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Recent advances in understanding genetic variants associated with economically important traits in sheep

Song-Song XU, Meng-Hua LI

《农业科学与工程前沿（英文）》 2017年第4卷第3期页码 279-288 doi: 10.15302/J-FASE-2017151

摘要： Sheep are one of the most economically important domesticated animals for human society. However, genetic improvements for the key traits associated with meat, growth, milk, wool, reproduction, horns and tails progress slowly using conventional crossbreeding methods. With the development and utilization of high-throughput screening technologies over the last decade, a list of functional genes and genetic variants associated with these traits has been identified. This review covers recent genome-wide studies on sheep productive traits using high-throughput screening technologies, including those based on single-nucleotide polymorphisms and copy number variants at the whole-genome level (e.g., genome-wide association studies), transcriptome and DNA methylation sequences. Additionally, comprehensive information on functional genes and genetic variants associated with economically important traits in sheep is provided.

关键词： sheep high-throughput screening productive traits genome-wide studies

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Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

《医学前沿（英文）》 2015年第9卷第2期页码 146-161 doi: 10.1007/s11684-014-0373-8

摘要：

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

关键词： obesity genetics genome-wide association studies body mass index fat mass- and obesity-associated gene

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SARS-CoV-2 variants, immune escape, and countermeasures

《医学前沿（英文）》 2022年第16卷第2期页码 196-207 doi: 10.1007/s11684-021-0906-x

摘要： Coronavirus disease 2019 (COVID-19) has become a global pandemic disease. SARS-CoV-2 variants have aroused great concern and are expected to continue spreading. Although many countries have promoted roll-out vaccination, the immune barrier has not yet been fully established, indicating that populations remain susceptible to infection. In this review, we summarize the literature on variants of concern and focus on the changes in their transmissibility, pathogenicity, and resistance to the immunity constructed by current vaccines. Furthermore, we analyzed relationships between variants and breakthrough infections, as well as the paradigm of new variants in countries with high vaccination rates. Terminating transmission, continuing to strengthen variant surveillance, and combining nonpharmaceutical intervention measures and vaccines are necessary to control these variants.

关键词： SARS-CoV-2 COVID-19 vaccine immune escape breakthrough prevention

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A review on the electric vehicle routing problems: Variants and algorithms

Hu QIN , Xinxin SU, Teng REN, Zhixing LUO

《工程管理前沿（英文）》 2021年第8卷第3期页码 370-389 doi: 10.1007/s42524-021-0157-1

摘要： Over the past decade, electric vehicles (EVs) have been considered in a growing number of models and methods for vehicle routing problems (VRPs). This study presents a comprehensive survey of EV routing problems and their many variants. We only consider the problems in which each vehicle may visit multiple vertices and be recharged during the trip. The related literature can be roughly divided into nine classes: Electric traveling salesman problem, green VRP, electric VRP, mixed electric VRP, electric location routing problem, hybrid electric VRP, electric dial-a-ride problem, electric two-echelon VRP, and electric pickup and delivery problem. For each of these nine classes, we focus on reviewing the settings of problem variants and the algorithms used to obtain their solutions.

关键词： electric vehicles routing recharging stations exact algorithms metaheuristics

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Penetrance estimation of variants in paroxysmal kinesigenic dyskinesia and infantile convulsions

《医学前沿（英文）》 2021年第15卷第6期页码 877-886 doi: 10.1007/s11684-021-0863-4

摘要： Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP) PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers. PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5%–80.7%) in relatives and 74.5% (95% CI 70.2%–78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%, P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%, P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.

关键词： penetrance PRRT2 paroxysmal kinesigenic dyskinesia infantile convulsions

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Identification of variants associated with sporadic thoracic aortic dissection: a case--control study

《医学前沿（英文）》 2021年第15卷第3期页码 438-447 doi: 10.1007/s11684-020-0826-1

摘要： Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10⁻⁶) after 10 000 times permutation test (P = 2.49 × 10⁻³). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.

关键词： sporadic thoracic aortic dissection exome sequencing gene COL3A1 case–control study extracellular matrix

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R158Q and G212S, novel pathogenic compound heterozygous variants in of Gitelman syndrome

