基于CSSL的水稻抽穗期QTL定位及遗传分析

抽穗期是水稻（Oryza sativa）品种的重要农艺性状之一,适宜的抽穗期是获得理想产量的前提。鉴定和定位水稻抽穗期基因/QTL,分析其遗传效应对改良水稻抽穗期至关重要。以籼稻品种9311（Oryzasativa ssp.indica‘Yangdao 6’）为受体,粳稻品种日本晴（Oryza sativa ssp.japonica‘Nipponbare’）为供体构建的94个染色体片段置换系群体为材料,以P≤0.01为阈值,对置换片段上的抽穗期QTL进行了鉴定。采用代换作图法共定位了4个控制水稻抽穗期的QTL,分别位于第3、第4、第5和第8染色体;QTL的加性效应值变化范围为–6.4––2.7,加性效应百分率变化范围为–6.4%––2.7%;qHD-3和qHD-8加性效应值较大,表现主效基因特征。为了进一步定位qHD-3和qHD-8,在目标区域加密16对SSR引物,qHD-3和qHD-8分别被界定在第3染色体RM3166–RM16206之间及第8染色体RM4085–RM8271之间,其遗传距离分别为13.9cM和6.4cM。研究结果为利用分子标记辅助选择改良水稻抽穗期奠定了基础。     

Human Leukocyte Antigen Class I Supertypes and HIV-1 Control in African Americans

The role of human leukocyte antigen (HLA) class I supertypes in controlling human immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been established. We examined the effects of the HLA-A and HLA-B alleles and supertypes on the outcomes of HIV-1 clade B infection among 338 African American women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were associated with favorable HIV-1 disease control (proportional odds ratio [POR] of 0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general, individual alleles within specific B supertypes exerted relatively homogeneous effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95% CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510. The associations of most B supertypes (e.g., B58s and B7s) were largely explained either by well-known effects of constituent B alleles or by effects of previously unimplicated B alleles aggregated into a particular supertype (e.g., B44s and B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher mean viral load (VL) and lower mean CD4 count (Pearson''s r = 0.63 and 0.62, respectively; P = 0.03). Among the genotypic supertypes, B58s and its member allele B*57 contributed disproportionately to the explainable VL variation. The study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B-infected African Americans and further dissected the contributions of individual class I alleles and their population frequencies to the supertype effects.African Americans in the United States have been affected disproportionately by the human immunodeficiency virus type 1 (HIV-1) epidemic. They accounted for only 13% of the U.S. population but for 47% of AIDS cases diagnosed in the United States in 2006 (14, 17). An HIV-1 vaccine would be of enormous benefit to this subpopulation. One strategy for HIV-1 vaccine development seeks to capitalize on the recognition and destruction of HIV-1-infected cells by cytotoxic T lymphocytes (CTLs) (32, 33, 35).CTL recognition is critically dependent on binding, presentation, and cell surface display of a variety of antigenic peptides (epitopes) by extremely polymorphic human leukocyte antigen (HLA) molecules. As the relative importance of increasing numbers of HIV-1 epitopes for individual HLA class I molecules has been recognized (9, 16), the feasibility of developing a vaccine tailored to every epitope and HLA specificity has come to seem more remote. Conceptualization of epitope specificity in terms of broad groupings (supertypes) of HLA molecules may provide a rational but simpler approach to this challenge.Several efforts have succeeded at consolidating the huge spectrum of individual HLA class I alleles into four HLA-A and five HLA-B supertype categories (37-39), based on the ability of different HLA class I molecules to present similar epitopes. Unlike individual allele frequencies, which vary greatly across ethnic groups, all nine supertypes (comprising most, but not all, HLA-A and HLA-B alleles) are present in all human populations. This more uniform representation of allele groups may confer an advantage in the form of balancing selection (38).HLA alleles within one supertype that share epitope binding specificities might be expected to demonstrate similar associations with HIV-1 outcomes or vaccine response; conversely, alleles within a supertype that differ substantially in function might be expected to show differential responses to natural infection or vaccines designed on the basis of supertype (2). Functional heterogeneity of alleles within the supertypes could be due to differences in the class I alleles themselves (e.g., variable epitope avidity or tolerance to viral mutations), in host background (genetic epistasis), or in the virus (e.g., clade-related epitope specificities or viral escape).Previous work has detected associations between the HLA class I supertypes and HIV-1 outcomes for Caucasians with clade B infections (34, 44) and for native Africans with clade A or C infections (23, 28). We are unaware of studies among African Americans in the context of clade B HIV-1 infection or of any systematic attempt to tease apart the independent contributions of supertypes and their individual class I alleles to HIV-1 outcomes. Here we document the frequencies of the HLA class I alleles and supertypes in the Reaching for Excellence in Adolescent Care and Health (REACH) and HIV Epidemiologic Research Study (HERS) cohorts, and we report the relative effects of those alleles and supertypes on the degree of HIV-1 disease control.     

