35例艾滋病患者高效联合抗反转录病毒治疗后血脂代谢及颈动脉中层厚度的研究

目的 研究获得性免疫缺陷综合征[艾滋病(AIDS)]患者经高效联合抗反转录病毒治疗(Highly active antiretroviral therapy,HAART)后所导致的血脂及心血管方面的副作用.方法 回顾性调查在我院治疗并门诊随访的35例男性人类免疫缺陷病毒1型(HIV-1)感染者,均接受相同HAART方案(d4T+3TC+EFV),平均年龄为38.5±15.3岁,平均抗病毒时间为24.6±17.5月,抗病毒治疗前平均CD4计数为69.5±34.6个/μl,比较抗病毒治疗前、后患者空腹血脂变化(包括三酰甘油、总胆固醇、高密度脂蛋白、低密度脂蛋白)并进行统计学分析.其中22例在本系列研究最后1次血脂测定时接受高分辨B超测定颈动脉内膜中层厚度(IMT)测定.结果 35例AIDS患者HAART前、后血三酰甘油分别为1.44±0.35mmol/L和2.07±0.54mmol/L(P ＜0.001);总胆固醇分别为4.96±0.46mmol/L和6.15±0.83mmol/L(P＜0.001);血高密度脂蛋白分别为1.06±0.01mmol/L和 1.04±0.01mmol/L(P＞0.05);血低密度脂蛋白分别为2.29±0.33 mmol/L和3.11±0.29mmol/L(P＜0.001).22例患者经Philips5000彩色B超仪测定IMT平均为0.86±0.14 mm,明显高于文献报道的正常值0.7±0.2mm.结论 HAART治疗艾滋病患者与血脂代谢异常及部分心血管并发症相关.     

接受高效抗逆转录病毒治疗的 HIV/AIDS患者血浆IL 35及其受体水平的动态变化

目的 检测接受高效抗逆转录病毒治疗(HAART)的人类免疫缺陷病毒(HIV)感染者/艾滋病(AIDS)患者血浆中白介素(IL) 35及其受体IL12rβ2、糖蛋白130(gp130)水平的动态变化及意义。 方法 选择我院2017年1月至2018年3月收治的41例HIV感染者/AIDS患者为研究对象,选择45例同期健康体检者为对照组。分别采集HIV/AIDS患者接受HAART药物0、1、6、12个月时的外周静脉血,检测血浆中的IL 35及其受体IL12rβ2、gp130水平,同时检测血浆HIV 1 RNA载量,分析IL 35与IL12rβ2、gp130、HIV 1 RNA以及IL12rβ2、gp130与HIV 1 RNA病毒载量的相关性。 结果 与对照组相比,接受HAART(0、1、6个月)时患者血浆中IL 35、IL12rβ2、gp130水平降低(均P结论 接受HAART的HIV/AIDS患者血浆IL 35及其受体IL12rβ2、gp130水平随着接受HAART时间的延长而逐渐升高,且与HIV 1 RNA载量关系密切。血浆IL 35及其受体IL12rβ2、gp130在抗HIV感染中可能发挥一定作用。     

Study of HIV-1 drug resistance in patients receiving free antiretroviral therapy in China

To investigate the prevalence of drug-resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment-naive and antiretroviral-treated patients infected with HIV/AIDS in Henan, China, a total of 431 plasma samples were collected in Queshan county between 2003 and 2004, from patients undergoing the antiretroviral regimen Zidovudine + Didanosine + Nevirapine (Azt+Ddi+Nvp). Personal information was collected by face to face interview. Viral load and genotypic drug resistance were tested. Drug resistance mutation data were obtained by analyzing patient-derived sequences through the HIVdb Program (http://hivdb.stanford.edu). Overall, 38.5% of treatment-naive patients had undetectable plasma viral load (VL), the rate significantly increased to 61.9% in 0 to 6 months treatment patients (mean 3 months) (P<0.005) but again significantly decrease to 38.6% in 6 to 12 months treatment patients (mean 9 months) (P<0.001) and 40.0% in patients receiving more than 12 months treatment (mean 16 months) (P<0.005). The prevalence of drug resistance in patients who had a detectable VL and available sequences were 7.0%, 48.6%, 70.8%, 72.3% in treatment-naïve, 0 to 6 months treatment, 6 to 12 months treatment, and treatment for greater than 12 months patients, respectively. No mutation associated with resistance to Protease inhibitor (PI) was detected in this study. Nucleoside RT inhibitor (NRTI) mutations always emerged after non-nucleoside RT inhibitor (NNRTI) mutations, and were only found in patients treated for more than 6 months, with a frequency less than 5%, with the exception of mutation T215Y (12.8%, 6/47) which occurred in patients treated for more than 12 months. NNRTI mutations emerged quickly after therapy begun, and increased significantly in patients treated for more than 6 months (P<0.005), and the most frequent mutations were K103N, V106A, Y181C, G190A. There had been optimal viral suppression in patients undergoing treatment for less than 6 months in Queshan, Henan. The drug resistance strains were highly prevalent in antiretroviral-treated patients, and increased with the continuation of therapy, with many patients encountering virological failure after 6 months therapy.     

