Importance Of Genetic Variation Research Articles

Demography and environment modulate the effects of genetic diversity on extinction risk in a butterfly metapopulation

Linking genetic diversity to extinction is a common goal in genomic studies. Recently, a debate has arisen regarding the importance of genetic variation in conservation as some studies have failed to find associations between genome-wide genetic diversity and extinction risk. However, only rarely are genetic diversity and fitness measured together in the wild, and typically demographic history and environment are ignored. It is therefore difficult to infer whether a lack of an association is real or obscured by confounding factors. To address these shortcomings, we analyzed genetic data from 7,501 individuals with extinction data from 279 meadows and mortality of 1,742 larval nests in a butterfly metapopulation. We found a strong negative association between genetic diversity and extinction when considering only heterozygosity in models. However, this association disappeared when accounting for ecological covariates, suggesting a confounding between demography and genetics and a more complex role for heterozygosity in extinction risk. Modeling interactions between heterozygosity and demographic variables revealed that associations between extinction and heterozygosity were context-dependent. For example, extinction declined with increasing heterozygosity in large, but not currently small populations, although negative associations between heterozygosity, extinction, and mortality were detected in small populations with a recent history of decline. We conclude that low genetic diversity is an important predictor of extinction, predicting >25% increase in extinction beyond ecological factors in certain contexts. These results highlight that inferences about the importance of genetic diversity for population viability should not rely on genomic data alone but require investments in obtaining demographic and environmental data from natural populations.

Leiomyoma and the importance of genetic variation on genes related to the vasculature system - CβS, MTHFR, NOS3, CYBA, and ACE1

ObjectiveThe link between the systemic vasculature system and tumor biology is here investigated by studying the contribution of CβS (844ins68), MTHFR (677C > T), NOS3 (4a/4b), CYBA (C242T), and ACE1 (I/D) genes to leiomyoma onset, uterus and leiomyoma volumes. MethodsDNA samples from 130 women with leiomyomas and 527 from healthy women were genotyped by PCR or PCR-RFLP. Qui-square (χ2) or Fisher’s exact test were used to test associations. All the mentioned tests were performed in IBM® SPSS® Statistics Version 28. Statistical significance was defined as a p-value < 0.05. ResultsResults revealed that CβS (in the codominant and allelic models, p = 0.044 and, p = 0.015, OR = 1.791 [1.114–2.879], respectively), MTHFR (in the codominant, allelic and dominant models, p = 0.009, p = 0.002, OR = 0.585 [0.416–0.824] and p = 0.003, OR = 0.527 [0.346–0.802], respectively) and ACE1 (dominant model, p = 0.045, OR = 0.639 [0.411–0.992]) genes are associated with leiomyoma onset. NOS3 4a4a genotype is associated with a lower uterus volume (p = 0.004). This study also uncovers intriguing epistatic interactions among some genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the CC genotype (MTHFR) and (+/+) (CβS; p = 0.003), 4b4b (NOS3; p = 0.006, OR = 2.050 [1.223–3.439]) or DD (ACE1; p < 0.001, OR = 2.362 [1.438–3.880]) were shown to be associated with the disease, while 4a presence (NOS3) in epistasis with I presence (ACE1), increased the effect protection having just the I allele presence (p = 0.029, OR = 0.446 [0.214–0.930]). ConclusionsWe conclude that variation in genes related to the systemic vascular system can play a role in the onset and development of leiomyoma.

Assessing the invasive potential of different source populations of ragweed (Ambrosia artemisiifolia L.) through genomically informed species distribution modelling.

