Loss of heterozygosity on chromosome 11p13 in primary bladder carcinoma

Although the occurrence of bladder cancer is common, the molecular events underlying the pathogenesis of this cancer remain ill-defined. A loss of heterozygosity (LOH) at specific chromosomal loci may predispose individuals to the development of bladder cancer but this has not been examined in detail. Furthermore, the role that deletion or inactivation of putative tumour suppressor genes might play in the genesis of bladder cancer has not been established. In this study, allelic deletion analysis on the short arm of chromosome 17 of patients with primary bladder tumours failed to show deletion at 17p13 (0/7), a region known to contain the p53 tumour suppressor gene. Chromosome 11p15 showed allelic deletion at the IGF2 locus (2/7: 29%) and the PTH locus (1/11: 9%). However, no deletion was observed at the CALCA locus (0/6). LOH at 11p13, a region containing the Wilm's tumour suppressor gene (WT1), was also studied. Analysis of LOH at 11p13 showed deletion at the CAT locus (13/18: 72%), the J/D11S414 locus (5/15: 33%), the WT1 locus (7/14: 50%) and the FSHB locus (6/16: 38%). The significance of these findings is discussed.     

Loss of chromosome 13 in cultured human vascular endothelial cells

In the vascular endothelium of human beings, telomere length is negatively related while the frequency of aneuploidy is positively related to donor age. Both in culture and in vivo the frequency of aneuploidy increases as telomere length is shortened. In this study we explored the relation between telomere length and aneuploidy in cultured human umbilical vein endothelial cells (HUVEC) by: (a) karyotype analysis and fluorescent in situ hybridization (FISH), (b) measurement of the terminal restriction fragments (TRF), and (c) assessment of replicative senescence by the expression of beta-galactosidase. Of 8 HUVEC strains, 7 cell strains lost chromosome 13, as shown by metaphase analysis and FISH of interphase cells. Five strains gained chromosome 11. In addition, five HUVEC strains became hypotetraploid shortly after the loss of chromosome 13. The loss of chromosome 13 was observed as early as PD 20, when mean TRF length was greater than 9 kb and the percentage of cells positive for beta-galactosidase was relatively low. The almost uniform loss of chromosome 13 suggests that this unique type of aneuploidy of HUVEC is the result of a progressive expression of clones with survival advantage.     

Mapping of seven polymorphic loci on human chromosome 13 by in situ hybridization

Summary Human chromosome 13 loci homologous to seven recombinant DNA probes were mapped using in situ hybridization of ³H-radiolabeled probes to metaphase chromosomes. Each of these seven probes reveals at least one restriction fragment length polymorphism, and thus each probe is potentially valuable in a genetic linkage map of this autosome. The data presented in this paper map the seven loci to specific regions of chromosome 13. This mapping should allow a future comparison of genetic distance with physical distance on this chromosome, and may permit better utilization of these probes in the clinical diagnosis of human chromosomal rearrangements involving chromosome 13.     

Loss of heterozygosity for alleles on chromosome II in cervical carcinoma.

The HeLa cell (a cervical carcinoma cell line) tumor-suppressor gene has been localized to the long arm of chromosome 11 by molecular genetic studies of nontumorigenic and tumorigenic hybrids derived from normal chromosome 11 x HeLa cell fusions. In the present study, 33 primary cervical carcinoma samples were analyzed using chromosome 11-specific polymorphic DNA markers. The RFLP analysis indicated a somatic loss of chromosome 11 heterozygosity in 10 (30%) of the primary tumors. Preferential loss of the long arm of the chromosome was observed in two of the primary tumors. In addition, at least eight-fold amplification of sequences in the q13 region, including those coding for the fibroblast growth factor-related gene (int-2), was observed in one of the primary tumors. These results suggest a possible role for gene(s) localized to chromosome 11, possibly that localized to the long arm in the development and/or progression of cervical carcinomas.     

Loss of chromosome Y in primary tumors

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贲门癌中染色体8p21-p23杂合性丢失的研究

目的 研究贲门癌中染色体8p21-p23杂合性丢失的情况。方法 采用激光捕获显微切割技术获得均质的肿瘤细胞及正常的胃粘膜细胞,多重置换扩增技术扩增捕获细胞的基因组DNA。PCR结合硝酸银染色方法分析19例贲门癌染色体8p21-p23的杂合性丢失。结果 在贲门癌中染色体8p21-p23的缺失频率非常高（63.2%）,我们确定了一个最小丢失区域. 结论 进一步明确此最小丢失区域内的抑癌基因将有助于贲门癌发生机制的阐明。     

Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13.