《医学前沿（英文）》页码 932-945 doi: 10.1007/s11684-022-0963-9

摘要： The dysfunction of Na⁺-Cl⁻ cotransporter (NCC) caused by mutations in solute carrier family12, member 3 gene (SLC12A3) primarily causes Gitelman syndrome (GS). In identifying the pathogenicity of R158Q and G212S variants of SLC12A3, we evaluated the pathogenicity by bioinformatic, expression, and localization analysis of two variants from a patient in our cohort. The prediction of mutant protein showed that p.R158Q and p.G212S could alter protein’s three-dimensional structure. Western blot showed a decrease of mutant Ncc. Immunofluorescence of the two mutations revealed a diffuse positive staining below the plasma membrane. Meanwhile, we conducted a compound heterozygous model—Ncc R156Q/G210S mice corresponding to human NCC R158Q/G212S. Ncc^R156Q/G210S mice clearly exhibited typical GS features, including hypokalemia, hypomagnesemia, and increased fractional excretion of K⁺ and Mg²⁺ with a normal blood pressure level, which made Ncc^R156Q/G210S mice an optimal mouse model for further study of GS. A dramatic decrease and abnormal localization of the mutant Ncc in distal convoluted tubules contributed to the phenotype. The hydrochlorothiazide test showed a loss of function of mutant Ncc in Ncc^R156Q/G210S mice. These findings indicated that R158Q and G212S variants of SLC12A3 were pathogenic variants of GS.

关键词： Gitelman syndrome mouse model compound heterozygous hypokalemia Slc12a3

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Novel variants in and and recurrent variant in underlying epidermolysis bullosa in five Chinese families

《医学前沿（英文）》页码 808-814 doi: 10.1007/s11684-021-0878-x

摘要： Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47G>A, p.W16*) in LAMA3, a known recurrent variant (c.74C>T, p.P25L) in KRT5, 2 novel (c.2531T>A, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187C>T, p.R2063W; c.7097G>A, p.G2366D; c.8569G>T, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.

关键词： epidermolysis bullosa LAMA3 COL7A1 KRT5 Chinese families

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U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population

null

《医学前沿（英文）》 2015年第9卷第4期页码 478-486 doi: 10.1007/s11684-015-0420-0

摘要：

Telomeres play a critical role in biological ageing by maintaining chromosomal integrity and preventing chromosome ends fusion. Epidemiological studies have suggested that inter-individual differences of telomere length could affect predisposition to multiple cancers, but evidence regarding esophageal squamous cell carcinoma (ESCC) was still uncertain. Several telomere length-related single nucleotide polymorphisms (TL-SNPs) in Caucasians have been reported in genome-wide association studies. However, the effects of telomere length and TL-SNPs on ESCC development are unclear. Therefore, we conducted a case-control study (1045 ESCC cases and 1433 controls) to evaluate the associations between telomere length, TL-SNPs, and ESCC risk in Chinese population. As a result, ESCC cases showed overall shorter relative telomere length (RTL) (median: 1.34) than controls (median: 1.50, P<0.001). More interestingly, an evident nonlinear U-shaped association was observed between RTL and ESCC risk (P<0.001), with odds ratios (95% confidence interval) equal to 2.40 (1.84–3.14), 1.36 (1.03–1.79), 1.01 (0.76–1.35), and 1.37 (1.03–1.82) for individuals in the 1st (the shortest), 2nd, 3rd, and 5th (the longest) quintile, respectively, compared with those in the 4th quintile as reference group. No significant associations were observed between the eight reported TL-SNPs and ESCC susceptibility. These findings suggest that either short or extremely long telomeres may be risk factors for ESCC in the Chinese population.

关键词： esophageal squamous cell carcinoma telomere length genetic variants susceptibility genome-wide association study

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新冠病毒变异株——新型mRNA疫苗能否经受挑战？

Jennifer Welsh

《工程（英文）》 2021年第7卷第6期页码 712-714 doi: 10.1016/j.eng.2021.04.005

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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between

Na Qin, Yuancheng Li, Cheng Wang, Meng Zhu, Juncheng Dai, Tongtong Hong, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary Goodman, Stig E. Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, H-Erich Wichmann, Heike Bickeboller, Gadi Rennert, Susanne Arnold, Paul Brennan, John K. Field, Sanjay Shete, Loic Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J. Hung, Angeline Andrew, Lambertus A. Kiemeney, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil Caporaso, Penella Woll, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Victoria L. Stevens, Guangfu Jin, David C. Christiani, Zhibin Hu, Christopher I. Amos, Hongxia Ma, Hongbing Shen

《医学前沿（英文）》 2021年第15卷第2期页码 275-291 doi: 10.1007/s11684-020-0779-4

摘要： Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER=1.95, =0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination

《医学前沿（英文）》 doi: 10.1007/s11684-022-0954-x

摘要： Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

关键词： COVID-19 convalescent SARS-CoV-2 inactivated vaccination neutralizing antibody B cell response

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Research progress on genetic improvement of