艾滋病患者CD4+T细胞基线值与长期高效抗逆转录病毒治疗免疫重建效果的相关性研究

目的:探讨艾滋病患者CD4~+T细胞基线值与长期高效抗逆转录病毒治疗免疫重建效果的相关性。方法:挑选进行长期高效抗逆转录病毒治疗的艾滋病患者120例,并按CD4~+T淋巴细胞计数基线值分为A组(≤100·μL~(-1))共66例和B组(100·μL~(-1))共54例,对两组患者的CD4~+T以及CD8~+T淋巴细胞计数变化进行定期观察以及统计分析。结果:经抗病毒治疗后,B组患者各个阶段的CD4~+T淋巴细胞计数回升水平明显优于A组,差异具有统计学意义(均P0.001);9个月内,B组CD4~+T淋巴细胞计数回升明显优于A组,差异具有统计学意义(P=0.003,P0.001,P=0.002);12个月后,两组患者CD4~+T淋巴细胞计数增幅并无明显差异,无统计学意义(P=0.061,P=0.219,P=0.738);经抗病毒治疗后,两组组患者各个阶段的CD8~+T淋巴细胞计数回升水平均无明显差异,无统计学意义(P=0.447,P=0.681,P=0.639,P=0.464,P=0.886,P=0.712)。结论:艾滋病患者免疫重建受CD4~+T淋巴细胞基线高低的直接影响,而CD8~+T淋巴细胞计数的回升相对较为缓慢。     

Updates on CRISPR-based gene editing in HIV-1/AIDS therapy

Although tremendous efforts have been made to prevent and treat HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. The combination antiretroviral therapy (cART), although able to suppress HIV-1 replication, cannot eliminate the proviral DNA integrated into the human genome and thus requires lifelong treatment that may lead to various side effects. In recent years, clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9) related gene-editing systems have been developed and designed as effective ways to treat HIV-1 infection. However, new gene-targeting tools derived from or functioning like CRISPR/Cas9, including base editor, prime editing, SHERLOCK, DETECTR, PAC-MAN, ABACAS, pfAGO, have been developed and optimized for pathogens detection and diseases correction. Here, we summarize recent studies on HIV-1/AIDS gene therapy and provide more gene-editing targets based on studies relating to the molecular mechanism of HIV-1 infection. We also identify the strategies and potential applications of these new gene-editing technologies for HIV-1/AIDS treatment in the future. Moreover, we discuss the caveats and problems that should be addressed before the clinical use of these versatile CRISPR-based gene targeting tools. Finally, we offer alternative solutions to improve the practice of gene targeting in HIV-1/AIDS gene therapy.     

Cancer survival in patients with HIV/AIDS in the era of highly active antiretroviral therapy in Taiwan: A population-based cohort study

