New alleles at microsatellite loci in CEPH families mainly arise from somatic mutations in the lymphoblastoid cell lines

In the analysis of 40 CEPH families, under the EUROGEM project, with a total of 29 microsatellites (26 CA-repeats, a TCTA-repeat within the vWFII-3 gene, a TTA-repeat within the PLA-2 gene, and an AAAT-repeat intragenic to the NF1 gene) from human chromosomes 12, 17, and 21, we have detected 21 cases of abnormal segregation of alleles in 16 pedigrees for a total of 14 markers (48%). In 11 cases, the abnormal transmissions were of somatic origin, 10 of which (91%) occurred in the lymphoblastoid cell lines. In 9 other cases, it was not possible to determine if the origin of the new alleles was somatic or germline, and in one case hemizygosity in several family members was observed, so its origin was germline. The 20 new mutations detected in the 22,852 meioses analysed represent a mutation frequency of 8.7 × 10^?4 per locus per allele. The germline mutation rate could be as high as 3.9 × 10^?4 per locus per gamete (from 0 to 3.9 × 10^?4), but the rate of somatic mutations detected in the study was much higher (4.8 × 10^?4 to 8.7 × 10^?4 per locus per allele). Individual mutation rates ranged from 0 to 3.8 × 10^?3. Among the markers analysed, all three that were tri- or tetranucleotide repeats showed one or two new alleles, compared to only 10 of the 26 (38%) CA-repeats showing mutations. Three CEPH families (102, 45 and 1333) each had several mutational events, and one individual (10210) had somatic mutations for two microsatellites from different chromosomes. The mutation rate at microsatellite loci within families, using DNA directly obtained from cells from the individual, is less than 1 × 10^?4 (true germline mutation rate), which should not affect the use of these markers in diagnosis and linkage. However, these results and previous data suggest that for DNA obtained from cell lines, mutations are much more frequent (1 × 10^?2?1 × 10^?3). © 1994 Wiley-Liss, Inc.     

湖南汉族人群HLA-DR位点等位基因多态性与鼻咽癌的相关性研究

目的：探讨湖南汉族人群HLA-DR位点等位基因多态性与鼻咽癌遗传易感性之间的关系。 方法： 应用PCR/SSO基因分型技术对93例湖南汉族鼻咽癌患者和93例健康对照作HLA-DRB1、-DRB3、-DRB4、-DRB5基因分型，采用χ2检验比较两组各位点等位基因频率、单倍型频率分布的差异。 结果： NPC组DRB1*1101明显低于对照组，DRB1*0801明显高于对照组, 但P值经Bonferroni校正后，差异均无显著（Pc>0.05）。 结论： 湖南汉族人群HLA-DR位点与鼻咽癌无明显相关。     

细针穿刺检测BRAFV600E突变丰度与甲状腺乳头状癌临床病理特征的相关性

目的：探讨术前细针穿刺基因检测BRAF^V600E突变丰度与甲状腺乳头状癌(papillary thyroid cancer,PTC)临床病理特征的关系。方法：回顾性统计2021年1月30日至2022年2月28日就诊于南京中医药大学附属中西医结合医院的301例患者临床资料,术前细针穿刺基因检测示BRAF^V600E突变(含突变丰度检测),所有患者完成甲状腺癌根治术,术后病理证实为甲状腺乳头状癌,分析BRAF^V600E基因突变丰度与临床病理特征的关系。结果：纳入301例患者,男91例,女210例,年龄42(33～51)岁,范围18～69岁。肿瘤直径>1 cm的患者BRAF^V600E基因突变丰度高于肿瘤直径≤1 cm者[29.05(18.03～37.56) vs.18.35(6.74～29.61),P<0.001],颈部淋巴结转移患者BRAF^V600E基因突变丰度高于无颈部淋巴结转移者[24.72(8.08～34.32) vs.18(8.68～28.54),P=0.040]...     

