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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., Results: To better understand the evolutionary relationships within Phyllostomidae, we developed chromosome paints from the bat species Macrotus californicus. We tested the potential of these paints as phylogenetic tools by looking for chromosomal signatures in two lineages of nectarivorous phyllostomids whose independent origins have been statistically supported by molecular phylogenies. By examining the chromosomal homologies defined by chromosome painting among two representatives of the subfamily Glossophaginae (Glossophaga soricina and Anoura cultrata) and one species from the subfamily Lonchophyllinae (Lonchophylla concava), we found chromosomal correspondence in regions not previously detected by other comparative cytogenetic techniques. We proposed the corresponding human chromosomal segments for chromosomes of the investigated species and found two syntenic associations shared by G. soricina and A. cultrata., Conclusion: Comparative painting with whole chromosome-specific paints of M. californicus demonstrates an extensive chromosomal reorganization within the two lineages of nectarivorous phyllostomids, with a large number of chromosomes shared between M. californicus and G. soricina. We show that the evolution of nectar-feeding bats occurs mainly by reshuffling of chiropteran Evolutionarily Conserved Units (ECUs). Robertsonian fusions/fissions and inversions seem to be important modifiers of phyllostomid karyotypes, and autapomorphic character states are common within species. Macrotus californicus chromosome paints will be a valuable tool for documenting the pattern of karyotypic evolution within Phyllostomidae radiation.

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). Chromosome analyses were performed at 8-week intervals over a period of at least 1 year, up to 3 years. Surprisingly, we demonstrate that chromosomal instability is the rule, rather than the exception, during long-term culture of LCLs. The most commonly observed acquired clonal aberration was trisomy 12, which emerged in all cell lines within 21 to 49 weeks after infection. Telomeric fusions indicating telomere shortening were found after ~21 weeks. After 1 year of cultivation, the proportion of cells with the original karyotype decreased to ≤10% in 7 of the 10 cell lines. To preserve cells with aberrant genomes, we conclude the cultivation time of LCLs must be restricted to the absolute minimum time required: [ABSTRACT FROM AUTHOR]

Two species of the monogeneric family Nycteridae were studied for the first time with chromosome banding techniques and chromosome painting. The diploid chromosome number of Nycteris macrotis and N. tragata is 40 and 38, respectively. Both karyotypes differ by a translocation, a telomeric fusion and a pericentric inversion. The genus Nycteris shows a highly derived karyotype where the 25 chiropteran evolutionarily conserved units (ECUs) are represented in 37 segments. Chromosome painting with Myotis probes revealed three common features of Nycteris and Emballonura, which are not present in Taphozous. From a cytogenetic point of view, Nycteris is therefore closer related to Emballonura than to Taphozous. Further, an additional synapomorphy for Vespertilioniformes is described, i.e. the synteny of a segment homologous to human chromosome 13 and ECU12a-22a in elements homologous to Myotis chromosome MMY6. [ABSTRACT FROM AUTHOR]

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). As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae), focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems. [ABSTRACT FROM AUTHOR]

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. Integration of empirical data with proposed models of chromosome evolution was performed to understand the probable conditions for Tonatia's karyotypic evolution. Results: The trajectory of reorganization of chromosome blocks since the common ancestor of Glossophaginae and Phyllostominae subfamilies suggests that multiple tandem fusions, as well as disruption and fusions of conserved phyllostomid chromosomes were major drivers of karyotypic reshuffling in Tonatia. Considerable variation in the rates of chromosomal evolution between phyllostomid lineages was observed. Thirty-nine unique fusions and fission events reached fixation in Tonatia over a short period of time, followed by ~12 million years of chromosomal stasis. Physical mapping of repetitive DNA revealed an unusual accumulation of LINE-1 sequences on centromeric regions, probably associated with the chromosomal dynamics of this genus. Conclusions: Multiple rearrangements have reached fixation in a wave-like fashion in phyllostomid bats. Different biological features of Tonatia support distinct models of rearrangement fixation, and it is unlikely that the fixations were a result of solely stochastic processes in small ancient populations. Increased recombination rates were probably facilitated by expansion of repetitive DNA, reinforced by aspects of taxon reproduction and ecology. [ABSTRACT FROM AUTHOR]