Objectives: HIV-related immunosuppression has been associated with the development of AIDS-defining malignancies. We examined the overall survival of HIV-infected patients who developed cancer. Design: A retrospective cohort study. Methods: Using the Taiwan Longitudinal Health Insurance Database, we compared patients diagnosed with HIV (n = 9918) between January 1, 2002, and December 31, 2007 with age-matched controls (n = 99,180). Each patient was followed until the end of 2009 (least 2 years after the initial HIV diagnosis) to evaluate the incidence of malignancies. Results: The risk of overall malignancies in the HIV-infected cohort was 1.88 times higher than the risk of a first malignancy in the age-matched non-HIV infected cohort (incidence rate ratio [IRR]) = 2.05, p < 0.0001). The diagnosis of a malignancy was negatively correlated with survival in the HIV-infected cohort (p < 0.0011), and HIV infection had a synergistic effect on the survival of patients with malignancies compared with the non-HIV infected cohort, all of who had been newly diagnosed with cancer (p < 0.0001). However, the difference in the risk of developing nasopharyngeal carcinoma (NPC), a highly prevalent malignancy in Taiwan, between the two cohorts was not significant (IRR = 0.22, 95% CI = 0.03–1.65). Conclusions: The risk of cancer in HIV-infected patients in Taiwan has increased significantly in the era of highly active antiretroviral therapy. A history of HIV significantly affected the survival of the patients in our study cohort after they developed cancer.Evidence level: 2B.     

HIV阳性患者肠道菌群特征对联合抗反转录病毒治疗效果的预测

观察人类免疫缺陷病毒(HIV)阳性患者肠道菌群特征对联合抗反转录病毒治疗(cART)效果的预测作用, 以期为HIV阳性患者的抗病毒治疗获益评估提供辅助手段。

前瞻性选取我院2017年1月至2020年1月收治95例HIV阳性患者为研究对象, 均于治疗前收集患者资料, 分析患者肠道菌群特征, 实施cART治疗, 治疗6个月后评估疗效, 将患者划分为有效组和无效组, 采用回归分析检验HIV阳性患者肠道菌群特征与cART疗效的关系, 并分析肠道菌群特征对cART疗效的预测效能。

95例HIV阳性患者中共有69例cART治疗有效, 26例治疗无效。回归分析结果显示, HIV RNA载量、免疫球蛋白(Ig)A、IgG水平及肠道屎肠球菌、粪肠球菌、大肠埃希菌、乳杆菌、双歧杆菌数量均与HIV阳性患者治疗效果有关(OR=18.964、42 376.484、4.183、8.585、14.358、15.134、9.297、10.223, 均P < 0.001)。受试者工作曲线(ROC)显示, HIV阳性患者肠道屎肠球菌、粪肠球菌、大肠埃希菌、乳杆菌、双歧杆菌数量用于预测cART治疗无效风险的曲线下面积(AUC)均 > 0.80, 均有一定预测效能。

HIV阳性患者cART治疗的总有效率较低, 其疗效与HIV RNA载量、Ig水平及肠道菌群特征密切相关, 其中肠道主要菌群数量可用于预测HIV阳性患者cART治疗无效的风险。

     

Serotypes of Cryptococcus neoformans isolated from patients prior to and during the AIDS era in Thailand

One hundred and eighty-seven strains of Cryptococcus neoformans isolated from patients in Thailand were charcterized by biochemical varieties relating to serogroups. Canavanine-glycine-bromothymol blue (CGB) agar was used for differentiating the varieties of C. neoformans. Slide agglutination tests were performed with Crypto Check (Iatron, Inc., Tokyo) to determine their serotypes. Fifty-five percent (10 out of 18) of the pre-AIDS isolates were serotype B, 28% were serotype A, 5% were serotype D, and an unexpected 11% (2 out of 18) were serotype C. These are the first to be recorded in Asia. In contrast, among the 169 clinical isolates obtained between January 1993 and March 1995 (AIDS epidemic), serotype A was outstandingly predominant-93% (157 out of 169), serotype B was relatively low (3.6%) and both serotypes D and AD were 1.8%. The pattern of serotypes of the 59 isolates from known HIV-positive patients was closely similar to the total isolates during the AIDS epidemic. In determining the varieties of C. neoformans by CGB, only 1 of the 187 isolates gave a false reaction. On the basis of our findings, we believe that in the pre-AIDS era either C. neoformans var. gattii serorype B or serotype C were the common causative agents of cryptococcosis in Thailand. The advent of AIDS changed the pattern of serotypes with serotype A becoming predominant as has been reported world wide.     

