An alternative route for multistep tumorigenesis in a novel case of hereditary renal cell cancer and a t(2;3)(q35;q21) chromosome translocation.

Through allele-segregation and loss-of-heterozygosity analyses, we demonstrated loss of the translocation-derivative chromosome 3 in five independent renal cell tumors of the clear-cell type, obtained from three members of a family in which a constitutional t(2;3)(q35;q21) was encountered. In addition, analysis of the von Hippel-Lindau gene, VHL, revealed distinct insertion, deletion, and substitution mutations in four of the five tumors tested. On the basis of these results, we conclude that, in this familial case, an alternative route for renal cell carcinoma development is implied. In contrast to the first hit in the generally accepted two-hit tumor-suppressor model proposed by Knudson, the familial translocation in this case may act as a primary oncogenic event leading to (nondisjunctional) loss of the der(3) chromosome harboring the VHL tumor-suppressor gene. The risk of developing renal cell cancer may be correlated directly with the extent of somatic (kidney) mosaicism resulting from this loss.     

Shoot Sr concentrations in relation to shoot Ca concentrations and to soil properties

This work was aimed to investigate whether shoot Sr concentrations of plant species are related to respective Ca concentrations and to soil properties and to compare the Sr-Ca observed ratios (OR), defined as the quotient of the ratios Sr/Ca in shoots and in the soil solution or in the extractable form, among species and soils. Ten pasture plant species were grown in pots (1-L volume) filled with eight soils differing in the various physicochemical characteristics. Each pot received 50 mg Sr except those of the soil with the highest cation exchange capacity (C.E.C.) that received 100 mg Sr per pot. For each soil, shoot Sr concentrations of species were linearly and positively related with the respective Ca concentrations. C.E.C, organic matter content and Ca in the soil solution or in the extractable form were the only soil properties that were related, all negatively, with shoot Sr concentrations. The ratio of extractable Sr and Ca was positively and linearly related with the ratio of Sr and Ca. in the soil solution. OR was affected by both species and soils. Most of OR values of all species in all soils ranged between 0.8 and 1.5, except for the grass Agrostis capillaris which had the highest values for most of soils. This indicates that Agrostis capillaris compared to other species, takes up proportionally more Sr than Ca.     

Parnassia palustris: a genetically diverse species in Scandinavia

Patterns of variation at nine enzyme loci were examined in 528 plants representing diploid and tetraploid populations of Parnassia palustris s. l. in Europe to assess genetic variation patterns and migration history. Half of the plants showed a unique multilocus phenotype and 75% of all phenotypes occurred only in Scandinavia. Diploid populations showed similar levels of genetic diversity as other widespread outbreeding species with animal-mediated pollination and F -statistics indicated excessive heterozygosity and low rates of gene flow among them. In spite of dramatic population histories caused by the ice ages, diploid populations have maintained the same genetic diversity in Scandinavia as in central and southern Europe. Northern populations have apparently been established through the gradual advance of genetically variable populations and patterns of variation at individual loci indicate different migration routes, from the south-south-west and the east-north-east, respectively. The data strongly support a repeated autoploid origin of the tetraploid cytotype which has been much more successful than the diploid progenitors in colonizing new land since the last ice age. High genetic diversity in Scandinavia has apparently been obtained by a combination of immigration of plants from different source areas and recurrent formation of autotetraploids from diploid progenitors.  © 2003 The Linnean Society of London, Botanical Journal of the Linnean Society , 2003, 142 , 347−372.     

Inverted meiosis and the evolution of sex by loss of complementation

Inverted meiosis, in which sister chromatids segregate before homologous chromosomes, is a common aberration of conventional meiosis (in which sister chromatids segregate after homologous chromosomes) and is routinely observed in certain species. This raises an evolutionary mystery: what is the adaptive advantage of the more common, conventional order of segregation in meiosis? I use a population genetic model to show that asexual mutants arising from inverted meiosis are relatively immune from the deleterious effects of loss of complementation (heterozygosity), unlike the asexual mutants arising from conventional meiosis, in which loss of complementation can outweigh the two‐fold cost of meiosis. Hence, asexual reproduction can replace sexual reproduction with inverted meiosis, but not with conventional meiosis. The results are in line with analogous considerations on other alternative types of reproduction and support the idea that amphimixis is stable in spite of the two‐fold cost of meiosis because loss of complementation in mutant asexuals outweigh the two‐fold cost.     

Isozyme variation and species relationships in peanut and its wild relatives (Arachis L. — Leguminosae)

Summary Arachis hypogaea (peanut or groundnut) is an AABB allotetraploid whose precise ancestry is not yet clear. Its closest diploid relatives are the annual and perennial wild species included with it in the section Arachis. Variation in these species for 11 different enzymes was studied by starch-gel electrophoresis. Differences attributed to at least 13 genetic loci were found among eight enzymes, while three enzymes appeared uniform throughout the section. Values for Nei's genetic distance were calculated for all pairs of species and were used to estimate relationships. All diploid species, apart from two whose validity had previously been questioned, could be distinguished by their overall zymotypes, but few contained unique alleles. When species were grouped by their mean genetic distances, they formed two clusters, which agreed reasonably well with the division of the section into annual versus perennial species. The single B-genome species was an outlier within the annual group. A. hypogaea showed fixed heterozygosity at four loci (in ssp. hypogaea) or six loci (in ssp. fastigiata), which agrees with previous conclusions that the peanut is an allotetraploid. None of the diploids included in this survey could be conclusively identified as donors of either the A or the B genome to the tetraploids. The two subspecies of A. hypogaea differed consistently in two of the thirteen putative loci studied. This may call into question the simple hypothesis that A. hypogaea originated from just two diploid species.     

