Increased genome size is caused by heterochromatin addition in two non-related bat species, Hesperoptenus doriae and Philetor brachypterus (Vespertilionidae, Chiroptera, Mammalia).

The average genome size (GS) of bats, which are the only mammals capable of powered flight, is approximately 18% smaller than that of closely related mammalian orders. The low nuclear DNA content of Chiroptera is comparable to that of birds, which are also characterized by a high metabolic rate. Only a few chiropteran taxa possess notable amounts of constitutive heterochromatin.

Evidence for multi-copy Mega-NUMTs in the human genome.

The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals.

Long-term Culture of EBV-induced Human Lymphoblastoid Cell Lines Reveals Chromosomal Instability.

To preserve material for future genetic studies, human B-lymphocytes from whole blood samples are routinely transformed into lymphoblastoid cell lines (LCLs) by in vitro infection with Epstein-Barr virus. To determine the rate and frequency of chromosomal changes during long-term culture, we established 10 LCLs (from eight individuals). Before transformation, these cases showed a normal karyotype (three cases), a small supernumerary marker chromosome (three cases), or an aberrant karyotype (four cases).

Generation of functional cardiomyocytes from rat embryonic and induced pluripotent stem cells using feeder-free expansion and differentiation in suspension culture.

The possibility to generate cardiomyocytes from pluripotent stem cells in vitro has enormous significance for basic research, disease modeling, drug development and heart repair. The concept of heart muscle reconstruction has been studied and optimized in the rat model using rat primary cardiovascular cells or xenogeneic pluripotent stem cell derived-cardiomyocytes for years. However, the lack of rat pluripotent stem cells (rPSCs) and their cardiovascular derivatives prevented the establishment of an authentic clinically relevant syngeneic or allogeneic rat heart regeneration model.

Chromosomal Evolution in Chiroptera.

Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62).

Demonstration of 5-Methylcytosine-Rich DNA Sequences in Chiroptera.

5-Methylcytosine-rich heterochromatic regions were demonstrated in metaphase chromosomes of 5 species of Chiroptera by indirect immunofluorescence using a monoclonal anti-5-methylcytosine antibody. These species belong to 4 genera and 2 families and are characterized by divergent karyotypes. One species (Glauconycteris beatrix) has an extremely low diploid chromosome number of 2n = 22 with only meta- to submetacentric elements and remarkably large amounts of constitutive heterochromatin located in the centromeric and pericentromeric regions of all chromosome pairs.

Wing Membrane Biopsies for Bat Cytogenetics: Finding of 2n = 54 in Irish Rhinolophushipposideros (Rhinolophidae, Chiroptera, Mammalia) Supports Two Geographically Separated Chromosomal Variants in Europe.

In Europe, 2 different diploid chromosome numbers, 2n = 54 and 2n = 56, have been described in the lesser horseshoe bat (Rhinolophushipposideros). The eastern form with 2n = 56 extends from the Czech Republic to Greece. To date, specimens with 54 chromosomes have been reported only from Spain and Germany.

Multiple Small Supernumerary Marker Chromosomes Resulting from Maternal Meiosis I or II Errors.

We present 2 cases with multiple de novo supernumerary marker chromosomes (sSMCs), each derived from a different chromosome. In a prenatal case, we found mosaicism for an sSMC(4), sSMC(6), sSMC(9), sSMC(14) and sSMC(22), while a postnatal case had an sSMC(4), sSMC(8) and an sSMC(11). SNP-marker segregation indicated that the sSMC(4) resulted from a maternal meiosis II error in the prenatal case.

Integration of molecular cytogenetics, dated molecular phylogeny, and model-based predictions to understand the extreme chromosome reorganization in the Neotropical genus Tonatia (Chiroptera: Phyllostomidae).

Background: Defining factors that contributed to the fixation of a high number of underdominant chromosomal rearrangements is a complex task because not only molecular mechanisms must be considered, but also the uniqueness of natural history attributes of each taxon. Ideally, detailed investigation of the chromosome architecture of an organism and related groups, placed within a phylogenetic context, is required. We used multiple approaches to investigate the dynamics of chromosomal evolution in lineages of bats with considerable karyotypic variation, focusing on the different facets contributing to fixation of the exceptional chromosomal changes in Tonatia saurophila.

Mitotic stability of small supernumerary marker chromosomes depends on their shape and telomeres - a long term in vitro study.

Mosaicism is present in more than 50% of the cases with small supernumerary marker chromosomes (sSMCs) and karyotype 47,XX,+mar/46,XX or 47,XY,+mar/46,XY. Recently we provided first evidence that the mitotic stability of sSMC is dependent on their structure, i.e.

Karyotype evolution in the horseshoe bat Rhinolophus sedulus by whole-arm reciprocal translocation (WART).