高活性酪氨酸解氨酶的表征及其在对香豆酸生物合成中应用

对香豆酸(p-coumaric acid)具有抗菌、抗氧化和预防心血管疾病的作用,也是许多重要化合物的前体或中间体,被广泛应用于食品、化妆品和医药等领域。酪氨酸解氨酶(tyrosine ammonia-lyase,TAL)能直接催化酪氨酸脱氨生成对香豆酸。然而,缺少高活性和高底物耐受性的酪氨酸解氨酶限制了对香豆酸的高效生物合成。为了提高对香豆酸的合成能力,本研究挖掘了2个黄杆菌来源的酪氨酸解氨酶,分别是柱状黄杆菌(Flavobacterium columnare)来源的Fc-TAL2和顺天黄杆菌(Flavobacterium suncheonense)来源的Fs-TAL。异源表达纯化表征分析显示,Fc-TAL2和Fs-TAL的最适温度和最适pH相同,分别为55℃、pH 9.5。在最适条件下,Fs-TAL的比酶活为82.47 U/mg,而Fc-TAL2的比酶活为13.27 U/mg。结构模拟和比对分析显示,内盖环上保守的Y50残基酚羟基朝向和到底物的距离是造成Fs-TAL活性高于Fc-TAL2的主要原因。全细胞催化研究进一步证实Fs-TAL具有较高活性和特异性,能够催化10 g/L酪氨酸...     

Investigation into the Concanavalin A reactivity, fucosylation and oligosaccharide microheterogeneity of α1-acid glycoprotein expressed in the sera of patients with rheumatoid arthritis

α₁-Acid glycoprotein (AGP) exists as an heterogeneous population of glycosylated variants (glycoforms) in plasma. The concentration of AGP increases some 2–5 fold in certain pathophysiological states exemplified by the chronic inflammatory disease, rheumatoid arthritis (RA). Moreover, the expressed glycosylation pattern alters in such conditions, indicating functional significance that is likely to be related to the oligosaccharide heterogeneity. We have investigated the heterogeneity of AGP glycosylation using the technique of high pH anion-exchange chromatography (HPAEC). AGP was isolated from the blood of RA sufferers, partially separated by Concanavalin A (Con A) affinity chromatography into bound and non-bound fractions and was enzymatically deglycosylated. Chromatography on the pellicular HPAE resin at pH 13 separated the released oligosaccharides and allowed a comparison of profiles in terms of branching and fucosylation. Results demonstrate an abnormal RA AGP glycosylation, with a tendency towards tri- and tetra-antennary oligosaccharides and enhanced fucosylation, in addition to the possible existence of penta-sialylated RA AGP glycoforms.     

HIV/AIDS患者抗病毒治疗前HIV-1耐药情况调查及外周血CD8+T细胞CD38表达水平研究

摘要 目的：分析人免疫缺陷病毒/艾滋病（HIV/AIDS）患者抗病毒治疗前HIV-1耐药以及影响因素,探讨HIV/AIDS患者外周血CD₈⁺T细胞CD₃₈表达（CD₈⁺CD₃₈⁺T淋巴细胞百分比）与CD₄⁺T淋巴细胞计数的相关性。方法：选择2016年3月至2019年12月我院接诊的442例HIV/AIDS患者（HIV/AIDS组）和163例同期于我院进行体检的健康志愿者（对照组）,HIV/AIDS组扩增pol基因,进行HIV-1基因耐药分析,检测CD₈⁺CD₃₈⁺T淋巴细胞百分比、CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数。分析HIV/AIDS患者HIV-1耐药的影响因素,分析CD₈⁺CD₃₈⁺T淋巴细胞百分比与CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数相关性。结果：HIV/AIDS组442例HIV/AIDS患者中376例获得HIV-1 pol基因序列,HIV-1耐药35例,耐药率9.31%（35/376）。单因素分析结果显示耐药组和非耐药组在年龄、文化程度、感染途径、HIV病毒载量方面差异有统计学意义（P＜0.05）。多因素Logistic回归分析结果显示同性性传播、注射吸毒、高HIV病毒载量是HIV/AIDS患者抗病毒治疗前HIV-1耐药的危险因素（P＜0.05）。HIV/AIDS组外周血CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数低于对照组（P＜0.05）,CD₈⁺CD₃₈⁺T淋巴细胞百分比高于对照组（P＜0.05）。CD₈⁺CD₃₈⁺T淋巴细胞百分比与CD₄⁺T淋巴细胞计数、CD₈⁺T淋巴细胞计数呈负相关（P＜0.05）。结论：抗病毒治疗前HIV/AIDS患者存在一定HIV-1耐药率,传播途径、HIV-1病毒载量与HIV-1耐药有关。CD₈⁺T细胞表面CD₃₈过表达与HIV/AIDS 患者CD₄⁺T T细胞的过度消耗有关。     

