Chromosome Y-specific DNA in related human XX males

Human 'XX males' are sterile males whose chromosomes seem to be those of a normal female. About 1 in 20,000 males has a 46, XX karyotype, and most cases are sporadic, that is, they are without familial clustering. It has long been argued that maleness in XX males may result from the undetected presence of a small, testis-determining fragment of the Y chromosome, and there is strong evidence for this in sporadically occurring XX males. Indeed, the genomes of three of four sporadic XX males tested were found to contain certain Y-specific DNA sequences. A pedigree in which three XX males occur has been interpreted as being consistent with autosomal recessive inheritance of maleness, and it has been argued that the basis of XX maleness in this family is fundamentally different from that in the sporadic cases. However, we report here that these related XX males, like the sporadic cases, contain portions of the Y chromosome. The portion of the Y chromosome present in one of the three XX males differs from that present in the other two.     

Cloning and Analysis of RGAs from 5th Chromosome in Gossypiumn arboreum

棉花是最主要的天然纤维作物,深入进行棉花基因组研究具有重要意义.采用酶解、前后低渗和轻压相结合的方法制备亚洲棉染色体中期膜载片,激光法分离亚洲棉第5号单染色体,建单染色体扩增池后克隆其抗病基因同源序列(RGAs),获得P7、P12、P19和P23等4个序列.序列比对和聚类分析表明,这4条序列均为NBS-LRR类RGAs,P7、P12、P19聚成一类,它们之间的同源性很高,P23聚成另一类,与黑松的RPS2和油菜的RGA30同源性较高.为该染色体分子标记开发、基因克隆乃至全序列测定奠定基础.     

Mutational hotspot in the p53 gene in human hepatocellular carcinomas.

Human hepatocellular carcinomas (HCC) from patients in Qidong, an area of high incidence in China, in which both hepatitis B virus and aflatoxin B1 are risk factors, were analysed for mutations in p53, a putative tumour-suppressor gene. Eight of the 16 HCC had a point mutation at the third base position of codon 249. The G----T transversion in seven HCC DNA samples and the G----C transversion in the other HCC are consistent with mutations caused by aflatoxin B1 in mutagenesis experiments. No mutations were found in exons 5,6,8 or the remainder of exon 7. These results contrast with p53 mutations previously reported in carcinomas and sarcomas of human lung, colon, oesophagus and breast; these are primarily scattered over four of the five evolutionarily conserved domains, which include codon 249 (refs 4-9). We suggest that the mutant p53 protein may be responsible for a selective clonal expansion of hepatocytes during carcinogenesis.     

Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines

Although mutations in cell cycle regulators or spindle proteins can perturb chromosome segregation, the causes and consequences of spontaneous mitotic chromosome nondisjunction in human cells are not well understood. It has been assumed that nondisjunction of a chromosome during mitosis will yield two aneuploid daughter cells. Here we show that chromosome nondisjunction is tightly coupled to regulation of cytokinesis in human cell lines, such that nondisjunction results in the formation of tetraploid rather than aneuploid cells. We observed that spontaneously arising binucleated cells exhibited chromosome mis-segregation rates up to 166-fold higher than the overall mitotic population. Long-term imaging experiments indicated that most binucleated cells arose through a bipolar mitosis followed by regression of the cleavage furrow hours later. Nondisjunction occurred with high frequency in cells that became binucleated by furrow regression, but not in cells that completed cytokinesis to form two mononucleated cells. Our findings indicate that nondisjunction does not directly yield aneuploid cells, but rather tetraploid cells that may subsequently become aneuploid through further division. The coupling of spontaneous segregation errors to furrow regression provides a potential explanation for the prevalence of hyperdiploid chromosome number and centrosome amplification observed in many cancers.     

Telomere reduction in human colorectal carcinoma and with ageing

We have hypothesized that end-to-end chromosome fusions observed in some tumours could play a part in genetic instability associated with tumorigenesis and that fusion may result from the loss of the long stretches of G-rich repeats found at the ends of all linear chromosomes. We therefore asked whether there is telomere loss or reduction in common tumours. Here we show that in most of the colorectal carcinomas that we analysed, there is a reduction in the length of telomere repeat arrays relative to the normal colonic mucosa from the same patient. We speculate on the consequences of this loss for tumorigenesis. We also show that the telomere arrays are much smaller in colonic mucosa and blood than in fetal tissue and sperm, and that there is a reduction in average telomere length with age in blood and colon mucosa. We propose that the telomerase is inactive in somatic tissues, and that telomere length is an indicator of the number of cell divisions that it has taken to form a particular tissue and possibly to generate tumours.     

