Genetic diversity of HLA system in two populations from Hidalgo,Mexico: Pachuca and rural Hidalgo

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 122 Mexicans from the state of Hidalgo living in the city of Pachuca (N = 41) and rural communities (N = 81), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in Hidalgo include eight Native American and one European haplotypes. Admixture estimates revealed that the main genetic components in Hidalgo are Native American (58.93 ± 2.16% by ML; 54.51% of Native American haplotypes) and European (32.49 ± 2.88% by ML; 28.69% of European haplotypes), and a relatively high African genetic component (8.58 ± 0.93% by ML; 6.97% of African haplotypes).     

Genetic diversity of HLA system in two populations from Tamaulipas,Mexico: Ciudad Victoria and rural Tamaulipas

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 148 Mexicans from the state of Tamaulipas living in Ciudad Victoria (N = 23) and rural communities (N = 125), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in the state of Tamaulipas include ten Native American, three European and one African haplotypes. Admixture estimates revealed that the main genetic components in the state of Tamaulipas are Native American (54.69 ± 0.93% by ML; 47.65% of Native American haplotypes) and European (34.66 ± 5.62% by ML; 33.56% of European haplotypes), and a relatively high African genetic component (10.65 ± 5.05% by ML; 12.42% of African haplotypes).     

Psoriasis risk SNPs and their association with HIV-1 control

Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n = 366), (2) Individuals with primary HIV infection in the Options cohort (n = 675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n = 987). We found a strong association of two psoriasis MHC variants, rs9264942 and rs3021366, with both HIV-1 controller status and viral load, and identified another Class III MHC variant rs9368699 to be strongly associated with viral load. A number of genetic variants outside the MHC (SOX5, TLR9, SDC4, PROX1, IL12B, TLR4, MBL-2, TYK2, IFIH1) demonstrated nominal significance. Overall, our data suggest that several psoriasis variants within the MHC have a robust impact on HIV-1 control, while variants outside the MHC require further investigation.     

LMP基因多态性及其在母胎间共享与子痫前期相关性研究

目的:探讨孕妇及胎儿巨大多功能蛋白酶体(LMP)基因多态性及母胎LMP共享与重度子痫前期的关系。方法:利用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)方法对2006年7月至2010年8月于我院住院治疗的77例重度子痫前期母胎和200例正常妊娠母胎的LMP2、LMP7基因进行多态性对应分析。结果:(1)LMP2-R/R、LMP7-B/B在重度子痫前期组孕妇分布频率明显低于对照组,LMP2-R/H在重度子痫前期组孕妇分布频率明显高于对照组,OR值分别为0.211,0.238,4.594;(2)LMP2及LMP7共12种等位基因型在重度子痫前期组和对照组胎儿间分布的差异无统计学意义;(3)母胎间共享一个基因重度子痫前期组明显低于对照组,共享四个基因型者重度子痫前期组明显高于对照组,OR值分别为0.051和5.360。结论:LMP2-R/H可能是重度子痫前期的易感基因,LMP2-R/R、LMP7-B/B可能是重度子痫前期的保护基因。母胎LMP基因共享率高对重度子痫前期的发生可能是独立因素。     

Next-generation HLA typing of 382 International Histocompatibility Working Group reference B-lymphoblastoid cell lines: Report from the 17th International HLA and Immunogenetics Workshop

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.     

17th IHIW component “Immunogenetics of Ageing” – New NGS data

The ‘Immunogenetics of Aging’ project is a component introduced in the 14th International HLA and Immunogenetics Workshop (IHIW) and developed further within subsequent workshops. The aim was to determine the relevance of immunogenetic markers, focusing on HLA, cytokine genes, and some innate immunity genes, for successful aging and an increased capacity to reach the extreme limits of life-span. Within the 17th IHIW we applied Next Generation Sequencing methods to refine further HLA associations at allele level in longevity, and to extend our knowledge to additional loci such as HLA-DQA1, HLA-DPB1 and HLA-DPA1. Analysis of relatively small number of healthy elderly and young controls from four populations showed that some HLA class I and class II alleles were significantly positively associated with healthy aging. Additionally we observed statistically significant differences in HLA allele distribution when the analysis was performed separately in elderly females and males compared to sex-matched young controls. Haplotypes, probably associated with better control of viral and malignant diseases were increased in the elderly sample. These preliminary NGS data could confirm our hypotheses that survival and longevity might be associated with selection of HLA alleles and haplotypes conferring disease resistance or susceptibility. Therefore HLA alleles and haplotypes could be informative immunogenetic markers for successful ageing.     

CCR5 polymorphism and plague resistance in natural populations of the black rat in Madagascar

Madagascar remains one of the world's largest plague foci. The black rat, Rattus rattus, is the main reservoir of plague in rural areas. This species is highly susceptible to plague in plague-free areas (low-altitude regions), whereas rats from the plague focus areas (central highlands) have evolved a disease-resistance polymorphism. We used the candidate gene CCR5 to investigate the genetic basis of plague resistance in R. rattus. We found a unique non-synonymous substitution (H184R) in a functionally important region of the gene. We then compared (i) CCR5 genotypes of dying and surviving plague-challenged rats and (ii) CCR5 allelic frequencies in plague focus and plague-free populations. Our results suggested a higher prevalence of the substitution in resistant animals compared to susceptible individuals, and a tendency for higher frequencies in plague focus areas compared to plague-free areas. Therefore, the CCR5 polymorphism may be involved in Malagasy black rat plague resistance. CCR5 and other undetermined plague resistance markers may provide useful biological information about host evolution and disease dynamics.     

Genetic diversity of HLA system in two populations from Michoacán,Mexico: Morelia and rural Michoacán

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 498 Mexicans from the state of Michoacán living in the city of Morelia (N = 150) and rural communities (N = 348), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Michoacán include 12 Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Michoacán are Native American (48.79 ± 1.44%) and European (43.10 ± 0.86%), while African genetic component is less apparent (8.11 ± 0.85%). Our findings add to the growing knowledge on the population genetics of Western Mexico and provide new HLA data on populations from Michoacán.     

Immunogenetics of disease resistance in fish: A comparative approach

The study of the genetic regulation of infectious disease resistance depends on the availability of inbred lines or selection lines of the species under investigation. The small numbers of such lines of fish has limited the strategy in teleosts to studies of associations between disease and immune/health traits. Attempts to correlate genetic differences in immune responsiveness with survival after experimental challenge with pathogenic bacteria have failed to define immune parameters that can substantially aid selection for genetic resistance to infectious diseases. Advantages and disadvantages of selection strategies as illustrated by mouse and chicken models are discussed. In this study we summarize the present situation in fish as well as our attempts to develop gynogenetic lines of carp for immunogenetic research. Copyright     

家族性多发性硬化（4例报告）

报告两个家系共４例多发性硬化病人，包括一对姐妹和一对母女，其中一个家系成员作了ＨＬＡ型别检测。结果说明免疫遗传因素可能是多发性硬化病因的一个重要方面。