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81.
Killer‐cell immunoglobulin‐like receptors (KIR) and their human leukocyte antigen (HLA) ligands play a central role in immunity and human health. These molecules are encoded by gene families with copy number variation, extreme levels of sequence diversity and complex expression patterns. The rapid evolution of KIR and HLA genes and their associations with infectious diseases, pregnancy disorders, immunopathologies and outcome of cell transplantation have generated considerable interest from immunologists, geneticists and clinicians. Until recently, however, analyses have been stuck at low‐level resolution, focusing primarily on presence or absence of KIR genes. This is changing with the advent of modern high throughput sequencing, cell phenotyping and bioinformatics. These developments allow high‐resolution analysis and much deeper understanding of KIR evolution and KIR function. The impending deluge of high dimensional data brings inevitably new challenges in analysis, interpretation and communication of results, but the benefits are already tangible. The diversity of KIR across worldwide human populations is being catalogued at the allele level. Structures of KIR molecules and their interactions with HLA–peptide complexes are being determined. How KIR modulate natural killer cell education is being defined. Ligands for activating KIR, elusive for many years, are being discovered. KIR gene complexes and their related receptor gene families are being characterized in animal models and livestock breeds. These advances are helping to generate a more complete picture of the impact of KIR variation in health and disease and offer new opportunities for immunotherapy, as highlighted in a recent meeting (The Tenth KIR Workshop, April 2017 Cambridge, UK). 相似文献
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Advances in genetics hold promise for integrating genomics into vaccine safety research. Given the rarity of many vaccine adverse effects, and the challenges in finding sufficient numbers of patients to study, consideration should be given to employing the Vaccine Adverse Event Reporting System (VAERS) for genetic studies of vaccine adverse events. VAERS could be used to build a repository of biospecimens allowing for the systematic evaluation of vaccine adverse events. If successful, such research would enable the identification of specific subgroups of people at particularly increased risk for adverse events. 相似文献
84.
Mycobacterium abscessus is an emerging cause of respiratory disease and soft tissue infections. Whole genome sequencing and other molecular approaches are enhancing our understanding of outbreaks, antibiotic resistance mechanisms, and virulence properties, and of the phylogeny of the M. abscessus complex. Infection models are providing further insights into factors such as colony phenotype that impact host-pathogen interactions. This paper reviews recent developments in our understanding of genetic variation in M. abscessus and the potential relevance for disease and treatment. 相似文献
85.
深低温对全脑缺血大鼠海马即早基因组表达的影响 总被引:1,自引:0,他引:1
目的筛选出深低温对全脑缺血大鼠海马影响的即早差异表达基因。方法建立大鼠体外循环模型,实验分成两组,常温缺血组(n=3):常温条件下停循环全脑缺血5min;低温缺血组(n=3):深低温条件下停循环全脑缺血5min。采用Affymetrix大鼠全基因组芯片检测两组动物海马基因表达的变化,获取差异表达基因。结果筛选出差异表达基因共有75个,其中39个基因表达有统计学意义(P〈0.01),上调33个,下调42个。结论深低温对全脑缺血大鼠海马即早基因表达有明显影响,这些差异表达基因可能与深低温脑保护作用相关。 相似文献
86.
Use of genomics to select antibacterial targets 总被引:1,自引:0,他引:1
Pucci MJ 《Biochemical pharmacology》2006,71(7):1066-1072
The problem of antibiotic resistance has eroded the usefulness of our arsenal of effective antibiotics. There is a need for new strategies to discover and develop new, effective drugs. The advent of the microbial genomics era has provided a wealth of information on a variety of microorganisms. This has allowed the identification and/or validation of a number of gene products that could serve as targets for the discovery of novel antibacterial agents. New genetic techniques and approaches have arisen in an attempt to exploit this newly available genomic data. Both random and targeted gene disruption efforts have proven effective in this process. Many of these methods would have been difficult to accomplish without DNA sequence and bioinformatics analyses. Several targets have been selected to further characterize and screen for inhibitors and one has yielded two clinical candidates. 相似文献
87.
Fernández Madrid F 《Cancer letters》2005,230(2):187-198
A plethora of promising breast cancer-associated autoantigens have been cloned by immunoscreening cDNA expression libraries with breast cancer sera or identified using proteomics, yet no biomarkers, whether individual autoantigens or panels of antigens developed using antibody-based methods have been validated and incorporated to routine oncologic practice for the early diagnosis of breast cancer. Recently, the addition of genomics, proteomics and high throughput technology to traditional immunological techniques has revived the interest in this field, and some of the most promising breast cancer autoantigens are in the process of being validated prospectively in large cohorts of patients with breast cancer. In addition, some of the identified breast cancer-associated autoantigens are recognized by T-cells and may prove to have a role in the treatment of breast cancer in the future. Autoantibodies found in breast cancer patient sera provide important clues about their significance. The discovery of breast cancer-associated antigens has provocative implications beyond the quest for novel diagnostic biomarkers, because autoantibodies target molecules involved in signal transduction, cell cycle regulation, cell proliferation and apoptosis, all of them key processes in carcinogenesis. Molecular components of the DNA double-strand break repair machinery as well as several members of the rapamycin-sensitive pathway elicit an autoantibody response in breast cancer. Data obtained by screening cDNA expression libraries of breast cancer antigens with autoantibodies present in breast cancer sera suggest that autoantibodies in cancer sera may be linked to the process of apoptosis. The studies reviewed here, clearly demonstrate the participation of autoimmunity in breast cancer to an extent previously unsuspected, which may have broad implications for the discovery of molecular targets for drug therapy and cancer biomarkers in general. 相似文献
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下一代测序技术在分子诊断中的应用 总被引:1,自引:0,他引:1
DNA测序是破译人类疾病的一种强大技术,尤其在癌症方面。飞速发展的下一代测序(next—generation sequencing,NGS)极大降低了测序成本,并且实现了高通量,这使我们可以获得整个基因组的序列,以及那些临床上确诊病人的全部基因组信息。然而下一代测序技术带来诸多益处的同时也带来了挑战,那就是怎样使这个技术在临床诊断中成为常规手段。本文就目前NGS的几大技术平台原理,在临床诊断中的应用,以及目前面临的挑战等进行综述。 相似文献