The genetic composition of founding populations is likely to play a key role in determining invasion success. Individual genotypes may differ in habitat preference and environmental tolerance, so their ability to colonize novel environments can be highly variable. Despite the importance of genetic variation on invasion success, its influence on the potential distribution of invaders is rarely investigated. Here, we integrate population genomics and ecological niche models (ENMs) into a single framework to predict the distribution of globally invasive common ragweed (Ambrosia artemisiifolia) in Australia. We identified three genetic clusters for ragweed and used these to construct cluster-specific ENMs and characterize within-species niche differentiation. The potential range of ragweed in Australia depended on the genetic composition and continent of origin of the introduced population. Invaders originating from warmer, wetter climates had a broader potential distribution than those from cooler, drier ones. By quantifying this change, we identified source populations most likely to expand the ragweed distribution. As prevention remains the most effective method of invasive species management, our work provides a valuable way of ranking the threat posed by different populations to better inform management decisions.

Impact of Genetic Variants in the Nicotine Metabolism Pathway on Nicotine Metabolite Levels in Smokers.

Nicotine metabolism is a major factor in nicotine dependence, with approximately 70% to 80% of nicotine metabolized to cotinine in Caucasians. Cotinine formation is catalyzed primarily by CYP2A6, which also converts cotinine to trans-3'-hydroxycotinine (3HC). The goal of the present study was to examine the effects of CYP2A6 deficiency on nicotine metabolism profiles in vivo and the importance of genetic variants in nicotine-metabolizing enzyme genes on urinary nicotine metabolites levels. Urine samples from 722 smokers who participated in the Singapore Chinese Health Study were analyzed using UPLC-MS/MS to detect nicotine and eight of its urinary metabolites, and a total of 58 variants in 12 genes involved in nicotine metabolism were investigated in 475 of these subjects with informative genotyping data. Urine samples stratified by the ratio of 3HC/cotinine exhibited a 7-fold increase in nicotine-N'-oxide, a 6-fold increase in nicotine-Glucuronide (Gluc), and a 5-fold decrease in 3HC-Gluc when comparing the lower versus upper 3HC/cotinine ventiles. Significant (P < 0.0001) associations were observed between functional metabolizing enzyme genotypes and levels of various urinary nicotine metabolites, including CYP2A6 genotype and levels of nicotine, nicotine-Gluc, nicotine-N'-oxide and 3HC, UGT2B10 genotype and levels of cotinine, nicotine-Gluc and cotinine-Gluc, UGT2B17 genotype and levels of 3HC-Gluc, FMO3 genotype and levels of nicotine-N'-oxide, and CYP2B6 genotype and levels of nicotine-N'-oxide and 4-hydroxy-4-(3-pyridyl)-butanoic acid. These data suggest that several pathways are important in nicotine metabolism. Genotype differences in several nicotine-metabolizing enzyme pathways may potentially lead to differences in nicotine dependence and smoking behavior and cessation.

Pharmacogenomics: Relevance and opportunities for clinical pharmacology

Pharmacogenomics: Relevance and opportunities for clinical pharmacology

Historical Demographic Processes Dominate Genetic Variation in Ancient Atlantic Cod Mitogenomes

Ancient DNA (aDNA) approaches have been successfully used to infer the long-term impacts of climate change, domestication, and human exploitation in a range of terrestrial species. Nonetheless, studies investigating such impacts using aDNA in marine species are rare. Atlantic cod (Gadus morhua), is an economically important species that has experienced dramatic census population declines during the last century. Here, we investigated 48 ancient mitogenomes from historical specimens obtained from a range of archeological excavations in northern Europe dated up to 6,500 BCE. We compare these mitogenomes to those of 496 modern conspecifics sampled across the North Atlantic Ocean and adjacent seas. Our results confirm earlier observations of high levels of mitogenomic variation and a lack of mutation-drift equilibrium—suggestive of population expansion. Furthermore, our temporal comparison yields no evidence of measurable mitogenomic changes through time. Instead, our results indicate that mitogenomic variation in Atlantic cod reflects past demographic processes driven by major historical events (such as oscillations in sea level) and subsequent gene flow rather than contemporary fluctuations in stock abundance. Our results indicate that historical and contemporaneous anthropogenic pressures such as commercial fisheries have had little impact on mitogenomic diversity in a wide-spread marine species with high gene flow such as Atlantic cod. These observations do not contradict evidence that overfishing has had negative consequences for the abundance of Atlantic cod and the importance of genetic variation in implementing conservation strategies. Instead, these observations imply that any measures toward the demographic recovery of Atlantic cod in the eastern Atlantic, will not be constrained by recent loss of historical mitogenomic variation.

