中国广东地区汉族人群补体C4单倍型分析

采用改良的国际补体参考实验室方法,检测广东地区汉族人群补体C4单倍型。在156条无关染色体中,共检出14种C4单倍型:A3B1频率最高(0.3269),A3B2(0.2436)和A4B2(0.1090)次之,以下依次为A4B1(0.0705);AQ0B2和AQ0B1(均为0.0641);A2B1(0.0321);A3BQ0(0.0256);A3B5和A3B4(均为0.0192);A5B4、AQ0B4、AQ0B96和AQ0BQ0频率最低(均为0.0064)。其中A4B2和A2B1呈正向连锁不平衡。将广东汉族与其它不同种族群体的数据进行比较,发现广东汉族C4单倍型分布具有明显特点。     

我国藏族人群补体第四成分单倍型的分布分析

采用武汉同济医科大学中澳友谊补体实验室仿国际标准Ｃ４定型程序改进后建立的方法，对９９名无血缘关系的藏族人进行补体Ｃ４单倍型检测。对１９８个Ｃ４单倍型检测结果分析，我国藏族人群Ｃ４单倍型频率以Ａ３Ｂ１最高（０．４１９２），Ａ３Ｂ２次之（０．１８６８），以下依次是：Ａ４Ｂ２（０．０７０７）、Ａ２Ｂ１（０．０７０７）、Ａ３Ｂ５（０．０４５４）等。在Ｃ４Ａ座位上发现８个型别：Ｃ４Ａ５、４、３、２、１、３４     

Detecting Genes and Gene–Gene Interactions for Age-Related Macular Degeneration with a Forest-based Approach

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. Genetic mechanisms underlying AMD are complex. Understanding the etiology of AMD is important because of the significant health and social concerns. In this article, we describe a forest-based approach to systematically identifying multiple genes, gene–gene interactions, and gene–environment interactions underlying complex diseases in genome-wide case-control studies and the application of this approach to a published dataset on AMD. Our analysis not only confirmed two known haplotypes, ACTCCG (on chromosome 1 with a p-value of 1.98e-6) and TCTGGACGACA (on chromosome 7 with a p-value of 9.81e-3), but also revealed two novel haplotypes, GATAGT (on chromosome 5 with a p-value of 3.46e-3) and TCTTACGTAGA (on chromosome 12 with a p-value of 3.16e-2). Thus, the significance of this work is two-fold. First, we propose a powerful and robust method to identify high-risk haplotypes and their interactions; second, we reveal potential genetic variants associated with AMD.     

Distribution of Y-chromosome haplogroups in Serbian population groups originating from historically and geographically significant distinct parts of the Balkan Peninsula

Our study enrolled 1200 Serbian males originating from three geographical regions in the Balkan Peninsula inhabited by Serbs: present-day Serbia, regions of Old Herzegovina and Kosovo and Metohija. These samples were genotyped using the combination of 23 Y-chromosomal short tandem repeats (Y-STRs) loci and 17 Ychromosomal single nucleotide polymorphisms (Y-SNPs) loci for the haplotype and haplogroup analysis in order to characterize in detail Y chromosome flow in the recent history. Serbia’s borders have changed through history, forcing Serbs constantly to migrate to different regions of Balkan Peninsula. The most significant migration waves in the recent history towards present-day Serbia occurred from the regions of Old- Herzegovina and Kosovo and Metohija that lie in the south-west/south. High haplotype diversity and discrimination capacity were observed in all three datasets, with the highest number of unique haplotypes (381) and discrimination capacity (0.97) detected in the samples originating from the present-day Serbia. Haplogroup composition didn’t differ significantly among datasets, with three dominant haplogroups (I-M170, E-P170 and R-M198), and haplogroup I-M170 being the most frequent in all three datasets. Haplogroup E-P170 was the second most dominant in the dataset originating from geographical region of Kosovo and Metohija, whereas haplogroup R-M198 was the second most prevalent in the dataset from historical region of Old Herzegovina. Based on the phylogenetic three for haplogroup I constructed within this study, haplogroup I2a1-P37.2 was the most dominant within all three datasets, especially in the dataset from historical region of Old Herzegovina, where 182 out of 400 samples were derived for SNP P37.2. Genetic distances between three groups of samples, evaluated by the Fst and Rst statistical values, and further visualized through multidimensional scaling plot, showed great genetic similarity between datasets from Old Herzegovina and present-day Serbia. Genetic difference in the haplogroup distribution and frequency between datasets from historical region of Old Herzegovina and from geographical region of Kosovo and Metohija was confirmed with highest Fst and Rst vaules. In this study we have distinguished genetic structure, diversity and haplogroup frequencies within 1200 Serbian males from three datasets, relationships among them as well as with other Balkan and European populations, which is useful for studying recent demographic history.     

