Fetal Mesenchymal Stromal Cells: an Opportunity for Prenatal Cellular Therapy

PURPOSE OF REVIEW: The aim of the study is to provide an overview on the possibility of treating congenital disorders prenatally with mesenchymal stromal cells (MSCs). RECENT FINDINGS: MSCs have multilineage potential and a low immunogenic profile and are immunomodulatory and more easy to expand in culture. Their ability to migrate, engraft and differentiate, or act via a paracrine effect on target tissues makes MSCs candidates for clinical therapies. Fetal and extra-fetal MSCs offer higher therapeutic potential compared to MSCs derived from adult sources. SUMMARY: MSCs may be safely transplanted prenatally via ultrasound-guided injection into the umbilical cord. Due to these characteristics, fetal MSCs are of great interest in the field of in utero stem cell transplantation for treatment of congenital disease

Living with Osteogenesis Imperfecta: A qualitative study exploring experiences and psychosocial impact from the perspective of patients, parents and professionals

BACKGROUND: Osteogenesis Imperfecta (OI) is a rare genetic condition characterised by increased bone fragility. Recurrent fractures, pain and fatigue have a considerable impact on many aspects of the life of a person affected with OI and their families. OBJECTIVE: To improve our understanding of the impact of OI on the daily lives of individuals and families and consider how the condition is managed so that support needs can be better addressed. METHODS: Semi-structured qualitative interviews (n = 56) were conducted with adults affected with OI, with (n = 9) and without children (n = 8), parents of children affected with OI (n = 8), health professionals (n = 29) and patient advocates (n = 2). Interviews were digitally recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Three overarching themes are described: OI is not just a physical condition, parenting and family functioning and managing the condition. Fractures, chronic pain and tiredness impact on daily life and emotional well-being. For parents with OI, pain, tiredness and mobility issues can limit interactions and activities with their children. Specialist paediatric health services for OI were highly valued. The need for more emotional support and improved coordination of adult health services was highlighted. CONCLUSIONS: Our findings allow a better understanding of the day-to-day experiences of individuals and families affected with OI. Supporting emotional well-being needs greater attention from policy makers and researchers. Improvements to the coordination of health services for adults with OI are needed and an in-depth exploration of young people's support needs is warranted with research focused on support through the teenage years

Y-SNPs Do Not Indicate Hybridisation between European Aurochs and Domestic Cattle

Background: Previous genetic studies of modern and ancient mitochondrial DNA have confirmed the Near Eastern origin of early European domestic cattle. However, these studies were not able to test whether hybridisation with male aurochs occurred post-domestication. To address this issue, Götherström and colleagues (2005) investigated the frequencies of two Y-chromosomal haplotypes in extant bulls. They found a significant influence of wild aurochs males on domestic populations thus challenging the common view on early domestication and Neolithic stock-rearing. To test their hypothesis, we applied these Y-markers on Neolithic bone specimens from various European archaeological sites. Methods and Findings: Here, we have analysed the ancient DNA of 59 Neolithic skeletal samples. After initial molecular sexing, two segregating Y-SNPs were identified in 13 bulls. Strikingly, our results do not support the hypothesis that these markers distinguish European aurochs from domesticated cattle. Conclusions: The model of a rapid introduction of domestic cattle into Central Europe without significant crossbreeding with local wild cattle remains unchallenged

Human inbreeding has decreased in time through the Holocene

The history of human inbreeding is controversial. In particular, how the development of sedentary and/or agricultural societies may have influenced overall inbreeding levels is unclear. Here we present an approach for reliable estimation of runs of homozygosity (ROH) in genomes with ≥3x mean sequence coverage across >1 million SNPs, and apply this to 411 ancient Eurasian genomes from the last 15,000 years. We show that the frequency of inbreeding, as measured by ROH, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to small population size instead of consanguinity. We observed singular cases of high consanguinity only among members of farming societies

Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia

Population genomic studies of ancient human remains have shown how modern-day European population structure has been shaped by a number of prehistoric migrations. The Neolithization of Europe has been associated with large-scale migrations from Anatolia, which was followed by migrations of herders from the Pontic steppe at the onset of the Bronze Age. Southwestern Europe was one of the last parts of the continent reached by these migrations, and modern-day populations from this region show intriguing similarities to the initial Neolithic migrants. Partly due to climatic conditions that are unfavorable for DNA preservation, regional studies on the Mediterranean remain challenging. Here, we present genome-wide sequence data from 13 individuals combined with stable isotope analysis from the north and south of Iberia covering a four-millennial temporal transect (7, 500–3, 500 BP). Early Iberian farmers and Early Central European farmers exhibit significant genetic differences, suggesting two independent fronts of the Neolithic expansion. The first Neolithic migrants that arrived in Iberia had low levels of genetic diversity, potentially reflecting a small number of individuals; this diversity gradually increased over time from mixing with local hunter-gatherers and potential population expansion. The impact of post-Neolithic migrations on Iberia was much smaller than for the rest of the continent, showing little external influence from the Neolithic to the Bronze Age. Paleodietary reconstruction shows that these populations have a remarkable degree of dietary homogeneity across space and time, suggesting a strong reliance on terrestrial food resources despite changing culture and genetic make-up

Typing Late Prehistoric Cows and Bulls—Osteology and Genetics of Cattle at the Eketorp Ringfort on the Öland Island in Sweden

Human management of livestock and the presence of different breeds have been discussed in archaeozoology and animal breeding. Traditionally osteometrics has been the main tool in addressing these questions. We combine osteometrics with molecular sex identifications of 104 of 340 morphometrically analysed bones in order to investigate the use of cattle at the Eketorp ringfort on the Öland island in Sweden. The fort is dated to 300–1220/50 A.D., revealing three different building phases. In order to investigate specific patterns and shifts through time in the use of cattle the genetic data is evaluated in relation to osteometric patterns and occurrence of pathologies on cattle metapodia. Males were genotyped for a Y-chromosomal SNP in UTY19 that separates the two major haplogroups, Y1 and Y2, in taurine cattle. A subset of the samples were also genotyped for one SNP involved in coat coloration (MC1R), one SNP putatively involved in resistance to cattle plague (TLR4), and one SNP in intron 5 of the IGF-1 gene that has been associated to size and reproduction

Genomic insights into the conservation status of the world’s last remaining Sumatran rhinoceros populations

Highly endangered species like the Sumatran rhinoceros are at risk from inbreeding. Five historical and 16 modern genomes from across the species range show mutational load, but little evidence for local adaptation, suggesting that future inbreeding depression could be mitigated by assisted gene flow among populations. Small populations are often exposed to high inbreeding and mutational load that can increase the risk of extinction. The Sumatran rhinoceros was widespread in Southeast Asia, but is now restricted to small and isolated populations on Sumatra and Borneo, and most likely extinct on the Malay Peninsula. Here, we analyse 5 historical and 16 modern genomes from these populations to investigate the genomic consequences of the recent decline, such as increased inbreeding and mutational load. We find that the Malay Peninsula population experienced increased inbreeding shortly before extirpation, which possibly was accompanied by purging. The populations on Sumatra and Borneo instead show low inbreeding, but high mutational load. The currently small population sizes may thus in the near future lead to inbreeding depression. Moreover, we find little evidence for differences in local adaptation among populations, suggesting that future inbreeding depression could potentially be mitigated by assisted gene flow among populations