How stable are genomes of tropical woody plants? Heterozygosity in C-banded karyotypes ofPorcelia as compared withAnnona (Annonaceae) andDrimys (Winteraceae)

InPorcelia goyazensis (2n = 18) Giemsa C-banding patterns differ from those ofAnnona reticulata (2n = 14) and reveal structural heterozygosity. The amplitude of karyological variation in theAnnonaceae is greater than expected for a primitive woody family. In a comparison with other tropical angiosperm groups, the highly differentiated karyotype ofDrimys brasiliensis (2n = 86) is interpreted as being the end-point of numerous karyological changes.     

杂色山雀的婚外父权与配偶间的遗传相容性无关

婚配制度作为一种进化稳定对策是动物对某一环境包括种群内部环境适应的结果。据统计,约92%的鸟类为社会性单配制,但单配制鸟类中很多都存在婚外父权现象,表现出社会性婚配制度与遗传性婚配制度的不一致性。杂色山雀(Parus varius)是一种社会性单配制的小型森林洞巢鸟,其是否存在婚外父权现象至今尚未见报道。通过对杂色山雀进行亲权鉴定以确定其有无婚外父权现象及婚外父权的比例,结果显示:45.45%(20/44)的巢存在婚外父权,14.39%(38/264)的后代为婚外子代,说明杂色山雀具有较高的婚外父权水平。进一步探究其婚外父权的发生原因,结果如下:(1)有、无婚外父权巢的社会性亲本之间的遗传相似性无显著差异(P=0.504);(2)有婚外父权巢中婚内子代和无婚外父权巢中子代的杂合度(P=0.118)以及有婚外父权巢中婚外子代与婚内子代的杂合度(P=0.206)均无显著差异。(3)有婚外父权巢中的婚内子代与婚外子代间8项体征指标比较,差异均不显著(Ps0.05)。综上,社会性单配制杂色山雀婚外父权的发生与配偶间的遗传相容性无关,还有待从其他角度进行探究。     

Allelic loss at the GPx-1 locus in cancer of the head and neck

Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously implicated in the risk and development of lung and breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in squamous cell carcinomas of the head and neck. The frequency of a polymorphism at codon 198 resulting in either a leucine or a proline at that position was surveyed by comparing 133 DNA samples obtained from head and neck tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs exhibited fewer pro/leu heterozygotes as compared to DNA obtained from the cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic alanine repeat sequences in the same gene. The analysis revealed an approximately 42% reduction in heterozygosity in the DNA from the tumor samples. In order to assess loss of heterozygosity (LOH) at the GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and microscopically normal tissues adjacent to the tumor, derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues at the tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly linked to it, is an early event in the development of this type of malignancy. Author to whom all correspondence and reprint requests should be addressed. These authors contributed equally to this work.     

Correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma

Androgen-induced proliferation shutoff gene AS3, also known as APRIN, is a growth inhibitory gene that is in itially implicated inprostate cancer. This gene is required for androgen-dependent growth arrest and is a primary target for 1,25(OH)2D3 and androgens. Alle-lic loss at AS3 locus has been linked to a variety of cancers. However, the correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma (ESCC) is not well established. In this study, the genomic and expression alterations of AS3 in ESCC and their clinical significance are evaluated. Loss of beterozygosity (LOH) analysis using an AS3 intragenic mierosatellite marker D13S171 revealed 72% allelic loss at AS3 locus in ESCC, which is significantly correlated with higher pathological grade (P=0.042).RT-PCR examination showed that AS3 mRNA obviously decreased in 44% tumors and its down-regulation was correlated with the sex of patients (P=0.03). Furthermore, the correlation between genomic and expression alterations of AS3 gene was analyzed in 18 ESCC specimens, which indicated that the consistency between allelic loss and decreased mRNA expression of AS3 was relatively poor. The results of this study indicate that the aberrant expression of AS3 may be involved in the tumorigenesis of esophagus and is responsible for the male predominance of ESCC.     

喉鳞癌Apaf-1基因表达及启动子区甲基化研究

喉鳞癌细胞存在多种癌基因和抑癌基因异常,Apaf-1(apoptotic protease activating factor-1)基因是诱导细胞凋亡的肿瘤抑制基因。为探讨Apaf-1基因在喉鳞癌发生中的作用,应用半定量PCR方法分析Apaf-1的表达,用比较基因组杂交(Comparative Genomic Hybrodization,CGH)和杂合性丢失(Loss of Heterozygosity,LOH)分析方法对喉鳞癌病人Apaf-1基因所在的12q22—23区域缺失情况进行研究．并用甲基化特异PCR对该基因启动子区甲基化情况进行了分析。结果表明：11例喉鳞癌组织出现Apaf-1 mRNA表达明显下调,占40．7％(11／27),而6例良性喉肿瘤未发现缺失或下调;CGH分析发现,18例喉鳞癌仅发现2例存在12q22-23区域缺失,未发现扩增;LOH分析发现,72例喉癌组织Apaf-1基因的5个多态位点LOH发生频率低,分别为18．2％(D12S346)、13．9％(D12S1706)、18．2％(D12S327)、22．2％(D12S1657)和16．6％(D12S393),11例出现Apaf-1 mRNA下调的喉癌组织均检测到启动子区甲基化,而16例Apaf-1 mRNA表达未下调者仅1例有甲基化,两者有显著差异(x^2检验,P=0．0001)。通过以上结果,首次证实Apaf-1基因与喉鳞癌相关,在喉鳞癌中Apaf-1基因缺失发生率低．提示启动子区甲基化是该基因失活的首要机制。