Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the approximately 60% SMC derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. The clinical outcome of an SMC is difficult to predict as they can have different phenotypic consequences because of (1). differences in euchromatic DNA-content, (2). different degrees of mosaicism, and/or (3). uniparental disomy (UPD) of the chromosomes homologous to the SMC. Here, we present 35 SMCs, which are derived from all human chromosomes, apart from chromosome 6, as demonstrated by the appropriate molecular cytogenetic approaches, such as centromere-specific multicolor fluoresence in situ hybridization (cenM-FISH), multicolor banding (MCB), and subcentromere-specific multicolor FISH (subcenM-FISH). In nine cases without an aberrant phenotype, neither partial proximal trisomies nor UPD could be detected. Abnormal clinical findings, such as psychomotoric retardation and/or craniofacial dysmorphisms, were associated with seven of the cases in which subcentromeric single-copy probes were proven to be present in three copies. Conversely, in eight cases with a normal phenotype, proximal euchromatic material was detected as partial trisomy. UPD was studied in 12 cases and subsequently detected in two of the cases with SMC (partial UPD 4p and maternal UPD 22 in a der(22)-syndrome patient), indicating that SMC carriers have an enhanced risk for UPD. At present, small proximal trisomies of 1p, 1q, 2p, 6p, 6q, 7q, 9p, and 12q seem to lead to clinical manifestations, whereas partial proximal trisomies of 2q, 3p, 3q, 5q, 7p, 8p, 17p, and 18p may not be associated with significant clinical symptoms. With respect to clinical outcome, a classification of SMCs is proposed that considers molecular genetic and molecular cytogenetic characteristics as demonstrated by presently available methods.

High-resolution array CGH utilizing sets of overlapping BAC and PAC clones ("tiling path") covering the whole genome is a powerful novel tool for fast detection of submicroscopic chromosome deletions or duplications. We describe the successful application of a submegabase resolution whole genome "tiling path" BAC array to confirm and characterize a de novo interstitial deletion of chromosome 15. The deletion has a size of 5.3 Mb and is located within chromosome band 15q14, distal to the Prader-Willi/Angelman region. The affected girl had a heart defect, cleft palate, recurrent infections, and developmental delay. In contrast to GTG banding, array CGH determined the exact number of deleted genes and thus allowed the identification of candidate genes for cleft palate (GREM1, CX36, MEIS2), congenital heart defect (ACTC, GREM1, CX36, MEIS2), and mental retardation (ARHGAP11A, CHRNA7, CHRM5).

Robertsonian translocations were found among mice captured on one of the Orkney islands in North Scotland, around Barcelona in Spain, and in Southern Germany around the cities of Tübingen and Ravensburg. Mice from Denmark, Poland, Astrachan in the Soviet Union Israel, and Egypt were found to be free of Robertsonian translocations. The Robertsonian variations in mice from Scotland and Spain are probably of independent origin and mostly likely also unrelated to the Alpine-Apennine system. On the other hand, the variation in mice from Southern Germany may be a part of the Alpine system. Hybrid zones were found near Barcelona and near Ravensburg. In the latter almost all the mice were heterozygous for at least one Robertsonian translocation, and often for several translocations. Three out of 14 typed mice were heterozygous for four metacentric chromosomes. The analysis revealed the existence of nine Robertsonian translocations not previously described: Rb(3.14)7Tu, Rb(4.10)8Tu, Rb(6.13)9Tu, and Rb(9.12)10Tu in Scotland; Rb(4.14)11Tu, Rb(6.10)13Tu, Rb(9.11)14Tu, and Rb(12.13)15Tu in Spain, and Rb(2.5)2Tu in Southern Germany.

In a subclone of 1ID13 mouse fibroblasts latently infected with bovine papillomavirus type 1 (BPV-1) DNA, the viral genome occurred as a mixture of extrachromosomal circular monomers and oligomers. Multiple copies were also associated with the host cell genome, predominantly at a single site in a head-to-tail tandem array. We examined the replicative intermediates of extrachromosomal forms of BPV-1 DNA by using two-dimensional gel electrophoresis. The results obtained indicate that initiation of DNA replication occurred near the center of the EcoRI-BamHI 5.6-kilobase fragment. In some molecules, however, this fragment was replicated from one end to the other by means of a single fork initiated elsewhere. Termination also occurred within this fragment. The EcoRI-BamHI 2.3-kilobase fragment replicated as a DNA molecule containing a termination site for DNA replication and also by means of a single fork traversing the fragment from one end to the other. Thus, replication forks proceeded through these fragments in different manners, apparently depending on whether they were part of a monomer, a d'imer, a trimer, or higher oligomers. These observations lead to the conclusion that initiation of DNA replication in BPV-1 DNA takes place at or close to plasmid maintenance sequence 1. From this point, replication proceeds bidirectionally and termination occurs approximately 1800 opposite the origin. The results obtained are consistent with one or more replication origins being quiescent in BPV-1 DNA oligomers. Viral genomes capable of being established as extrachromosomal elements are useful model systems to study the regulation of DNA replication in eucaryotic cells. EpsteinBarr virus (EBV) and bovine papillomavirus (BPV) are two such systems currently under investigation (for a review, see references 8, 19, and 26).Papillomaviruses are widespread in nature. They are highly host specific and propagate primarily in the terminally differentiated epidermal cells of the warts they produce. A subset of the BPVs, among which the fully sequenced BVP-1 DNA is the most thoroughly studied (9), can readily transform established rodent fibroblast cell lines in culture (for a review, see reference 12). These transformed cell lines have been reported to carry multiple copies of circular extrachromosomal genomes of BPV-1; however, they produce no infectious virus (20,21 The ability to replicate autonomously as an extrachromosomal element is of particular interest for BPV-1 as a plasmid cloning vector (11,31) and also as a model system to study the regulation of DNA replication in eucaryotic cells (8,26). Examples of integrated viral DNA as well as the presence of extrachromosomal oligomeric copies have also been reported (2,4,15,32,39).Genetic analysis led to the identification of two cis-acting sequences in the BPV-1 genome that, together with another trans-acting sequence, appear to allow the viral DNA to be maintained as an extrachromosomal element (23). These * Corresponding author.cis-acting sequences were designated plasmid maint...

An extra segment in chromosome 1 between bands C5 and D has been found in wild mouse populations. Its size varies between 6.1 % and 30.1 % of the length of a standard chromosome 1. It differs among individuals and populations but is constant in a genetically homogeneous line. According to its staining properties and variation in length it is a homogeneously staining region (HSR), a kind of segment otherwise found only in cell lines under strong selection and in tumor cells. G-banding gives a homogeneous staining of medium intensity. With C-banding, staining is positive, though lighter than that of centromeric heterochromatin. Fluorescence is dull with Hoechst 33258 and bright with mithramycin. The extra segment does not contain mouse satellite DNA sequences in any quantity detectable by in situ hybridization. Such an extra segment was found in several European populations of mice from Spain to Russia. It is carried through the germ line. It has been introduced into a laboratory mouse strain, and, by recombination, inserted into a Robertsonian metacentric chromosome for easier handling and identification.