A recombinant DNA library enriched for portions of human chromosome 13 has been constructed from a hamster-human somatic cell hybrid that contained human chromosomes 13, 12, and 6p. A total of 733 phages were identified that contain human DNA inserts, and 46 single-copy subfragments have been derived and used as probes on Southern transfers of genomic DNA isolated from unrelated individuals. From this set, nine fragments revealing polymorphic loci (RFLP) in Msp I- or Taq I-digested DNA have been identified, of which three are polymorphic with both enzymes. Six of these probes have been shown to segregate concordantly with human chromosome 13 in a somatic cell hybrid mapping panel, and the RFLPs at these loci have been shown to behave as codominant Mendelian alleles. Additionally, hybridization to DNA isolated from cells containing various deletions of chromosome 13 has allowed regional localization. This recombinant DNA library will be useful in the study of retinoblastoma as well as in the study of the mechanisms responsible for abnormalities of this autosome.     

TSPY variants in six loci on the human Y chromosome

We have studied the structure, organization, and evolution of the human TSPY gene family by mapping three sequence variants identified through RT-PCR analysis onto genomic clones derived from two different YAC contigs. TSPY gene family members occur in at least six locations on the human Y chromosome, and each cluster contains a unique combination of variants. Our data further suggest that an 18-bp tandem duplication found in TSPY exon 1 originated from an unequal sister chromatid exchange between two tandemly arranged TSPY clusters.     

Deletions in human chromosome arms 11p and 13q in primary hepatocellular carcinomas

Normal liver and hepatocellular carcinoma (HCC) genotypes were compared at loci on most of the human chromosomes with probes that detect restriction fragment length polymorphisms. Six of fourteen tumors exhibited loss of heterozygosity of one or more markers on 11p. Ten patients were informative for loci on 13q, and 5 of these 10 exhibited loss of heterozygosity for one or more of the 13q markers. Altogether, 9 of the 14 patients showed loss of a polymorphic allele for one or more loci on either 11p or 13q. A survey of loci on 16 additional chromosomes indicated that the deletions were not due to a general loss of heterozygosity in HCCs. Quantitative densitometry showed that each of the 10 deletions resulted in hemizygosity (no reduplication) of the remaining allele in tumor tissue. In contrast to hereditary embryonal tumors, in which reduplication of the remaining chromosome is the rule, simple deletion appears to be the primary mechanism responsible for the loss of heterozygosity in these adult, nonhereditary HCCs. These data show that HCCs arising in hepatitis B virus carriers are a genetically heterogeneous group of tumors, some of which may arise through 13q alterations, some through 11p alterations, some with both chromosomes altered, and some with both intact.     

Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme

Recessive mutations, revealed by loss of the wild-type allele, have been associated with the development of a variety of cancers in children and adults. Polymorphic chromosome 10 markers were used to screen paired tumor and lymphocyte DNA samples in 13 patients with glioblastoma multiforme. Ten patients showed loss of constitutional heterozygosity in the tumor samples. This finding suggests that a recessive gene involved in the development of glioblastoma multiforme is present on chromosome 10.     

Synteny mapping of human chromosome 8 loci in cattle

Four genes having homologous loci on the short arm of human chromosome 8 have been mapped to two different bovine syntenic groups. The gene coding for the tissue-type plasminogen activator mapped with GSR, a human chromosome 8 marker, of syntenic group U14 while lipoprotein lipase and the medium and light neurofilament polypeptide genes were shown to be syntenic with the human chromosome 9 marker GGTB2 of syntenic group U18.     

Parental origin-dependent, male offspring-specific transmission-ratio distortion at loci on the human X chromosome.

