Gene Frequencies Research Articles

Polymorphism of KIR Genes in Women with Human Papillomavirus Infection

Molecular biology screening techniques for early detection of human papillomavirus (HPV) infection in the National CervicalUterine Cancer Program in Cuba provide the opportunity to treat premalignant lesions and prevent progression to cervicaluterine cancer. Objectives: To identify 14 high-risk HPV genotypes in women aged 30 to 50 with negative previous cytology and to identify the polymorphism of killer immunoglobulin-like receptor (KIR) genes in a subsample of HPV-positive women. Methods: HPV screening tests were performed on 3,115 women using the COBAS 4800 system with the HPV COBAS kit (Roche, Germany). For KIR gene typing, 60 randomly selected HPV-positive women were analyzed using a molecular method based on hybridization probes on a LUMINEX flow analyzer with the LIFECODES KIR-SSO typing kit (Immucor, USA). Results: 295 (9.5%) women tested positive for one of the 14 high-risk genotypes. The highest percentage of positive women was found among those aged 30 to 39 years (12.0%). Fourteen women had coinfection with HPV16 or HPV18 along with another highrisk genotype. There was a high frequency of genes encoding activating receptors such as KIR 2DL1 (98.3%), KIR 2DL3 (98.3%), and KIR 2DS4*all full length (93.3%). Conclusions: The prevalence of HPV in Cuban women with normal cytology is lower than the global average, with activating KIR genes predominating among positive cases.

Analysis of the Allelofund of Semi-Fine-Wool Sheep of the Pechora Population Using STR Markers

The polymorphism of microsatellites was studied in semi-fine-wool sheep in the Romney-Marsh type of the Pechora population, bred with the participation of the now extinct northern short-tailed aboriginal sheep. Evaluation of the differentiation of groups of sheep of different genesis by the frequencies of STR loci genes, identification of private alleles and cluster analysis did not allow to obtain information about the allelofund of the aboriginal sheep. Absorption crossing into an improved breed with the selection of a crossbred population according to the target standards of semi-fine-wool breeds, apparently, led to the loss of the gene pool characteristic of the northern aboriginal sheep by the Pechora sheep.

Effect of the Rs2923234 and Rs1049112 Single Nucleotide Polymorphisms of Salivary Acidic Proline-rich Protein on Dental Caries in Young Children: An Analytical Cross-sectional Molecular Study

Introduction: We aimed to use polymerase chain reaction (PCR) on genomic deoxyribonucleic acid (DNA) to detect the Db allele and the rs2923234 and rs1049112 single nucleotide polymorphisms (SNPs) of the salivary acidic proline-rich proteins (PRPs) to determine their relationship with dental caries in young children. Methods: DNA was extracted from saliva samples of preschool children aged 3 to 5 years. PCR primers designed around exon 3 of the PRH1 locus yielded a 416-base product representing Db for gel electrophoresis and a 519-base product representing the rs2923234 and rs1049112 SNPs for Sanger sequencing. The data were analyzed using a logistic regression model and a multilayer perceptron artificial neural network. Results: Forty children with severe caries and 40 caries-free children completed the study. The frequency of the Db gene was 16.3% in the entire study group. The rs2923234 SNP was a marginally significant (P = 0.053) predictor for the dependent variable (caries-free or severe caries). However, the rs1049112 (P = 0.407) and the Db allele (P = 0.442) were not significant predictors. Conclusion: The rs29232334 SNP could be considered a potential genetic predictor for caries susceptibility.

Status Nutrisi dan Hemoglobin Setelah Pemberian Transfusi pada Penderita Thalasemia

