Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease

Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.     

miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration

microRNAs (miRNAs) function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that miRNAs canalize development and provide genetic robustness. Here, we uncover a previously unidentified regulatory layer of chemokine signaling by miRNAs that confers genetic robustness on primordial germ cell (PGC) migration. In zebrafish, PGCs are guided to the gonad by the ligand Sdf1a, which is regulated by the sequestration receptor Cxcr7b. We find that miR-430 regulates sdf1a and cxcr7 mRNAs. Using target protectors, we demonstrate that miR-430-mediated regulation of endogenous sdf1a (also known as cxcl12a) and cxcr7b (i) facilitates dynamic expression of sdf1a by clearing its mRNA from previous expression domains, (ii) modulates the levels of the decoy receptor Cxcr7b to avoid excessive depletion of Sdf1a and (iii) buffers against variation in gene dosage of chemokine signaling components to ensure accurate PGC migration. Our results indicate that losing miRNA-mediated regulation can expose otherwise buffered genetic lesions leading to developmental defects.     

Common variation at 10p12.31 near MLLT10 influences meningioma risk

To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.     

Cryptogams, vascular plants, and soil hydrological relations: some preliminary results from the semiarid woodlands of eastern Australia

Grazed and ungrazed sites were examined in a semiarid woodland in eastern Australia to determine relationships within various types of cryptogams, and the role of cryptogams in pasture dynamics, infiltration, and water erosion. Strong relationships were found between vascular plant cover and cover of cryptogams for nine rangeland sites over an 18-month period. In the absence of vascular plants, sites with low cover of cryptogams were dominated by algae. The presence of a cryptogamic crust had no significant effect on infiltration at ungrazed sites but significantly increased infiltration at some grazed sites. Splash erosion was very low on soils with at least 50% cryptogam cover. Below this level splash erosion increased markedly, along with the proportion of fine sediments lost.     

Winter habitats and foods of Blue Grouse in the Sheeprock Mountains, Utah

Winter habitat use and food habits of Blue Grouse ( Dendragapus obscurus ) were studied in an isolated Utah desert mountain range that contained little typical Douglas-fir ( Pseudotsuga menziesii ) winter habitat. Habitat use was concentrated in the Douglas-fir and pinyon ( Pinus edulis )-juniper ( Juniperus spp. ) habitat. Douglas-fir and pinyon pine were the most consumed foods. Other foods that represented >15% of the composition of an individual fecal sample were limber pine ( Pinus flexilis ), mahogany ( Cercocarpus ledifoliu ), juniper, and an Anteunaria-Cirsium type. The breadth in winter diet indicates that Blue Grouse may successfully occupy other habitats when typical winter habitat is scarce.     

Changes in kit fox–coyote–prey relationships in the Great Basin Desert, Utah

Variation in kit fox ( Vulpes macrotis ) population parameters can be influenced by vegetative cover and the distribution and abundance of other predator and prey species. Dramatic changes to Great Basin Desert habitats, which can potentially impact mammalian species, have occurred in some areas in Utah. We examined kit fox demographics and prey populations from 1999 to 2001 on Dugway Proving Ground (DPG), a U.S. Army facility in Utah, and compared some parameters to historical levels (1956–1958, 1966–1969). Adult survival rates were fairly consistent between 1999 and 2000 and between 1999 and 2001; however, survival was greater in 2001 than in 2000. Reproductive rates ranged from 1.0 to 3.8 pups per female in 1999–2000 and were similar to historical numbers (1.0–4.2 pups per female). We found a decrease in pre-whelping kit fox density from the 1960s (0.12 foxes ? km –2 ) to 1999–2001 (0.04 foxes ? km –2 ); however, densities were similar between the current study and the 1950s (0.08 foxes ? km –2 ). Using 9 years of data, we found density dependence between reproductive rates of the current year and annual fox density from the previous year. Using 7 years of data, we found a slight correlation between kit fox annual density and a 1-year lag in leporid abundance, even though leporid abundance was lower during the present study than it was historically. Compared to historical levels, current small mammal abundance and species composition has changed in several habitats. Kit fox breeding density and annual density were inversely correlated with coyote ( Canis latrans ) density. Changes to the landscape at DPG, especially due to invasion of cheatgrass ( Bromus tectorum ) and addition of artificial water sources, have caused a change in available kit fox habitat and prey species, and have increased the abundance of coyotes, the kit fox's major competitor.     

Breeding biology and flower visitors of the rare White River penstemon, Penstemon scariosus var. albifluvis (Scrophulariaceae)

We studied the breeding system and flower visitors of White River penstemon, a rare endemic from the Uintah Basin of eastern Utah and western Colorado. Bagging treatments and hand-pollination treatments showed that Penstemon scariosus var. albifluvis has a mixed mating system: while some seeds and fruits are produced through selfpollination (both autogamy and geitonogamy), significantly more are produced when flowers are cross-pollinated. The primary flower visitors, and likely pollinators, were several species of native twig- and ground-nesting bees in the families Apidae, Halictidae, and Megachilidae. We found no differences in fruit or seed production between open-pollinated controls and hand-outcrossed flowers, suggesting that pollinator visits were sufficient to maximize female reproductive success. Management plans to conserve White River penstemon must recognize that full reproductive success of this rare plant taxon relies on a suite of pollinating bees, and that the species richness and abundances of bee visitors should be maintained.