Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer

Much of the genetic predisposition to colorectal cancer (CRC) in humans is unexplained. Studying a Caucasian-dominated population in the United States, we showed that germline allele-specific expression (ASE) of the gene encoding transforming growth factor-beta (TGF-beta) type I receptor, TGFBR1, is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls. ASE results in reduced expression of the gene, is dominantly inherited, segregates in families, and occurs in sporadic CRC cases. Although subtle, the reduction in constitutive TGFBR1 expression alters SMAD-mediated TGF-beta signaling. Two major TGFBR1 haplotypes are predominant among ASE cases, which suggests ancestral mutations, but causative germline changes have not been identified. Conservative estimates suggest that ASE confers a substantially increased risk of CRC (odds ratio, 8.7; 95% confidence interval, 2.6 to 29.1), but these estimates require confirmation and will probably show ethnic differences.     

Loss of IGF2 imprinting: a potential marker of colorectal cancer risk

Loss of imprinting (LOI), an epigenetic alteration affecting the insulin-like growth factor II gene (IGF2), is found in normal colonic mucosa of about 30% of colorectal cancer (CRC) patients, but it is found in only 10% of healthy individuals. In a pilot study to investigate the utility of LOI as a marker of CRC risk, we evaluated 172 patients at a colonoscopy clinic. The adjusted odds ratio for LOI in lymphocytes was 5.15 for patients with a positive family history [95% confidence interval (95% CI), 1.70 to 16.96; probability P = 0.002], 3.46 for patients with adenomas (95% CI, 1.14 to 11.37; P = 0.026), and 21.7 for patients with CRC (95% CI, 3.48 to 153.6; P = 0.0005). LOI can be assayed with a DNA-based blood test, and it may be a valuable predictive marker of an individual's risk for CRC.     

BLM642-1290重组解旋酶的优化表达

Bloom综合症(Bloom's syndrome)是人类一种少见的常染色体隐性遗传疾病,BLM基因突变导致这种疾病的发生,患者染色体极不稳定,是多种癌症的易患体,其致病机理不清楚.该研究在优化诱导表达温度、时间、IPTG质量浓度、pH值、培养基种类以及培养基成分的基础上,建立了BLM642-1290重组蛋白表达、分离和纯化方法.最优表达务件为IPTG 0.45 mmol/L,诱导温度18℃,诱导表达时间20 h,pH值7.0.在LB培养基中添加终质量浓度为5 mmol/L的EDTA能够增加蛋白的表达量.该实验所建立的方法为进一步开展Bloom综合症的研究奠定了基础.     

BLM642-1290重组解旋酶的优化表达

Bloom综合症(Bloom s syndrome)是人类一种少见的常染色体隐性遗传疾病,BLM基因突变导致这种疾病的发生,患者染色体极不稳定,是多种癌症的易患体,其致病机理不清楚.该研究在优化诱导表达温度、时间、IPTG质量浓度、pH值、培养基种类以及培养基成分的基础上,建立了BLM642-1290重组蛋白表达、分离和纯化方法.最优表达条件为IPTG0.45 mmol/L,诱导温度18℃,诱导表达时间20 h,pH值7.0.在LB培养基中添加终质量浓度为5 mmol/L的EDTA能够增加蛋白的表达量.该实验所建立的方法为进一步开展Bloom综合症的研究奠定了基础.     

A phosphatase associated with metastasis of colorectal cancer

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.     

Permanent translocation heterozygosity and sex determination in East african mistletoes

Viscum fischeri has 2n = 23 chromosomes in male plants. These fornm 7 bivalents and a translocation chain of 9 chromosomes during meiosis. Pollen with 11-and 12-chromosome genomes is thus produced. Female plants have 2n = 22 chromosomes and produce 11 bivalents during meiosis. Sex determination is technically a rare multiple X-multiple Y type, but more importantly it provides the mechanism whereby permanent translocation heterozygosity is maintained in the system. In a second species, Viscum engleri, male plants have 2n=28 chromosomes associating as 11 bivalents and a ring of 6 chomosomes at meiosis.     

Obstructive lung disease and alpha-1-antitrypsin deficiency gene heterozygosity

The phenotypes of serum alpha(1)-antitrypsin were determined by antigenantibody crossed electrophoresis. There were five homozygotes and 25 heterozygotes for the deficiency gene found in a group of 103 patients with obstructive lung disease. The frequency of heterozygotes was 14 and 9 percent in two control groups with different mean ages of 36 and 80. There was only one heterozygote among 39 healthy males over 70 years of age. Heterozygosity may be a predisposing factor in chronic obstructive lung disease, especially in the male population.     

