样本量对等位基因检出数量的影响

以中国37个不同民族9个常染色体STR基因座的群体遗传研究数据资料为例，探讨群体遗传学研究中常染色体STR基因座等位基因检出数量与样本量之间的关系，即样本量对等住基因检出数量的影响。结果显示在一定范围之内，样本量的大小与所观测到的不同基因座等位基因检出数量之间存在正相关关系。当超过一定范围时，样本量的继续增加不再明显影响等位基因的检出数量。杂合度较低的位点随样本量的变化波动较大，杂合度较高的位点随样本量的变化波动较小。     

Additive Effects of Older Brothers and Homosexual Brothers in the Prediction of Marriage and Cohabitation

Research has shown that male homosexuality tends to cluster in families and that homosexual males have, on average, a greater number of older brothers than do heterosexual males. This study investigated whether the former, between-families effect and the latter, within-families effect are additive. The subjects were 717 full siblings over age 40 reported by 343 heterosexual and homosexual male probands examined in Southern Ontario in 1994–1995. The sibling's history of legal marriage or cohabitation in a heterosexual relationship was taken as a proxy variable for sexual orientation. There were no significant findings for the female siblings. As expected, the never-married male siblings were more likely to come from the sibships of the homosexual probands, and they had a greater average number of older brothers. A bootstrapped logistic regression analysis showed that an additive model best explained the male siblings' data. The results suggest that the familial aggregation of male homosexuality cannot be explained by the birth order effect and that older brothers and family membership reflect separate influences on sexual orientation or sexual orientation-correlated behavior.     

Influenza A virus-induced apoptosis is a multifactorial process: exploiting reverse genetics to elucidate the role of influenza A virus proteins in virus-induced apoptosis

Three influenza viruses, A/Puerto Rico/8/34-A/England/939/69 clone 7a (H3N2), A/Fiji/15899/83 (H1N1), and A/Victoria/3/75 (H3N2), induce different levels of apoptosis in vitro at equal moi; Clone 7a > A/Victoria > A/Fiji. Previous studies have shown that several viral proteins from clone 7a and A/Fiji, including PB2, NA, NS1, M1, and M2, induce apoptosis when expressed individually fused to the herpes simplex virus tegument protein, VP22. However, this did not reflect viral protein-protein-RNA interactions known to occur within infected cells. To explore the role of viral proteins in apoptosis under infection conditions, recombinant viruses with single or triple gene exchanges were generated using A/Victoria or clone 7a as the background virus. Inserting the A/Fiji NS or PB2 gene into A/Victoria or clone 7a significantly reduced the level of apoptosis compared to the parent virus while clone 7a PA or NP genes increased apoptosis. Inserting A/Fiji NA or HA or clone 7a NS, M, NA, or HA genes individually into A/Victoria had no significant effect on apoptosis. Surprisingly, inserting the M, NA, and HA genes of A/Fiji together into clone 7a reduced apoptosis, whereas inserting clone 7a M, NA, and HA together into A/Fiji increased apoptosis. These results suggest that no single virus protein induces apoptosis and that the combination of genes required may be strain specific, highlighting the difficulty of predicting the virulence of new strains that arise in nature. No support for the view that apoptosis is essential for high virus yields was obtained as high virus yields were obtained with viruses that induced both high and low levels of apoptosis.     

C基因截短的HBV复制与包装

目的 探讨C基因截短型HBV变异体的复制与包装。方法 采用分子克隆、人工定点突变等技术构建C基因截短型HBV变异体质粒，用脂质体法转染HepG2细胞，提取细胞内及培养上清液中DNA分别进行Southem杂交，PCR及实时定量荧光PCR分析。结果 经DNA测序及酶切鉴定证实C基因截短型HBV质粒载体构建成功；C基因截短型HBV为复制缺损型，与辅助质粒共转染HepG2细胞，可在细胞内及培养上清液中检测到HBV各种DNA构型；DNA定量分析提示C基因截短型HBV的包装效率较野生型HBV提高3～40倍。结论 C基因截短型HBV变异体为复制缺损型，单独转染后不能在肝细胞内包装与复制，但在缺失包装信号ε的相应辅助病毒辅助下可有效复制并包装成子代病毒颗粒分泌到胞外，且包装效率大大提高。     