More than 5,000 babies are born suffering thalassemia (beta thalassemia major and beta thalassemia Hb E) annually from around the world and 80% of births occur in developing countries (Kantharaj & Chandrashekar, 2018). In Indonesia alone, the frequency of beta thalassemia genes ranges from 3-10% with 2,500 babies born each year and there are 10,531 more patients experiencing thalassemia (Kemenkes, 2019). The general objective of this study was to identify the relationship between nutritional status and changes in hemoglobin levels after transfusion in children with thalassemia at RSD Gunungjati Cirebon. This research method uses descriptive correlation by using a cross sectional. The sample of this research is thalassemia in Gunung Jati Hospital, Cirebon City, totaling 35 respondents using accidental sampling technique. The instrument used is a data and measurement recapitulation sheet. The nutritional status data recapitulation sheet containing components (gender, age, weight, TB) and measurement of Hb before and after blood transfusion using EasyTouch GCHB, as well as data analysis using the Spearman rank, was carried out on July 4-15, 2022. The results of the univariate analysis of the study This is in the category of good nutritional status as many as 18 respondents (51.4%) and an increase in hemoglobin levels of 18 respondents (51.4%) in thalassemia children at Gunungjati Hospital, Cirebon. The results of this study found that there was no relationship between nutritional status and changes in hemoglobin levels in thalassemia children at RSD Gunungjati Cirebon with a value (p = 0.252 > = 0.05).Suggestions for this study are that families and patients should strive to carry out the education provided by nurses and explore more knowledge related to thalassemia, especially nutritional intake.

Goat genetic and phenotypic variation of body measurement traits in a sample of the Venezuelan creole goat population

Variation within a given population is due basically to environmental and genetic deviations among the individuals. Genetic deviations are heritable and therefore the base for selection. In animal production, reproduction of outstanding individuals is allowed in a higher degree to improve forthcoming generations. The genetic variation is a property of genes influencing the traits and genes frequency may change among populations, basically due to genetic drift and animal husbandry. Phenotypic and genetic variation of morphological quantitative traits was estimated in the Venezuelan Creole goat population. The additive direct genetic variation or heritable fraction out of the total phenotypic variance found in this study is indicative that most traits evaluated can be improved through selection which should be taken into consideration in any breeding program.

Evaluation of Genetic Diversity and Virulence Potential of Legionella pneumophila Isolated from Water Supply Systems of Residential Buildings in Latvia.

Legionella is an opportunistic pathogen with a biphasic life cycle that occasionally infects humans. The aim of the study was to assess the distribution of virulence genes and genetic diversity among L. pneumophila isolated from water supply systems of residential buildings in Latvia. In total, 492 water samples from 200 residential buildings were collected. Identification of Legionella spp. was performed according to ISO 11731, and 58 isolates were subjected to whole-genome sequencing. At least one Legionella-positive sample was found in 112 out of 200 apartment buildings (56.0%). The study revealed extensive sequence-type diversity, where 58 L. pneumophila isolates fell into 36 different sequence types. A total of 420 virulence genes were identified, of which 260 genes were found in all sequenced L. pneumophila isolates. The virulence genes enhC, htpB, omp28, and mip were detected in all isolates, suggesting that adhesion, attachment, and entry into host cells are enabled for all isolates. The relative frequency of virulence genes among L. pneumophila isolates was high. The high prevalence, extensive genetic diversity, and the wide range of virulence genes indicated that the virulence potential of environmental Legionella is high, and proper risk management is of key importance to public health.

Roles of NRF2 in DNA damage repair.

The transcription factor NF-E2-related factor 2 (NRF2) is a master regulator widely involved in essential cellular functions such as DNA repair. By clarifying the upstream and downstream links of NRF2 to DNA damage repair, we hope that attention will be drawn to the utilization of NRF2 as a target for cancer therapy. Query and summarize relevant literature on the role of NRF2 in direct repair, BER, NER, MMR, HR, and NHEJ in pubmed. Make pictures of Roles of NRF2 in DNA Damage Repair and tables of antioxidant response elements (AREs) of DNA repair genes. Analyze the mutation frequency of NFE2L2 in different types of cancer using cBioPortal online tools. By using TCGA, GTEx and GO databases, analyze the correlation between NFE2L2 mutations and DNA repair systems as well as the degree of changes in DNA repair systems as malignant tumors progress. NRF2 plays roles in maintaining the integrity of the genome by repairing DNA damage, regulating the cell cycle, and acting as an antioxidant. And, it possibly plays roles in double stranded break (DSB) pathway selection following ionizing radiation (IR) damage. Whether pathways such as RNA modification, ncRNA, and protein post-translational modification affect the regulation of NRF2 on DNA repair is still to be determined. The overall mutation frequency of the NFE2L2 gene in esophageal carcinoma, lung cancer, and penile cancer is the highest. Genes (50 of 58) that are negatively correlated with clinical staging are positively correlated with NFE2L2 mutations or NFE2L2 expression levels. NRF2 participates in a variety of DNA repair pathways and plays important roles in maintaining genome stability. NRF2 is a potential target for cancer treatment.

