Zoo-FISH in the European mole (Talpa europaea) detects all ancestral Boreo-Eutherian human homologous chromosome associations

Zoo-FISH with human whole-chromosome paint probes delineated syntenic association of human homologous chromosome segments 3-21, 14-15, 16-19, 4-8, 7-16 and 12-22 (twice) in the European mole (Talpa europaea, Talpidae, Eulipotyphla, Mammalia). These segment associations represent shared ancestral Boreo-Eutherian traits, half of which were previously not described for Eulipotyphla. The karyotype of the European mole acquired a minimum of 19 translocations and six inversions compared to the presumed Boreo-Eutherian ancestor. Copyright (c) 2006 S. Karger AG, Basel

Subjektive Hörverbesserung durch Cochleaimplantatversorgung

1. Zusammenfassung 1.1 Hintergrund und Ziele Erste Versuche ein elektrisches Hören zu erreichen liegen um das Jahr 1800. Am 25. Februar 1957 wurde in Paris das erste funktionierende Cochlea-Implantat eingesetzt. Es sind nach Stand 01. März 2016 weltweit ca. 500.000 Menschen mit einem Cochlea-Implantat versorgt, davon ca. 45.000 in Deutschland lebend. Die Ursachen einer Ertaubung sind vielfältig. Mit wachsender Erfahrung bei der Cochlea-Implantation wurde die Indikation zunehmend erweitert. Bei der Operation geht die Tendenz zu immer minimal-invasiveren und schonenderen Verfahren. Der Rehabilitation kommt ein besonders hoher Stellenwert zu. Zur Beurteilung der Lebensqualität bei audiologischen Maßnahmen wurden in den vergangenen Jahrzehnten zahlreiche Fragebogeninventare erstellt. Speziell für die Cochlea-Implantat-Versorgung wurde der Hearing Implant Sound Quality Index (HISQUI) entwickelt. Ziel dieser Studie war es, das Maß der subjektiven Hörverbesserung durch die Cochlea-Implantat-Versorgung darzustellen und dieses in Korrelation zu audiometrischen Messmethoden wie Ton- und Sprachaudiogramm zu setzen. 1.2 Material und Methoden Die prä- und postoperativen Daten von 57 mit Cochlea-Implantaten (CIs) versorgten Patienten an der Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) wurden im Rahmen dieser Studie retrospektiv ausgewertet. Zur Einschätzung des subjektiven Hörvermögens wurde der HISQUI-Fragebogen mit 19 Fragen herangezogen. In die Auswertungen miteingeschlossen wurden die Punktewerte des HISQUI19 -Fragebogens vor und nach der Operation. Tonaudiogramm und Einsilberverstehen im Freiburger Test wurden als audiometrische Maße des Hörvermögens verwendet. Dabei wurden das Einsilberverstehen vor und nach der Operation und die mittlere Tonhörschwelle des besseren Ohres vor der Operation ermittelt. 1.3 Ergebnisse und Beobachtungen Der Median des HISQUI-Scores stieg durchschnittlich von 53,0 vor der Operation auf 69,0 nach der Operation. Auch in allen sieben Subskalen des Fragebogeninventars wurde eine signifikante Verbesserung der Einschätzung nachgewiesen. Im Freiburger Einsilbertest lag der Mittelwert des Sprachverstehens des besseren Ohres bei 65 dB vor der Operation bei 39,0 % [± 29,5 % SD], der Mittelwert des CI-Ohres nach der Operation bei 60,0 % [± 22,8 % SD]. Eine Korrelation von HISQUI-Scores und Einsilberverstehen war vor der Operation mit rSp = 0,53 und nach der Operation mit rSp = 0,36 zu verzeichnen. Zudem korrelierte der 4FPTA (= four frequency pure tone average)-Wert des besseren Ohres negativ mit rSp = - 0,48 mit dem HISQUI-Gesamtscore vor der Operation. Eine signifikante Korrelation zwischen dem HISQUI19, sowohl präoperativ als auch postoperativ, und dem Implantationsalter (p = 0,23 und p = 0,84), dem Hörverlust in Jahren (p = 0,67 und p = 0,98) und dem Geschlecht (p = 0,48 und p = 0,97) oder postoperativ mit der CI-Seite (p = 0,21), war nicht zu verzeichnen (p > 0,05). 1.4 Schlussfolgerungen Nahezu alle Patienten erreichten durch die CI-Versorgung eine Verbesserung des Hörvermögens sowohl in ihren subjektiven Einschätzungen als auch in dem unter identischen Bedingungen gemessenem Sprachverstehen. Die geringste Verbesserung findet sich in der Subskala zur Sprecherunterscheidung (SU). Dies ist zu erwarten, da bei der Stimmerkennung die Frequenzauflösung eine besondere Rolle spielt und diese bei CI-Systemen eher schlecht ist. Die mäßige Korrelation von subjektiven und objektiven Messmethoden unterstreicht die Bedeutung der Erhebung von Daten zur subjektiven Lebensqualität und Zufriedenheit der Patienten. Durch eine Kombination von subjektiven Aussagen und Sprachverstehensmessungen erhält man ein umfassenderes Bild der Hörleistungen von CI-Trägern. Unzufriedenheit der Patienten kann dadurch zeitnah erkannt, analysiert und behoben werden. 