An Association Between a Microsatellite Polymorphism at the DRD5 Gene and the Liability to Substance Abuse: Pilot Study

We have conducted a population-based association study of substance abuse and a microsatellite at the dopamine D5 receptor locus (DRD5) in a sample of European–American males and females with substance dependence (SA) or without any psychiatric disorder. Overrepresentation of the most frequent allele (148 bp) was found in males in the SA group (OR = 2.2, P= .02); this finding was reproduced in females (OR = 5.4, p< .001). The difference in the frequencies of this allele between SA males and SA females was statistically significant. The genotype coded in accordance with the dose of this allele correlated with substance abuse liability in males and females (stronger in females) and with novelty seeking in females. There was no evidence of correlation between the genotypes of spouses that could be induced by assortative mating for the liability to substance abuse. The data suggest that the DRD5 locus is involved in the variation and sex dimorphism of substance abuse liability.CEDAR is a consortium between St. Francis Medical Center and the University of Pittsburgh.     

The spectrum of complement alternative pathway-mediated diseases

Summary: The complement system has once again come into prominence in the therapeutic development arena. The recent approval of an inhibitory monoclonal antibody, eculizumab, which is directed against complement component C5 for the disease paroxysmal nocturnal hemoglobinuria has provided the initial validation of this system as a therapeutic target. Preclinical studies using animal models and human-derived samples demonstrate that inhibition of complement ameliorates many inflammatory and autoimmune disease manifestations. Major efforts continue to define the most optimal means to block complement activation in a cost-effective manner. Because the system is initiated through three pathways and generates at least six immunoregulatory and pro-inflammatory mediators, there is substantial complexity to this problem. One pathway, designated the alternative pathway, has recently been shown to play a particularly important role in preclinical disease models. Further evidence of the importance of the alternative pathway has been provided by studies of human diseases, where mutations or dysfunctional polymorphisms that promote activation of this pathway are highly associated with the diseases atypical hemolytic uremic syndrome, dense deposit disease, and age-related macular degeneration. This article reviews evidence in support of the essential role of the alternative pathway in the generation of tissue injury and the rationale for development of therapies that modulate its activity.     

COMT Gene Polymorphism Is Associated with Declarative Memory in Adulthood and Old Age

Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.     

Depletion of mitochondrial DNA in HIV-1-infected patients and its amelioration by antiretroviral therapy

Mitochondrial DNA (mtDNA) of peripheral blood mononuclear cells (PBMCs) collected from Human immunodeficiency virus 1 (HIV-1)-infected patients and healthy controls were measured longitudinally using real-time polymerase chain reaction to evaluate the effects of antiretroviral agents on mtDNA synthesis in vivo and to assess the value of monitoring mtDNA in PBMCs to predict adverse events amongst these patients. MtDNA levels in PBMCs were significantly decreased in treatment-naive HIV-1-infected patients compared with healthy people. MtDNA levels were not only significantly correlated with CD4(+) T-cell count, but also inversely correlated with HIV-1 viral load. MtDNA levels in untreated patients and healthy controls were stable during the period of observation. On the other hand, amongst patients treated with regimens containing AZT/3TC or d4T/3TC, mtDNA increased during treatment and recovered to levels comparable to healthy controls. In contrast, mtDNA decreased immediately after the initiation of an AZT/ddC-containing regimen. We did not find a correlation between mtDNA levels and changes in clinical parameters. There was no significant difference in mtDNA levels between patients with and those without lipoatrophy. Furthermore, there was no obvious difference in mtDNA levels amongst those patients exhibiting signs and symptoms of peripheral neuropathy. In conclusion, the decrease in mtDNA levels in PBMCs amongst HIV-1-infected patients and its amelioration by antiretroviral therapy may suggest the influence of direct effects on mitochondria or mtDNA by HIV-1 infection. Further investigations are needed to elucidate the mechanisms contributing to decreased mtDNA and the value of mtDNA measurement in the care of HIV-1-infected individuals.