Genetic polymorphism of the Dab2 gene and its association with Type 2 Diabetes Mellitus in the Chinese Uyghur population.

The human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China. A total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies. We found that in the Uygur population studied, for both rs2255280 and rs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CC vs. CA + AA) between T2DM patients and the controls (P < 0.05). After adjusting for confounders, the recessive model (CC vs. CA + AA) of both rs2255280 and rs2855512 remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to -22.755], P = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to -21.013], P = 0.033). The genotypes (AA/CA/CC) and recessive models (CC vs. CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all P < 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (all P > 0.05). The present study suggests that the variation of the Dab2 gene loci rs2255280 and rs2855512 is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China.

Screening of potato breedung lines for the potato virus Y resistance genes Rychc and Ryadg

Goal. Molecular identification of carriers of the potato virus Y (PVY) resistance genes Rychc and Ryadg among potato lines of the Polissia Research Station of the Institute of Potato Growing of the National Academy of Agrarian Sciences of Ukraine.&#x0D; Methods. Seventy potato lines produced by the Polissia Research Station of the Institute of Potato Growing were studied. We used molecular markers indicating the presence of specific Ry genes in the genome of the potato lines. Those genes are responsible for the plant’s response to the pathogen by the extreme resistance (ER) type: the Ryo186 marker for the identification of the Rychc gene, and RYSC-3 for the determination of the Ryadg resistance gene. The gene Ry chc, derives from Solanum chacoense, and the Ryadg gene from S. tuberosum ssp. andigena. For determining the PVY resistance genes, PCR analysis was used, and PCR products were analyzed by electrophoresis in an agarose gel supplemented with ethidium bromide to visualize amplicons.&#x0D; Results. Screening of carriers of resistance alleles with the molecular marker Ruo186 showed that 53 lines (75.72%) carried the resistance gene Rychc. The Ryadg resistance allele was identified in 7 lines (10%) using the RYSC-3 marker. Among the analyzed sample, there were three lines (4.2%) which simultaneously carried both PVY resistance genes: P.17.36-8, P.16.21-8, and P.17.21/36. When compared with the studies of other authors, in our sample of potato breeding lines we have mostly a similar percentage of occurrence of the Ryadg gene and a much higher frequency of the Rychc gene.&#x0D; Conclusions. Thus, the potato lines of the Polissia Research Station of the Institute of Potato Growing with the identified resistance genes have the potential for extreme resistance to most PVY strains, including the PVYNTN strain.

Molecular Detection of Plasmid-Mediated Quinolone Resistance Genes (qnrA and aac(6′)-Ib-cr) in Drug Resistant Escherichia coli, Sudan

Background: The quinolone group, a synthetic antimicrobial, is widely used worldwide to treat many diseases, including those caused by Gram-negative bacteria. Escherichia coli and others are among the bacteria that produce quinolone resistance genes (qnr) such as qnrA and aac(6′)-Ib-cr. &#x0D; Objective: The present study aimed to the isolate Escherichia coli from patients attending some Hospitals in Wad Medani city, identification of drug resistance patterns and detection of the frequency of quinolones resistance genes; qnrA and aac(6′)-Ib-cr among isolated strains.&#x0D; Methods: A cross-sectional descriptive, hospital-based study included 119 Escherichia coli strains was conducted. A designed questionnaire used for demographic data collection and the attitude toward antimicrobials usage. Clinical specimens were processed for aerobic bacterial isolation and identification. Antimicrobial sensitivity performed by Kirby Bauer disc diffusion technique according to the CLSI guidelines. Presence of qnrA and aac(6′)-Ib-cr genes was assessed by multiplex PCR.&#x0D; Results: Most strains of Escherichia coli originated from urine 53.8% (64/119) and wounds 42.9% (51/119) specimens. Meropenem had the best effect against tested strains with susceptibility of 85% (101/119). Multiplex PCR assay, using specific primers, demonstrated that 41.2% (49/119) and 37.8% (45/119) of isolated Escherichia coli possessed qnrA and aac(6′)-Ib-cr genes respectively.&#x0D; Conclusion: The high rate of qnrA and aac (6)-Ib-cr genes among Escherichia coli necessitate the usage of molecular tools in detecting the genetic determinants of drug resistance microorganisms in countries such as Sudan.