We have analyzed the transmission of maternal alleles at loci spanning the length of the X chromosome in 47 normal, genetic disease-free families. We found a significant deviation from the expected Mendelian 1:1 ratio of grandpaternal:grandmaternal alleles at loci in Xp11.4-p21.1. The distortion in inheritance ratio was found only among male offspring and was manifested as a strong bias in favor of the inheritance of the alleles of the maternal grandfather. We found no evidence for significant heterogeneity among the families, which implies that the major determinant involved in the generation of the non-Mendelian ratio is epigenetic. Our analysis of recombinant chromosomes inherited by male offspring indicates that an 11.6-cM interval on the short arm of the X chromosome, bounded by DXS538 and DXS7, contains an imprinted gene that affects the survival of male embryos.     

A map of 22 loci on human chromosome 22.

We constructed a genetic linkage map of the entire long arm of human chromosome 22 with 30 polymorphic markers, defining 22 loci. The map consists of a continuous linkage group 110 cM long, when male and female recombination fractions are combined; average distance between the loci is 5.2 cM. All loci were placed on the map with high support against alternative orders (odds in excess of 1000:1). The order of loci presented in our map is in full agreement with that of the previous linkage maps of chromosome 22 and with the physical assignment of markers. Two markers included in this map, KI-831 (D22S212) and pEFZ31 (D22S32), allowed us to better define the region of the (11;22) translocation breakpoint specific for Ewing sarcoma. Ten additional polymorphic markers were placed on the 22-loci map with odds lower than 1000:1 against alternative locations. In total, we have introduced 29 new markers on the linkage map of chromosome 22.     

Loss of heterozygosity atBRCA1/2 loci in hereditary and sporadic ovarian cancers

Loss of heterozygosity atBRCA1/2 loci in breast and ovarian tumors is a suggested risk factor for germlineBRCA1/2 mutation status. We evaluated the presence of losses of selected microsatellite markers localized on chromosomes 17 and 13q in hereditary and sporadic ovarian tumors. 151 consecutive primary ovarian tumors (including 21 withBRCA1/2 mutations and 130 without the mutations) were screened for loss of heterozygosity at loci on chromosomes 17 and 13q. Losses of heterozygosity of at least one microsatellite marker localized on chromosomes 17 and 13q were revealed in 123 (81.5%) and 104 (68.9%) tumors, respectively. Losses of all informative markers on chromosomes 17 and 13 occurred in 30 (19.9%) and 31 (20.5%) tumors, respectively. There was no difference in the frequency of losses atBRCA1 intragenic markers (D17S855 and D17S1323) between BRCA1-positive and BRCA1-negative patients. The frequency of losses on chromosome 17 was higher in high-grade than in low-grade carcinomas. Loss of heterozygosity on chromosomes 17 and 13q is a frequent phenomenon in both hereditary and sporadic ovarian cancers. The frequency of losses atBRCA1 intragenic markers in the ovarian tumor tissue is not strongly related to the presence ofBRCA1 germline mutations.     

Number of alleles at the incompatibility loci in Secale cereale L.

Summary Two experiments were performed to estimate the number of alleles at the two incompatibility loci of rye in the variety Halo. In one experiment I₁ progenies from enforced selfing under controlled conditions were isolated. In the other experiment a genotype, homozygous at both incompatibility loci, was used as pollinator for a sample of the Halo population, which was regarded as an equilibrium population. Genotypes, which are homozygous at both incompatibility loci, can be found after selfing. The estimate for the number of alleles was 6 to 7 at one locus and 12 to 13 at the other locus.     

Assigning alleles to different loci in amplifications of duplicated loci

Duplicated loci, for example those associated with major histocompatibility complex (MHC) genes, often have similar DNA sequences that can be coamplified with a pair of primers. This results in genotyping difficulties and inaccurate analyses. Here, we present a method to assign alleles to different loci in amplifications of duplicated loci. This method simultaneously considers several factors that may each affect correct allele assignment. These are the sharing of identical alleles among loci, null alleles, copy number variation, negative amplification, heterozygote excess or heterozygote deficiency, and linkage disequilibrium. The possible multilocus genotypes are extracted from the alleles for each individual and weighted to estimate the allele frequencies. The likelihood of an allele configuration is calculated and is optimized with a heuristic algorithm. Monte‐Carlo simulations and three empirical MHC data sets are used as examples to evaluate the efficacy of our method under different conditions. Our new software, mhc‐typer V1.1, is freely available at https://github.com/huangkang1987/mhc-typer .