Identification of Medically Actionable Secondary Findings in the 1000 Genomes

The American College of Medical Genetics and Genomics (ACMG) recommends that clinical sequencing laboratories return secondary findings in 56 genes associated with medically actionable conditions. Our goal was to apply a systematic, stringent approach consistent with clinical standards to estimate the prevalence of pathogenic variants associated with such conditions using a diverse sequencing reference sample. Candidate variants in the 56 ACMG genes were selected from Phase 1 of the 1000 Genomes dataset, which contains sequencing information on 1,092 unrelated individuals from across the world. These variants were filtered using the Human Gene Mutation Database (HGMD) Professional version and defined parameters, appraised through literature review, and examined by a clinical laboratory specialist and expert physician. Over 70,000 genetic variants were extracted from the 56 genes, and filtering identified 237 variants annotated as disease causing by HGMD Professional. Literature review and expert evaluation determined that 7 of these variants were pathogenic or likely pathogenic. Furthermore, 5 additional truncating variants not listed as disease causing in HGMD Professional were identified as likely pathogenic. These 12 secondary findings are associated with diseases that could inform medical follow-up, including cancer predisposition syndromes, cardiac conditions, and familial hypercholesterolemia. The majority of the identified medically actionable findings were in individuals from the European (5/379) and Americas (4/181) ancestry groups, with fewer findings in Asian (2/286) and African (1/246) ancestry groups. Our results suggest that medically relevant secondary findings can be identified in approximately 1% (12/1092) of individuals in a diverse reference sample. As clinical sequencing laboratories continue to implement the ACMG recommendations, our results highlight that at least a small number of potentially important secondary findings can be selected for return. Our results also confirm that understudied populations will not reap proportionate benefits of genomic medicine, highlighting the need for continued research efforts on genetic diseases in these populations.     

Seasonal variations on water relations ofAmygdalus communis L. under drip irrigated and non irrigated conditions

Almond plants (Amygdalus communis L.) of the Garrigues variety were grown in the field drip irrigated and rainfed. Leaf water potential (Ψ) and leaf conductance (g₁) were determined throughout one growing season. Pre-dawn measurement for Ψ in the irrigated treatment was consistent through the growing season, whereas in the rainfed treatment it decreased gradually. Ψ values at midday (Ψ minimum) was closely dependent on atmospheric evaporative demand, and their recovery was quicker in the wet treatment than in the dry. The g₁ values were higher in the wet than dry treatments, decreasing in both cases by leaf ageing. Maximum values for g₁ were reached when evaporative demand was highest in the day. The relationship between Ψ and g₁ revealed a decrease in the hysteresis throughout the growing season, being most marked in the dry treatment. The results highlight the close dependence of Ψ and g₁ on evaporative demand, leaf ageing and irrigtion treatment during the growing season.     

Leaf water potential and leaf conductance during the growing season in almond trees under different irrigation regimes

Seasonal changes in leaf water potential (Φ) and leaf conductance (g₁) were determined in almond trees under different irrigation regimes. The development of water stress in the rainfed treatment induced a specific seasonal dynamics of Φ values and an important reduction in g₁ values. A decrease in g₁ values occurred independently of the irrigation treatment through the growing season. No statistically significant differences were obtained in g₁ values within the drip irrigated treatments.     

Endoderm-secreted factor stimulates growth of embryonal carcinoma stem cells

Summary Stem cells of the embryonal carcinoma cell line called H6 can be induced to differnetiate to endoderm-like cells by retinoic acid (3×10⁻⁶ M). We have detected a diffusible and stable factor which is secreted by H6 endoderm-like cells and stimulates the growth of H6 stem cells. The stimulation by the endoderm-like cells is considereably greater than that by mouse fibroblasts or H6 stem cells themselves. No reciprocal stimulation of endoderm-like cells by stem cells occurs. Part but not all of the stimulation might be due to extracellular matrix proteins or to insulin-like growth factor type 2, each of which also stimulates the growth of H6 stem cells. Insulin causes no such stimulation. This work was supported by research rant no. CA-16754 from the National Cancer Institute to J. W. L. E. L. G. was supported by an American Heart Association Medical Student Research Award. Editor's Statement This paper presents a good example of cooperativity between undifferentiated teratoma stem cells and differentiated parietal endoderm-derived countrparts in terms of growth support. It raises the interesting question of the relationship between factors produced by paprietal and visceral endoderm cells. Gordon H. Sato     

A new species of Sicyos (Cucurbitaceae) from Chiapas,Mexico

Sicyos motozintlensis is described from the vicinity of Motozintla de Mendoza, Chiapas. It shows a strong similarity toS. chiriquensis Hammel & D’Arcy from Panama.