Molecular epidemiology of antibiotic-resistant Escherichia coli among clinical samples isolated in Azerbaijan, Iran.

The immediate emergence of resistant bacteria poses an increasingly growing problem to human society and the increasing prevalence of antibiotic resistance in Escherichia coli strains is one of the most important health problems. This study aimed to review the molecular epidemiology of drug resistance among clinical isolates of E. coli in north-west portion of Iran Azerbaijan. A complete of 219 clinical isolates of E. coli had been collected from the various clinical samples. The disk diffusion and agar dilution assays were used to determine antimicrobial susceptibility. The presence of antibiotics resistance genes was carried out by the PCR method. The highest susceptibility was shown to imipenem (3%) and fosfomycin (3%), and the most antibiotic resistance was presented to ampicillin (99%). The highest frequent ESBL gene among isolates was bla CTXM-15 in 70% followed by blaCMY-2 in 67%, and blaTEM-1 in 46%. The most common fluoroquinolone (FQ) resistance genes were oqxB (34%), followed by oqxA (25%), and qnrB (18%). The frequency of tetracycline resistance genes (tetA, tetB, tetC, and tetD) were detected in 24.8%, 31.6%, 1.8%, and 4.2%, respectively. The highest frequent genes to fosfomycin were fosA 10%, fosA3 30%, fosC 40%, and fosX 20%. The dominant founded aminoglycosides resistant genes were armA (12.96%) and npmA (4.93%). The prevalence of antibiotics resistance in the tested E. coli isolates was high in Azerbaijan, Iran and these findings showed that E. coli is one of the major drug-resistant pathogens.

Асоціація поліморфізмів генів GSTP1(A313G), MTHFR (С677T) та IL-10 (C819T) із ризиком виникнення гліобластоми

гліобластома одна з найбільш поширених злоякісних пухлин головного мозку з вкрай низькою виживаністю. Незважаючи на досягнення у вивченні молекулярного патогенезу та біології пухлин мозку, причини виникнення гліобластоми залишаються нез’ясованими. Дослідження останніх років вказують, що зміни у генах, які беруть участь у проліферації, диференціації та апоптозі клітин, можуть впливати на ризик виникнення онкологічних захворювань. Тож метою роботи було дослідити поліморфізми генів GSTP1(A313G), MTHFR (С677Т) та IL-10 (C819T) у хворих на гліобластому та проаналізувати їх зв’язок із ризиком розвитку цієї патології. Біологічним матеріалом для аналізу поліморфізмів генів GSTP1, MTHFR та IL-10 слугувала периферична кров хворих на гліобластому та практично здорових людей. Дослідження поліморфізмів генів проводилось за допомогою методу алель-специфічної ПЛР із використанням власних пар детекторів TaqMan MGB на основі флуоресцентних барвників, що призначені для виявлення однонуклеотидних замін. Встановлено, що частота мутантного алеля G гена GSTP1 у хворих становила 53,6% проти 32% у групі практично здорових людей. Розподіл генотипів гена GSTP1 у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга та статистично відрізнялась від показника у групі практично здорових людей і становив 0,538 проти 0,320 (χ2 = 13,10, р = 0,003). Визначено, що ризик виникнення гліобластоми є в 4,88 разів вищим у осіб, що є гомозиготними носіями мутантного алелю гена GSTP1 (генотип G313G) у порівнянні з іншими поліморфними варіантами. В результаті наших досліджень, було встановлено, що частота мутантного алеля С гена IL-10 у хворих становила 48,8%, що значно перевищує відповідний показник у групі практично здорових людей – 25%. Встановлено, що розподіл генотипів гена IL-10 у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга, частота мутантного алеля С гена IL-10 статистично відрізнялась від показника у групі практично здорових людей та становила 0,488 проти 0,250 (χ2 = 18,32, р = 0,00002). Встановлено, що існує асоціація між поліморфізмом гена IL-10 (C819T) та ризиком виникнення гліобластоми, у гомозиготних носіїв із генотипом Т819Т, ризик захворіти збільшується у 6,40 рази. Також нами було встановлено, що частота мутантного алелю Т гена MTHFR у хворих становила 35,0% проти 28,1% у групі практично здорових людей. Розподіл генотипів гена MTHFR у групі хворих відповідав закону генетичної рівноваги Харді-Вайнберга, а розподіл частот поліморфних варіантів ген показав відсутність статистично достовірних відмінностей між групою хворих та групою практично здорових людей (χ2 = 1,43 р = 0,23). Не було встановлено асоціації між поліморфізмом гена MTHFR (С677Т) і ризиком виникнення гліобластоми.

Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon

BackgroundGabon is a malaria-threatened country with a stable and hyperendemic transmission of Plasmodium falciparum monoinfection. Malaria drug resistance is widely spread in many endemic countries around the world, including Gabon. The molecular surveillance of drug resistance to antifolates and artemisinin-based combination therapy (ACT) is one of the strategies for combating malaria. As Plasmodium parasites continue to develop resistance to currently available anti-malarial drugs, this study evaluated the frequency of the polymorphisms and genetic diversity associated with this phenomenon among the parasites isolates in Gabon.MethodsTo assess the spread of resistant haplotypes among the malaria-infected population of Libreville, single nucleotide polymorphisms linked to sulfadoxine–pyrimethamine (SP) and artemisinin drugs resistance were screened for P. falciparum dihydrofolate reductase (Pfdhfr), P. falciparum dihydropteroate synthase (Pfdhps), and P. falciparum kelch 13-propeller domain (Pfk13) point mutations.ResultsThe analysis of 70 malaria-positive patient samples screened for polymorphism showed 92.65% (n = 63) mutants vs. 7.35% (n = 5) wild parasite population in Pfdhfr, with high prevalence mutations at S108N(88.24%, n = 60), N51I(85.29%, n = 58), C59R(79.41%, n = 54); however, I164L(2.94%, n = 2) showed low frequency mutation. No wild haplotype existed for Pfdhps, and there were no mutations at the K540E, A581G, and A613T/S positions. However, the mutation rate at A437G(93.38%, n = 62) was the highest, followed by S436A/F(15.38%, n = 10). A higher frequency of quadruple IRNI–SGKAA (69.84%) than quintuple IRNI–(A/F)GKAA (7.94%) mutations was observed in the Pfdhfr–Pfdhps combination. Furthermore, none of the mutations associated with ACT resistance, especially those commonly found in Africa, were observed in Pfk13.ConclusionsHigh polymorphism frequencies of Pfdhfr and Pfdhps genes were observed, with alternative alanine/phenylalanine mutation at S436A/F (7.69%, n = 5) for the first time. Similar to that of other areas of the country, the patterns of multiple polymorphisms were consistent with selection owing to drug pressure. Although there was no evidence of a medication failure haplotype in the studied population, ACT drug efficacy should be regularly monitored in Libreville, Gabon.

Decrease in the resistance level of Blattella germanica (Linnaeus) (Blattodea: Ectobiidae) to insecticides after being reared without selection pressure for ten years

This study aims to investigate changes in resistance to insecticides over a ten-year period in five strains of German cockroaches, Blattella germanica (Linnaeus), which had previously shown resistance to deltamethrin, propoxur, and fipronil in 2012. The five strains were reared in a laboratory without exposure to insecticides for ten years. In 2022, they were tested for resistance to the same insecticides using a topical application method. The resistance ratio (RR50) was calculated for each strain to determine the level of resistance to each insecticide. The study found that German cockroaches, initially resistant, became less resistant or even susceptible after being reared in a laboratory without insecticide exposure for over ten years. This decrease in resistance was observed in all strains, but the reduction pattern varied, apparently influenced by the type of insecticide. For instance, the MDN2 strain, which initially had a very high level of resistance (RR50: 1019.74 -fold) to deltamethrin, became susceptible (RR50: 1 -fold). Similarly, the ACH2 strain, initially classified as highly resistant to propoxur (RR50: 48.64 -fold), and the strain with high resistance (RR50: 12.21 -fold) to fipronil, both became susceptible. The study also discussed potential mechanisms for the decrease in resistance, including reduced frequency of resistance genes and fitness costs. The findings suggest that rearing German cockroaches in a laboratory without insecticide treatment can lead to a decrease in resistance to commonly used insecticides. These findings can be used to develop more effective methods for controlling German cockroaches.

The mechanisms of metabolic resistance to pyrethroids and neonicotinoids fade away without selection pressure in the tarnished plant bug Lygus lineolaris.

