Genotype-genotype Interaction Research Articles

Ribozyme Mutagenic Evolution: Mechanisms of Survival.

Primeval populations replicating at high error rates required a mechanism to overcome the accumulation of mutations and information deterioration. Known strategies to overcome mutation pressures include RNA processivity, epistasis, selection, and quasispecies. We investigated the mechanism by which small molecular ribozyme populations can survive under high error rates by propagating several lineages under different mutagen concentrations. We found that every population that evolved without mutagen went extinct, while those subjected to mutagenic evolution survived. To understand how they survived, we characterized the evolved genotypic diversity, the formation of genotype-genotype interaction networks, the fitness of the most common mutants for each enzymatic step, and changes in population size along the course of evolution. We found that the elevated mutation rate was necessary for the populations to survive in the novel environment, in which all the steps of the metabolism worked to promote the survival of even less catalytically efficient ligases. Besides, an increase in population size and the mutational coupling of genotypes in close-knit networks, which helped maintain or recover lost genotypes making their disappearance transient, prevented Muller's ratchet and extinction.

Evidence of the involvement of the polymorphisms near MSX1 gene in non-syndromic cleft lip with or without cleft palate

ObjectiveNon-syndromic cleft lip, with or without cleft palate (NSCL/P) is a common craniofacial birth defect, characterised by an incomplete separation between nasal and oral cavities without any other congenital anomaly in humans. Several genes which play a role in cell differentiation, migration, growth and apoptosis, have been associated with clefting. The purpose of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) near MSX1 gene and NSCL/P among South Indian population. MethodsA case-control analysis of five single nucleotide polymorphisms near MSX1 gene (rs11726039, rs868257, rs6446693, rs1907998 and rs6832405) was carried out in 173 patients with NSCL/P and 176 unaffected controls to determine their association with NSCL/P. ResultsAll SNPs were polymorphic in the study population. Comparisons of allele and genotype frequencies revealed that the C variant allele and the TC/CC genotypes of rs11726039 was significantly higher in controls than in the NSCL/P group (OR: 0.63; 95% CI: 0.41−0.097; p=0.037). However, neither of these findings remained significant after Bonferroni correction for multiple comparisons. The frequencies of rs868257, rs6446693, rs1907998 and rs6832405 minor alleles and genotypes were similar between the control and NSCL/P groups. No significant linkage disequilibrium (LD) was observed. Genotype-genotype interaction and the haplotype analysis did not reveal any significant association with NSCL/P. ConclusionsThe study results were suggestive of a positive association between MSX1 rs11726039 and NSCL/P in the South Indian population.

Differential gene expression and alternative splicing in insect immune specificity.

BackgroundEcological studies routinely show genotype-genotype interactions between insects and their parasites. The mechanisms behind these interactions are not clearly understood. Using the bumblebee Bombus terrestris/trypanosome Crithidia bombi model system (two bumblebee colonies by two Crithidia strains), we have carried out a transcriptome-wide analysis of gene expression and alternative splicing in bees during C. bombi infection. We have performed four analyses, 1) comparing gene expression in infected and non-infected bees 24 hours after infection by Crithidia bombi, 2) comparing expression at 24 and 48 hours after C. bombi infection, 3) determining the differential gene expression associated with the bumblebee-Crithidia genotype-genotype interaction at 24 hours after infection and 4) determining the alternative splicing associated with the bumblebee-Crithidia genotype-genotype interaction at 24 hours post infection.ResultsWe found a large number of genes differentially regulated related to numerous canonical immune pathways. These genes include receptors, signaling pathways and effectors. We discovered a possible interaction between the peritrophic membrane and the insect immune system in defense against Crithidia. Most interestingly, we found differential expression and alternative splicing of immunoglobulin related genes (Dscam and Twitchin) are associated with the genotype-genotype interactions of the given bumblebee colony and Crithidia strain.ConclusionsIn this paper we have shown that the expression and alternative splicing of immune genes is associated with specific interactions between different host and parasite genotypes in this bumblebee/trypanosome model.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-1031) contains supplementary material, which is available to authorized users.

