Heritability of immunity traits and disease resistance of bighead catfish, Clarias macrocephalus Günther, 1864.

Disease outbreak is a major obstruction for intensive aquaculture worldwide. One of the promising solutions is genetic improvement by selective breeding, providing that a sufficient proportion of additive genetic variance (measured by heritability-h2) of disease resistance traits exists. In addition, immunity traits are of interest as potential indirect targeted traits for disease resistance. In this study, the genetic parameters of resistance to Aeromonas hydrophila were reported for the first time in the bighead catfish, Clarias macrocephalus Günther, 1864 which is an important parental species for the production of the commercially important hybrid C. macrocephalus × C. gariepinus. The analyses were performed on 736 data records obtained from 74 full-sib families (31 half-sib families) produced by factorial mating design. The results showed that the heritability of survival rate after disease (Aeromonas hydrophila) challenge (intraperitoneal injection with 0.1 ml containing 1 × 106 CFU/ml of A. hydrophila) was low to moderate (0.05 ±â€¯0.02-0.27 ±â€¯0.15). The immune traits (bactericidal activity-BA, lysozyme activity-LA, and alternative complement activity-ACH50) had low to moderate heritability (h2BA = 0.05 ±â€¯0.02; h2LA = 0.16 ±â€¯0.04; h2ACH50 = 0.31 ±â€¯0.06) while heritability of hematocrit (Hct) was also low (h2Hct = 0.17 ±â€¯0.04). The results suggested the possibility to improve resistance to A. hydrophila by selection, while the possibility to use immunity traits as indirect selection criteria for disease resistance is still unclear.

Multigenerational cohorts in patients with asthma and allergy.

Recent observations that disease risk can be transmitted across generations without the need for direct exposure of the child to the index environmental insult has sparked interest in transgenerational inheritance. Epigenetics describes processes that modify gene expression without a change in the nucleotide sequence. Epigenetic processes can be induced in response to environmental exposures, can influence disease risk, and might explain these multigenerational effects. In experimental models a number of epigenetic mechanisms have been identified that could mediate vertical transmission of epigenetic inheritance. However, relevance of these findings to human disease is not yet clear. An alternative model is one in which transgenerational inheritance of disease risk requires the presence of exposure-related diseases in the mother during pregnancy (termed induced epigenetic transmission model). A number of cross-sectional studies have investigated multigenerational effects in allergy and asthma. However, given the early-life origins of asthma and allergy, birth cohort studies are ideal to investigate the effect of genetic predisposition, epigenetics, and environmental exposures, avoiding pitfalls, such as recall bias and confounding by ongoing exposures, disease, and treatment. The well-characterized 3 generations of the Isle of Wight cohort include 2 consecutive birth cohorts, providing longitudinal data that can be studied for epigenetic transfer of information, such as the effect of grand parental smoking or exposure to other toxic compounds. Further large multigenerational birth cohorts are needed to establish the clinical relevance of this phenomenon and differentiate between vertical and induced transmission models, which might influence future preventive strategies.

[THE ENVIRONMENT AND AUTOIMMUNE DISEASES].

The immune system carefully distinguishes between self and non-self-components. Therefore, any small deviation of this balanced function may result in an autoimmune activity and harm against self-antigens (autoantigens). The link between autoimmune diseases and various heredity and environmental factors has been discussed in numerous studies. The infectious factor is still considered to be the most important environmental factor leading to the development of autoimmune disease. Recent studies associated new environmental factors to autoimmunity, such as excessive salt consumption. In this paper, we summarize the relationship between environmental factors and autoimmune diseases covering innovations in this field.

[ANTI-Hsp60 ANTIBODIES IN ARTERIAL HYPERTENTION DIFERENT DEGREE OF SEVERITY].

