Aneuploidy in the normal, Alzheimer's disease and ataxia-telangiectasia brain: differential expression and pathological meaning.

Recently it has been suggested that the human brain contains aneuploid cells; however the nature and magnitude of neural aneuploidy in health and disease remain obscure. Here, we have monitored aneuploidy in the cerebral cortex of the normal, Alzheimer's disease (AD) and ataxia telangiectasia (AT) brain by molecular cytogenetic approaches scoring more than 480,000 neural cells. Using arbitrarily selected set of DNA probes for chromosomes 1, 7, 11, 13, 14, 17, 18, 21, X and Y we have determined the mean rate of stochastic aneuploidy per chromosome as 0.

Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation.

Background: Submicroscopic imbalances in the subtelomeric regions of the chromosomes are considered to play an important role in the aetiology of mental retardation (MR). The aim of the study was to evaluate a quantitative PCR (qPCR) protocol established by Boehm et al. (2004) in the clinical routine of subtelomeric testing.

Unbalanced chromosome 1 abnormalities leading to partial trisomy 1q in four infants with Down syndrome and acute megakaryocytic leukemia.

Background: Children with Down syndrome (DS) have an increased risk of childhood acute leukemia, especially acute megakaryoblastic leukemia (AMKL) also called acute myeloid leukemia (AML) type M7. Here four yet unreported infants with such malignancies are reported.

Results: An unbalanced translocation involving chromosome 1 was identified by GTG banding in all cases.

The hierarchically organized splitting of chromosomal bands for all human chromosomes.

Background: Chromosome banding is widely used in cytogenetics. However, the biological nature of hierarchically organized splitting of chromosomal bands of human chromosomes is an enigma and has not been, as yet, studied.

Results: Here we present for the first time the hierarchically organized splitting of chromosomal bands in their sub-bands for all human chromosomes.

A new chromosomal three-way rearrangement involving MLL masked by a t(9;19)(p11;p13) in an infant with acute myeloid leukemia.

Infants diagnosed with acute myelogenous leukemia (AML) are likely to have subtypes M4 or M5 characterized by 11q23 abnormalities like a t(9;11)(p22;q23). Detection of all possible types of chromosomal abnormalities, including mixed lineage leukemia (MLL) gene rearrangements at 11q23, is of importance for the identification of biological subgroups, which might differ in drug resistance and/or clinical outcome. Here, we report the clinical, conventional banding and molecular cytogenetics data of a 6-month-old boy with an AML-M5 presenting with a unique cryptic rearrangement involving the MLL gene: a three-way t(9;19;11)(p11.

Delineation of yet unknown cryptic subtelomere aberrations in 50% of acute myeloid leukemia with normal GTG-banding karyotype.

Acute myeloid leukemia (AML) is a heterogeneous disease with respect to clinical prognosis and acquired chromosomal aberrations. After routine banding cytogenetic analysis 45% of AML patients show a normal karyotype (NK-AML). For a better understanding of development and progression in AML, it is important to find markers which could be primary genetic aberrations.

Characterization of a prenatally assessed de novo supernumerary minute ring chromosome 20 in a phenotypically normal male.

Background: The heterogeneous group of small supernumerary marker chromosomes (sSMCs) presents serious counseling problems, especially if they are present de novo and diagnosed prenatally. The incidence has been estimated at 1 in 1000 prenatal samples. We present a case of mosaic sSMC diagnosed prenatally after amniocentesis.

Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo.

Objective: The hepatic integration of human adipose tissue derived mesenchymal stem cells (hAT-MSCs) in vivo with or without prior differentiation to hepatocyte-like cells in vitro was investigated.

Methods And Results: Cells, isolated either from peritoneal or subcutaneous adipose tissue, expressed mesenchymal stem cell surface markers and featured multiple lineage differentiation. Under conditions favouring hepatocyte differentiation, hAT-MSCs gained hepatocytic functions in vitro including urea formation, glycogen synthesis, cytochrome P450 enzyme activity, and expression of hepatocyte-specific transcripts of carbamoylphosphate synthetase, albumin and cytochrome P450 type 3A4 (CYP3A4).

Chromosome distribution in human sperm - a 3D multicolor banding-study.

Background: Nuclear architecture studies in human sperm are sparse. By now performed ones were practically all done on flattened nuclei. Thus, studies close at the in vivo state of sperm, i.

Complex chromosome rearrangement in a child with microcephaly, dysmorphic facial features and mosaicism for a terminal deletion del(18)(q21.32-qter) investigated by FISH and array-CGH: Case report.

We report on a 7 years and 4 months old Greek boy with mild microcephaly and dysmorphic facial features. He was a sociable child with maxillary hypoplasia, epicanthal folds, upslanting palpebral fissures with long eyelashes, and hypertelorism. His ears were prominent and dysmorphic, he had a long philtrum and a high arched palate.

Dynamic mosaicism manifesting as loss, gain and rearrangement of an isodicentric Y chromosome in a male child with growth retardation and abnormal external genitalia.

