Biomedical subjects

Gaby Lederer

Publications and source records attributed to Gaby Lederer.

3 recordsLinked to original sources

PubMed2006

Delineation of a 2q deletion in a girl with dysmorphic features and epilepsy.

In recent years, the spectrum of available methods for the characterization of chromosomal aberrations has significantly increased. Micro-array technologies now allow the rapid fine mapping of small genomic imbalances. Here we used various technologies to characterize a de novo translocation t(2;15) in a girl with dysmorphic features, severe developmental delay and frequent seizures. Multiplex-FISH (M-FISH) excluded the involvement of other chromosomes than chromosomes 2 and 15. We used an oligonucleotide array containing more than 10.000 SNPs, that is, the GeneChip Mapping 10K 2.0 SNP Affymetrix array, and readily fine-mapped a deletion in chromosomal region 2q24.1 --> 2q31.1. The extent of this deletion was verified with multicolor BAC-clone hybridizations. The deletion has a size of about 13 Mb and is within a gene rich region containing about 76 genes. Interestingly, several of these genes are ion channel genes or genes involved in neuron differentiation, so that the frequently occurring seizures are probably due to loss or haploinsufficiency of one or more of these genes.

Abnormalities, Multiple↗

PubMed2004

Analysis of gene expression patterns and chromosomal changes associated with aging.

Age is the largest single risk factor for the development of cancer in mammals. Age-associated chromosomal changes, such as aneuploidy and telomere erosion, may be vitally involved in the initial steps of tumorigenesis. However, changes in gene expression specific for increased aneuploidy with age have not yet been characterized. Here, we address these questions by using a panel of fibroblast cell lines and lymphocyte cultures from young and old age groups. Oligonucleotide microarrays were used to characterize the expression of 14,500 genes. We measured telomere length and analyzed chromosome copy number changes and structural rearrangements by multicolor interphase fluorescence in situ hybridization and 7-fluorochrome multiplex fluorescence in situ hybridization, and we tried to show a relationship between gene expression patterns and chromosomal changes. These analyses revealed a number of genes involved in both the cell cycle and proliferation that are differently expressed in aged cells. More importantly, our data show an association between age-related aneuploidy and the gene expression level of genes involved in centromere and kinetochore function and in the microtubule and spindle assembly apparatus. To verify that some of these genes may also be involved in tumorigenesis, we compared the expression of these genes in chromosomally stable microsatellite instability and chromosomally unstable chromosomal instability colorectal tumor cell lines. Three genes (Notch2, H2AFY2, and CDC5L) showed similar expression differences between microsatellite instability and chromosomal instability cell lines as observed between the young and old cell cultures suggesting that they may play a role in tumorigenesis.

Adult↗

PubMed2002

Multicolor FISH in two and three dimensions for clastogenic analyses.

Chemicals may induce both numerical and structural aberrations. In addition to these chromosomal mutations, chemicals may render cells genetically unstable, which may result in chromosomal instability. For a detailed analysis, sophisticated approaches at single cell resolution are needed. Such approaches have become feasible by recent developments in molecular cytogenetics. In particular, new multicolor fluorescence in situ hybridization (FISH) technologies allow us now to study the effects of chemicals on chromosomes with unprecedented resolution. FISH provides opportunities to analyze the genome in two dimensions, i.e. on metaphase spreads, or in three dimensions, i.e. in interphase nuclei. An arsenal of diverse multicolor FISH approaches has been developed, which allows the analysis of the entire genome with one hybridization on metaphase spreads or the detailed visualization of selected chromosomal regions within intact interphase nuclei. These developments have been complemented by new resources for DNA probes, which have evolved from the human genome project. Here we will review the latest developments and provide some examples in which multicolor FISH technologies were applied to elucidate the effect of chemicals on chromosomes.

Animals↗