More than 12.1 million people with hypertension (32.2% of the adult population) were registered in Ukraine according to the official statistics on 1 January 2011. The etiopathogenesis of AH is not fully established. Hsp60 is the molecular chaperon/chaperonin, and it's expression significantly increases in response to different kinds of stress (emotional stress, infections, smoking etc). Elevated blood pressure is a mechanical stress to the endothelium and it can induce expression of heat-shock protein 60 (Hsp60) on the endothelial cell surface. Endothelial cells in the vessel wall can be damaged by (auto) immune reactions to Hsp60 present on the cell surface. Elevation of anti-Hsp60 in the circulation is associated with the presence and severity of coronary heart disease, atherosclerosis development, pathological changes in the small vessels of the brain etc etc. Specificity of the anti-Hsp60 antibodies and their role in the pathogenesis of AH has not been established. The aim of this work was to identify the level of anti-Hsp60 antibodies in the sera of patients with AH. 128 patients with AH were examined. To define level of anti-Hsp60 antibodies the sera 39 patients with AH, including 12 clinically healthy individuals (the family history are included the AH cases)--1 group, 19 patients with stage 2--2 group and 8 patients with stage 3--3 group were examined. The control group included 112 blood donors. Anti-Hsp60 antibodies in sera were determined by ELISA and immunobloting (Western-blotting). Recombinant piotein GroEL Escherihia coli (prokaryotic homologue of human Hsp60) and human Hsp60 were used as antigens. Average of levels of antibodies against GroEL and human Hsp60 in the serum of all groups twice exeeded the value of the control (P < 0.001). Antibodies to prokaryotic Hsp60 were prevailed in patients with AH. The seropositive serum to Hsp60 were detectived in patients, that had the risk of the AH complications by ELISA and immunoblotting. In addition, highly reactive IgG anti-Hsp60 antibodies purified by affinity chromatography from human sera of patients with AH recognized GroEL and human Hsp60 in immunoblotting. Elevated levels of anti-Hsp60 antibody in sera of patients with AH stage 3 correlated with pronounced changes in the target organs such as a massive recurrent hemorrhage into the retina, acute ischemic stroke, cardiosclerosis and angionephrosclerosis. It may indicate the involvement of anti-Hsp60 antibodies in the development of the target organ damage.

Estudo de mutações pontuais de BRCA1, BRCA2, CHEK2 e TP53 em pacientes com alto risco para câncer de mama e ovário hereditário / Study of point mutations of BRCA1, BRCA2, CHEK2, and TP53 in patients at high risk for hereditary breast and ovarian cancer

INTRODUÇÃO: BRCA1, BRCA2, CHEK2 e TP53 são os principais genes supressores tumorais associados às síndromes de câncer de mama e ovário hereditário (HBOC) e Li-Fraumeni (LFS/LFL). Em cânceres hereditários, a frequência de mutações em genes de baixa penetrância, como CHEK2, está entre 1-10%, entretanto nos genes de alta penetrância, como BRCA1/2 e TP53, a frequência é <1%. Até o momento, estudos feitos no Brasil apenas descreveram apenas o perfil de susceptibilidade genética de populações das regiões sul/sudeste. OBJETIVO: Analisar a ancestralidade e oito mutações dos genes BRCA1, BRCA2, CHEK2 e TP53 em 102 pacientes com alto risco para HBOC do Nordeste do Brasil...

INTRODUCTION: BRCA1, BRCA2, CHEK2 and TP53 are the mainly tumor suppressor genes associated with Hereditary Breast and Ovarian Cancer (HBOC) and Li-Fraumeni (LFS/LFL) syndromes. In hereditary cancers the frequency of mutations in susceptibility genes of low penetrance like CHEK2 is 1-10%, while in genes of high penetrance as BRCA1/2 and TP53 is <1%. Until now, the studies done in Brazil only described the susceptibility profile of populations from the south/southeast regions. OBJECTIVE: To analyze the ancestry and eight mutations of BRCA1, BRCA2, CHEK2 and TP53 genes in 102 patients at high-risk for HBOC from the Northeast of Brazil...

Association study by genetic clustering detects multiple inflammatory response loci in non-inbred mice

We tested the possibility to map loci affecting the acute inflammatory response (AIR) in an (AIRmax AIRmin) F2 intercrossmouse population derived from non-inbred parents, by association analysis in the absence of pedigree information. Using 1064 autosomal single nucleotide polymorphisms (SNPs), we clustered the intercross population into 12 groups of genetically related individuals. Association analysis adjusted for genetic clusters allowed to identify two loci, inflammatory response modulator 1 (Irm1) on chromosome 7 previously detected by genetic linkage analysis in the F2 mice, and a new locus onchromosome 5 (Irm2), linked to the number of infiltrating cells in subcutaneous inflammatory exudates (Irm1: P»6.3 10 7; Irm2: P»8.2 10 5) and interleukin 1 beta (IL-1b) production (Irm1: P»1.9 10 16; Irm2: P»1.1 10 6). Use of a polygenic model based on additive effects of the rare alleles of 15 or 18 SNPs associated at suggestive genome-wide statistical threshold(Po3.4 10 3) with the number of infiltrating cells or IL-1b production, respectively, allowed prediction of the inflammatory response of progenitor AIR mice. Our findings suggest the usefulness of association analysis in combination with genetic clustering to map loci affecting complex phenotypes in non-inbred animal species.