinese PE patients.

High incidence and geographic distribution of cleft palate cases in Finland are associated with a regulatory variant in IRF6.

In Finland the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We performed a genome-wide association study for orofacial clefts, which include CL/P and CP, in the Finnish population. We identified rs570516915, a single nucleotide polymorphism that is highly enriched in Finns and Estonians, as being strongly associated with CP ( P = 5.25 × 10 -34 , OR = 8.65, 95% CI 6.11-12.25), but not with CL/P ( P = 7.2 × 10 -5 ), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland ( P = 8.82 × 10 -28 ) and Estonia ( P = 1.25 × 10 -5 ). The risk allele of rs570516915 disrupts a conserved binding site for the transcription factor IRF6 within a previously characterized enhancer upstream of the IRF6 gene. Through reporter assay experiments we found that the risk allele of rs570516915 diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6 , suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.

Detection of the effect of the KISS1 gene on reproductive parameters in Saanen goats

The KISS1 gene, which activates G protein-coupled receptor-54 (GPR54) and plays a crucial role in the neuroendocrine regulation of GnRH secretion, is known to encode a family of neuropeptides called kisspeptins. Therefore, the KISS1 gene is thought to be associated with sexual maturity, offspring development, and estrus. The g.2124T&gt;A polymorphism of the KISS1 gene, is believed to affect the reproductive system, has been studied in Indonesian goat breeds, Damascus, Zarabi, Baladi, Gaddi, Kaligesing, Guanzong, Xianong Saanen and Boer goat breeds until now. These studies are generally related to determining polymorphism frequencies or the effect of genotype on litter size. No studies have been found on the effect of the KISS1 gene on luteal structures, especially in Saanen goats. The study aims to determine the allele and genotype frequencies of the KISS1 gene g.2124T&gt;A SNP by the PCR-RFLP method and define the relationship between the genotypic structures and reproductive parameters such as luteal growth, maximum corpus luteum diameter, and mating rate in Saanen goats (n=30). According to the results, the genotype frequencies in Saanen goats for the KISS1 gene g.2124T&gt;A were 10.35%, 55.17%, and 34.48% for AA, TT and AT, respectively. Moreover, the genotypic structure did not have a statistically significant effect on investigated fertility characteristics. The average values of expected heterozygosity (He), observed heterozygosity (Ho), the effective number of alleles (Ne), fixation index values (FIS), and the polymorphism information content (PIC) were 0.3996, 0.3448, 1.6655, 0.8629 and 0.855, respectively. The Hardy-Weinberg chi-square (χ2) value was found to be 0.5435. In conclusion, it was found necessary to study the KISS1 - g.2124T&gt;A polymorphism in larger herds with different gene pools as a reason for the existence of genotypic variation and the narrow population size.

Association between OX40L polymorphism and type 2 diabetes mellitus in Iranians

IntroductionDiabetes mellitus (DM) is one of the leading causes of morbidity and mortality worldwide. It is a multifactorial disease that genetic and environmental factors contribute to its development. The aim of the study was to investigate the association of OX40L promoter gene polymorphisms with type 2 diabetes mellitus (T2DM) in Iranians.Materials and methodsThree hundred and sixty-eight subjects including 184 healthy subjects and 184 T2DM patients were enrolled in our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to detect genotype and allele frequencies of rs3850641, rs1234313 and rs10912580. In addition, SNPStats web tool was applied to estimate haplotype frequency and linkage disequilibrium (LD).ResultsThe distribution of tested polymorphisms was statistically different between the T2DM patients and healthy subjects (P < 0.01). rs1234313 AG (OR = 0.375, 95% CI = 0.193–0.727, P = 0.004) and rs10912580 AG (OR = 0.351, 95% CI = 0.162–0.758, P = 0.008) genotypes were associated with the decreased risk of T2DM in Iranians. Moreover, our prediction revealed that AAG (OR = 0.46, 95% CI= (0.28–0.76), P = 0.0028) and GAG (OR = 0.24, 95% CI= (0.13–0.45), P < 0.0001) haplotypes were related to the reduced risk of the disease. However, the tested polymorphisms had no effect on biochemical parameters and body mass index (BMI) in the patient group (P > 0.05).ConclusionOur findings revealed that OX40L promoter gene polymorphisms are associated with T2DM. Moreover, genotype and allelic variations were related to the decreased risk of T2DM in Iranians. Further studies are recommended to show whether these polymorphic variations could affect OX40/OX40L interaction or OX40L phenotype.