The Nir1 locus in barley is tightly linked to the nitrite reductase apoprotein gene Nii

pBNiR1, a cDNA clone encoding part of the barley nitrite reductase apoprotein, was isolated from a barley (cv. Maris Mink) leaf cDNA library using the 1.85 kb insert of the maize nitrite reductase cDNA clone pCIB808 as a heterologous probe. The cDNA insert of pBNiR1 is 503 by in length. The nucleotide coding sequence could be aligned with the 3 end of other higher plant nitrite reductase apoprotein cDNA sequences but diverges in the 3 untranslated region. The whole-plant barley mutant STA3999, previously isolated from the cultivar Tweed, accumulates nitrite after nitrate treatment in the light, has very much lowered levels of nitrite reductase activity and lacks detectable nitrite reductase cross-reacting material due to a recessive mutation in a single nuclear gene which we have designated Nir1. STA3999 has the characteristics expected of a nitrite reductase apoprotein gene mutant. Here we have used pB-NiR1 in RFLP analysis to determine whether the mutation carried by STA3999 is linked to the nitrite reductase apoprotein gene locus Nii. An RFLP was identified between the wild-type barley cultivars Tweed (major hybridising band of 11.5 kb) and Golden Promise (major hybridising band of 7.5 kb) when DraI-digested DNA was probed with the insert from the partial barley nitrite reductase cDNA clone, pBNiR1. DraI-digested DNA from the mutant STA3999 also exhibited a major hybridising band of 11.5 kb after hybridisation with the insert from pBNiR1. F₁ progeny derived from the cross between the cultivar Golden Promise and the homozygous nir1 mutant STA3999 were heterozygous for these bands as anticipated. Co-segregation of the Tweed RFLP band of 11.5 kb and the mutant phenotype (leaf nitrite accumulation after nitrate treatment/loss of detectable nitrite reductase cross-reacting material at M_r 63000) was scored in an F₂ population of 312 plants derived from the cross between the cultivar Golden Promise and the homozygous mutant STA3999. The Tweed RFLP band of 11.5 kb and the mutant phenotype showed strict co-segregation (in approximately one quarter (84) of the 312 F₂ plants examined). Only those F₂ individuals heterozygous for the RFLP pattern gave rise to F₃ progeny which segregated for the mutant phenotype. We conclude that the nir1locus and the nitrite reductase apoprotein gene Nii are very tightly linked.     

Expression of Cry1Ac in Transgenic Tobacco Plants Under the Control of a Wound-Inducible Promoter (AoPR1) Isolated from Asparagus officinalis to Control Heliothis virescens and Manduca sexta

Expression of cry1Ac gene from Bacillus thuringiensis (Bt) was evaluated under the control of a wound-inducible AoPR1 promoter from Asparagus officinalis in transgenic tobacco plants. The leaves of transgenic plants were mechanically wounded to evaluate the activity of the AoPR1 promoter in driving the expression of Cry1Ac protein at the wound site. Our results indicate that mechanical wounding of transgenic plants was effective in inducing the expression of Cry1Ac protein. As a result of this induction, the accumulated levels of Cry1Ac protein increased during 6–72 h post-wounding period. The leaves of transgenic tobacco plants were evaluated for resistance against Heliothis virescens and Manduca sexta in insect bioassays in two different ways. The detached tobacco leaves were either fed directly to the insect larvae or they were first mechanically wounded followed by a 72 h post-wounding feeding period. Complete protection of mechanically wounded leaves of transgenic plants was observed within 24 h of the bioassay. The leaves of transgenic plants fed directly (without pre-wounding) to the larvae achieved the same level of protection between 24 and 72 h of the bioassay.     

