Digital Agenesia in Martina Franca Donkey Foal: A Case Report

A 4-day-old male Martina Franca donkey foal was evaluated for a forelimb alteration.Clinical examination and radiographs revealed the agenesia of the distal digit.Biochemical parameters were normal, and ultrasonographic evaluation did not identifyany relievable organ alteration. Karyotype study revealed an abnormality on chromosome1. The foal was discharged with a distal limb bandage in which a palmar splint wasapplied. A poor prognosis for the functionality of the limb was given. In endangeredspecies, such as the Martina Franca donkey, the excessive inbreeding could result in anincrease in genetic disorders. These findings shed new light on the possible pathogenesisof the digital dysgenesia. The study of the karyotype could be a useful approach to detectgenetic alterations that could or could not be expressed in the animal, especially inendangered species in which a risk of an excessive inbreeding is considerable. Thesedefects should be considered in the choice and selection of the breeders.[...

Characterization and in vitro differentiation potency of early-passage canine amnion- and umbilical cord-derived mesenchymal stem cells as related to gestational age

Fetal adnexa are a noncontroversial source of mesenchymal stem cells (MSCs) with high plasticity, proliferation rate and ability to differentiate towards multiple lineages. Mesenchymal SCs have been characterized for both their stemness and their differentiation abilities. Recently, the scientific debate has focused on MSCs selection and on establishing predictable elements to discriminate the cells with most promising potential in regenerative medicine. In this study, we characterized and followed in vitro proliferation and differentiation potency of canine amniotic membrane MSCs (AM-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) isolated from fetuses at early (35-40 days) and late (45-55 days) gestational ages. We found that cells from both fetal gestational ages showed similar features. In all examined cell lines, the morphology of proliferating cells typically appeared fibroblast-like and the population doubling of cells, cultured up to passage 10, significantly increased with passage number. In both cell types, cell viability and chromosomal number and structure were not affected by gestational age. In AM- and UCM-MSCs of both gestational phases, the expression of embryonic (Oct-4) and mesenchymal stemness (CD29, CD44) markers was observed. Hematopoietic and histocompatibility markers were never found in any sample. Cells of the two cell types at P3 showed multipotent abilities and differentiated to neurocytes and osteocytes, as demonstrated by specific stains and molecular analysis. These results indicated that MSCs retrieved from UCM and AM in early and late fetal phase of gestation could be used in regenerative medicine approaches in the dog

7q35q36.3 deletion and concomitant 20q13.2q13.33 duplication in a newborn: familiar case

OBJECTIVE: Array-CGH is a powerful tool in identifying and characterizing complex genomic rearrangements smaller than 5-10 megabase (Mb), for which classical cytogenetic approaches are not sensitive enough. The use of Array-CGH has increased of 10-20% the detection rate of unbalanced cryptic rearrangements, such as deletions and/or duplications.PATIENTS AND METHODS: We present here the first report of a patient with 7q35q36.3 microdeletion and concomitant 20q13.2q13.33 microduplication detected by array-CGH and confirmed by reiterative FISH experiments associated with dysmorphism, development delay, Long QT syndrome (LOTS), complex congenital heart disease, pulmonary hypertension, hypotonia, respiratory distress, cognitive deficit.RESULTS: We proved that this unbalanced rearrangement was due to an adjacent-1 segregation that occurred in the mother, carrier of a balanced translocation between chromosomes 7 and 20. The same unbalanced rearrangements were also found in the proband's maternal uncle, who had been given a clinical diagnosis of Dandy-Walker/Rubinstein-Taybi syndromes in the past. Given the above-mentioned observations, the proband's uncle is not affected by Dandy-Walker/Rubinstein-Taybi syndromes, but by a genomic syndrome highlighted by array-CGH.CONCLUSIONS: The Array-CGH allowed us to understand that the loss of several genes is expressed with clinical manifestations due to the concomitance of several syndromes, each related to the malfunction of a "specific disease gene". For these reasons, the genotype-phenotype correlation in these cases is more complex. This study confirms that the array-CGH is useful in identifying pathologies that were considered idiopathic until a few years ago

The bonobo genome compared with the chimpanzee and human genomes.

Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other

Recurrent inversion toggling and great ape genome evolution

Inversions play an important role in disease and evolution but are difficult to characterize because their breakpoints map to large repeats. We increased by sixfold the number (n = 1,069) of previously reported great ape inversions by using single-cell DNA template strand and long-read sequencing. We find that the X chromosome is most enriched (2.5-fold) for inversions, on the basis of its size and duplication content. There is an excess of differentially expressed primate genes near the breakpoints of large (>100 kilobases (kb)) inversions but not smaller events. We show that when great ape lineage-specific duplications emerge, they preferentially (approximately 75%) occur in an inverted orientation compared to that at their ancestral locus. We construct megabase-pair scale haplotypes for individual chromosomes and identify 23 genomic regions that have recurrently toggled between a direct and an inverted state over 15 million years. The direct orientation is most frequently the derived state for human polymorphisms that predispose to recurrent copy number variants associated with neurodevelopmental disease

Evolutionary and functional impact of common polymorphic inversions in the human genome

Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. Here, we develop a new high-throughput genotyping method based on probe hybridization and amplification, and we perform a complete study of 45 common human inversions of 0.1-415 kb. Most inversions promoted by homologous recombination occur recurrently in humans and great apes and they are not tagged by SNPs. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.This work was supported by research grants ERC Starting Grant 243212 (INVFEST) from the European Research Council under the European Union Seventh Research Framework Programme (FP7), BFU2013-42649-P and BFU2016-77244-R funded by the Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund (FEDER, EU), and 2014-SGR-1346 and 2017-SGR-1379 from the Generalitat de Catalunya (Spain) to M.C., a PIF PhD fellowship from the Universitat Autònoma de Barcelona (Spain) to C.G.D., a La Caixa Doctoral fellowship to J.L.J., and a FPI PhD fellowship from the Ministerio de Economía y Competitividad (Spain) to M.O. and I.N. M.G.V. was supported in part by POCI-01-0145-FEDER-006821 funded through the Operational Programme for Competitiveness Factors (COMPETE, EU) and UID/BIA/50027/2013 from the Foundation for Science and Technology (FCT, Portugal)