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. For the first time, we present the karyotype of the horseshoe bat species Rhinolophus sedulus (2n = 28, FNa = 52), where a WART between 2 metacentric autosomes was detected by G-banding and confirmed by FISH with painting probes of the vespertilionid bat Myotis myotis. Among the 6 specimens analyzed, 2 showed the heterozygous condition of the WART, 1 showed the presumed ancestral, and 3 specimens showed the derived homozygous state. As the existence of a hybrid zone at the sampling locality is thought to be rather improbable, the WART may indicate ongoing karyotype evolution in this taxon. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. Results Here, the overall yet reported 412 complex sSMC are summarized. They constitute 8.4% of all yet in detail characterized sSMC cases. The majority of the complex sSMC is contributed by patients suffering from Emanuel syndrome (82%). Besides there are a der(22)t(8;22)(q24.1;q11.1) and a der(13)t(13;18)(q11;p11.21) or der(21)t(18;21)(p11.21;q11.1) = der(13 or 21)t(13 or 21;18) syndrome. The latter two represent another 2.6% and 2.2% of the complex sSMC-cases, respectively. The large majority of complex sSMC has a centric minute shape and derives from an acrocentric chromosome. Nonetheless, complex sSMC can involve material from each chromosomal origin. Most complex sSMC are inherited form a balanced translocation in one parent and are non-mosaic. Interestingly, there are hot spots for the chromosomal breakpoints involved. Conclusions Complex sSMC need to be considered in diagnostics, especially in non-mosaic, centric minute shaped sSMC. As yet three complex-sSMC-associated syndromes are identified. As recurrent breakpoints in the complex sSMC were characterized, it is to be expected that more syndromes are identified in this subgroup of sSMC. Overall, complex sSMC emphasize once more the importance of detailed cytogenetic analyses, especially in patients with idiopathic mental retardation. [ABSTRACT FROM AUTHOR]

Background: Heterochromatic variants of pericentromere of chromosome 9 are reported and discussed since decades concerning their detailed structure and clinical meaning. However, detailed studies are scarce. Thus, here we provide the largest ever done molecular cytogenetic research based on >300 chromosome 9 heteromorphism carriers. Results: In this study, 334 carriers of heterochromatic variants of chromosome 9 were included, being 192 patients from Western Europe and the remainder from Easter-European origin. A 3-color-fluorescence in situ hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix) and 8 different locus-specific probes were applied for their characterization. The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9 heteromorphic patterns. In this study, 17 different variants were detected including five yet unreported; the most frequent were pericentric inversions (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%), and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity, a new short nomenclature for the yet reported 24 heteromorphic patterns of chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants could be narrowed down using locus-specific probes. Conclusions: Based on this largest study ever done in carriers of chromosome 9 heteromorphisms, three of the 24 detailed variants were more frequently observed in Western than in Eastern Europe. Besides, there is no clear evidence that infertility is linked to any of the 24 chromosome 9 heteromorphic variants. [ABSTRACT FROM AUTHOR]

Rubinstein–Taybi syndrome (RSTS) is a well-known autosomal dominant mental retardation syndrome with typical facial and skeletal abnormalities. Previously, we have reported two patients presenting with RSTS and additional clinical features including failure to thrive, seizures, and intractable infections (Bartsch et al. in Eur J Hum Genet 7:748–756, ). Recently we identified a third patient with this condition, termed here severe RSTS, or chromosome 16p13.3 deletion syndrome. The three patients died in infancy, and all displayed a specific mutation, a chromosomal microdeletion including the 3′-end of the CREBBP gene. Using fluorescence in situ hybridization and closely spaced DNA probes, we characterized the deletion intervals in these patients and in three individuals with a deletion of CREBBP and typical RSTS. The deleted DNA segments were found to greatly vary in size, spanning from ∼40 kb to >3 Mb. Four individuals, including the patients with severe RSTS, exhibited deletions containing gene/s in addition to CREBBP. The patients with severe RSTS all had deletions comprising telomeric neighbor genes of CREBBP, including DNASE1, a dominant gene encoding a nuclease that has been associated with systemic lupus erythematodes. Our findings suggest that severe RSTS is distinct from RSTS and represents a novel true contiguous gene syndrome (chromosome 16p13.3 deletion syndrome). Because of the risk of critical infections and high mortality rate, we recommend that the size of the deletion interval should be determined in CREBBP deletion-positive patients with RSTS, especially in young children. Further studies are needed to delineate the clinical spectrum of the new disorder and to clarify the role of DNASE1. [ABSTRACT FROM AUTHOR]

