Suchergebnisse

Single nucleotide polymorphisms (SNPs) have a great potential in genetic identification and introgression studies of honey bees (Apis mellifera). To achieve SNPs full power in genetic analysis, they must be screened in a rapid, accurate and cost-effective manner. Matrix-assisted laser desorption-ionization–time-of-flight (MALDI–TOF) mass spectrometry is a promising tool for the high-throughput screening of SNPs at an affordable cost in the post-genome sequencing era. In this study, a reduced SNP panel has been validated for Iberian honey bees (A. m. iberiensis) and a pooling strategy is presented for allele frequencies determination by using MALDI-TOF technology. The reduced SNP panel contains 127 most ancestry-informative loci design in the dark honey bee (A. m. mellifera). We demonstrate the utility of this methodology in samples of Iberian honey bees (A. m. iberiensis) selected for its pathogen tolerance and in genomic DNA pools. The described method reduces costs and time and enables genotyping of up to thousands of honey bee samples by taking advantage of the high-throughput MALDI-TOF technology. ; This research is funded through FEDER and INIA (E-RTA2014-00003-C03 and 01), Regional Government of Murcia (19908/GERM/2015, Fundación Séneca) and BeeHope project (138573-BiodivERsA/0002/2014). I. Muñoz acknowledges the support of a Saavedra Fajardo fellowship from the Fundación Séneca (20036/SF/16). ; info:eu-repo/semantics/publishedVersion

Chronic kidney disease (CKD) is a major public health concern around the world. UMOD gene variants are linked to a higher incidence of hypertension and CKD in the general population. This study aimed to investigate the role of uromodulin rs13333226 and rs13333144 genes association with chronic kidney disease.The study samples were divided into two groups. The first group included 100patient samples and 70 chosen among them were under the dialysis and had kidney failure aged between 18-88 years old. The second group included 30 samples from healthy individuals who were used as a control. One of the ways used to identify the genotype is the tetra-primers amplification refractory mutation system–polymerase chain reaction (ARMS–PCR). Regarding the results of SNP (rs13333226 and rs13333144), the genotypes GG (OR=150.3), and AA (OR=0.01) for rs13333226. The genotypes GG (OR=0.02) and TT(OR=140.4) for rs13333144 when comparing between patients and control (P≤ 0.01), they were observed when the odds ratio is less than 1 means they are preventive factors, while OR more than 1 means the risk increase (P≤ 0.01). It was concluded that there was an association between SNP (rs13333226 and rs13333144) and uromodulin in kidney diseases. Where genotype GG) rs13333226) and TT (rs13333144) represents a risk factor and AA rs13333226 and GG rs13333144 represents a protective factor.

Zhihong Wang,1,* Peng Tang,2,* Surong Hua,1 Junyi Gao,1 Bin Zhang,3 Hua Wan,4 Qixi Wu,4 Jiaxin Zhang,5 Ge Chen1 1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; 2Department of Breast and Thyroid Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China; 3Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China; 4Research and Development Department, Beijing USCI Medical Laboratory, Beijing, People's Republic of China; 5Department of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China*These authors contributed equally to this workCorrespondence: Ge ChenDepartment of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuai Fu Yuan Hu Tong, Beijing, 100730, People's Republic of China, Tel +86 156 1123 3738, Fax +86 156 69152600, Email chenge@pumch.cn; Jiaxin ZhangDepartment of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, No. 99, Huaihai West Road, Xuzhou, 221004, People's Republic of China, Tel +86 180 5226 8693, Fax +86 180 85802306, Email zhangjiaxin1969@163.comPurpose: To describe the genetic landscape and clinical characteristics of Chinese patients diagnosed with papillary thyroid cancer (PTC) and to determine which high-risk genetic characteristics suggest a likelihood of lymph node metastasis (LNM) and lateral lymph node metastasis (LLNM).Patients and Methods: Data from previously untreated patients with PTC collected between May 2018 and December 2020 from 14 hospitals in China were analyzed retrospectively. High-risk pathologic characteristics were defined as T3/T4, N(+), and N1b(+) stages. All patients were tested for 57 genes by second-generation sequencing. The t-test, chi-square test, and Fisher's exact test were performed for statistical analysis.Results: Overall, 395 patients were enrolled in this study. The prevalence of BRAF mutation was 78.53%. BRAF mutant allele frequency (MAF) > 16.93% was associated with a significantly higher risk of LNM, LLNM, and T3 + T4 stage compared with a low-risk group, defined by a MAF < 2.54% (odd ratios [ORs] for each risk=3.38, 3.46, and 8.54, respectively), and an intermediate-risk group, defined by a MAF of 2.54% to 16.93% (ORs=2.04, 2.07, and 4.07, respectively). The population with RET fusion had higher T, N, and N1b stages (ORs for each stage=10.40, 7.60, and 8.77, respectively) compared with a RET-negative population. Similar conclusions about T, N, and N1b stages were observed in relation to multiple driver gene mutations (ORs for each stage=7.48, 2.80, and 7.04, respectively) compared with population without multiple driver mutations. These genetic characteristics may be suggestive of high clinical risk. However, regardless of genetic profiles, patients younger than age 45 years had greater rates of LNM and LLNM.Conclusion: The main driver gene in this study, BRAF, differs significantly between the United States (79% vs 51%) and other countries. The Chinese population in this study that experienced more aggressive tumor biology had a BRAF MAF greater than 16.93%, exhibited RET fusion events, and had multiple driver gene mutations; thus, these traits may be considered high-risk genetic characteristics in PTC that could warrant aggressive treatment in such population.Keywords: papillary thyroid cancer, lymph node metastasis, high risk clinicopathological characteristics, genotypes

