Multiple Genes Influence BMI on Chromosome 7q31–34: The NHLBI Family Heart Study

The National Heart, Lung, and Blood Institute Family Heart Study (FHS) genome‐wide linkage scan identified a region of chromosome 7q31–34 with a lod score of 4.9 for BMI at D7S1804 (131.9 Mb). We report the results of linkage and association to BMI in this region for two independent FHS samples. The first sample includes 225 FHS pedigrees with evidence of linkage to 7q31–34, using 1,132 single‐nucleotide polymorphisms (SNPs) and 7 microsatellites. The second represents a case–control sample (318 cases; BMI >25 and 325 controls; BMI <25) derived from unrelated FHS participants who were not part of the genome scan. The latter set was genotyped for 606 SNPs, including 37 SNPs with prior evidence for association in the linked families. Although variance components linkage analysis using only SNPs generated a peak lod score that coincided with the original linkage scan at 131.9 Mb, a conditional linkage analysis showed evidence of a second quantitative trait locus (QTL) near 143 cM influencing BMI. Three SNPs (rs161339, rs12673281, and rs1993068) located near the three genes pleiotrophin (PTN), diacylglycerol (DAG) kinase iota (DGKι), and cholinergic receptor, muscarinic 2 (CHRM2) demonstrated significant association in both linked families (P = 0.0005, 0.002, and 0.03, respectively) and the case–control sample (P = 0.01, 0.0003, and 0.03, respectively), regardless of the genetic model tested. These findings suggest that several genes may be associated with BMI in the 7q31–34 region.     

Genetic associations with micronutrient levels identified in immune and gastrointestinal networks

The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physiological processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6–14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_PC1 levels were significantly associated with (1) single-nucleotide polymorphisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune functions, as identified in a global network of metabolic/protein–protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene–nutrient interactions. The systems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0408-4) contains supplementary material, which is available to authorized users.     

Fecal mutagens and Bacteroides fragilis levels in the feces of dimethylhydrazine-treated rats: influence of diet

In a study designed to investigate the effects of dietary synergisms on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis, fecal pellets were examined for the presence of direct-acting fecal mutagens and levels of Bacteroides fragilis group organisms. Intraperitoneal injections of DMH at 10 mg/kg were given for 16 weeks (weeks 3-18) to 160 male F344 rats consuming 4 supplemental dietary factors in all possible combinations. The dietary factors examined were wheat bran (15%), cholesterol (1%), beef tallow (18%) and indole-3-carbinol (IC) (0.1%). Feces were collected 3, 10, 17, 24 and 31 weeks after commencing the dietary treatments and dichloromethane extracts were assayed using the Salmonella typhimurium TA100 without metabolic activation. The numbers of B. fragilis group organisms were enumerated in feces collected at the same time. Most feces samples were negative for mutagens but extracts from weeks 17-31 showed a significant mutagenic response from the IC factor in the diet. The fecal levels of B. fragilis were significantly increased by the inclusion of cholesterol in the diets. The B. fragilis counts and fecal mutagen production were not correlated (r = 0.09), although species of the B. fragilis group have been implicated in the production on human fecal mutagens.     

Ultrastructural ontogeny of leaf cavity trichomes inAzolla implies a functional role in metabolite exchange

Summary Anabaena azollae is associated with two types of multicellular epidermal trichomes inAzolla leaf cavities, the simple and branched hairs. The observation of transfer cell ultrastructure in some hair cells led to speculation that the cavity hairs might participate in metabolite exchange between the symbionts. The developmental ontogeny of cavity trichomes is described here, using transmission electron microscopy, with a goal of improving our understanding of possible functions of these structures in the symbiosis. The observations have established that all cells of simple and branched hairs develop the structural characteristics of transfer cells, but not simultaneously. Rather, there is an acropetal succession of transfer cell ultrastructure beginning in terminal cells, moving to body cells where present, and ending in stalk cells. The transfer cell stage is followed immediately by senescence in all hair cells. The timing of transfer cell differentiation, considered together with information from other studies, suggests that branched hairs may be involved in exchange of fixed nitrogen between the symbionts, while simple hairs may participate in exchange of fixed carbon fromAzolla toAnabaena. Contribution no. 869 from the Battelle-C. F. Kettering Research Laboratory.     