Heavy selection pressure prompted the development of resistance in a serious cotton pest tarnished plant bug (TPB), Lygus Lineolaris in the mid-southern USA. Conversely, a laboratory resistant TPB strain lost its resistance to five pyrethroids and two neonicotinoids after 36 generations without exposure to any insecticide. It is worthwhile to examine why the resistance diminished in this population and determine whether the resistance fade away has practical value for insecticide resistance management in TPB populations. A field-collected resistant TPB population in July (Field-R1) exhibited 3.90-14.37-fold resistance to five pyrethroids and two neonicotinoids, while another field-collected TPB population in April (Field-R2) showed much lower levels of resistance (0.84-3.78-fold) due to the absence of selection pressure. Interestingly, after 36 generations without exposure to insecticide, the resistance levels in the same population (lab-R) significantly decreased to 0.80-2.09-fold. The use of detoxification enzyme inhibitors had synergistic effects on permethrin, bifenthrin and imidacloprid in resistant populations of L. lineolaris. The synergism was more pronounced in field-R2 than lab-S and lab-R TPB population. Moreover, esterase, GST, and P450 enzyme activities increased significantly by approximately 1.92-, 1.43-, and 1.44- fold in field-R1, respectively, and 1.38-fold increased P450 enzyme activities in field-R2 TPB population, compared to the lab susceptible (lab-S) TPB. In contrast, the three enzyme activities in the lab-R strain were not significantly elevated anymore relative to the lab-S population. Additionally, field-R1 TPB showed elevated expression levels of certain esterase, GST and P450 genes, respectively, while field-R2 TPB overexpressed only P450 genes. The elevation of these gene expression levels in lab-R expectedly diminished to levels close to those of the lab susceptible (lab-S) TPB populations. Our results indicated that the major mechanism of resistance in TPB populations was metabolic detoxification, and the resistance development was likely conferred by increased gene expressions of esterase, GST, and P450 genes, the fadeaway of the resistance may be caused by reversing the overexpression of esterase, GST and P450. Without pesticide selection, resistant gene (esterase, GST, P450s) frequencies declined, and detoxification enzyme activities returned to lab-S level, which resulted in the recovery of the susceptibility in the resistant TPB populations. Therefore, pest's self-purging of insecticide resistance becomes strategically desirable for managing resistance in pest populations. This article is protected by copyright. All rights reserved.

Development of a multiplex panel with 36 insertion/deletion markers (InDel) for individual identification.