放疗后复发鼻咽癌微卫星不稳定和杂合性缺失改变的研究

目的比较放疗后复发鼻咽癌（NPC）与初诊NPC中染色体微卫星不稳定（MSI）和杂合性缺失（LOH）发生情况。方法选择1p、3p、3q、4q、9q、11q、13q、14q的12个微卫星多态性位点,显微切割分离22例初诊和18例放疗后复发NPC组织和正常组织,提取DNA,经PCR扩增及聚丙烯酰胺凝胶电泳和硝酸银染色,进行MSI及LOH分析研究。结果（1）8个位点发生了LOH：复发癌与初诊癌相比,LOH发生率在D1S2697位点为28.6%比20.0%,在D13S133位点为30.0%比20.0%,在D9S1682位点为7.7%比9.1%;D5S433和D14S65位点只在复发癌中发生LOH,分别为33.3%和6.7%;D13S263、D4S350、D14S258位点只在初诊癌发生LOH,分别为20.0%、33.3%、16.6%。（2）11个位点发生了MSI：4个位点在复发癌和初诊癌中都发生MSI,4个位点只在复发癌中发生MSI,3个位点只在初诊癌中发生MSI。结论 D1S2697、D13S133、D5S433位点可能含有与放疗后复发NPC相关的肿瘤抑制基因,放疗后复发NPC中MSI发生率呈增高趋势,提示部分放疗后复发NPC与原发癌可能属不同细胞克隆起源。     

哮喘患者12号染色体微卫星不稳定性和杂合性丢失的研究

目的了解广东湛江地区哮喘患者12号染色体微卫星不稳定性（microsatellite instability,MSI）及杂合性丢失（loss of heterozygosity,LOH）情况。方法采用PCR、聚丙烯凝胶电泳及硝酸银染色法对30例哮喘患者和30例健康对照者外周血及痰液DNA中12q13.11-24.31上10个微卫星位点进行检测。结果健康对照者未发现任何微卫星改变现象。30例哮喘患者中,8例（26.7%）患者痰液DNA有一个或多个位点发生微卫星改变（包括MSI和LOH）。结论湛江地区哮喘患者痰液DNA中12号染色体上可检测到MSI和LOH现象。微卫星改变可能与哮喘之间存在一定的相关性,MSI和LOH可能在哮喘发病机制中起一定的作用。     

竞争风险模型在女性乳腺癌预后预测研究中的应用

目的 探索竞争风险模型在乳腺癌患者预后预测中的应用,并与传统生存分析结果进行比较.方法 运用K-M方法估算总体风险率;采用原因别风险模型进行多因素分析,评价复发和转移的影响因素.结果 K-M方法的风险率高于竞争风险情况下的风险率.肿瘤大小和个人乳腺疾病史是复发的独立预后因素.结论 竞争风险模型在乳腺癌患者的预后预测中更合理、更客观.     

四川省主要杂交稻组合DNA杂合性的比较

利用9个随机引物分析了近年来四川省选育的籼型杂交水稻新组合的DNA杂合性。结果表明,不同的引物揭示多态性的能力存在差异;同一引物在不同的水稻组合间扩增的多态性也不一样。14个组合DNA杂合性变异较小,分布于0.2283～0.3451之间。14个组合可以分为3类,但经t检验表明,13个组合与汕优63无显著差异。     

猪个体基因杂合度对胴体性状的影响

134头F2 代杂种猪 (大白×梅山 )在平均体重 88kg时屠宰。用分布在 1、 2和 6号染色体上的 2 4个微卫星座位估计个体基因杂合度 ,分析 1 3个胴体性状随个体基因杂合度增加的变化规律。结果表明 ,屠宰率、胴体重、花油率、板油率、腰部膘厚、胸部膘厚、肩部膘厚、皮率、瘦肉率和脂肪率在各个体基因杂合度 (hi)水平间无显著差异(P >0 0 5 )。胴体长、眼肌面积和骨率在各hi 水平间差异显著 ,hi 小于 0 6时皮率与骨率随hi 增加逐渐降低 ,大于 0 6时随hi 增加而增加 ,而瘦肉率的变化趋势与皮率和骨率恰恰相反。眼肌面积随hi 增加而上下波动。胴体长则随hi 水平的增加而逐渐降低。hi 在 0 6 0～ 0 6 5时 ,胴体长和眼肌面积性状值较高 ,而骨率达最低值 ,表明在生产中可以将个体基因杂合度控制在 0 6 0～ 0 6 5 ,从而综合利用这些性状 ,以提高猪的胴体生产性能