Geographical contrasts of Y-chromosomal haplogroups from wild and domestic goats reveal ancient migrations and recent introgressions.

By their paternal transmission, Y-chromosomal haplotypes are sensitive markers of population history and male-mediated introgression. Previous studies identified biallelic single-nucleotide variants in the SRY, ZFY and DDX3Y genes, which in domestic goats identified four major Y-chromosomal haplotypes, Y1A, Y1B, Y2A and Y2B, with a marked geographical partitioning. Here, we extracted goat Y-chromosomal variants from whole-genome sequences of 386 domestic goats (75 breeds) and seven wild goat species, which were generated by the VarGoats goat genome project. Phylogenetic analyses indicated domestic haplogroups corresponding to Y1B, Y2A and Y2B, respectively, whereas Y1A is split into Y1AA and Y1AB. All five haplogroups were detected in 26 ancient DNA samples from southeast Europe or Asia. Haplotypes from present-day bezoars are not shared with domestic goats and are attached to deep nodes of the trees and networks. Haplogroup distributions for 186 domestic breeds indicate ancient paternal population bottlenecks and expansions during migrations into northern Europe, eastern and southern Asia, and Africa south of the Sahara. In addition, sharing of haplogroups indicates male-mediated introgressions, most notably an early gene flow from Asian goats into Madagascar and the crossbreeding that in the 19th century resulted in the popular Boer and Anglo-Nubian breeds. More recent introgressions are those from European goats into the native Korean goat population and from Boer goat into Uganda, Kenya, Tanzania, Malawi and Zimbabwe. This study illustrates the power of the Y-chromosomal variants for reconstructing the history of domestic species with a wide geographical range.

Patterns of homozygosity in insular and continental goat breeds.

BACKGROUND: Genetic isolation of breeds may result in a significant loss of diversity and have consequences on health and performance. In this study, we examined the effect of geographic isolation on caprine genetic diversity patterns by genotyping 480 individuals from 25 European and African breeds with the Goat SNP50 BeadChip and comparing patterns of homozygosity of insular and nearby continental breeds. RESULTS: Among the breeds analysed, number and total length of ROH varied considerably and depending on breeds, ROH could cover a substantial fraction of the genome (up to 1.6 Gb in Icelandic goats). When compared with their continental counterparts, goats from Iceland, Madagascar, La Palma and Ireland (Bilberry and Arran) displayed a significant increase in ROH coverage, ROH number and FROH values (P value < 0.05). Goats from Mediterranean islands represent a more complex case because certain populations displayed a significantly increased level of homozygosity (e.g. Girgentana) and others did not (e.g. Corse and Sarda). Correlations of number and total length of ROH for insular goat populations with the distance between islands and the nearest continental locations revealed an effect of extremely long distances on the patterns of homozygosity. CONCLUSIONS: These results indicate that the effects of insularization on the patterns of homozygosity are variable. Goats raised in Madagascar, Iceland, Ireland (Bilberry and Arran) and La Palma, show high levels of homozygosity, whereas those bred in Mediterranean islands display patterns of homozygosity that are similar to those found in continental populations. These results indicate that the diversity of insular goat populations is modulated by multiple factors such as geographic distribution, population size, demographic history, trading and breed management.

Organ explant culture of neonatal rat ventricles: a new model to study gene and cell therapy.

Testing cardiac gene and cell therapies in vitro requires a tissue substrate that survives for several days in culture while maintaining its physiological properties. The purpose of this study was to test whether culture of intact cardiac tissue of neonatal rat ventricles (organ explant culture) may be used as a model to study gene and cell therapy. We compared (immuno) histology and electrophysiology of organ explant cultures to both freshly isolated neonatal rat ventricular tissue and monolayers. (Immuno) histologic studies showed that organ explant cultures retained their fiber orientation, and that expression patterns of α-actinin, connexin-43, and α-smooth muscle actin did not change during culture. Intracellular voltage recordings showed that spontaneous beating was rare in organ explant cultures (20%) and freshly isolated tissue (17%), but common (82%) in monolayers. Accordingly, resting membrane potential was -83.9±4.4 mV in organ explant cultures, -80.5±3.5 mV in freshly isolated tissue, and -60.9±4.3 mV in monolayers. Conduction velocity, measured by optical mapping, was 18.2±1.0 cm/s in organ explant cultures, 18.0±1.2 cm/s in freshly isolated tissue, and 24.3±0.7 cm/s in monolayers. We found no differences in action potential duration (APD) between organ explant cultures and freshly isolated tissue, while APD of monolayers was prolonged (APD at 70% repolarization 88.8±7.8, 79.1±2.9, and 134.0±4.5 ms, respectively). Organ explant cultures and freshly isolated tissue could be paced up to frequencies within the normal range for neonatal rat (CL 150 ms), while monolayers could not. Successful lentiviral (LV) transduction was shown via Egfp gene transfer. Co-culture of organ explant cultures with spontaneously beating cardiomyocytes increased the occurrence of spontaneous beating activity of organ explant cultures to 86%. We conclude that organ explant cultures of neonatal rat ventricle are structurally and electrophysiologically similar to freshly isolated tissue and a suitable new model to study the effects of gene and cell therapy.