MODY 2: Mutation identification and molecular ancestry in a Brazilian family

Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil.     

互联网教育对超声住培教学的影响及思考

目的分析互联网教育对超声专业住培医师教学的影响。方法将我科接受超声专业住院医师规范化培训的50名住培医师为研究对象,其中以2019年1~4月的住培医师为对照组,以2020年1~4月的住培医师为实验组。对照组以传统教学方式教学,实验组以互联网教学为主要教学方式,两组住培医师通过考试成绩(笔试及技能)及问卷调查方法评估不同时期超声规范化培训的教学效果结果实验组的笔试和技能考核成绩低于对照组(P<0.05),考试通过率低于对照组(P<0.05)。从两组的问卷调查结果显示,实验组的住培医师认为在激发学习兴趣、提升交流能力、提高技能操作、满意带教老师、师生互动良好5个方面的肯定评价低于对照组(P<0.05);两组住培医师在关注人文关怀、临床思维培养2个方面比较,差异无统计学意义(P>0.05);两组在培养自学能力方面的肯定评价比较,实验组明显高于对照组(P<0.05)。与对照组比较,教师对实验组的教学气氛活跃、住培医师态度积极性及检查操作规范、报告书写规范4个方面的评价较低(P<0.05);教师对两组的课程安排与进度合理性的评价无差异性(P>0.05)。结论短期研究结果显示,以互联网教学为主的教学方式对超声住培教学质量造成一定负面影响,需加以教育经验总结,为今后教学工作的改进奠定基础。     

《免疫学基础与病原生物学》移动交互式数字教材在“抗疫”时期在线教学中的应用

新型冠状病毒肺炎疫情暴发以来,全国各级各类学校延期开学,但停课不停教、停课不停学。各学校教师利用各种网络资源开展在线教学,也为深入挖掘"互联网+教育"教学新模式带来了契机。本文以《免疫学基础与病原生物学》移动交互式数字教材(云教材)应用为例,介绍如何应用移动交互式数字教材创设合理的学习情境,从而实现交互式学习,提升线上学习教学效果。     

新型冠状病毒肺炎疫情对高校微生物学教学带来的挑战与发展机遇

突如其来的新型冠状病毒肺炎疫情使得网上在线教学成为这段时间的唯一教学方式。这一方面给高校的广大师生提出了新的挑战,但同时也给近年来一直进行的高等教育开放式教育教学改革发展潮流按下了加速键。《微生物学通报》以"第十七届全国微生物学教学和科研及成果产业化研讨会"为契机邀稿组织出版的这期"高等院校教学主题刊",很好地反映了近年来在开放式教育形势下我国微生物学教学改革与人才培养的最新进展和发展态势,其中也有文章介绍了疫情期间选择和使用线上教学技术的经验。期望该主题刊的出版有助于进一步促进广大微生物学教师强化互联网意识,打造"互联网+"思维,重塑课堂教学形态,通过广大教师间的教改经验交流与合作,进一步促进我国微生物学课程建设水平与教学质量的全面提升。     

Phenotype and Micro-array characterization of duplication 11q22.1-q25 and review of the literature

Partial duplication of 11q is related to several malformations like growth retardation, intellectual disability, hypoplasia of corpus callosum, short nose, palate defects, cardiac, urinary tract abnormalities and neural tube defects. We have studied the clinical and molecular characteristics of a patient with severe intellectual disabilities, dysmorphic features, congenital inguinal hernia and congenital cerebral malformation which is referred to as cytogenetic exploration. We have used FISH and array CGH analysis for a better understanding of the double chromosomic aberration involving a 7p microdeletion along with a partial duplication of 11q due to adjacent segregation of a paternal reciprocal translocation t(7;11)(p22;q21) revealed after banding analysis. The patient's karyotype formula was: 46,XY,der(7)t(7;11)(p22;q21)pat. FISH study confirmed these rearrangement and array CGH technique showed precisely the loss of at least 140 Kb on chromosome7p22.3pter and 33.4 Mb on chromosome11q22.1q25. Dysmorphic features, severe intellectual disability and brain malformations could result from the 11q22.1q25 trisomy. Our study provides an additional case for better understanding and delineating the partial duplication 11q.     

