Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ～10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.     

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.     

Seedling size and survival for Chrysothamnus nauseosus

Seedling size and survival in relation to summer drought were examined for Chrysothamnus nauseosus growing under field and greenhouse conditions. In the field, summer survival rates were less than 2% annually for the three years monitored. The effect of initial seedling height on subsequent survival was examined in both the field and greenhouse by grouping seedlings into live and dead categories on each census date and comparing initial heights for seedlings in these categories. For a majority of the census dates, the initial height of surviving seedlings was greater than the initial height of those that subsequently died (significant differences ranged from 1 to 8 mm), indicating that seedlings that were taller at the initiation of the drought period had a higher probability of survival. In the greenhouse, taller seedlings had greater shoot and root biomass and rooting depth. Seedlings that are larger (i.e., taller and have greater aboveground biomass) in late spring appear to have a higher probability of surviving summer drought due to greater rooting depth and hence increased access to moisture in deeper soil layers. Seed availability and safe sites for germination were probably not limiting since large numbers of seedlings successfully germinated in a patchy pattern during the study period. Seedling size and probability of survival were not related to either seedling density or the distance to nearest seedling neighbor. Survival through summer drought appears to be the main limitation to seedling recruitment in this population.     

List of Idaho Scolytidae (Coleoptera) and notes on new records

Reported are 105 species of Scolytidae (Coleoptera) from Idaho. About one-third of these are rarely collected, of which 22 species are known from a single locality each. Twelve species reported from Idaho for the first time are: Carphoborus carri Swaine, C. sansoni Swaine, Phloeosinus hoferi Blackman, Conophthorus monophyllae Hopkins, Dryocoetes betulae Hopkins, Ips confuses (LeConte), Pityophthorus absonus Blackman, P. aquilus Blackman , P. blandus Blackman, P. deletus LeConte, P. sculptor Blackman, and Xyleborinus saxeseni (Ratzeburg). Significant extensions of the known distributions in Idaho are reported for seven other scolytids; Alniphagus aspericollis (LeConte), Dendroctonus murrayanae Hopkins, Phloeotribus lecontei Schedl, Procryphalus mucronatus (LeConte), Trypophloeus populi Hopkins, Xyleborus dispar (Fabricius), and X. intrusus Blandford. Xyleborus dispar especially needs study in anticipation that it may become increasingly important in Idaho fruit trees and other woody plants including ornamentals and shade trees.     

Dynamic landforms and plant communities in a pluvial lake basin

Mapping units were developed based on landform, soils, and plant communities for the 40,000 ha of salt desert vegetation located below the maximum level of pluvial Lake Gilbert in Grass Valley, Nevada. Lake plain, beach, and bar features of the pluvial lake provide the dominant landforms. Fine textured lake sediments have produced salt- and Na-affected soils. The distribution and structure of plant communities are related to depth of the groundwater table, fluctuations in this depth, and the salt content of the groundwater. Wind and water erosion combine to continually evolve new environments for colonization by plants in this ecosystem.       

Canids from the late Pleistocene of Utah

Two canids, Vulpes vulpes and Canis lupus , are recorded from shoreline deposits of Lake Bonneville in north central Utah. Both species are new records in the Pleistocene sediments of Utah and add to our scarce knowledge of the large carnivores that inhabited the shoreline environments of Lake Bonneville.     

Inventory of Utah crayfish with notes on current distribution

Crayfish distribution and composition in Utah are poorly documented. Based upon limited collections, the native Pacifastacus gambelii is widespread and often abundant in the Bear and Weber river drainages and is occasionally represented in smaller tributaries to the Great Salt Lake and to the Raft River. Pacifastacus leniusculus was collected from Utah County and Procambarus clarkii from Tooele County; the origin of these populations is not known. The nonnative crayfish Orconectes virilis is currently abundant in the Virgin, Price, and Duchesne river basins and the Glen Canyon, Flaming Gorge, Deer Creek, and Starvation reservoirs; it is expanding in Huntington North, Scofield, and Willard reservoirs. Further work is required to develop a more complete inventory and monitor the impacts on aquatic ecosystems of expanding nonnative crayfish populations. Surreptitious stockings can be dealt with only if the public is made aware of the adverse consequences of ill-conceived introductions.     

Comparative ecology of Sarcobatus baileyi and Sarcobatus vermiculatus in estern California

Greasewood ( Sarcobatus ) is a succulent-leaved, halophytic shrub of North American origin. The genus comprises 2 species: Sarcobatus baileyi and Sarcobatus vermiculatus. Sarcobatus vermiculatus is common throughout much of western North America, but S. baileyi is much more limited in distribution and was previously thought to be endemic to Nevada. Here we document and describe a S. baileyi population in eastern California, comparing its morphology and ecology to an adjacent S. vermiculatus population. Morphologically, S. baileyi is smaller in stature but produces larger seeds; however, fewer S. baileyi seeds germinated and survived a 20-day laboratory incubation compared to seeds of S. vermiculatus. Sarcobatus baileyi has higher leaf Na concentrations and operates at much lower plant water potentials than S. vermiculatus under field conditions; however, no significant differences were observed between the 2 species in long-term water-use efficiency as measured by leaf δ13C. Leaf Na concentrations were very low in both species. Overall, these species differ greatly in a number of traits that are consistent with the upland, nonphreatophytic character of S. baileyi, which is in stark contrast to the phreatophytic character of S. vermiculatus. Both species, however, are very salt tolerant and have low leaf N concentrations, indicating the low nutrient availability and the potentially high salinity of their extreme habitats. Further investigation of comparable desert ridge environments should be conducted to determine the extent of S. baileyi in eastern California, and common garden comparisons of the 2 species should be conducted to compare their ecophysiological traits. El ";greasewood” ( Sarcobatus ) es un arbusto halofítico de origen norteamericano con hojas suculentas. El género consta de dos especies: Sarcobatus baileyi y Sarcobatus vermiculatus. Aunque S. vermiculatus es común en gran parte del oeste de Norteamerica, S. baileyi tiene una distribución mucho más limitada. Se pensaba anteriormente que S. baileyi era endémico a Nevada, pero aquí documentamos y describimos una población en el este de California, comparando su morfología y ecología con las de una población adyacente de S. vermiculatus. Morfológicamente, S. baileyi es más pequeña de altura, pero produce semillas más grandes. Sin embargo, menos semillas de S. baileyi germinaron y sobrevivieron a una incubación en laboratorio de 20 días, comparado con S. vermiculatus. Sarcobatus baileyi opera con potenciales de agua mucho más bajos que los de S. vermiculatus en condiciones de campo y tiene mayores concentraciones de Na en sus hojas. No obstante, no se observaron diferencias significativas en la eficiencia del uso de agua a largo plazo, medida en términos de δ13C entre las 2 especies. Las concentraciones de N en las hojas fueron muy bajas en ambas especies. En general, estas especies difieren mucho en varios rasgos que son consistentes con el carácter no freatofítico de S. baileyi de tierras altas, el cual contrasta claramente con el carácter freatofítico de S. vermiculatus. Ambas especies, sin embargo, son bastante tolerantes a la sal y tienen concentraciones bajas de N en hojas, lo cual indica la baja disponibilidad de nutrientes y la potencial alta salinidad en sus hábitats extremos. Investigaciones adicionales en ambientes comparables de bordes desérticos deberán llevarse a cabo para determinar la extensión S. baileyi en el este de California, además de comparaciones de las dos especies en jardín para comparar sus rasgos ecofisiológicos.