Genetic diversity of HLA system in a population sample from Aguascalientes,Mexico

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 95 Mexicans from the state of Aguascalientes to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes in the state of Aguascalientes include four Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Aguascalientes are Native American (54.53 ± 3.22% by ML; 44.21% of Native American haplotypes) and European (44.34 ± 0.45% by ML; 40.53% of European haplotypes), and a relatively low African genetic component (1.13 ± 2.33% by ML; 5.26% of African haplotypes).     

Genetic diversity of HLA system in two populations from Nuevo León,Mexico: Monterrey and rural Nuevo León

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 665 Mexicans from the state of Nuevo León living in the city of Monterrey (N = 226) and rural communities (N = 439), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Nuevo León include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nuevo León are Native American (54.53 ± 0.87% by ML; 48.88% of Native American haplotypes) and European (38.67 ± 4.06% by ML; 32.59% of European haplotypes), and a less prominent African genetic component (6.80 ± 4.30% by ML; 8.26% of African haplotypes).     

Genetic diversity of HLA system in two populations from Tlaxcala,Mexico: Tlaxcala city and rural Tlaxcala

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1011 Mexicans from the state of Tlaxcala residing in the city of Tlaxcala (N = 181) and rural communities (N = 830), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes in Tlaxcala are all of Native American origin. Admixture estimates revealed that the main genetic components are Native American (75.13 ± 1.56% by ML; 69.24% based on of Native American haplotypes) and European (16.10 ± 4.98% by ML; 19.74% of European haplotypes), with a less prominent African genetic component (8.78 ± 4.09% by ML; 4.35% of African haplotypes).     

TNF-α promoter single nucleotide polymorphisms and haplotypes associate with susceptibility of immune thrombocytopenia in Chinese adults

Objective

Tumor necrosis factor-alpha (TNF-α) participates as a candidate susceptibility factor for immune thrombocytopenia (ITP). This study attempted to investigate the association between five single nucleotide polymorphisms (SNPs) spanning the TNF-α promoter and the susceptibility of primary ITP in Chinese Han adults.

Methods

In 215 adult primary ITP patients and 206 healthy controls, SNPs were detected by PCR-RFLP and PCR-SSP. The χ² test or fisher’s exact test was used to compare frequencies of genotypes and alleles between patients and controls. Haplotypes were analyzed with the SHEsis online program. TNF-α, IFN-γ and Galectin-9 mRNA of 35 newly diagnosed adult ITP patients and 35 healthy controls were detected by qRT-PCR.

Results

The haplotype GGC (−238G/−308G/−857C) of TNF-α promoter was significantly associated with a decreased susceptibility of primary ITP, especially in males. The relative levels of mRNA expression of TNF-α, IFN-γ and Gal-9 in adult active primary ITP patients was significantly up-regulated compared with patients in remission and controls.

Conclusions

This study represented the first report that the haplotype GGC of TNF-α was differentially associated with the susceptibility of primary ITP in Chinese Han adults. The up-regulation of TNF-α, IFN-γ and Galectin-9 was significantly correlated with active primary ITP in adult patients.     

The IPD-IMGT/HLA Database – New developments in reporting HLA variation

IPD-IMGT/HLA is a constituent of the Immuno Polymorphism Database (IPD), which was developed to provide a centralised system for the study of polymorphism in genes of the immune system. The IPD project works with specialist groups of nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The primary database within the IPD project is the IPD-IMGT/HLA Database, which provides a locus-specific database for the hyper-polymorphic allele sequences of the genes in the HLA system, also known as the human Major Histocompatibility Complex. The IPD-IMGT/HLA Database was first released over 17 years ago, building on the work of the WHO Nomenclature Committee for Factors of the HLA system that was initiated in 1968. The IPD-IMGT/HLA Database enhanced this work by providing the HLA community with an online, searchable repository of highly curated HLA sequences. Many of the genes encode proteins of the immune system and are hyper polymorphic, with some genes currently having over 4000 known allelic variants. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website, http://www.ebi.ac.uk/ipd/imgt/hla.     

Support vector machine algorithms in the search of KIR gene associations with disease

Killer-cell immunoglobulin-like receptors (KIR) are membrane proteins expressed by natural killer cells and CD8 lymphocytes. The KIR system consists of 17 genes and 614 alleles, some of which bind human leukocyte antigens (HLA). Both KIR and HLA modulate susceptibility to haematological malignancies, viral infections and autoimmune diseases. Molecular epidemiology studies employ traditional statistical methods to identify links between KIR genes and disease. Here we describe our results at applying artificial intelligence algorithms (support vector machines) to identify associations between KIR genes and disease. We demonstrate that these algorithms are capable of classifying samples into healthy and diseased groups based solely on KIR genotype with potential use in clinical decision support systems.     