In recent years, the insertion/deletion (InDel) polymorphism has become a preferred genetic marker in forensic genetics due to its low mutation rates and small amplicon sizes. In this study, a 36-InDelplex identification panel, consisting of autosomal 34 InDel loci, 1 Y InDel locus, and amelogenin, was developed, and gene frequencies in the Turkish population were determined. The loci of the InDel panel with global minimum allele frequencies (MAF) ≥ 0.4 were selected from the 1000 Genomes Project Phase 3 data. The amplicon sizes of the loci were designed in the range of 69-252 bp. In the validation study of the developed panel, analysis threshold, dynamic range, sensitivity, stochastic threshold, inhibitor tolerance, and reproducibility parameters were studied by following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. The sensitivity studies indicated that complete and reliable InDel profiles could be obtained with 0.25 ng of DNA. A population study was evaluated using 250 samples from Turkey. The mean observed heterozygosity ratio (Ho) of all loci was 0.48. The combined discrimination power (CPD) is 0.999999999990867 and the combined exclusion probability (CPE) was 0.9930. The population comparison was also made using Turkish and the five major populations from the 1000 Genomes Phase 3 populations' data (Africa, Europe, East Asia, South Asia, and America). In conclusion, the results showed that the 36-InDelplex panel is a reliable, sensitive, and accurate system that is suitable for human identification and population genetics purposes.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: ALK-positive anaplastic large cell lymphomas (ALCL) are characterized by rearrangements involving the ALK gene on chromosome 2. The translocation t(2;5) (p23;q35) resulting in the NPM1::ALK gene fusion is detected in the majority of ALCL. In 10%–20% of ALCL, ALK is fused to various other partner genes. Compared to NPM1::ALK, variant ALK-fusion proteins are not expressed in the nucleus. The frequency, distribution, and possible prognostic significance of the different variant ALK partner genes have not been analyzed in population-based studies so far. We investigated all patients with ALK-positive ALCL with exclusive cytoplasmic ALK-expression diagnosed in a uniformly treated cohort of ALCL patients in the NHL-BFM study group. Patients and Methods: Between 2000 and 2017, 312 children and adolescents were diagnosed with an ALK-positive ALCL in Austria, Germany, Switzerland and the Czech Republic, and included in the ALCL 99 trial or the NHL-BFM registry 2012. Reference pathology demonstrated exclusive cytoplasmic ALK-staining in 49 tumors. Formalin-fixed-paraffin-embedded or frozen tumors of 43/49 patients were available for molecular analyses. Tumor-DNA was analyzed by an ALK-specific genomic capture high throughput sequencing assay. ALK-partner gene-specific RT-PCR assays were used to identify the respective partner genes when tumor cDNA was available. Results: 41 of 43 available tumors with exclusive cytoplasmic ALK-staining could be analyzed. 13 were NPM1::ALK positive and 28 tumors had a variant ALK partner. TPM3::ALK (n = 9, 32%) and ATIC::ALK (n = 8, 29%) were the most common variant partner genes. XPOI could be identified as a novel ALK fusion partner. The patients´ characteristics of ALCL expressing Variant::ALK were comparable to those with NPM1::ALK fusions. The five-year event-free survival (EFS) and overall survival were comparable between the 284 NPM1::ALK and the group of 28 different Variant::ALK-expressing patients. However, none of the 9 patients with TPM3::ALK positive ALCL relapsed, compared to 5 relapses among 8 patients with ATIC::ALK positive ALCL. Conclusions: In our population-based cohort of ALK-positive ALCL-patients, less than 10% carried variant ALK-fusion partners, 60% of which were TPM3 or ATIC. In patients with exclusive cytoplasmic ALK staining patterns, NPM1::ALK positivity should be excluded by molecular analysis. The tendency of a different relapse risk between ATIC::ALK and TPM3::ALK -positive ALCL-patients suggests that the fusion partner might confer tumor aggressiveness or drug resistance. The research was funded by: KNACK DEN KREBS Fördergemeinschaft Kinderkrebs-Zentrum Hamburg e.V. and HAMBURGER STIFTUNG ZUR FÖRDERUNG DER KREBSBEKÄMPFUNG Keyword: diagnostic and prognostic biomarkers No conflicts of interests pertinent to the abstract.

Spectrum of MECP2 mutations in Iranian Azeri Turkish Rett syndrome patients

Rett syndrome is an X-linked dominant neurodevelopmental disorder that occurs mostly in females. De novo mutations in the MECP2 gene have an important role in the appearance of the features of this syndrome. We planned to study spectrum of MECP2 mutations in Rett syndrome patients and their clinical symptoms. A cohort of 29 patients referred by neurologists from Iranian Azeri Turks was screened. Then direct sequencing was utilized to characterize the spectrum of mutations in the MECP2 gene in Rett syndrome patients. A total of 10 different mutations on MECP2 gene were detected in 22 patients. We identified 2 (9%) frameshift, 10 (45.64%) nonsense, 8 (36.4%) missense mutations, and 2(9%) large deletions. In this cohort, one of the detected deletions was novel, namely 1023-1096del74nt. Random X chromosome inactivation in females’ cells and different MECP2 mutations can cause a phenotypic variability between patients. This is the first report regarding the spectrum of MECP2 mutation and phenotypic spectrum in Iranian Azeri Turks with Rett syndrome. Our finding confirms a high mutation frequency (75.8%) of MECP2 gene in Iranian Rett syndrome patients.

Carbapenemase genes and mortality in patients with carbapenem-resistant Enterobacterales, Atlanta, Georgia, 2011–2020

