Evaluation and classification of severity for 176 genes on an expanded carrier screening panel

Background

Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity-related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG).

Methods

Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene.

Results

Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four.

Conclusion

This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait-based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation.

     

Spawning patterns in the leopard grouper, <Emphasis Type="Italic">Mycteroperca rosacea</Emphasis>, in comparison with other aggregating groupers

We documented the spawning patterns of the leopard grouper, Mycteroperca rosacea, from April to June 2005 in the central Gulf of California, Mexico to draw comparisons with other aggregate-spawning groupers and provide information useful for management of their fishery. Adults formed spawning aggregations of 150 to >700 individuals at specific sites, and spawning occurred daily at these sites from late April through early June. Courtship occurred throughout the day, but spawning was restricted to the evening hours. Adults spawned in groups of 6–40 fish, and pair-spawning was not observed. The group-spawning behavior of adults and the gonosomatic indices of mature males (maximum = 7.2%) suggest that sperm competition was present. The site-specificity of leopard grouper spawning aggregations and diel spawning period were typical of most aggregating groupers, and the size and structure of these aggregations was similar to other species in the genus Mycteroperca. Leopard grouper behavior patterns were unusual in that spawning aggregations persisted for extended periods, spawning was not synchronized with the lunar cycle, and adults aggregated during non-spawning periods. The extensive duration and site-specificity of spawning aggregations and the propensity of M. rosacea to form aggregations year-round increases the vulnerability of the species to overfishing. Policies that limit harvest from these aggregations are needed to improve the management of leopard grouper fisheries in the Gulf of California.     

Metabolic suppression in thecosomatous pteropods as an effect of low temperature and hypoxia in the eastern tropical North Pacific

Many pteropod species in the eastern tropical North Pacific Ocean migrate vertically each day, transporting organic matter and respiratory carbon below the thermocline. These migrations take species into cold (15–10°?C) hypoxic water (<20?μmol O₂ kg^?1) at depth. We measured the vertical distribution, oxygen consumption and ammonia excretion for seven species of pteropod, some of which migrate and some which remain in oxygenated surface waters throughout the day. Within the upper 200?m of the water column, changes in water temperature result in a?~60–75?% reduction in respiration for most species. All three species tested under hypoxic conditions responded to low O₂ with an additional?~35–50?% reduction in respiratory rate. Combined, low temperature and hypoxia suppress the metabolic rate of pteropods by?~80–90?%. These results shed light on the ways in which expanding regions of hypoxia and surface ocean warming may impact pelagic ecology.     

Monitoring iodine-129 in air and milk samples collected near the Hanford Site: an investigation of historical iodine monitoring data

While other research has reported on the concentrations of (129)I in the environment surrounding active nuclear fuel reprocessing facilities, there is a shortage of information regarding how the concentrations change once facilities close. At the Hanford Site, the Plutonium-Uranium Extraction (PUREX) chemical separation plant was operating between 1983 and 1990, during which time (129)I concentrations in air and milk were measured. After the cessation of chemical processing, plant emissions decreased 2.5 orders of magnitude over an 8-year period. An evaluation of (129)I and (127)I concentration data in air and milk spanning the PUREX operation and post-closure period was conducted to compare the changes in environmental levels. Measured concentrations over the monitoring period were below the levels that could result in a potential annual human dose greater than 1 mSv. There was a measurable difference in the measured air concentrations of (129)I at different distances from the source, indicating a distinct Hanford fingerprint. Correlations between stack emissions of (129)I and concentrations in air and milk indicate that atmospheric emissions were the major source of (129)I measured in environmental samples. The measured concentrations during PUREX operations were similar to observations made around a fuel reprocessing plant in Germany. After the PUREX Plant stopped operating, (129)I concentration measurements made upwind of Hanford were similar to the results from Seville, Spain.     

Phytase,high-available-phosphorus corn,and storage effects on phosphorus levels in pig excreta

Phosphorus-based land application limits for manure have increased the importance of optimizing diet P management and accurately characterizing the bioavailability of manure P. We examined the effects of pig (Sus scrofa) diets formulated with high-available-P corn and phytase on P levels in excreta and slurry stored for 30, 60, 90, 120, and 150 d. Twenty-four pigs (approximately 14 kg each) were fed one of four low-P diets: (i) normal corn, no phytase (control); (ii) normal corn with 600 phytase units kg(-1) (PHY); (iii) high-available-P corn, no phytase (HAP); and (iv) high-available-P corn with 600 phytase units kg(-1) (HAP + PHY). Fresh fecal and stored slurry dry matter (DM) was analyzed for total phosphorus (TP), dissolved molybdate-reactive phosphorus (DRP), dissolved organic phosphorus (DOP), acid-soluble reactive phosphorus (ASRP), acid-soluble organic phosphorus (ASOP), and phytate phosphorus (PAP). The PHY, HAP, and HAP + PHY diets significantly (alpha = 0.05) decreased fecal TP 19, 17, and 40%, respectively, compared with the control. Dissolved reactive P was 36% lower in the HAP + PHY diet compared with the other diets. Relative fractions (percent of TP) of DRP, DOP, ASOP, and PAP in slurry generally decreased with storage time up to 150 d, with the largest decreases occurring within 60 to 90 d. Diet-induced differences in relative fractions of DRP, DOP, ASRP, and PAP were significant when averaged across storage times, simulating a mixed-age slurry. Relative fractions of DRP in simulated mixed-age slurries were higher in HAP and HAP + PHY diets, indicating that diet may affect P losses under certain P-based application scenarios.     

Empirical Estimation of Stream Discharge Using Channel Geometry in Low‐Gradient,Sand‐Bed Streams of the Southeastern Plains

Manning's equation is used widely to predict stream discharge (Q) from hydraulic variables when logistics constrain empirical measurements of in‐bank flow events. Uncertainty in Manning's roughness (n_M) is the major source of error in natural channels, and sand‐bed streams pose difficulties because flow resistance is affected by flow‐dependent bed configuration. Our study was designed to develop and validate models for estimating Q from channel geometry easily derived from cross‐sectional surveys and available GIS data. A database was compiled consisting of 484 Q measurements from 75 sand‐bed streams in Alabama, Georgia, South Carolina, North Carolina (Southeastern Plains), and Florida (Southern Coastal Plain), with six New Zealand streams included to develop statistical models to predict Q from hydraulic variables. Model error characteristics were estimated with leave‐one‐site‐out jackknifing. Independent data of 317 Q measurements from 55 Southeastern Plains streams indicated the model (Q = A_cR_H^0.6906S^0.1216; where A_c is the channel area, R_H is the hydraulic radius, and S is the bed slope) best predicted Q, based on Akaike's information criterion and root mean square error. Models also were developed from smaller Q range subsets to explore if subsets increased predictive ability, but error fit statistics suggested that these were not reasonable alternatives to the above equation. Thus, we recommend the above equation for predicting in‐bank Q of unbraided, sandy streams of the Southeastern Plains.