The genus Xenopus as a multispecies model for evolutionary and comparative immunobiology of the 21st century

The Xenopus model for immunological research offers a collection of invaluable research tools including MHC-defined clones, inbred strains, cell lines, and monoclonal antibodies. Further, the annotated full genome sequence of Xenopus tropicalis and its remarkable conservation of gene organization with mammals, as well as ongoing genome mapping and mutagenesis studies in X. tropicalis, add a new dimension to the study of immunity. In this paper, we review uses of this amphibian model to study: the development of the immune system; vascular and lymphatic regeneration; immune tolerance; tumor immunity; immune responses to important emerging infectious diseases; and the evolution of classical and non-classical MHC class I genes. We also discuss the rich potential of the species with different degrees of polypoidy resulting from whole genome-wide duplication of the Xenopodinae subfamily as a model to study regulation at the genome level.     

儿童发作性睡病的免疫遗传特征

目的　探讨儿童发作性睡病的免疫遗传特征及其在该病的诊断、治疗和判断预后中的作用。方法　对 4 0例临床表现和各项检查、多次小睡潜伏时间试验 (MSLT)均符合发作性睡病诊断标准的患者 ,用序列特异性引物体外基因扩增 (PCR SSP)方法进行HLA DRB1 15低分辨、DRB1 15及DQB1 6高分辨测定基因型 ,并和 91例正常对照组进行比较。结果　患者组中HLA DRB1 15的阳性率为 92 .5 % (37 4 0 ) ,且大部分为DRB1 15 0 1(RR =2 3.33,χ2 =4 7.12 ,Pc<0 .0 1)和DQB1 0 6 0 2(RR =2 0 .6 9,χ2 =4 3.6 1,Pc<0 .0 1) ,差异均有显著性。有 2例患者为DRB1 15 0 2、DQB1 0 6 0 1。DQB1 0 6 0 1的基因频率在患者组中有明显下降 ,但经P值校正后无统计学意义 (χ2 =4 .19,Pc >0 .0 5 )。结论　儿童发作性睡病与HLA DRB1 15 0 1和DQB1 0 6 0 2有显著相关 ,为该病免疫遗传特征的一个主要标志。     

Impact of population admixture on the distribution of immune response co-stimulatory genes polymorphisms in a Brazilian population

Co-stimulatory molecules are essential in the orchestration of immune response and polymorphisms in their genes are associated with various diseases. However, in the case of variable allele frequencies among continental populations, this variation can lead to biases in genetic studies conducted in admixed populations such as those from Brazil. The aim of this study was to evaluate the influence of genomic ancestry on distributions of co-stimulatory genes polymorphisms in an admixed Brazilian population. A total of 273 individuals from the north of Brazil participated in this study. Nine single nucleotide polymorphisms in 7 genes (CD28, CTLA4, ICOS, CD86, CD40, CD40L and BLYS) were determined by polymerase chain reaction-restriction fragment length polymorphism. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. The analysis showed that the main contribution was European (43.9%) but also a significant contribution of African (31.6%) and Amerindian (24.5%) ancestry. ICOS, CD40L and CD86 polymorphisms were associated with genomic ancestry. However there were no significant differences in the proportions of ancestry for the other SNPs and haplotypes studied. Our findings reinforce the need to apply AIMs in genetic association studies involving these polymorphisms in the Brazilian population.     

Multidisciplinary approach to understand the pathogenesis of gastric cancer

Gastric carcinoma remains a common disease worldwide with a dismal prognosis. Therefore, it represents a very important health problem. It occurs with a high incidence in Asia and is one of the leading causes of cancer death in the world. Although the incidence and mortality of gastric carcinoma are decreasing in many countries, gastric cancer still represents the second most frequent malignancies in the world and the fourth in Europe. The 5-year survival rate of gastric carcinoma is low. The etiology and pathogenesis are not yet fully known. The study of gastric cancer is important in clinical medicine as well as in public health. Over the past 15 years, integrated research in molecular pathology has clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of the development and progression of gastric cancer. Gastric cancer, as all cancers, is the end result of the interplay of many risk factors as well as protective factors. Although epidemiological evidence indicates that environmental factors play a major role in gastric carcinogenesis, the role of immunological, genetic, and immunogenetic factors are thought to contribute to the pathogenesis of gastric carcinoma. Among the environmental factors, diet and Helicobacter pylori are more amenable to intervention aimed at the prevention of gastric cancer. The aim of the present paper is to review and include the most recent published evidence to demonstrate that only a multidisciplinary approach will lead to the advancement of the pathogenesis and prevention of gastric cancer. On the immunogenetic research it is clear that evidence is accumulating to suggest that a genetic profile favoring the proinflammatory response increases the risk of gastric carcinoma.