Effects of season and physical condition on the gastrointestinal helminth community of white-tailed deer from the Texas Edwards Plateau

Eighty-six adult female white-tailed deer, Odocoileus virginianus (Zimmermann), collected over a 12-mo period in the Texas Edwards Plateau, harbored six species of nematodes (Haemonchus contortus, Gongylonema pulchrum, Oesophagostomum venulosum, Ostertagia ostertagi, Cooperia sp., and Apteragia odocoilei), and two cestodes (Moniezia sp. and Taenia hydatigena). The patterns of distribution of the three common species of gastrointestinal helminths (H. contortus, O. venulosum, and G. pulchrum) were overdispersed. When analyzed for the main and interactive effects of the extrinsic and intrinsic variables of season and physical condition, respectively, aggregated abundances in H. contortus and O. venulosum appeared to result from the main effect of seasonal changes operating over the collective populations of these two species rather than from the intrinsic factor of physical condition operating within selected subpopulations. Abomasal parasite counts do not appear to be a useful index for monitoring herd condition of white-tailed deer from this geographic region.     

Elaeophorosis in Barbary sheep and mule deer from the Texas Panhandle

Adult Elaeophora schneideri were recovered from the common carotid artery and its branches in 14 of 14 mule deer, Odocoileus hemionus, and 3 of 9 Barbary sheep or aoudads, Ammotragus lervia, from Palo Duro Canyon in the Texas Panhandle. Gross cutaneous lesions attributable to elaeophorosis in the Barbary sheep varied from small circumscribed scars up to 10 cm in diameter usually on the poll or orbital region to extensive proliferative irregular encrustations on the frontal, temporal and orbital regions, sometimes extending to the ears and muzzle. Individual lesions varied from slate-gray scarred areas to brown proliferative edematous and hyperemic encrustations, sometimes with depigmented pustules a few millimeters in diameter. Microscopic lesions ranged from granulation tissue to severe pyogranulomatous reactions with neutrophils, eosinophils, lymphocytes and plasma cells as the primary infiltration. Foreign body giant cells and/or microfilariae were not observed. Microscopic changes in the carotid arteries and their branches were limited to small villous projections on the intimal surface apparently resulting from medial hyperplasia. Cutaneous lesions attributable to elaeophorosis were not observed in mule deer. Histopathologic lesions in the carotid arteries of mule deer were similar to those observed in Barbary sheep. The comparative pathology of elaeophorosis in various hosts is reviewed and discussed in terms of its pathology in Barbary sheep. The potential ramifications of this infection on the expanding aoudad population in the southwestern United States require that elaeophorosis be considered in the management of this species, particularly in areas with sympatric mule deer populations.     

Cryopreservation of immature embryos of Theobroma cacao

Immature, white zygotic embryos of Theobroma cacao L. (cacao) retained the ability to produce callus and to undergo somatic embryogenesis after slow hydrated freezing and desiccated fast freezing in liquid nitrogen. The highest rate of somatic embryogenesis occurred in embryos which were precultured on a medium containing 3% sucrose, frozen slowly with cryoprotectants before exposure to liquid nitrogen, and recovered on a medium containing 3 mg/liter NAA. Embryos precultured on media containing sucrose increasing to 21% had a higher rate of survival but were less embryogenic after freezing. These results suggest that immature embryos might be used for long-term germplasm storage of T. cacao germplasm.     

Serologic survey of selected zoonotic disease agents in black-tailed jack rabbits from western Texas

A serologic survey for the agents of Rocky Mountain spotted fever (RMSF) (Rickettsia rickettsii), Borrelia spp. including the causative agent for Lyme disease (Borrelia burgdorferi), and plague (Yersinia pestis) was conducted on blood samples collected from 30 and 46 black-tailed jack rabbits (Lepus californicus) from an urban environment in Lubbock, Texas (USA) during winter 1987 and the following spring 1988, respectively. Antibody titers to the agents of RMSF and borreliosis were detected in sera of 28 and 1% of the jack rabbits, respectively. Neither organisms (rickettsiae and/or spirochetes) nor their associated antigens were detected in any of the tissue or whole blood samples; plague antibodies were not detected in the 76 jack rabbits sampled. Four of 18 ticks (Dermacentor parumapertus) removed from 12 jack rabbits were positive for RMSF using the fluorescent antibody test. The black-tailed jack rabbit is a common wildlife species living in close proximity to higher density human populations in many areas of the southwestern United States. Our results indicate the potential importance of urban populations of this mammal as reservoirs for at least one important zoonotic disease, RMSF, in western Texas.