SBT、SSOP法分析湖北土家族妇女HLA-A2超型各等位基因及与宫颈癌的关联

目的通过检测湖北土家族人群HLA-A2超型(包含A*0201、A*0202、A*0203、A*0204、A*0205、A*0206、A*0207、A*6802、A*6901)各等位基因,分析与宫颈癌关联的等位基因及其结构与功能特点.方法提取湖北土家族正常人群236名育龄妇女及59例原发性宫颈癌患者外周血DNA,采用SBT(sequence based typing)、SSOP(Sequence Specific Oligonucleotide Probes)HLA基因分型技术,对HLA-A2超型各等位基因型进行分型,比较宫颈癌病例组和正常对照组中HLA-A2超型中相应等位基因型构成比的差异,并分析相关等位基因的结构特点.结果有7种HLA-A2超型等位基因HLA-A*0201(17.3%)HLA-A*0202(9.5%)HLA A*0203(1.4%)HLA-A*0204(3.8%)HLA-A*0205(3.1%)HLA-A*0206(10.8%)HLA-A*0207/0215N(9.8%),其中HLA-A*0202和HLA A*0206在正常对照组和宫颈癌病人组的构成比有显著性差异(p＜0.05),HLA-A*0202(OR=0.24,95%CI=0.05～0.48)和HLA A*0206(OR=0.2,95%CI=0.67～1.07)对于宫颈癌发生的易感性有保护作用.结论湖北土家族人群HLA-A*0201所占比例最高达17.3%,HLA-A*0202和HLA-A*0206对于宫颈癌发生的易感性有保护作用.     

XRCC1单核苷酸多态及单体型分布与乳腺癌的相关研究

目的：探讨X线交叉互补基因1（XRCC1）外显子C26304T、G27466A和G28152A三处最常见的单核苷酸多态性（single nucleotide polymorphism，SNP）与乳腺癌的关系。方法：以自然人群为基础的病例对照研究方法，对84例乳腺癌患者组和以1：3成组频数匹配原则获得的252例对照组进行研究，XRCC1 C26304T、G27466A和G28152A SNPs基因分型采用聚合酶链反应-限制性内切酶片段长度多态性（polymerase chain reaction—restriction fragment length polymorphism，PCR—RFLP）分析方法。单体型分布采用EH linkage software 1．2分析软件进行预测和比较。结果：乳腺癌患者组和对照组吸烟状况分布差异有显著性，病例组曾经或现在吸烟个体比例7．1％明显高于对照组2．0％（P〈0．05），性别、年龄、饮酒状况及一二级亲属家族恶性肿瘤史等基本特征因素分布差异均无显著性（P〉0．05）。C26304T、G27466A和G28152A SNPs多态基因型和多态等位基因分布在两组间分布差异均无显著性（P〉0．05）。经上述因素校正后，XRCC1 SNPs与乳腺癌发病没有显著相关关系（P〉0．05）。应用EH linkage software 1．2单体型分析软件显示，XRCC1 SNPs在各组内均存在连锁不平衡现象，CGG、CGA、CAG和TGG是最常见的4类单体型。单体型组间分布同样不存在显著性差异（P〉0．05）。结论：XRCC1 C26304T、G27466A和G28152A SNPs与乳腺癌的风险没有相关关系，各SNPs存在连锁不平衡现象，CGG、CGA、CAG和TGG是最常见的4类单体型。     