一种新的哮喘易感性基因——哮喘易感性G蛋白耦联受体

哮喘是一种多基因遗传病,近来发现许多染色体区域的多种基因与哮喘相关。哮喘易感性G蛋白耦联受体（G protein-coupled receptor for asthma susceptibility,GPRA）是新近发现的一种与哮喘易感性相关的候选基因。研究发现该基因的多态性与哮喘、支气管高反应性和血清高IgE水平相关。GPRA基因编码的产物属于G蛋白耦联受体超家族（GPCR）,其可编码七种不同的蛋白亚型。     

HLA-frequencies of Austrian umbilical cord blood samples

We investigated HLA-A, HLA-B, and HLA-DRB1 gene frequencies in 1368 unrelated Austrian umbilical cord blood samples. HLA-C gene frequencies were investigated in a subgroup of 503 samples. HLA typing was performed via sequenced-based typing (SBT). The aim of this study was to examine the HLA diversity in a large Austrian population sample. In addition we present results of a subsample of 100 samples at a subtype level. This study is the first systematic investigation of donated umbilical cord blood samples in the Austrian population.     

A new disease allele for the p.C30071R mutation in titin causing hereditary myopathy with early respiratory failure

Hereditary myopathy with early respiratory failure is an autosomal dominant myopathy caused by mutations in the 119th fibronectin-3 domain of titin. To date all reported patients with the most common mutation in this domain (p.C30071R) appear to share ancestral disease alleles. We undertook this study of two families with the p.C30071R mutation to determine whether they share the same haplotype as previously reported British families or whether the mutation arose as a de novo event. We sequenced the 119th fibronectin-3 domain in these two probands and flanking polymorphisms associated with the British haplotype in hereditary myopathy with early respiratory failure. A family of Indian descent had a haplotype that was not compatible with the British shared haplotype. Cloning of the 119th fibronectin-3 domain in this patient demonstrated polymorphisms rs191484894 and novel noncoding variant c.90225C>T on the same allele as the mutation, which is distinct from previously reported British families. This proves that the p.C30071R mutation itself (rather than the haplotype containing this mutation) causes hereditary myopathy with early respiratory failure and suggests its independent origin in different ethnic groups.     

Pfcrt haplotypes and in-vivo chloroquine response in Sundergarh district, Orissa, India

The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) were analyzed as markers of chloroquine (CQ) resistance in the blood samples of patients from two sites of different intensities of malaria transmission (high, n=70; low, n=68) in Sundergarh district of Orissa, India and correlated with the in-vivo response. Early treatment failure (ETF) was significantly more frequent in the high endemic area (32.9 vs. 7.4%, P<0.001), with children below 5 years suffering more. A high frequency of pfcrt K76T mutation was observed in both the areas (87.1 vs. 79.4%, P=0.22). Patients carrying pfcrt 76T were the most likely to develop ETF (odds ratio 36; 95% CI 3.35-1653.3; P<0.001). The ratio of 76T:K76 was 22:9 and 11:14, respectively, in high and low endemic areas (odds ratio 3.1; 95% CI 0.9-11.03; P=0.04), which may be used as a measure of drug pressure. Sequences of pfcrt codons 72-76 showed 16 of the CQ-resistant haplotypes to be SVMNT, 5 CVMNT and 12 CVIET. The CQ-sensitive haplotypes were mostly CVMNK in 10 samples; CVIEK in 2 samples. Both Southeast Asian and South American haplotypes were present, with the latter predominating.