Abstract: GTG-banded karyotypes are presented for Scotoecus hirundo (; ), Rhogeessa alleni (; ), Scotophilus kuhlii (; ) and Scotophilus leucogaster (; ). These three genera belong to the family Vespertilionidae and have previously been placed into the tribe “Nycticeiini” (Tate 1942). Karyological analysis, however, points to a close relationship of Scotoecus hirundo to the tribes Pipistrellini and Vespertilionini (sensu Volleth and Heller 1994). Rhogeessa (Baeodon) alleni, a member of the karyologically diverse genus Rhogeessa, has two fusion chromosomes in common with the genus Plecotus. Together with morphological (Hill and Harrison 1987) and molecular-genetic results (Hoofer and Van Den Bussche 2003), chromosome analysis suggests a closer relationship of Plecotini and Rhogeessa. The two species examined of the genus Scotophilus show differences only in two small autosomal pairs and the Y chromosome. Chromosomal data did not reveal closer relationships of this genus to any other vespertilionid tribe. [Copyright &y& Elsevier]

Small supernumerary marker chromosomes (SMCs) are present in about 0.05% of the human population. In approximately 30% of SMC carriers (excluding the ~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. [ABSTRACT FROM AUTHOR]

A thorough study of the heterochromatin organisation in the pericentromeric region and the proximal long (q) and short (p) arms of human chromsome 9 (HSA 9) revealed homology between 9p12 and 9q1321.1, two regions that are usually not distinguishable by molecular cytogenetic techniques. Furthermore, the chromosomal regions 9p12 and 9ql 3-21.1 showed some level of homology with the short arms of the human acrocentric chromosomes. We studied five normal controls and 51 clinical cases: 48 with chromosome 9 heteromorphisms, one with an exceptionally large inversion and two with an additional derivative chromosome 9. Using fluorescence in situ hybridisation (FISH) with three differentially labelled chromosome 9-specific probes we were able to distinguish 12 heteromorphic patterns in addition to the most frequent pattern (defined as normal). In addition, we studied one inversion 9 case with the recently described multicolour banding (MCB) technique. Our results, and previously published findings, suggest several hotspots for recombination in the pericentromeric heterochromatin of HSA 9. They also demonstrate that constitutional inversions affecting the pericentromeric region of chromosome 9 carry breakpoints located preferentially in 9p12 or 9q13-21.1 and less frequently in 9q12. [ABSTRACT FROM AUTHOR]

A contiguous deletion encompassing the genes for dystrophin, cytochrome b(-245) beta-subunit (CYBB), retinitis pigmentosa GTPase regulator (RPGR), and OTC was detected in a female patient only suffering from OTC deficiency while symptoms of the other conditions were not present. [ABSTRACT FROM AUTHOR]

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. their shape. Thus, here we performed a long term in vitro study on 12 selected cell lines from the Else Kröner–Fresenius-sSMC-cellbank ( http://ssmc-tl.com/ekf-cellbank.html ) to test mitotic sSMC stability systematically. The obtained results showed that inverted duplicated shaped and also the so-called complex sSMCs (group 1) are by far more stable, than centric-minute- or ring-shaped sSMCs (groups 2). Generally speaking, the percentage of cells with group-1-sSMCs remained stable over 90 days of cell culture, while that of group-2-sSMCs in parts dramatically decreased. In one group-2-cell line the sSMC was even lost completely after 30 days of in vitro culture, in others the sSMC was depleted in up to 40% of the cells. Still the highest rate of sSMC loss was recorded during EBV-transformation. Overall, the major difference between groups 1 and 2 was the number of telomeres per sSMC. In group 1 the sSMCs had “original” telomeres at both of their ends; in group 2 the sSMCs had either no, possibly secondary acquired and/or only one original telomere. This absence of protective telomeric sequences in group 2 seems to make sSMC more susceptible for loss during cell division. Still, also a growth advantage of cells without sSMC cannot be neglected entirely. [ABSTRACT FROM AUTHOR]