scholarly journals Design of method for detecting single nucleotide polymorphisms of DNA non-coding region rs17185536: potential diagnostic value

2019 ◽  
Vol 3 (22) ◽  
pp. 11-14
Author(s):  
A. S. Gorbenko ◽  
M. A. Stolyar ◽  
Yu. Yu. Komarovsky ◽  
M. A. Mikhalev ◽  
V. V. Potylitsyna ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Large Scale ◽  
Uterine Fibroids ◽  
Primary Myelofibrosis ◽  
Original Method ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Myeloproliferative Diseases ◽  
Hereditary Susceptibility ◽  
Chronic Myeloproliferative Diseases

A large-scale study of DNA sequencing databases (Jorgenson E., et al., 2018) to search for hereditary susceptibility to early erectile dysfunction revealed an association with the rs17185536-T polymorphism regulating the expression of topologically associating domain, among which is the SIM1 gene, which plays an important role in maintaining mass body and sexual function. The proximity of the rs17185536 locus to the CCNC (cyclin C), PRDM13 (histone methyltransferase) and USP45 (ubiquitin-specific peptidase 45) genes suggests the possible involvement of this polymorphism in the pathogenesis and other diseases associated with impairments of these genes.Materials and methods. The study included a total of 280 people: 81 of which were healthy donors, 116 pregnant women, 25 patients with polycythemia vera, 29 with essential thrombocythemia, and 29 with primary myelofibrosis.Results. Using the original method of determining the polymorphism rs17185536, the allele of specific PCR-RT showed that the prevalence of the T allele among all examined patients was 19 %, and variants of the genotypes: C/C with 73 %, C/T with 23 % and T/T with 4 %, which corresponds to Winkler e. a. data. The absence of statistically significant differences in the frequency of occurrence of this polymorphism in the pathology of pregnancy and in chronic myeloproliferative diseases indicates a low probability of involvement of rs17185536-T in the pathogenesis of these diseases. In the group of pregnant women, there is an association of the rs17185536-T allele with obesity, uterine fibroids and the development of preeclampsia.Conclusions. For the first time, using the original method of analysis, it was confirmed that the Russian population has a comparable prevalence of the gene of hereditary susceptibility to impotence. Despite the topographic proximity of the rs17185536 locus to the genes regulating the repair and functioning of DNA, its polymorphisms do not affect the risk of chronic myeloproliferative diseases developing. The association of the rs17185536-T allele with the risk of developing a pregnancy pathology requires further study.

Genomic characteristics of endometrial cancer in China.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17569-e17569
Author(s):  
Hong Zheng ◽  
Lina Cui ◽  
Bei Zhang ◽  
Xiaochen Zhao
Keyword(s):  
Endometrial Cancer ◽  
Large Scale ◽  
White Blood Cells ◽  
Molecular Classification ◽  
The Cancer Genome Atlas ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Genomic Studies

e17569 Background: Molecular classification of endometrial cancer has been applied in patient stratification and treatment strategy. Although the Cancer Genome Atlas project and other genomic studies have established comprehensive molecular classification, its genomic characteristics in Chinese endometrial cancer remain unclear. Methods: Tumor tissue and matched white blood cells from 316 patients with endometrial cancer underwent next-generation sequencing (NGS), which targeted the whole coding region of 733 or 381 genes. Endometrial cancer was classified into four subtypes according to genomic characteristics: polymerase (POLE) ultramutated, microsatellite instability (MSI), TP53 wild type (TP53wt), and TP53 mutant (TP53mut). Tumor mutation burden (TMB) was calculated based on the number of somatic single nucleotide variants and indels in examined coding regions. Deleterious or suspected deleterious genes were included for analysis. Genomic instability was also evaluated with Homologous Recombination Deficiency (HRD) score by over 10, 000 single-nucleotide polymorphisms distributed across human genome. HRD algorithm combined loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI) and large-scale state transition score (LST). Results: The 316 endometrial cancer patients were divided into four subtypes: POLE ultramutated (16, 5.06%), MSI tumors (70, 22.2%), TP53wt (131, 41.5%), and TP53mut (99, 31.3%). Median TMB was 26.5 mut/Mb in overall cohort and POLE ultramutated subtype possessed the highest TMB (181 mut/Mb), followed by MSI (54.1 mut/Mb), TP53mut (7.11 mut/Mb) and TP53wt (6.61 mut/Mb) subtypes. POLE, PTEN, LRP1B, BRCA2 and ATRX were the top frequently mutated genes in POLE ultramutated subtype, which mutation rate are more that 80%. The most frequent mutations were detected in ARID1A, PTEN, PIK3CA in MSI subtype, TP53, PIK3CA, PTEN in TP53mut subtype, and PTEN, PIK3CA, ARID1A in TP53wt subtype. HRD score was significantly higher in TP53mut subtype, followed by TP53wt, MSI and POLE ultramutated subtype (median HRD score, 21.7, 6.15, 3.65 and 0; P < 0.001). Conclusions: Our study revealed the heterogeneous genomic characteristics of four molecular subtypes in Chinese endometrial cancer. POLE ultramutated and MSI subtypes display higher TMB. TP53mut subtype showed genome features of HRD and would likely benefit from HRD-targeted therapy.

