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.

     

Correction to: Globally regional life cycle analysis of automotive lithium-ion nickel manganese cobalt batteries

Mitigation and Adaptation Strategies for Global Change - The article Globally regional life cycle analysis of automotive lithium-ion nickel manganese cobalt batteries written by Jarod C. Kelly,...     

Variation in pelagic larval growth of Atlantic billfishes: the role of prey composition and selective mortality

Atlantic blue marlin (Makaira nigricans) and sailfish (Istiophorus platypterus) larvae were collected from 10 monthly cruises (June–October 2003 and 2004) across the Straits of Florida to test (1) whether growth differed between the more productive western region near the Florida shelf, and the less productive eastern region toward the Bahamas, and (2) whether growth was related to prey consumption. Examination of larval sagittal otoliths revealed that instantaneous growth and daily growth during the first 2–3 weeks of life did not vary significantly between the two regions for either species. However, recent growth during the last two full days prior to collection was greater in the west for blue marlin larvae. Recent growth of blue marlin larvae <9 mm SL (primarily zooplanktivorous) was significantly related to prey composition (faster growth when higher proportions of Farranula copepods were consumed). Western larvae grew faster and had higher proportions of Farranula in their guts. Trends for sailfish larvae were not significant. In both species, comparison of early growth between <9 and ≥9 mm SL size groups indicated that growth trajectories diverged around 5–8 mm SL, the time when billfish larvae become capable of piscivory. Significantly faster growth of larger (older) larvae suggests that mortality was selective for fast growers and that the transition to piscivory may be a critical point in the early life of billfish.     

Population structure of two deep-sea hydrothermal vent gastropods from the Juan de Fuca Ridge, NE Pacific

The gastropods Lepetodrilus fucensis and Depressigyra globulus are abundant faunal components of animal communities at deep-sea hydrothermal vents along the Juan de Fuca Ridge in the NE Pacific. The population structure and recruitment pattern of both species were studied using modal decomposition of length–frequency distributions. Gastropod populations were collected from Axial Volcano and Endeavour Segment in 2002 and 2003. Polymodal size–frequency distributions, particularly at Axial Volcano vent sites, suggest a discontinuous recruitment pattern for D. globulus. In contrast, there were no distinct peaks visible in the distributions of L. fucensis, suggesting a continuous recruitment pattern for this species. For both species, distributions were positively skewed towards the smaller length–classes, implying post-settlement mortality is high. However, variations in growth, due to short- and long-term variability in environmental conditions in the hydrothermal vent habitat, as well as biological interactions, may also be influencing the distribution and abundance of subsequent life-history stages. Using maximum shell lengths from populations of known ages, the growth rate of L. fucensis was estimated as 9.6 μm day⁻¹, indicating adulthood would be reached in ∼1 year. Our results suggest that, despite occupying the same habitat, abundance and population structure are regulated by different biotic and abiotic processes in L. fucensis and D. globulus.