Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

© 2017 The Author(s). The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-a, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-a), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit residing either in the westernized environment of Denmark or in the rural area of Greenland. Our results showed that lung function was associated with genetic variants in ORMDL3, with polymorphisms having a significant interaction with place of residence. LT-a SNP rs909253 and rs1041981 were significantly associated with bronchitis risk. LT-a SNP rs2844484 was related to dermatitis susceptibility and was significantly influenced by the place of residence. The observed gene-phenotype relationships were exclusively present in one population and absent in the other population. We conclude that the genotype-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases

Can edaphic factors demonstrate landscape-scale differences in vegetation responses to grazing ?

We focused on land units as landscape characteristics and selected seven typical land units on a land catena comprising two areas of southern Mongolia. Hierarchical analysis was used to test the hypothesis that a land unit’s edaphic factors could explain the differences in vegetation responses to grazing. We established the survey sites at increasing distances from a livestock camp or water point within each land unit, then analysed patterns of change in floristic and functional compositions, vegetation volume and soil properties within each land unit to reveal differences in vegetation responses to grazing. We also examined the variations in floristic and functional compositions across land units to identify the edaphic factors that may underlie these differences. Changes in vegetation and soil properties at increasing distances from a camp or water point within each land unit were into three different patterns. Ordination techniques consistently indicated that land unit groups categorised using edaphic factors corresponded to those categorised using response patterns. Our study revealed that edaphic factors were responsible for the observed landscape-scale differences in vegetation responses to grazing in the study areas. In addition, the mechanisms underlying vegetation responses to grazing may have been primarily determined by edaphic factors

ATM promotes apoptosis and suppresses tumorigenesis in response to Myc

Overexpression of the c-myc oncogene contributes to the development of a significant number of human cancers. In response to deregulated Myc activity, the p53 tumor suppressor is activated to promote apoptosis and inhibit tumor formation. Here we demonstrate that p53 induction in response to Myc overexpression requires the ataxia-telangiectasia mutated (ATM) kinase, a major regulator of the cellular response to DNA double-strand breaks. In a transgenic mouse model overexpressing Myc in squamous epithelial tissues, inactivation of Atm suppresses apoptosis and accelerates tumorigenesis. Deregulated Myc expression induces DNA damage in primary transgenic keratinocytes and the formation of γH2AX and phospho-SMC1 foci in transgenic tissue. These findings suggest that Myc overexpression causes DNA damage in vivo and that the ATM-dependent response to this damage is critical for p53 activation, apoptosis, and the suppression of tumor development