Cutaneous ulcers following hydroxyurea therapy

Phlebologie ◽  
2004 ◽  
Vol 33 (06) ◽  
pp. 202-205 ◽  
Author(s):  
K. Hartmann ◽  
S. Nagel ◽  
T. Erichsen ◽  
E. Rabe ◽  
K. H. Grips ◽  
...  
Keyword(s):  
Side Effects ◽  
Side Effect ◽  
Antineoplastic Agent ◽  
Limited Time ◽  
Myeloproliferative Diseases ◽  
Dermatological Side Effects ◽  
Chronic Myeloproliferative Diseases ◽  
Hydroxyurea Therapy

SummaryHydroxyurea (HU) is usually a well tolerated antineoplastic agent and is commonly used in the treatment of chronic myeloproliferative diseases. Dermatological side effects are frequently seen in patients receiving longterm HU therapy. Cutaneous ulcers have been reported occasionally.We report on four patients with cutaneous ulcers whilst on long-term hydroxyurea therapy for myeloproliferative diseases. In all patients we were able to reduce the dose, or stop HU altogether and their ulcers markedly improved. Our observations suggest that cutaneous ulcers should be considered as possible side effect of long-term HU therapy and healing of the ulcers can be achieved not only by cessation of the HU treatment, but also by reducing the dose of hydroxyurea for a limited time.

scholarly journals Polymorphism Detection of GDF9 Gene and Its Association with Litter Size in Luzhong Mutton Sheep (Ovis aries)

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 571
Author(s):  
Fengyan Wang ◽  
Mingxing Chu ◽  
Linxiang Pan ◽  
Xiangyu Wang ◽  
Xiaoyun He ◽  
...  
Keyword(s):  
Litter Size ◽  
Tertiary Structure ◽  
Novel Mutation ◽  
Major Gene ◽  
Ovis Aries ◽  
Nucleotide Polymorphisms ◽  
Economic Traits ◽  
Coding Region ◽  
Association Analyses ◽  
Gdf9 Gene

Litter size is one of the most important economic traits in sheep. GDF9 and BMPR1B are major genes affecting the litter size of sheep. In this study, the whole coding region of GDF9 was sequenced and all the SNPs (single nucleotide polymorphisms) were determined in Luzhong mutton ewes. The FecB mutation was genotyped using the Sequenom MassARRAY®SNP assay technology. Then, the association analyses between polymorphic loci of GDF9 gene, FecB, and litter size were performed using a general linear model procedure. The results showed that eight SNPs were detected in GDF9 of Luzhong mutton sheep, including one novel mutation (g.41769606 T > G). The g.41768501A > G, g.41768485 G > A in GDF9 and FecB were significantly associated with litter size in Luzhong mutton ewes. The g.41768485 G > A is a missense mutation in the mature GDF9 protein region and is predicted to affect the tertiary structure of the protein. The results preliminarily demonstrated that GDF9 was a major gene affecting the fecundity of Luzhong mutton sheep and the two loci g.41768501A > G and g.41768485 G > A may be potential genetic markers for improving litter size.

scholarly journals A SNP assay for assessing diversity in immune genes in the honey bee (Apis mellifera L.)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dora Henriques ◽  
Ana R. Lopes ◽  
Nor Chejanovsky ◽  
Anne Dalmon ◽  
Mariano Higes ◽  
...  
Keyword(s):  
Apis Mellifera ◽  
Honey Bee ◽  
Large Scale ◽  
Medium Density ◽  
Nucleotide Polymorphisms ◽  
Functional Variation ◽  
Immune Genes ◽  
Wide Range ◽  
Scale Range ◽  
Innate Immune Genes

AbstractWith a growing number of parasites and pathogens experiencing large-scale range expansions, monitoring diversity in immune genes of host populations has never been so important because it can inform on the adaptive potential to resist the invaders. Population surveys of immune genes are becoming common in many organisms, yet they are missing in the honey bee (Apis mellifera L.), a key managed pollinator species that has been severely affected by biological invasions. To fill the gap, here we identified single nucleotide polymorphisms (SNPs) in a wide range of honey bee immune genes and developed a medium-density assay targeting a subset of these genes. Using a discovery panel of 123 whole-genomes, representing seven A. mellifera subspecies and three evolutionary lineages, 180 immune genes were scanned for SNPs in exons, introns (< 4 bp from exons), 3’ and 5´UTR, and < 1 kb upstream of the transcription start site. After application of multiple filtering criteria and validation, the final medium-density assay combines 91 quality-proved functional SNPs marking 89 innate immune genes and these can be readily typed using the high-sample-throughput iPLEX MassARRAY system. This medium-density-SNP assay was applied to 156 samples from four countries and the admixture analysis clustered the samples according to their lineage and subspecies, suggesting that honey bee ancestry can be delineated from functional variation. In addition to allowing analysis of immunogenetic variation, this newly-developed SNP assay can be used for inferring genetic structure and admixture in the honey bee.

