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.

     

Imprecision of dose predictions for radionuclides released to the environment: An application of a Monte Carlo simulation technique

An evaluation of the imprecision in dose predictions has been performed using current dose assessment models and present knowledge of the variability or uncertainty in model parameter values. The propagation of parameter uncertainties is demonstrated using a Monte Carlo technique for elemental ¹³¹I transported via the pasture-cow-milk-child pathway. The results indicate that when site-specific information is not available the imprecision inherent in the predictions for this pathway is potentially large. Generally, the 99th percentile in thyroid dose for children was predicted to be approximately an order of magnitude greater than the median value. The potential consequences of the imprecision in dose for radiation protection purposes are discussed.     

The Importance of the Water Conservation Areas in the Everglades to the Endangered Wood Stork (Mycteria americana)

During 1985–1989, numbers of the endangered Wood Stork ( Mycteria americana ) in the Water Conservation Areas of the Everglades, Florida, showed an annual peak in February or March of 1233 to 7874 birds. The annual maxima are significantly greater in dry years than in wet years (P < 0.05). Most storks are nonbreeders and are found foraging in open habitats along the eastern and southern parts of Conservation Area 1 and Conservation Area 2A and along the west-central side of Conservation Area 3A. In dry years, large numbers move into the southern half of Conservation Area 3A. We estimated that in spring, the total southeastern United States population of Wood Storks is between 14,000 and 20,000 individuals. The annual maxima of the water conservation areas were at least 8% to 10% of the total southeastern U.S. population in wet years and possibly as much as 55% in dry years. The Water Conservation Areas appear to be critical foraging habitat for wintering storks, especially during drought years when most of the rest of south Florida is dry. Changes in the management of these areas could have a major impact on the status of storks throughout the southeastern United States.     

Adsorption and desorption of metolachlor and metolachlor metabolites in vegetated filter strip and cultivated soil

Previous studies have indicated that dissolved-phase metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(methoxy-1-methylethyl) acetamide] transported in surface runoff is retained by vegetative filter strips to a greater degree than either metolachlor oxanilic acid 12-[(2-ethyl-6-methylphenyl) (2-methoxy-1-methylethyl)amino]-2-oxo-acetic acid] (OA) or metolachlor ethanesulfonic acid [2-[(2-ethyl-6-methylphenyl) (2-methoxy-1-methylethyl-1)amino]-2-oxoethanesul-fonic acid] (ESA), two primary metabolites of metolachlor. Adsorption-desorption of ESA and OA in vegetated filter strip soil (VFSS) has not been evaluated, yet these data are required to assess the mobility of these compounds in VFSS. The objective of this experiment was to compare metolachlor, ESA, and OA adsorption and desorption parameters between VFSS and cultivated soil (CS). Adsorption and desorption isotherms were determined using the batch equilibrium procedure. With the exception of a 1.7-fold increase in organic carbon content in the VFSS, the evaluated chemical and physical properties of the soils were similar. Sorption coefficients for metolachlor were 88% higher in VFSS than in CS. In contrast, sorption coefficients for ESA and OA were not different between soils. Relative to metolachlor, sorption coefficients for ESA and OA were at least 79% lower in both soils. Metolachlor desorption coefficients were 59% higher in the VFSS than in the CS. Desorption coefficients for ESA and OA were not different between soils. Relative to metolachlor, desorption coefficients for ESA and OA were at least 66% lower in both soils. These data indicate that the mobility of ESA and OA will be greater than metolachlor in both soils. However, higher organic carbon content in VFSS relative to CS may limit the subsequent transport of metolachlor from the vegetated filter strip.