Prevalence of ras gene mutations in human colorectal cancers

A combination of DNA hybridization analyses and tissue sectioning techniques demonstrate that ras gene mutations occur in over a third of human colorectal cancers, that most of the mutations are at codon 12 of the c-Ki-ras gene and that the mutations usually precede the development of malignancy.     

亚洲棉5号染色体RGAs克隆与分析

棉花是最主要的天然纤维作物,深入进行棉花基因组研究具有重要意义.采用酶解、前后低渗和轻压相结合的方法制备亚洲棉染色体中期膜载片,激光法分离亚洲棉第5号单染色体,建单染色体扩增池后克隆其抗病基因同源序列(RGAs),获得P7、P12、P19和P23等4个序列.序列比对和聚类分析表明,这4条序列均为NBS-LRR类RGAs,P7、P12、P19聚成一类,它们之间的同源性很高,P23聚成另一类,与黑松的RPS2和油菜的RGA30同源性较高.为该染色体分子标记开发、基因克隆乃至全序列测定奠定基础.     

A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases

Using DNA transfection analysis on NIH 3T3 cells, activated human oncogenes have been isolated from a variety of fresh solid tumours. Thyroid neoplasias show a wide range of lesions varying from slowly progressive well-differentiated tumours to anaplastic highly malignant neoplasms. Therefore they represent an attractive model to investigate the role of oncogene activation in different stages of the neoplastic state. Here we report the detection of transforming activity in DNAs extracted from five thyroid papillary carcinomas and two of their respective lymph-nodal metastases.     

人类疱疹病毒6、7、8型与巨细胞病毒对大肠肿瘤致病的协同作用

目的:检测HHV-6、7、8及CMV在大肠肿瘤中的感染,探讨其致病的协同作用。方法:取20例大肠肿瘤标本,其中10例良性病变(炎性息肉、乳头状瘤和绒毛状腺瘤),10例恶性病变(癌和腺瘤恶变)。应用巢式PCR法,分别检测两组病变组织中HHV-6、7、8和MCV的DNA片段。结果:HHV-6检测结果表明恶性病变组阳性反应率为90%(9/10),良性病变组阳性反应率为60%(6/10),其产物为132bpDNA片段;HHV-7检测结果示恶性病变组阳性反应率为40%(4/10),良性病变组阳性反应率为0(0/10),其产物为92bpDNA片段;HHV-8检测结果示恶性病变组阳性反应率为90%(9/10),良性病变组阳性反应率为20%(2/10),其产物为177bpDNA片段;检测CMV结果示恶性病变样本组阳性反应率为100%(10/10),良性病变样本组阳性反应率为100%(10/10),其产物为85bpDNA片段。结论:CMV在良、恶性大肠肿瘤病变中均有较高的感染率,HHV-6、7、8在恶性病变组中感染率较良性组高,是需要警惕的致病因素。     

水稻第6染色体S5区重叠群构建、基因注释与OS-APH的克隆分析

以通过图位克降所获得的Cosmid克降R2119序列信息为基础，构建了一个长为586kb的粳稻第6染色体S5座位的BAC重叠群（JS5-BC）。通过生物信息学方法，对JS5-BC进行了基因注释，确定该区域含有46个基因位点。经功能预测，JS5-BC重叠群中仔在3个主要的基因家族，分别是木葡聚糖岩藻糖基转移酶、脂酶和黄素氧化还原酶。JS5-BC中注释基因的一个显著特点是功能相关基因密集存在，如与植物细胞壁的合成代谢相父的3个基因、与呼吸链能量代谢的黄素氧化还原酶的4个基因等都是如此。为了验证基因注释的可靠性，克降了广亲和品种Cp17品种的OSAPH基因的cDNA，并检测了该基因的表达模式，为注释基因提供了分子证据。