Genetic Variation in the α7 Nicotinic Acetylcholine Receptor is Associated with Delusional Symptoms in Alzheimer’s Disease

Psychotic symptoms are common in Alzheimer’s disease (AD) and have a negative impact on quality of life. It is suggested that psychotic symptoms may be attributed to genetic risk factors which are revealed during neurodegeneration. CHRNA7, the gene for the α7 nicotinic acetylcholine receptor, has been associated with schizophrenia in linkage and association studies. Hence we investigated single SNPs and haplotypes in CHRNA7 in relation to AD with psychosis in a large, well-characterised and previously described cohort within the Northern Ireland population. A significant association between delusions and the T allele of rs6494223 (P = 0.014, OR = 1.63, CI = 1.22–2.17) was found. This suggests that the α7 receptor may be a suitable target for the treatment of AD with psychosis.     

Vitamin D receptor haplotypes protect against development of colorectal cancer

Objective We investigated the association of vitamin D receptor polymorphisms and colorectal cancer incidence in a Caucasian population. Methods Frequencies of the vitamin D receptor gene polymorphisms 23005G>A (CDX-2), 27823C>T (FokI), 60890G>A (BsmI), 61050G>A (Tru9I), 61888G>T (ApaI), and 61968T>C (TaqI) were determined in a series of 256 colorectal cancer patients and 256 patients without malignant disease (case-control study) using polymerase chain reaction and restriction fragment length polymorphism genotyping assays (PCR-RFLP). Haplotype analysis based on the six genetic loci was applied to the received genotypes. Results Pairwise linkage disequilibrium between BsmI, ApaI, TaqI, and Tru9I was confirmed (P < 0.001). Allele frequencies did not differ between the groups. There was no association between any single variant and colorectal cancer. However, haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) were inversely associated with colorectal cancer incidence (P < 0.001), the odds being 15.0 times smaller [odds ratio (OR) 0.067; 95% confidence interval (CI), 0.016–0.284] and 5.3 times smaller (OR 0.188; 95% CI 0.077–0.461), respectively, compared with noncarriers. Conclusion Our findings suggest that vitamin D receptor haplotypes BsmI(G)#TaqI(C) and BsmI(A)#TaqI(T) have a protective effect against colorectal cancer in Caucasians.     

主成分分析与聚类分析在民族分化研究中的应用比较

目的 比较主成分分析与聚类分析两种聚类方法对13个人群进行分类的结果。方法 采用两种数值分类方法并用Y染色体的12种单体型的双等位基因频率数据，对朝鲜族等13个人群进行分类，分析群体间,阐明民族的起源。结果 两种分类方法得到的结果不尽相同。主成分分析可以减少无关指标的影响，但是在简化数据降低维数的过程中又有可能丢失信息。聚类分析充分利用原始数据信息，但无法排除无关指标的“噪音”干扰。结论 主成分分析与聚类分析都适宜做多维复杂数据的分类研究，但在实际应用中，应运用两种分类方法得到的结果结合领域知识给出客观、合理的结论。     

Extending the discrete Laplace method: incorporating multi-copy loci,partial repeats and null alleles

The discrete Laplace method can be used to estimate the frequency of a Y-chromosomal STR haplotype using a random sample from the population. Two limitations of the method are the assumptions that each profile has exactly one allele at every locus and that this allele has an integer repeat number. We relax these assumptions to allow for multi-copy loci, partial repeats and null alleles. We show how the parameters to the extension of the model can be estimated by numerical optimisation using an off-the-shelf solver. Concordance with the discrete Laplace method is obtained when the data satisfy the more stringent assumptions of the original method. We also investigate the performance of the (extended) discrete Laplace method when used to assign match probabilities for haplotypes. A simulation study shows that as more loci are used, match probabilities are underestimated more severely. This is consistent with the hypothesis that the discrete Laplace method cannot model the matches that arise by being identical by descent (IBD). As the number of loci increases the fraction of matches that are IBD increases. Simulation provides support that the discrete Laplace can model those matches that arise from identity by state (IBS) only.     

蛋白C-1641A/-1654C单倍型与脓毒症凝血功能的相关性研究北大核心CSCD

目的探讨蛋白C -1641A/-1654C单倍型与中国汉族脓毒症患者凝血功能紊乱的相关性。方法采用直接测序法检测脓毒症患者蛋白C -1641A>G (rs1799809)和-1654C>T(rs1799808)位点的基因型, 分析其单倍型并根据单倍型分为两组, -1641A/-1654C(简称AC)单倍型携带者和非AC单倍型携带者。同时, 采用非配对t检验或Mann-WhitneyU检验进行分析, 比较两组间凝血/纤溶参数, 包括部分活化凝血活酶时间、凝血酶原时间、凝血酶原时间国际标准化比值、凝血酶时间、纤维蛋白原和D -二聚体等, 以及APC水平的差异。结果本研究共纳入174例脓毒症患者, 其中60例为AC单倍型携带者, 114例为非AC单倍型携带者。与非AC单倍型携带者相比, AC单倍型携带者的血小板计数明显减少, 部分活化凝血活酶时间明显延长, 蛋白C活化显著降低, 而其他凝血/纤溶参数包括凝血酶原时间、凝血酶原时间国际标准化比值、凝血酶时间、纤维蛋白原和D -二聚体差异无统计学意义。结论本研究发现蛋白C -1641A/-1654C单倍型导致脓毒症患者循环中的活化蛋白C水平降低、血小板计数减少, 部分活化凝血活酶时间延长。该结果表明, 脓毒症患者蛋白C -1641A/-1654C单倍型可能直接影响活化蛋白C水平, 进而导致脓毒症凝血功能紊乱。     

KIR genotype and haplotype frequencies in the multi-ethnic population of Malaysia

Killer cell immunoglobulin-like receptors (KIR) genotype and haplotype frequencies have been reported to vary distinctly between populations, which in turn contributes to variation in the alloreactivity of natural killer (NK) cells. Utilizing the diverse KIR genes to identify suitable transplant donors would prove challenging in multi-ethnic countries, even more in resource-limited countries where KIR genotyping has not been established. In this study, we determined the KIR genotypes from 124 unrelated Malaysians consisting of the Malays, Chinese, Indians, and aboriginal people through polymerase chain reaction sequence-specific primer (PCR-SSP) genotyping and employing an expectation–maximization (EM) algorithm to assign haplotypes based on pre-established reference haplotypes. A total of 27 distinct KIR haplotypes were discerned with higher frequencies of haplotype A (55.2%) than haplotype B (44.8%). The most frequent haplotypes were cA01:tA01 (55.2%), cB01:tB01 (18.1%), and cB02:tA01 (13.3%), while the least frequent haplotypes were cB03:tB01 (1.2%), cB04:tB03 (0.4%), and cB03:tA01 (0.4%). Several haplotypes were identified to be unique to a specific ethnic group. The genotype with the highest frequency was genotype AB (71.8%), followed by AA (19.4%), and BB (8.9%). The Indians exhibited the lowest genotype AA but the highest genotype BB, whereas genotype BB was absent in the aboriginal people. Despite the limitations, the genotype and haplotypes in the Malaysian population were successfully highlighted. The identification of ethnic-specific KIR genotypes and haplotypes provides the first step to utilizing KIR in identifying suitable transplant donors to further improve the transplant outcome in the Malaysian population.