Chuanping YANG

《农业科学与工程前沿（英文）》 2017年第4卷第4期页码 391-401 doi: 10.15302/J-FASE-2017183

摘要： Suk. is one of the most widely distributed species of , the fourth most valuable timber species in north-eastern China and also a common tree species for landscaping. Over the past 30 years, effective progress has been made in genetic improvement and molecular breeding of . There has been extensive research on breeding techniques, including the collection and conservation of germplasm resources, provenance trials, intensive breeding techniques, crossbreeding and asexual propagation techniques, ploidy breeding and mutation breeding technology, genome sequencing, gene cloning, transgenic and molecular mechanisms of wood formation. A germplasm resource collection has been established by collecting different provenances, and full-sib and half-sib families. In addition, the geographic variation patterns of provenances have been revealed, and the provenance division and superior provenance selections made. flowering and seeding have been improved through intensive breeding techniques. Interspecific hybridization, intraspecific hybridization and parallel crosses were made using fine parents, and intensive seed orchards have been established. Systems of asexual propagation, including cuttings, grafting and tissue culture have been established. A tetraploid was successfully constructed and a triploid seed orchard established. The growth, wood property and resistance genes of have been cloned. An efficient transgenic system mediated by was established, and genes encoding insect resistance, drought resistance and salt tolerance, lignin synthesis, flowering, hormone transport and balance obtained. molecular markers were developed and the high density genetic map constructed. All this research has provided a model and data for the foundation of forest genetic improvement and applied research.

关键词： Betula platyphylla genetic improvement molecular breeding seed orchard

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Interplay between diet and genetic susceptibility in obesity and related traits

Tiange Wang, Min Xu, Yufang Bi, Guang Ning

《医学前沿（英文）》 2018年第12卷第6期页码 601-607 doi: 10.1007/s11684-018-0648-6

摘要：

The incidence of obesity has been rapidly increasing, and this condition has become a major public health threat. A substantial shift in environmental factors and lifestyle, such as unhealthy diet, is among the major driving forces of the global obesity pandemic. Longitudinal studies and randomized intervention trials have shown that genetic susceptibility to obesity may interact with dietary factors in relation to the body mass index and risk of obesity. This review summarized data from recent longitudinal studies and intervention studies on variations and diets and discussed the challenges and future prospects related to this area and public health implications.

关键词： diet genetic susceptibility obesity interaction

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Optimal design of steel skeletal structures using the enhanced genetic algorithm methodology

Tugrul TALASLIOGLU

《结构与土木工程前沿（英文）》 2019年第13卷第4期页码 863-889 doi: 10.1007/s11709-019-0523-9

摘要： This study concerns with the design optimization of steel skeletal structures thereby utilizing both a real-life specification provisions and ready steel profiles named hot-rolled I sections. For this purpose, the enhanced genetic algorithm methodology named EGAwMP is utilized as an optimization tool. The evolutionary search mechanism of EGAwMP is constituted on the basis of generational genetic algorithm (GGA). The exploration capacity of EGAwMP is improved in a way of dividing an entire population into sub-populations and using of a radial basis neural network for dynamically adjustment of EGAwMP’s genetic operator parameters. In order to improve the exploitation capability of EGAwMP, the proposed neural network implementation is also utilized for prediction of more accurate design variables associating with a new design strategy, design codes of which are based on the provisions of LRFD_AISC V3 specification. EGAwMP is applied to determine the real-life ready steel profiles for the optimal design of skeletal structures with 105, 200, 444, and 942 members. EGAwMP accomplishes to increase the quality degrees of optimum designations Furthermore, the importance of using the real-life steel profiles and design codes is also demonstrated. Consequently, EGAwMP is suggested as a design optimization tool for the real-life steel skeletal structures.

关键词： design optimization genetic algorithm multiple populations neural network

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标题作者时间类型操作

Recent advances in understanding genetic variants associated with economically important traits in sheep

Song-Song XU, Meng-Hua LI

期刊论文

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

期刊论文

SARS-CoV-2 variants, immune escape, and countermeasures

期刊论文

A review on the electric vehicle routing problems: Variants and algorithms

Hu QIN , Xinxin SU, Teng REN, Zhixing LUO

期刊论文

Penetrance estimation of variants in paroxysmal kinesigenic dyskinesia and infantile convulsions

期刊论文

Identification of variants associated with sporadic thoracic aortic dissection: a case--control study

期刊论文

R158Q and G212S, novel pathogenic compound heterozygous variants in of Gitelman syndrome

期刊论文

Novel variants in and and recurrent variant in underlying epidermolysis bullosa in five Chinese families

期刊论文

U-shaped association between telomere length and esophageal squamous cell carcinoma risk: a case-control study in Chinese population

null

期刊论文

新冠病毒变异株——新型mRNA疫苗能否经受挑战？

Jennifer Welsh

期刊论文

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between

期刊论文

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination

期刊论文

Research progress on genetic improvement of

Chuanping YANG

期刊论文

Interplay between diet and genetic susceptibility in obesity and related traits

Tiange Wang, Min Xu, Yufang Bi, Guang Ning

期刊论文

Optimal design of steel skeletal structures using the enhanced genetic algorithm methodology

Tugrul TALASLIOGLU

期刊论文

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