2. Abstract 2.1 Background and Objectives First attempts to achieve electric hearing have been made since the beginning of the 19th century. On 25 February 1957, the first functioning cochlear implant was inserted. As of March 2016, about 500,000 people worldwide were fitted with cochlear implants, 45.000 in Germany alone. The causes of deafness are diverse. Increasing cochlear implant experience expanded its indication. The surgery itself is becoming increasingly less invasive and more gentle procedures are applied. Particularly high priority is given to rehabilitation. During the past decades various questionnaires were developed to evaluate the quality of life within audiological measures. The Hearing Implant Sound Quality Index (HISQUI) was generated specifically for cochlear implantation. The objective of this study was to demonstrate subjective hearing improvement through cochlear implantation and to correlate the results with audiometric measuring methods such as pure-tone and speech audiometry. 2.2 Materials and Methods Within the framework of this study, pre- and postoperative data of 57 patients supplied with cochlear implants (CIs) were analyzed retrospectively before and after cochlear implantation at the Friedrich-Alexander-University Erlangen-Nürnberg (FAU). The HISQUI questionnaire consisting of 19 questions was used as reference to evaluate the subjective hearing ability. The scores of the HISQUI19 were included in the evaluation pre- and post-operationally. Pure-tone audiometry and the Freiburger monosyllable word test were used as audiometric measurements of the hearing ability. The Freiburger monosyllable word test was recorded pre- and post-operationally, the 4FPTA (= four frequency pure tone average) of the better ear was recorded pre-operationally. 2.3 Results and observations On average, the mean HISQUI score increased from 53.0 pre-operationally to 69.0 post-operationally. Additionally, there was a significant improvement in all seven subgroups of the questionnaire divisions. In the Freiburger monosyllable word test the mean value of speech understanding of the better ear at a sound level of 65 dB was 39.0 % [± 29.5 % SD] pre-operationally, the mean value of the CI-implanted ear was 60.0 % [± 22.8 % SD] post-operationally. A correlation of rSp = 0.53 before the implantation and rSp = 0.36 after the implantation between HISQUI scores and the Freiburg monosyllable word test was recorded. In addition the 4FPTA (= four frequency pure tone average) of the better ear correlates negatively with rSp = -0.48 with the HISQUI total score before the surgery. There was no significant correlation between HISQUI19 and the age at implantation (p = 0.23 and p = 0.84), the hearing loss in years (p = 0.67 and p = 0.98) and the gender (p = 0.48 and p = 0.97) pre-operationally or post-operationally (p > 0.05). There was no significant correlation between HISQUI19 and the side of implantation (p = 0.21) post-operationally (p > 0.05). 2.4 Conclusions Almost all patients experienced improved hearing after their cochlear implantation, both in their subjective valuation and in their speech comprehension which was measured under identical conditions. The least improvement is found in the subscale called “distinguishing between different voices/speakers”. This is to be expected because frequency resolution plays an important part in voice authentication and frequency resolution is rather poor with CI Sytems. The moderate correlation of both subjective and objective measurement methods underlines the significance of enquiring the patients’ subjective perception and satisfaction. It is possible to get a comprehensive idea of the CI-recipients’ hearing performance through the combination of subjective statements and measurements of speech comprehensio

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. 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

Sex. Dev.