AbstractThe design and interpretation of genetic association studies depends on the relationship between the genotyped variants and the underlying functional variant, often parameterized as the squared correlation orr2measure of linkage disequilibrium between two loci. While it has long been recognized that placing a constraint on ther2between two loci also places a constraint on the difference in frequencies between the coupled alleles, this constraint has not been quantified. Here, quantification of this severe constraint is presented. For example, forr2≥ .8, the maximum difference in allele frequency is ± .06 which occurs when one locus has allele frequency .5. Forr2≥ .8 and allele frequency at one locus of .1, the maximum difference in allele frequency at the second locus is only ± .02. The impact on the design and interpretation of association studies is discussed.

This study was aimed to establish a database of autosomal Short Tandem Repeat (aSTR) DNA allele frequencies for an Iraqi population living in Baghdad city as a reference, therefore, a total of 456 unrelated individuals were analyzed at 15 STR DNA markers (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, CSF1PO, D19S433, D2S1338, D16S539) included in the Kit from Applied Biosystems. The obtained results revealed that the Combined Matching Probability (CMP) was estimated at 1 in 3.3287 × 10-18, and the Combined Discrimination Power (CDP) was greater than 0.98600987, which is comparable to values obtained with the many other allele frequency databases used in forensic investigations. It can be concluded that for identification purposes, it can be considered the multi-locus STR panels as a useful forensic tool.

SummaryThe allele frequency data of artificial populations were examined by several methods which test whether various configurations of allele frequencies are the result of drift or selection. Although no genotypic selective differences were included in these populations the methods indicated that selection was operating in some instances; hence the models are not reliable. Distinguishing between the actions of drift and selection would be facilitated if data for many loci were included, so that a notion of the variance of the genetic variation measure could be obtained.

<i>Objective:</i> To investigate the prevalence in the Michigan non-Hispanic Caucasian population of the C282Y, H63D and S65C mutations in the <i>HFE</i> gene associated with hereditary hemochromatosis. <i>Methods:</i> Polymerase chain reaction and restriction fragment length polymorphism analysis were performed on 3,532 blood samples from newborn screening cards provided by the state of Michigan. <i>Results:</i> More than 30% of Michigan Caucasians carry one <i>HFE</i> mutation, while 6% have two mutations. The allele frequency of the C282Y mutation is 5.7%, significantly higher than expected (p < 0.05), while the frequency of the H63D mutation is 14%, significantly lower than expected (p < 0.01). <i>Conclusions:</i> This is the first publication to examine <i>HFE</i> allele frequencies in an unbiased sample of the Caucasian population. Results indicate that the C282Y mutation may be more common in the non-Hispanic Caucasian population than previously reported, and medical problems related to iron overload may be a health concern for Michigan non-Hispanic Caucasians. Additional studies of penetrance for the C282Y allele are required to fully understand the impact of this information.

While several studies in a diverse set of species have shed light on the genes underlying adaptation, our knowledge on the selective pressures that explain the observed patterns lags behind. Drosophila melanogaster is a valuable organism to study environmental adaptation because this species originated in Southern Africa and has recently expanded worldwide, and also because it has a functionally well-annotated genome. In this study, we aimed to decipher which environmental variables are relevant for adaptation of D. melanogaster natural populations in Europe and North America. We analysed 36 whole-genome pool-seq samples of D. melanogaster natural populations collected in 20 European and 11 North American locations. We used the BayPass software to identify single nucleotide polymorphisms (SNPs) and transposable elements (TEs) showing signature of adaptive differentiation across populations, as well as significant associations with 59 environmental variables related to temperature, rainfall, evaporation, solar radiation, wind, daylight hours, and soil type. We found that in addition to temperature and rainfall, wind related variables are also relevant for D. melanogaster environmental adaptation. Interestingly, 23%–51% of the genes that showed significant associations with environmental variables were not found overly differentiated across populations. In addition to SNPs, we also identified 10 reference transposable element insertions associated with environmental variables. Our results showed that genome-environment association analysis can identify adaptive genetic variants that are undetected by population differentiation analysis while also allowing the identification of candidate environmental drivers of adaptation. ; We acknowledge the support from the European Drosophila Population Genomics Consortium (DrosEU), which is funded by a Special Topics Network (STN) grant from the European Society of Evolutionary Biology (ESEB). We also thank Thomas Flatt for comments on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (H2020-ERC-2014-CoG-647900). ; Peer reviewed