Isodicentric chromosomes are considered the most common structural abnormality of the human Y chromosome. Because of their instability during cell division, loss of an isodicentric Y seems mainly to lie at the origin of mosaicism in previously reported patients with a 45,X cell line. Here, we report on a similar case, which, however, turned out to be an example of dynamic mosaicism involving isodicentric chromosome Y and isochromosome Y after FISH with a set of chromosome Y-specific probes and multicolor banding.

A new unbalanced chromosomal abnormality in 1q31.1 to 1q32 without phenotypic consequences.

A familial duplication in the long arm of one chromosome 1 was detected due to recurrent abortions in a couple. The duplication was present in the male partner of the couple and in his mother, both clinically healthy. By reverse FISH, the duplication was determined to be located in 1q31.

Breakpoint mapping and complete analysis of meiotic segregation patterns in three men heterozygous for paracentric inversions.

Paracentric inversions (PAIs) are structural chromosomal rearrangements generally considered to be harmless. To date, only a few studies have been performed concerning the meiotic segregation of these rearrangements, using either the human-hamster fertilization system or fluorescence in situ hybridization (FISH) with centromeric or telomeric DNA probes. To improve the assessment of imbalances in PAI, we present a new strategy based on FISH assay using multiple bacterial artificial chromosome probes, which allow a precise localization of chromosome break points and the identification of all meiotic products in human sperm.

Novel complex t(V;9;22) rearrangements in three cases with chronic myeloid leukemia and a rare translocation in a case with classical Philadelphia chromosome.

The fusion gene BCR/ABL arises in connection with a complex translocation event in 2-10% of cases with chronic myeloid leukemia (CML). Due to causative treatment with Imatinib most cases with variant rearrangements show no specific prognostic significance, though the events of therapy resistance remain to be studied. Herein we report on three CML cases with complex chromosomal aberrations not observed before, involving chromosomal regions such as 1p32, 2q11 and 6q12.

Partial monosomy 7q34-qter and 21pter-q22.13 due to cryptic unbalanced translocation t(7;21) but not monosomy of the whole chromosome 21: a case report plus review of the literature.

Background: Autosomal monosomies in human are generally suggested to be incompatible with life; however, there is quite a number of cytogenetic reports describing full monosomy of one chromosome 21 in live born children. Here, we report a cytogenetically similar case associated with congenital malformation including mental retardation, motor development delay, craniofacial dysmorphism and skeletal abnormalities.

Results: Initially, a full monosomy of chromosome 21 was suspected as only 45 chromosomes were present.

A 7 Mb duplication at 22q13 in a girl with bipolar disorder and hippocampal malformation.

We identified a duplication of 22q13.1-q13.2 in a 10-year-old girl and demonstrated that this duplication was the recombinant product of a maternal intrachromosomal insertion.

Small supernumerary marker chromosomes (sSMC) in humans; are there B chromosomes hidden among them.

Background: Small supernumerary marker chromosomes (sSMC) and B-chromosomes represent a heterogeneous collection of chromosomes added to the typical karyotype, and which are both small in size. They may consist of heterochromatic and/or euchromatic material. Also a predominance of maternal transmission was reported for both groups.

Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: detailed molecular cytogenetic characterization and review of the literature.

Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content.

Variation in crossover interference levels on individual chromosomes from human males.

Crossovers (COs) generated by homologous recombination ensure the proper segregation of chromosomes during meiosis. COs exhibit interference, which leads to widely spaced COs along chromosomes. Strong positive CO interference has been found in humans.

Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity?

Background: Small supernumerary marker chromosomes (sSMC) are present ~2.6 x 106 human worldwide. sSMC are a heterogeneous group of derivative chromosomes concerning their clinical consequences as well as their chromosomal origin and shape.

A new small supernumerary marker chromosome, generating mosaic pure trisomy 16q11.1-q12.1 in a healthy man.

Here we report on a healthy and fertile 30 years old man, who was carrier of a small supernumerary marker chromosome (sSMC). The application of molecular techniques such as fluorescence in situ hybridisation (FISH), microdissection and reverse painting, helped to characterize the sSMC which resulted to be derived from chromosome 16. In fact, the presence of euchromatin material from the long arm (16q) in the sSMC was demonstrated, and the karyotype can be written as mos 47, XY,+min(16)(:p11.

Position of chromosomes 18, 19, 21 and 22 in 3D-preserved interphase nuclei of human and gorilla and white hand gibbon.

Background: Even though comparative nuclear architecture studies in hominoids are sparse, nuclear chromosome architecture was shown to be conserved during hominoid evolution. Thus, it is suspected that yet unknown biological mechanisms must underlie this observation.

Results: Here for the first time a combination of multicolor banding (MCB) and three-dimensional analysis of interphase cells was used to characterize the position and orientation of human chromosomes #18, #19, #21 and #22 and their homologues in primate B-lymphocytic cells.