枣ZjMADS1-box基因克隆与表达分析

以‘金丝4号’枣花蕾和叶片为材料,通过抑制消减杂交文库(SSH文库)的构建、RACE技术和半定量RT-PCR等方法,克隆了枣花发育基因并研究了其时空表达模式,为枣花发育机理研究奠定基础。结果表明:(1)从枣花SSH文库中鉴定出476bp的花发育B类PISTILLATA(PI)基因的EST序列,命名为ZjMADS1-box;通过RACE技术获得了枣ZjMADS1-box基因的全长cDNA序列。(2)枣ZjMADS1-box基因表现出PI基因的序列结构特征。其全长cDNA长度为957bp,编码220个氨基酸残基;在氨基酸序列水平上,该基因与巨桉EgM2(Eu-calyptus grandis M2)和白千层MqPI(Melaleuca quinquenervia PI)的相似性最高为72.6%,与辣椒CaPI(Capsi-cum annuum PI)的相似性最低为61.8%;系统进化树分析显示,枣ZjMADS1-box与MqPI和EgM2基因聚在一起;枣ZjMADS1-box基因编码蛋白的等电点为9.75,分子量为25 587.5Da,属亲水性的非分泌性蛋白。(3)Zj-MADS1-box基因在花器官中特异表达,在嫩茎、成熟叶、腋芽等营养器官中不表达;在4月30日和5月8日花蕾中的表达量略高于5月4日、5月12日、5月16日的表达量,但差异不显著。     

独行菜种子bHLH类转录因子基因家族及幼苗laICE1表达对冷胁迫的响应

该研究在转录组数据基础上,以独行菜(Lepidium apetalum Willd.)种子耐受和不能耐受低温萌发的2组样本为材料,对其bHLH转录因子家族成员进行分析,并对该家族成员表达差异极显著的laICE1基因进行克隆、序列分析、结构预测,以探讨独行菜幼苗中laICE1基因表达对低温胁迫的响应特征。结果表明:(1)萌发中的独行菜种子,至少有83个bHLH转录因子序列表达,相对于低温萌发停滞组,在低温萌发耐受组的独行菜种子中,有10个下调、13个上调、60个表达差异不显著。其中表达量极显著下调的序列c20009_g1具有1 503bp开放阅读框,GO注释到ICE1基因,该基因命名为laICE1。(2)laICE1基因编码500aa,蛋白分子量为54 635.19kD,理论等电点为5.45,分子式为C2364H3742N688O758S22;该蛋白具有保守结构域bHLH。(3)定量分析表明,laICE1基因在非低温胁迫的独行菜种子中的表达量显著低于一直处于低温胁迫中不能进行萌发的独行菜种子,这与转录组数据库中该序列表达情况一致;而laICE1基因在独行菜幼苗期经低温处理后,其表达量显著上调,表明laICE1基因可能在独行菜幼苗耐受低温生长中具有一定的作用。     

Mapping strategy for resistance genes in tomato based on RFLPs between cultivars: Cf9 (resistance to Cladosporium fulvum) on chromosome 1

Summary The contribution of introgressed regions derived from wild species to the genetic variation within the species of Lycopersicon esculentum was investigated by comparing the RFLP patterns of 2 introgression-free, obsolete cultivars (Moneymaker and Premier) and a modern cultivar (Sonatine) that carries at least 5 introgressed resistance genes. In this analysis 195 mapped nuclear markers were used in combination with 6 restriction enzymes. Among the 1170 probe-enzyme combinations tested, only 3 showed a polymorphism between the 2 introgression-free cultivars. On the other hand 24 probe-enzyme combinations were found to exhibit polymorphisms between Moneymaker and Sonatine. These represented ten polymorphic loci distributed among 5 linkage groups on chromosomes 1, 3, 4, 6, and 9.On the assumption that most of the polymorphic loci corresponded to introgressed chromosome segments of wild species carrying resistance genes, linkages between these loci and the component resistance genes were examined by RFLP analysis of pairs of near-isogenic lines differing only for one particular resistance gene, and a variety of commercial cultivars having different resistance gene compositions. Two of the polymorphic linkage groups could thus be ascribed to resistance genes whose map positions were already known: Cf2 on chromosome 6 and Tm2a on chromosome 9, whereas another marker, TG301 on chromosome 1, could be assigned to the Cladosporium fulvum resistance gene Cf9 with a hitherto disputable map position. By linkage analysis of a segregating F₂ population the genetic distance between the Cf9 gene and the marker TG301 was estimated at 5.5 ± 2.3 cM.