Leishmania donovani: Genetic diversity of isolates from Sudan characterized by PCR-based RAPD

Drug unresponsiveness in patients with visceral leishmaniasis (VL) is a problem in many endemic areas. This study aimed to determine genetic diversity of Leishmania donovani isolates from a VL endemic area in Sudan as a possible explanation for drug unresponsiveness in some patients. Thirty clinically stibogluconate (SSG)-sensitive isolates were made SSG-unresponsive in vitro by gradually increasing SSG concentrations. The sensitive isolates and their SSG-unresponsive counterparts were typed using mini-circle kDNA and categorized using PCR-RAPD. All the isolates were typed as L. donovani, the resulting PCR-RAPD characterization of the SSG-sensitive isolates gave three distinct primary genotypes while, the SSG-unresponsive isolates showed only a single band. L. donovani isolates from eastern Sudan are diverse; this probably resulted from emergence of new L. donovani strains during epidemics due to the pressure of widespread use of antimonials.In this communication the possible role of isolates diversity in antimonial unresponsiveness and the in vitro changing PCR-RAPD band pattern in SSG-unresponsive strains were discussed.     

Adiponectin and the mediation of HDL-cholesterol change with improved lifestyle: the Look AHEAD Study

Adipose tissue dysfunction plays a key role in the development of the metabolic abnormalities characteristic of type 2 diabetes (T2DM) and participates actively in lipid metabolism. Adiponectin, found abundantly in circulation and a marker of adipose health, is decreased in obese persons with T2DM. We investigated whether the changes in adiponectin with an intensive lifestyle intervention (ILI) for weight loss could potentially mediate the increase in low HDL-cholesterol (HDL-C) with ILI. Adiponectin and its fractions were determined using an ELISA with selective protease treatment in 1,397 participants from Look AHEAD, a trial examining whether ILI will reduce cardiovascular events in overweight/obese subjects with T2DM when compared with a control arm, diabetes support and education (DSE). Multivariable regression and mediational analyses were performed for adiponectin and its high-molecular-weight (HMW) and non-HMW fractions. ILI increased baseline HDL-C by 9.7% and adiponectin by 11.9%; changes with DSE were 1.3% and 0.2%, respectively (P < 0.0001). In a model including changes in weight, fitness, triglycerides, and glucose control and that adjusted for demographics and medical history, adiponectin changes remained significantly associated with HDL-C change. Data supported the contribution of changes in both HMW- and non-HMW-adiponectin to the improvement in HDL-C with ILI     

Mortality Associated with Diabetes and Cardiovascular Disease in Older Women

Background

Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women.

Methodology/Principal Findings

We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97–2.74, P<0.001) and diabetic women without CVD (HR 2.06, CI: 1.62–2.64, P<0.001) compared to non-diabetic women without existing CVD. All-cause, cardiovascular and coronary mortality of non-diabetic women with CVD were not significantly different from diabetic women without CVD.

Conclusions/Significance

Older diabetic women without CVD have a similar risk of cardiovascular mortality compared to non-diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems to extend to older women, supporting current guidelines for cardiovascular prevention.     

追踪方法学(TM)在医院评价工作中的应用研究

传统医院评价方法的缺陷要求在新一轮医院评价中创新医院评价方法。研究对追踪方法学的基本理论进行了梳理,并对海南省应用追踪方法学开展医院评价工作情况进行了总结,最后提出了对我国医院评价工作的建议。     

Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10⁻¹⁷). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10⁻⁵–1×10⁻¹⁹). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10⁻⁵, P _interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P _interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P _interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P _interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.