Robertsonian (centric) fusion or fission is one of the predominant modes of chromosomal rearrangement in karyotype evolution among mammals. However, in karyotypes composed of only bi-armed chromosomes, creation of new chromosomal arm combinations in one step is possible only via whole-arm reciprocal translocation (WART). Although this type of rearrangement has often been proposed to play an important role in chromosomal evolution, direct observations of WARTs remained rare, and, in most cases, were found in hybrids of chromosomal races in the genera Mus and Sorex.

Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome.

Marshall-Smith syndrome (MSS) is a very rare malformation syndrome characterized by typical craniofacial anomalies, abnormal osseous maturation, developmental delay, failure to thrive, and respiratory difficulties. Mutations in the nuclear factor 1/X gene (NFIX) were recently identified as the cause of MSS. In our study cohort of 17 patients with a clinical diagnosis of MSS, conventional sequencing of NFIX revealed frameshift and splice-site mutations in 10 individuals.

Taxonomic, bioacoustic and faunistic data on a collection of Tettigonioidea from Eastern Congo (Insecta: Orthoptera).

During a 14-day excursion in March 1990, 28 species of tettigonioids were found at Irangi (1º54'S, 28º27'E), ca.100 km north west of Bukavu at Lake Kivu (Democratic Republic of the Congo, formerly Zaire), and at other localities near Bukavu. One species -Arantia (Arantia) gracilicercata Heller sp.

Mitotic stability of small supernumerary marker chromosomes: a study based on 93 immortalized cell lines.

Small supernumerary marker chromosomes (sSMC) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. However, no detailed studies have been done for the mitotic stability of sSMC so far, mainly due to the lack of a corresponding in vitro model system. Recently, we established an sSMC-cell bank (Else Kröner-Fresenius-sSMC-cellbank) with >150 cell lines.

Chromosomal evolution among leaf-nosed nectarivorous bats--evidence from cross-species chromosome painting (Phyllostomidae, Chiroptera).

Background: New World leaf-nosed bats, Phyllostomidae, represent a lineage of Chiroptera marked by unprecedented morphological/ecological diversity and extensive intergeneric chromosomal reorganization. There are still disagreements regarding their systematic relationships due to morphological convergence among some groups. Their history of karyotypic evolution also remains to be documented.

Complex small supernumerary marker chromosomes - an update.

Background: Complex small supernumerary marker chromosomes (sSMC) constitute one of the smallest subgroups of sSMC in general. Complex sSMC consist of chromosomal material derived from more than one chromosome; the best known representative of this group is the derivative chromosome 22 {der(22)t(11;22)} or Emanuel syndrome. In 2008 we speculated that complex sSMC could be part of an underestimated entity.

16p11.2-p12.2 duplication syndrome; a genomic condition differentiated from euchromatic variation of 16p11.2.

Chromosome 16 contains multiple copy number variations (CNVs) that predispose to genomic disorders. Here, we differentiate pathogenic duplications of 16p11.2-p12.

High-resolution chromosome painting reveals the first genetic signature for the chiropteran suborder Pteropodiformes (Mammalia: Chiroptera).

Up to now, the composition of synteny-conserved segments in chiropteran karyotypes was studied by cross-species chromosome painting with probes derived from whole human (HSA) or chiropteran chromosomes only. Here, painting probes from the vespertilionid bat Myotis myotis were hybridized, for the first time, onto human metaphase chromosomes. The segmental composition of bat karyotypes was further refined by cross-species painting with probes derived from flow-sorted chromosomes of Tupaia belangeri and Eulemur macaco--two species with highly rearranged karyotypes.

The human genome puzzle - the role of copy number variation in somatic mosaicism.

The discovery of copy number variations (CNV) in the human genome opened new perspectives in the study of the genetic causes of inherited disorders and the etiology of common diseases. Differently patterned instances of somatic mosaicism in CNV regions have been shown to be present in monozygotic twins and throughout different tissues within an individual. A single-cell-level investigation of CNV in different human cell types led us to uncover mitotically derived genomic mosaicism, which is stable in different cell types of one individual.

A de novo unbalanced translocation leading to partial monosomy 9p23-pter and partial trisomy 15q25.3-qter associated with 46,XY complete gonadal dysgenesis, tall stature and mental retardation.

Syndromic forms of disorders of sex development constitute a challenge for clinical and molecular investigations. We report on a 12-year-old girl presenting with lack of pubertal development, tall stature and moderate mental retardation. Conventional karyotyping at the age of 3 years revealed a male karyotype (46,XY).

Early embryonic chromosome instability results in stable mosaic pattern in human tissues.

The discovery of copy number variations (CNV) in the human genome opened new perspectives on the study of the genetic causes of inherited disorders and the aetiology of common diseases. Here, a single-cell-level investigation of CNV in different human tissues led us to uncover the phenomenon of mitotically derived genomic mosaicism, which is stable in different cell types of one individual. The CNV mosaic ratios were different between the 10 individuals studied.