Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Micronutrient concentrations in respiratory syncytial virus and human metapneumovirus in Yemeni children

Background: Acute respiratory infections (ARI) cause significant childhood mortality. Nutritional homeostasis, particularly micronutrient levels, is important in modulating response to infection. More information is required regarding micronutrient levels in ARI viral infections, especially newly identified viruses such as human metapneumovirus (HMPV). Aim: To describe zinc, copper, selenium and vitamins A and E concentrations in children with respiratory syncytial virus (RSV) and/or HMPV in relation to levels of C-reactive protein (CRP). Methods: The presence of RSV/HMPV in nasopharyngeal aspirates (NPA) was identified in 246 children using RTPCR. Zinc, copper, selenium and vitamins A and E concentrations were measured using inductive coupled plasma mass spectrometry and high performance liquid chromatography. Results: 183 children had RSV, 39 had HMPV and 24 were co-infected. Zinc concentrations were lower in children with HMPV than in children with RSV or RSV/HMPV co-infection. Copper concentrations were lower in children with RSV than in children with RSV/ HMPV or HMPV and zinc/copper ratios were lower in children with HMPV/RSV or RSV than in children with HMPV alone. Retinol and alpha-tocopherol were lower in children with RSV than in children with HMPV. Most children had low selenium concentrations. Children with RSV and raised CRP (>5 mg/L) had higher copper and lower zinc/copper ratios than those with low CRP (<= 5 mg/L). Children with HMPV and raised CRP had higher copper and lower zinc concentrations than children with low CRP. Children with RSV/ HMPV and raised CRP had higher copper concentrations. Children with RSV/ HMPV and raised CRP had higher alpha-tocopherol concentrations. Conclusion: The profiles of micronutrients differ in children with RSV and HMPV and are confounded by CRP. These results may guide strategies for micronutrient supplementation in ARI

Acute phase proteins, interleukin 6, and heat shock protein 70 in broiler chickens administered with corticosterone

An experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CPN), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 d of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CPN, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP 70 density. Although CORT administration significantly increased feed intake, weight gain was significantly depressed. Administration of CORT also increased CORT, OVT, CPN, AGP, IL-6, and HSP 70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CPN and AGP. In conclusion, an elevation in CORT can induce an acute-phase response and HSP 70 expression. Thus, APP and HSP 70 may be of value as indicators of stress in poultry