甲状腺乳头状癌突变等位基因肿瘤异质性的临床及其与预后相关性研究

目的探讨突变等位基因肿瘤异质性(MATH)在甲状腺乳头状癌（PTC）中的临床意义。 方法从癌症基因图谱公共数据集下载并预处理PTC肿瘤测序数据及临床资料数据，分析MATH与PTC临床病理特征的相关性，使用Kaplan-Meier法进行生存分析，验证MATH对PTC患者的预后价值。 结果PTC患者中MATH值为2.57~93.72，平均29.45±16.19；将≥29.45者纳入高MATH组，<29.45者纳入低MATH组。高MATH组与低MATH组的患者年龄、性别、临床分期、BRAF基因型差异无统计学意义（P>0.05）。MATH不是PTC患者总体生存期（OS）的显著预测因素（P=0.4595）；在BRAF突变型PTC患者中，高MATH者的OS低于低MATH者（P=0.0252），而在BRAF野生型PTC患者中，高MATH者的OS高于低MATH者（P=0.0495）。 结论MATH可在BRAF突变型和野生型亚组中可预测PTC患者的预后及指导临床治疗。     

Association Between Gut Microbial Abundance and Sight-Threatening Diabetic Retinopathy

PurposeTo study the association between gut microbial abundance and sight-threatening diabetic retinopathy among patients with a history of type 2 diabetes mellitus.MethodsAn observational case-control study was performed using a sample population of diabetics referred to a tertiary eye institute. Sample subjects were identified as cases if they were diagnosed with sight-threatening diabetic retinopathy and controls if they were not but had at least a 10-year history of diabetes. Fecal swabs for all patients were collected for enumeration and identification of sequenced gut microbes. Statistical analyses were performed to associate the clinically relevant Bacteroidetes to Firmicutes relative abundance ratio (B/F ratio) with sight-threatening diabetic retinopathy and an optimal cutoff value for the ratio was identified using Youden''s J statistics.ResultsA sample size of 58 diabetic patients was selected (37 cases, 21 controls). No statistically significant difference in the relative abundance among the predominant phyla between the groups were found. In our univariate analysis, the B/F ratio was elevated in cases compared to controls (cases, 1.45; controls, 0.94; P = 0.049). However, this statistically significant difference was not seen in our multivariate regression model. Optimal cutoff value of 1.05 for the B/F ratio was identified, and significant clustering of cases above this value was noted in beta diversity plotting.ConclusionsNo difference in gut microbial abundance for any particular phylum was noted between the control and diseased population. Increased gut microbial B/F ratio can be a potential biomarker for the development of sight-threatening diabetic retinopathy among type 2 diabetic patients.     

Protein expression of various hepatic uridine 5′‐diphosphate glucuronosyltransferase (UGT) enzymes and their inter‐correlations: a meta‐analysis

Avoiding cytochrome P450 (CYP) related drug interactions in the development of new drug candidates means that glucuronidation by uridine 5′‐diphosphate glucuronosyltransferase (UGT) enzymes is expected to become a more prominent pathway in the metabolism of new drug candidates designed by pharmaceutical companies. Therefore, determining the abundance and activity of these enzymes is of value in the process of scaling in vitro data to in vivo metabolic parameters. Many of the studies involving the measurement of UGTs were conducted with too few samples, which did not provide a good indication of population values and the level of variability. Meta‐analysis is used in the current study to combine all reported values (eight studies that used LC‐MS isotope‐labelled standard targeted quantitative methods), detect inconsistencies between the various datasets and describe correlations of expression between the quantified UGT enzymes. Some heterogeneity was observed between studies, especially in the UGT1A4, 2B7 and 2B10 datasets. However, in the absence of information on the inter‐laboratory consistency of assays, it is difficult to assign these differences to the heterogeneity of the samples. Large inter‐individual variability was observed in the collated data across this family of enzymes. Positive correlations between the expression levels of certain UGT enzymes were found in the collated data. These included the pairs: UGT1A4/2B4 (r_s = 0.71, p < 0.0001, n = 82), UGT2B4/2B15 (r_s = 0.63, p < 0.0001, n = 83), UGT2B7/2B15 (r_s = 0.81, p < 0.0001, n = 99). These correlations can be explained by common regulatory mechanisms involved in the expression of these proteins. Copyright © 2014 John Wiley & Sons, Ltd.