Genomic regions associated with microdeletion/microduplication syndromes exhibit extreme diversity of structural variation

Segmental duplications (SDs) are a class of long, repetitive DNA elements whose paralogs share a high level of sequence similarity with each other. SDs mediate chromosomal rearrangements that lead to structural variation in the general population as well as genomic disorders associated with multiple congenital anomalies, including the 7q11.23 (Williams–Beuren Syndrome, WBS), 15q13.3, and 16p12.2 microdeletion syndromes. Population-level characterization of SDs has generally been lacking because most techniques used for analyzing these complex regions are both labor and cost intensive. In this study, we have used a high-throughput technique to genotype complex structural variation with a single molecule, long-range optical mapping approach. We characterized SDs and identified novel structural variants (SVs) at 7q11.23, 15q13.3, and 16p12.2 using optical mapping data from 154 phenotypically normal individuals from 26 populations comprising five super-populations. We detected several novel SVs for each locus, some of which had significantly different prevalence between populations. Additionally, we localized the microdeletion breakpoints to specific paralogous duplicons located within complex SDs in two patients with WBS, one patient with 15q13.3, and one patient with 16p12.2 microdeletion syndromes. The population-level data presented here highlights the extreme diversity of large and complex SVs within SD-containing regions. The approach we outline will greatly facilitate the investigation of the role of inter-SD structural variation as a driver of chromosomal rearrangements and genomic disorders.     

LOX-1 inhibition in myocardial ischemia-reperfusion injury: modulation of MMP-1 and inflammation

A recently identified lectin-like oxidized low-density lipoprotein receptor (LOX-1) mediates endothelial cell injury and facilitates inflammatory cell adhesion. We studied the role of LOX-1 in myocardial ischemia-reperfusion (I/R) injury. Anesthetized Sprague-Dawley rats were subjected to 60 min of left coronary artery (LCA) ligation, followed by 60 min of reperfusion. Rats were treated with saline, LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat IgG (10 mg/kg) before I/R. Ten other rats underwent surgery without LCA ligation and served as a sham control group. LOX-1 expression was markedly increased during I/R (P < 0.01 vs. sham control group). Simultaneously, the expression of matrix metalloproteinase-1 (MMP-1) and adhesion molecules (P-selectin, VCAM-1, and ICAM-1) was also increased in the I/R area (P < 0.01 vs. sham control group). There was intense leukocyte accumulation in the I/R area in the saline-treated group. Treatment of rats with the LOX-1 antibody prevented I/R-induced upregulation of LOX-1 and reduced MMP-1 and adhesion molecule expression as well as leukocyte recruitment. LOX-1 antibody, but not nonspecific IgG, also reduced myocardial infarct size (P < 0.01 vs. saline-treated I/R group). To explore the link between LOX-1 and adhesion molecule expression, we measured expression of oxidative stress-sensitive p38 mitogen-activated protein kinase (p38 MAPK). The activity of p38 MAPK was increased during I/R (P < 0.01 vs. sham control), and use of LOX-1 antibody inhibited p38 MAPK activation (P < 0.01). These findings indicate that myocardial I/R upregulates LOX-1 expression, which through p38 MAPK activation increases the expression of MMP-1 and adhesion molecules. Inhibition of LOX-1 exerts an important protective effect against myocardial I/R injury.     

Importance of Native Grassland Habitat for Den-Site Selection of Indian Foxes in a Fragmented Landscape

Fragmentation of native habitats is now a ubiquitous phenomenon affecting wildlife at various scales. We examined selection of den-sites (n = 26) by Indian foxes (Vulpes bengalensis) in a highly modified short-grassland landscape in central India (Jan-May, 2010). At the scale of the home-range, defined by an 800 m circular buffer around den sites, we examined the effect of land-cover edges and roads on selection of sites for denning using a distance-based approach. At the smaller den-area scale, defined by a 25 m x 25 m plot around den and paired available sites, the effect of microhabitat characteristics was examined using discrete-choice models. Indian foxes selected den-sites closer to native grasslands (t = -9.57, P < 0.001) and roads (t = -2.04, P = 0.05) than random at the home-range scale. At the smaller scale, abundance of rodents and higher visibility increased the odds of selection of a site by eight and four times respectively, indicating resource availability and predator avoidance to be important considerations for foxes. Indian foxes largely chose to den in human-made structures, indicated by the proportion of dens found in earthen bunds (0.69) and boulder piles (0.27) in the study area. With agricultural expansion and human modification threatening native short-grassland habitats, their conservation and effective management in human-dominated landscapes will benefit the Indian fox. The presence of some human-made structures within native grasslands would also be beneficial for this den-dependent species. We suggest future studies examine the impact of fragmentation and connectivity of grasslands on survival and reproductive success of the Indian fox.     

Scale‐dependent strategies for coexistence of mesocarnivores in human‐dominated landscapes

Identifying factors influencing the distribution of and interactions within carnivore communities is important for understanding how they are affected by human activities. Species differ in their ability to adapt to humans depending on their degree of specialization in habitat use and feeding habits. This results in asymmetric changes in the ecology of co‐occurring species that can influence their interactions. We investigated whether human infrastructures and free‐ranging domestic dogs (a species typically associated with humans) influenced the co‐occurrence and habitat use of mesocarnivores in a landscape of high human population density in Maharashtra, India. We used 40 camera trap locations during 233 trapping nights and used Bayesian co‐occurrence occupancy models to investigate the habitat use and coexistence of species at different spatial scales. Additionally, we investigated their temporal overlap in space use. Indian foxes altered their habitat use both spatially and temporally in order to avoid free‐ranging domestic dogs and other larger competitors. The use of human infrastructure by jackals and jungle cats was limited by the presence of dogs. Our results illustrate how habitat use of smaller carnivore species changes both spatially and temporally in order to avoid larger competitors. We also show that the presence of species associated with humans mediates the influence of human infrastructures on the habitat use of mesocarnivores. We highlight the importance of acknowledging the potential impact of urbanization not only on single species, but also on the interactions within the community.     

Consanguineous marriage in the capital city Sana'a, Yemen

Consanguineous marriage is traditionally common throughout the Eastern Mediterranean region, especially in the mainly Muslim countries. To date, there is little information on consanguinity in Yemen. The aim of this study was to ascertain the rate of consanguineous marriage and average coefficient of inbreeding in Sana'a City, Yemen. A population survey was conducted with the intention of covering married couples resident in Sana'a City by means of a multi-stage random sampling technique. A total of 1050 wives and husbands were interviewed on consanguinity in their households. The total incidence of consanguinity was 44-7% (95% CI 41.7-47.7%) with first-cousin marriages constituting 71.6% of the total consanguineous marriages and 32% of all marriages. Paternal parallel first cousins (Type I) accounted for 49% of first-cousin marriages. The average coefficient of inbreeding (F) was 0.02442. The incidence of consanguinity is relatively high in Yemen with predominantly first-cousin marriage. This might be related to the deeply rooted social and cultural beliefs in the country.