Tall women with breast cancer have poorer survival than short women.

Tall women are more likely to develop breast cancer (BC). High Mobility Group AT-Hook 1(HMGA1), an oncofetal protein, plays a role in the progression of breast cancer. Non-coding sequences proximal to HMGA1 contain variants associated with 4.83 cm taller height. In the current study, we used UK Biobank data to examine the relationship of HMGA1 to height, risk, and prognosis of women with breast cancer. Our analysis included all subjects with invasive BC that occurred either before or after participant enrollment and were recorded in the UK Biobank database using self-reported data and the International Classification of Diseases (ICD10, ICD9). We divided the subjects into three previously described three height groups: Short (< 155 cm), Medium (155 cm to 175 cm), Tall (> 175 cm). We analyzed the HMGA1 SNP rs41269028, a single nucleotide intron variant, C > T, minor allele frequency 0.044. SNP rs41269028 was previously evaluated in subjects with diabetes. Height of 9583 women with BC homozygous for the HMGA1 SNP rs41269028 major allele was 162.29 cm ± 6.18. Height of 944 women with BC who were carriers or homozygotes (CT + TT) of the minor allele T was 162.88 cm ± 6.001. This difference was significant (p = 0.005). The effect of height group on survival was significant (p = 0.032, log rank test). Tall women had the poorest survival. The effect of HMGA1 SNP rs41269028 genotype on BC risk (p = 0.602) and survival (p = 0.439, log rank test) was insignificant. We conclude that HMGA1 influences height, but we were unable to demonstrate that HMGA1 is related to increased incidence or poor prognosis of tall women with breast cancer. We did find that tall women with breast cancer have poorer survival than short women. Our finding that tall women have a worse prognosis is important because it could help the oncologist decide, along with other prognostic factors, whether adjuvant therapy is warranted.

Next-generation sequencing applied to non-syndromic tooth agenesis: A systematic literature review

BackgroundTo explore the genetic profile of Non-Syndromic Tooth Agenesis (NSTA) detected by Next-Generation Sequencing (NGS). MethodsA systematic review exploring PubMed, ScienceDirect, BMC, LILACS, Scopus, Embase and Web of Science was conducted. Studies investigating the genetic alterations involved in NSTA detected by NGS were selected. Data were extracted and risks of biases were evaluated. ResultsAfter screening 191 articles, 4 articles were included in this study. The overall qualities of the studies were considered high for 3 papers and low for the other one. Among 636 permanent missing teeth, second premolars and lateral incisors were the most affected ones. Whole exome sequencing and gene panel sequencing focusing either on exons plus exon-intron boundaries, or only exons were focused. Mutations on MSX1, PAX9, EDA, EDAR, AXIN2, WNT10A, LAMA3, DKK1, COL17A1, IRF6, LRP6, CHD7, CREBBP, EVC, LEF1, ROR2, TBX22, FGFR1 and TP63 were identified. Allelic frequencies of some variants were reported only in polish and Turkish populations and showing both slight and important variations. Moreover, Functional analysis was performed only for LRP6 variant in Turkish population. The published in-silico analyses of the proteins corresponding to the mutated LAMA3, MSX1 and WNT10 genes revealed a truncated protein for MSX1 and disulfide bridges destabilization for LAMA3 and WNT10A. ConclusionsSeveral genes were associated with NSTA and the candidacy of novel genes was suggested. Further research focusing on the exon-intron boundaries and the impact of mutations on the antisense transcripts should be carried out to better puzzle out their impact on the protein translation and structure.

A study of association of the VNTR MIR-137 rs58335419 with schizophrenia

The MIR137 gene encodes microRNA-137 (miR-137), which is a brain-enriched miR that is highly expressed in various brain regions. miR-137 has been identified as a modulator of processes involved in the pathogenesis of neuropsychiatric disorders. Functional polymorphism of variable number of tandem repeats (VNTR) rs58335419 was found in the regulatory region of the MIR137 gene. It is associated with a change in the expression of miR-137 and, as a result, with an increased risk of developing psychopathologies, including schizophrenia. In this study, we for the first time have analyzed the distribution of frequencies of alleles and genotypes of VNTR MIR137 in a large sample from the Russian population. The association of VNTR with the risk of schizophrenia has been studied. It was found that the presence of VNTR alleles with more than three repeats, as well as a genotype homozygous for such alleles, is associated with an increased risk of developing schizophrenia (OR = 1.4, 95% CI: 1.01-1.95).