Campomelic dysplasia (MIM 114290) is a severe malformation syndrome frequently accompanied by male-to-female sex reversal. Causative are mutations within the SOX9 gene on 17q24.3 as well as chromosomal aberrations (translocations, inversions or deletions) in the vicinity of SOX9 . Here, we report on a patient with muscular hypotonia, craniofacial dysmorphism, cleft palate, brachydactyly, malformations of thoracic spine, and gonadal dysgenesis with female external genitalia and müllerian duct derivatives in the presence of a male karyotype. X-ray examination and clinical examinations revealed no signs of campomelia. The combination of molecular cytogenetic analysis and array CGH revealed an unbalanced translocation between one chromosome 7 and one chromosome 17 [46,XY,t(7; 17)(q33;q24).ish t(7; 17) (wcp7+,wcp17+;wcp7+wcp17+)] with a deletion of approximately 4.2 Mb located about 0.5 Mb upstream of SOX9 . STS analysis confirmed the deletion of chromosome 17, which has occurred de novo on the paternal chromosome. The proximal breakpoint on chromosome 17 is localized outside the known breakpoint cluster regions. The deletion on chromosome 17q24 removes several genes. Among these genes PRKAR1A is deleted. Inactivating mutations of PRKAR1A cause Carney complex. To our knowledge, this is the first report of a patient with acampomelic campomelic dysplasia, carrying both a deletion and a translocation

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. However, they were stable in the T lymphocytes, immortalized B lymphoblastoid cells, and skin fibroblasts analyzed in each individual. Because these cell types have a common origin in the connective tissues, we suggest that mitotic changes in CNV regions may happen early during embryonic development and occur only once, after which the stable mosaic ratio is maintained throughout the differentiated tissues. This concept is further supported by a unique study of immortalized B lymphoblastoid cell lines obtained with 20 year difference from two subjects. We provide the first evidence of somatic mosaicism for CNV, with stable variation ratios in different cell types of one individual leading to the hypothesis of early embryonic chromosome instability resulting in stable mosaic pattern in human tissues. This concept has the potential to open new perspectives in personalized genetic diagnostics and can explain genetic phenomena like diminished penetrance in autosomal dominant diseases. We propose that further genomic studies should focus on the single-cell level, to better understand the aetiology of aging and diseases mediated by somatic mutations

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 unique study of immortalized B-lymphoblastoid cell lines obtained with 20 year interval from the same two subjects shows that mitotic changes in CNV regions may happen early during embryonic development and seem to occur only once, as levels of mosaicism remained stable. This finding has the potential to change our concept of dynamic human genome variation. We propose that further genomic studies should focus on the single-cell level, to understand better the etiology and physiology of aging and diseases mediated by somatic variations

Integrated Operational Taxonomic Units (IOTUs) in Echolocating Bats: A Bridge between Molecular and Traditional Taxonomy

Background: Nowadays, molecular techniques are widespread tools for the identification of biological entities. However, until very few years ago, their application to taxonomy provoked intense debates between traditional and molecular taxonomists. To prevent every kind of disagreement, it is essential to standardize taxonomic definitions. Along these lines, we introduced the concept of Integrated Operational Taxonomic Unit (IOTU). IOTUs come from the concept of Operational Taxonomic Unit (OTU) and paralleled the Molecular Operational Taxonomic Unit (MOTU). The latter is largely used as a standard in many molecular-based works (even if not always explicitly formalized). However, while MOTUs are assigned solely on molecular variation criteria, IOTUs are identified from patterns of molecular variation that are supported by at least one more taxonomic characteristic. Methodology/Principal Findings: We tested the use of IOTUs on the widest DNA barcoding dataset of Italian echolocating bats species ever assembled (i.e. 31 species, 209 samples). We identified 31 molecular entities, 26 of which corresponded to the morphologically assigned species, two MOTUs and three IOTUs. Interestingly, we found three IOTUs in Myotis nattereri, one of which is a newly described lineage found only in central and southern Italy. In addition, we found a level of molecular variability within four vespertilionid species deserving further analyses. According to our scheme two of them (i.e. M. bechsteinii and Plecotus auritus) should be ranked as unconfirmed candidate species (UCS). Conclusions/Significance: From a systematic point of view, IOTUs are more informative than the general concept of OTUs and the more recent MOTUs. According to information content, IOTUs are closer to species, although it is important to underline that IOTUs are not species. Overall, the use of a more precise panel of taxonomic entities increases the clarity in the systematic field and has the potential to fill the gaps between modern and traditional taxonomy