Probable role of β2‐adrenergic receptor gene haplotype in high‐altitude pulmonary oedema

The role of beta2-adrenergic receptor (ADRB2) in pulmonary oxygenation has been ascertained during altitude acclimatization, physical performance and lung fluid clearance, but little is known about its association with high-altitude pulmonary oedema (HAPE), a non-cardiogenic pulmonary oedema. In a case-control study, 110 unrelated HAPE patients (HAPE-p) and 143 unrelated HAPE-resistant (HAPE-r) controls matched on age and ethnicity were used to examine the association between eight single nucleotide polymorphisms (SNP) and disease. The eight SNP including three tag-SNP were genotyped from promoter and exonic regions of ADRB2. Robust methods for predicting geneotype-phenotype interactions, for example, multidimensional reduction (MDR) and moving-window haplotype analysis were applied. The haplotypes from 46A/G and 79C/G SNP of ADRB2 were associated with HAPE. The MDR model depicting disease association through genotype-genotype and genotype-phenotype interaction included SNP 46A/G, 79C/G and 523C/A. Its haplotype 46G_79C_523C was significantly overrepresented in HAPE-r (P = 0.0001; chi(2) = 14.95; OR = 4.52; 95% CI: 1.98-10.3). The global haplotype test showed significant association with HAPE (LRchi(2) = 86.69, P < 0.0001). A moving-window analysis revealed that haplotype -367C/T_46A/G_79C/G differed significantly between HAPE-p and HAPE-r (LRchi(2) = 22.5, P = 0.002). The MDR model depicted SNP 46A/G, 79C/G and 523C/A as the best combination predicting disease. conclusions: The haplotypes of ADRB2 consisting of the SNP, 46A/G and 79C/G, have a greater power for predicting HAPE.

Interacción entre genotipo y nutrición: interpretación de estudios epidemiológicos

EpidemiologicaL methods are increasingly used to assess the role of genetic factors and their interaction with environmental factors, in the occurrence of diseases in populations. Nutrition is one of the most relevant components of the interaction between the human being and the environment. Therefore, the interaction between susceptibility genotypes and nutritional risk factors has a great importance in the study of several chronic diseases. The aim of this article is to review different epidemiologic study designs and basic methods of analysis commonly used in the evaluation of the interaction between nutritional and genetic factors. These study designs and analytical methods are equally valid for the assessment of genotype-environment or genotype-genotype interaction.

β1-Adrenoceptor gene polymorphism predicts long-term changes in body weight

The genes controlling long-term weight changes are largely unknown. The beta1 (beta1)-adrenoceptor gene contains two nonsynonomous single nucleotide polymorphisms (SNPs), Ser49Gly and Gly389Arg, that both are functional in human cell lines. We investigated the influence of these two SNPs on short- and long-term changes in body mass index (BMI) in a population-based cohort of 761 women who were examined during pregnancy in 1984-1985 and 15 y thereafter. At entry, no genotype effect on BMI was found. After 15 y, the BMI of women carrying the Gly49-genotype (25.3+/-0.3 kg/m(2)) was higher (P<0.005) than that of Ser49-women (24.4+/-0.2 kg/m(2)). Also, the BMI-increase over 15 y was higher (P=0.018) in Gly49-women (3.3+/-0.2 kg/m(2)) than in Ser49-women (2.8+/-0.1 kg/m(2)). The odds ratio for being overweight after 15 y having the Gly49-genotype was 1.6 (confidence interval 1.1-2.3, P=0.01). No effect of SNP 389 alone on BMI was found but there was a genotype-genotype interaction. Those carrying the Gly49-Gly389 combination increased their BMI about 0.7 kg/m(2) more than other combinations (P=0.025). No genotype effect on BMI changes during pregnancy for either SNP was found. Polymorphism of the beta1-adrenoceptor gene influences long-term weight gain and the incidence of adult-onset overweight in women.