Background: Carbapenemase genes in carbapenem-resistant Enterobacterales (CP-CRE) may be transmitted between patients and bacteria. Reported rates of carbapenemase genes vary widely, and it is unclear whether having a carbapenemase gene portends worse outcomes given that all patients with CRE infections have limited treatment options. Methods: Using active population- and laboratory-based active surveillance data collected by the US CDC-funded Georgia Emerging Infections Program from 2011 to 2020, we assessed the frequency of carbapenemase genes in a convenience sample of CRE isolates using whole-genome sequencing (WGS), and we investigated risk factors for carbapenemase positivity. Only the first isolate per patient in a 30-day period was included. We compared characteristics of patients with CP-CRE and non–CP-CRE. Using multivariable log binomial regression, we assessed the association of carbapenemase gene positivity and 90-day mortality. Results: Of 284 CRE isolates, 171 isolates (60.2%) possessed a carbapenemase gene (Table 1), and KPC-3 was the most common carbapenemase gene (80.7%), with only 7 isolates possessing NDM (Table 2). No isolates possessed &gt;1 carbapenemase gene, and most isolates were from urine (82.4%) (Table 1). Carbapenemase gene positivity was associated with lower age, male sex, black race, infection with Klebsiella pneumoniae, polymicrobial infection, having an indwelling medical device, receiving chronic dialysis, and prior stay in a long-term acute-care hospital, long-term care facility, and/or prior hospitalization in the last year. The 90-day mortality rates were similar in patients with non–CP-CRE and CP-CRE: 24.8% versus 25.7% (P = .86). In multivariable analysis, carbapenemase gene presence was not associated with 90-day mortality (adjusted risk ratio, 0.82; 95% CI, 0.50–1.35) when adjusting for CCI, infection with Klebsiella pneumoniae, and chronic dialysis use. Conclusions: The frequency of CP-CRE among CRE was high in this study, but unlike prior studies, the 90-day mortality rates wer similar in patients with CP-CRE compared to non–CP-CRE. Our results provide novel associations (eg, lower age, male sex, infection with Klebsiella pneumoniae, and indwelling medical devices) that infection preventionists could use to target high-risk patients for screening or isolation prior to CP-CRE detection.Disclosure: None

Homologous recombination-related (HRR) gene mutations in patients with glioma and their relevance to genomic characteristics, tumor mutation burden (TMB), and prognosis.

e14023 Background: Homologous Recombination Repair (HRR) is one of the core repair methods for DNA double strand damage and the mutations of HRR pathway gene may be the main cause of many cancers. However, there is little research on the potential correlation between the molecular characteristics of HRR pathway genes and glioma. Our study explored HRR gene mutations in glioma patients and its relevance to genomic characteristics, tumor mutation burden (TMB) and prognosis. Methods: Samples from 367 glioma patients with a median age of 46 were detected by 551-gene panel or whole-exome sequencing (WES), and the WES data of 894 glioma patients were extracted from TCGA database ( http://cancergenome.nih.gov ). Among 367 glioma patients, 151 patients occurred HRR somatic mutations. Among them, 47.68% (72/151) patients carried HRR related pathogenic mutation (P/LP), and 52.32% (79/151) patients carried HRR benign/likely benign/variant of uncertain significance mutations (B/LB/VUS). The patients were divided into two groups according to whether patients carried HRR related pathogenic mutation, HRR P/LP group (72) and Non-HRR P/LP group (295). The differences of genomic characteristics, TMB and prognosis between HRR P/LP group and Non-HRR P/LP group were analyzed. Results: In 151 glioma patients harboring HRR somatic mutations, PTEN had the highest mutation frequency (49%; 74/151), followed by CHEK2, DNMT3A, BRCA2 and ATM, with mutation frequency of 11% (17/151), 10% (15/151), 9% (14/151）and 9% (14/151). Patients of HRR P/LP group and HRR B/LB/UVS group showed a significant difference at HRR pathway genes, including PTEN, RAD50, MSH6 and RAD21. In addition, differences of non-HRR pathway genes in HRR P/LP group and Non-HRR P/LP group were found. The mutation frequency of these differential genes was generally high in HRR P/LP group. However, compared to Non-HRR P/LP group, the mutation frequency of IDH1 in HRR P/LP group was significantly higher (Non-HRR P/LP 32% VS HRR P/LP 10%; P＜0.0001). The TMB value in Non-HRR P/LP group was significantly higher than that in HRR P/LP group (P＜0.0001), and the same trend of TMB in two groups was discovered in TCGA cohort (P＜0.0001). Importantly, a significant difference of overall survival (OS) in TCGA database was found between HRR P/LP group and Non-HRR P/LP group (P＜0.0001, HR =2.17, 95%CI: 1.54-3.06), and the median OS were 17.6 and 34.9 months, respectively. Conclusions: This study showed HRR pathway genes status was significantly related to the genomic characteristics, TMB and prognosis of glioma patients. Compared to patients in HRR P/LP group, patients in Non-HRR P/LP group had higher mutation frequency of IDH1, lower TMB value and better prognosis. The relationship between HRR pathway genes and glioma needs to be further explored.