Diagnostic utility of HFE variants in Spanish patients: Association with HLA alleles and role in susceptibility to acute lymphoblastic leukemia

Two single nucleotide polymorphisms (SNPs) in the Human Hemochromatosis (HFE) gene, C282Y and H63D, are the major variants associated to altered iron status and it is well known that these mutations are in linkage disequilibrium with certain Human Leukocyte Antigen (HLA)-A alleles. In addition, the C282Y SNP has been previously suggested to confer susceptibility to acute lymphoblastic leukemia (ALL). We have aimed to assess the diagnosis utility of these polymorphisms in a population of Spanish subjects with suspicion of hereditary iron overload and to evaluate the effect of their associations with HLA-A alleles on the susceptibility to ALL. Both the 63DD [OR = 4.31 (1.7–11.2)] and 282YY (p for trend = 0.02) genotypes were more frequently found among subjects with suspicion of iron overload than among controls. 282YY carriers displayed significantly higher transferrin saturation index (TSI) values (p < 0.001) as well as serum iron (p = 0.01) and ferritin (p = 0.01) levels. In addition, transferrin levels were lower in these subjects (p = 0.01). Likewise, patients who were carriers of the compound heterozygous diplotype (282CY/63HD) showed significantly higher TSI and serum iron and ferritin concentrations. The H63D SNP did not significantly affect the analytical parameters measured. All 282YY carriers and 69.2% of compound heterozygotes showed an altered biochemical index. The frequencies of the HFE SNPs in ALL pediatric patients were lower than those found in controls, whereas the HLA-A*24 allele was significantly overrepresented in the patients group [OR = 3.76 (1.9–7.3)]. No HFE-HLA-A associations were found to modulate the ALL risk. These results suggest that it may be useful to test for both HFE H63D and C282Y polymorphisms in patients with iron overload, as opposed to just genotyping for the C282Y SNP, which is customary in some healthcare centers. These HFE variants and their associations with HLA-A alleles were not observed to be relevant for the susceptibility to ALL in our population.     

Prenatal diagnosis and molecular cytogenetic characterization of a de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14)

We present prenatal diagnosis of de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14) and molecular cytogenetic characterization of the deletion using uncultured amniocytes. We review the phenotypic abnormalities of previously reported patients with similar proximal interstitial 4p deletions, and we discuss the functions of the genes of RBPJ, CCKAR, STIM2, PCDH7 and ARAP2 that are deleted within this region.     

Rule extraction in gene–disease relationship discovery

Background

Biomedical data available to researchers and clinicians have increased dramatically over the past years because of the exponential growth of knowledge in medical biology. It is difficult for curators to go through all of the unstructured documents so as to curate the information to the database. Associating genes with diseases is important because it is a fundamental challenge in human health with applications to understanding disease properties and developing new techniques for prevention, diagnosis and therapy.

Methods

Our study uses the automatic rule-learning approach to gene–disease relationship extraction. We first prepare the experimental corpus from MEDLINE and OMIM. A parser is applied to produce some grammatical information. We then learn all possible rules that discriminate relevant from irrelevant sentences. After that, we compute the scores of the learned rules in order to select rules of interest. As a result, a set of rules is generated.

Results

We produce the learned rules automatically from the 1000 positive and 1000 negative sentences. The test set includes 400 sentences composed of 200 positives and 200 negatives. Precision, recall and F-score served as our evaluation metrics. The results reveal that the maximal precision rate is 77.8% and the maximal recall rate is 63.5%. The maximal F-score is 66.9% where the precision rate is 70.6% and the recall rate is 63.5%.

Conclusions

We employ the rule-learning approach to extract gene–disease relationships. Our main contributions are to build rules automatically and to support a more complete set of rules than a manually generated one. The experiments show exhilarating results and some improving efforts will be made in the future.