scholarly journals Maternal adherence to micronutrient supplementation before and during pregnancy in Northwest China: a large-scale population-based cross-sectional survey

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e028843 ◽  
Author(s):  
Danmeng Liu ◽  
Yue Cheng ◽  
Shaonong Dang ◽  
Duolao Wang ◽  
Yaling Zhao ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Large Scale ◽  
Northwest China ◽  
Population Based ◽  
Shaanxi Province ◽  
Micronutrient Supplementation ◽  
Cross Sectional Survey ◽  
Start Time ◽  
Cross Sectional ◽  
Scale Population

ObjectivesTo report the situation of maternal micronutrient supplementation before and during pregnancy in Northwest China and to examine the rates of and factors related to the adherence to micronutrient supplementation among pregnant women in this region, where dietary micronutrient intake is commonly insufficient.DesignA large-scale population-based cross-sectional survey.SettingTwenty counties and ten districts of Shaanxi Province.ParticipantsA sample of 30 027 women were selected using a stratified multistage random sampling method. A total of 28 678 women were chosen for the final analysis after excluding those who did not provide clear information about nutritional supplementation before and during pregnancy.Main outcome measuresMaternal adherence to micronutrient supplementation (high and low) were the outcomes. They were determined by the start time and duration of use according to Chinese guidelines (for folic acid (FA) supplements) and WHO recommendations (for iron, calcium and multiple-micronutrient (MMN) supplements).ResultsIn total, 83.9% of women took at least one kind of micronutrient supplement before or during pregnancy. FA (67.6%) and calcium (57.5%) were the primarily used micronutrient supplements; few participants used MMN (14.0%) or iron (5.4%). Adherence to supplementation of all micronutrients was low (7.4% for FA, 0.6% for iron, 11.7% for calcium and 2.7% for MMN). Higher educational levels, higher income levels, urban residence and better antenatal care (including pregnancy consultation and a higher frequency of antenatal visits) were associated with high adherence to micronutrient supplementation.ConclusionMaternal micronutrient supplementation before and during pregnancy in Northwest China was way below standards recommended by the Chinese guidelines or WHO. Targeted health education and future nutritional guidelines are suggested to improve this situation, especially in pregnant women with disadvantaged sociodemographic conditions.

Sequence variants in the FcεRI alpha chain gene

2002 ◽  
Vol 93 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Toshiki Shikanai ◽  
Eric S. Silverman ◽  
Brian W. Morse ◽  
Craig M. Lilly ◽  
Hiroshi Inoue ◽  
...  
Keyword(s):  
Promoter Region ◽  
Population Substructure ◽  
Chain Gene ◽  
Polymorphism Analysis ◽  
Sequence Variants ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Alpha Chain ◽  
Asthmatic Patients ◽  
Single Stranded Conformational Polymorphism

There is a relationship between IgE levels and expression of high-affinity IgE receptors (FcεRI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the FcεRI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the FcεRI alpha chain gene with genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by using single-stranded conformational polymorphism analysis. No nonsynonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A/C transversion at −770 from the translation start site; a G/A transition at −664; and a T/C transition at −335. No differences in allele frequencies were detected between asthmatic subjects and controls. Homozygosity for the C variant at locus −335 was more common in Caucasian asthmatic patients with IgE levels in the lower quartile than in the upper quartile ( P = 0.032). An analysis of highly polymorphic SNPs indicated that this association is unlikely to be due to population substructure. We conclude that homozygosity for the C allele of FcεRI alpha chain variant is associated with lower IgE levels.

scholarly journals A NOTE ON PHASING LONG GENOMIC REGIONS USING LOCAL HAPLOTYPE PREDICTIONS

2006 ◽  
Vol 04 (03) ◽  
pp. 639-647 ◽  
Author(s):  
ELEAZAR ESKIN ◽  
RODED SHARAN ◽  
ERAN HALPERIN
Keyword(s):  
Large Scale ◽  
Computational Cost ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Novel Approach ◽  
Maximum Likelihood Criterion ◽  
The Common ◽  
Genomic Regions ◽  
High Computational Cost ◽  
Combining Information

The common approaches for haplotype inference from genotype data are targeted toward phasing short genomic regions. Longer regions are often tackled in a heuristic manner, due to the high computational cost. Here, we describe a novel approach for phasing genotypes over long regions, which is based on combining information from local predictions on short, overlapping regions. The phasing is done in a way, which maximizes a natural maximum likelihood criterion. Among other things, this criterion takes into account the physical length between neighboring single nucleotide polymorphisms. The approach is very efficient and is applied to several large scale datasets and is shown to be successful in two recent benchmarking studies (Zaitlen et al., in press; Marchini et al., in preparation). Our method is publicly available via a webserver at .

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