Association of a genetic variant in the AKT gene locus and cardiovascular risk factors

Cardiovascular disease (CVDs) is the leading cause of morbidity and death worldwide. Most genetic variants could be identified by several genome-wide-association-studies (GWAS), including within genes encoding proteins involved in the AKT/PI3K pathways that are related with an increased risk of metabolic syndrome and CVDs. Therefore, due to the importance of genetic variants in the prognosis of diseases, we examined the genetic polymorphism of AKT-rs1130233 located on chromosome 14 with cardiovascular risk factors. In this cross-sectional study, 721 subjects recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort study. The participants including 257 subjects with metabolic syndrome, 144 subjects with cardiovascular disease and 320 subjects as a control group. Anthropometric, biochemical and demographic information measures were prepared. Dietary assessment was managed by 24h dietary recall. DNA extraction and genotyping were carried out by using the TaqMan real-time-PCR based method. The association of AKT rs1130233 locus with dietary intakes, metabolic syndrome and cardiovascular risk factors were assessed. Data were analyzed by using SPSS 21 software. Frequencies of genotypes AA, AG and GG of the AKT rs1130233 polymorphism were 12.6%, 44.5% and 42.9% in subjects with metabolic syndrome and 9.7%, 39.6% and 50.7% in subjects with cardiovascular disease, respectively. The frequency of allele A and G in cardiovascular disease and metabolic syndrome population were 29.5%, 70.5% and 34.8%, 65.2%, respectively. We have found no significant association between the AKT rs1130233 polymorphism with cardiovascular risk factors and metabolic syndrome. The results of dietary intake showed that the levels of phosphorus intake (p=0.008), calcium intake (p=0.007) and iodine intake (p=0.04) were different in subjects with and without metabolic syndrome. And also, energy intake was significantly different in subjects with cardiovascular disease (p=0.01) compared to the control group. Our findings suggest that AKT rs1130233 was not associated with the risk of metabolic syndrome and cardiovascular disease in the Iranian population. More studies are needed to validate our results. We did functional analysis, due to certify our investigation about value of this genetic biomarker for CVD risk.

Next generation biological control – an introduction

Next generation biological control – an introduction

Impact of the Genetic–Environment Interaction on the Dynamic of Nitrogen Pools in Arabidopsis

Mineral nutrient availability and in particular nitrogen abundance has a huge impact on plant fitness and yield, so that plants have developed sophisticated adaptive mechanisms to cope with environmental fluctuations. The vast natural variation existing among the individuals of a single species constitutes a great potential to decipher complex traits such as nutrient use efficiency. By using natural accessions of Arabidopsis thaliana that differ for their pattern of adaptation to nitrogen stress, we investigated the plant response to nitrate supplies ranging from 0.01 mM up to 50 mM nitrate. The biomass allocation and the different nitrogen pools in shoot and in roots were monitored to establish the nutrition status of each plant. Analysis of variation for these traits revealed genetic differences between accessions for their sensibility to nitrate availability and for their capacity to produce shoot biomass with the same nitrogen nutrition index. From the correlation matrix of all traits measured, a statistical model was formulated to predict the shoot projected area from the nitrate supply. The proposed model points out the importance of genetic variation with respect to the correlation between root thickness and amino acids content in roots. The model provides potential new targets in plant breeding for nitrogen use efficiency.

Cerebrovascular Disease Knowledge Portal: An Open-Access Data Resource to Accelerate Genomic Discoveries in Stroke.

Stroke is a leading cause of death and disability across the globe, affecting 15 million people each year.1 Stroke represents an archetypical common complex disease with both genetic and environmental determinants2,3 playing a role in its occurrence. The proportion of stroke risk that can be attributed to genetic variation has been estimated to be 30%.4–6 Although this estimate provides an indication of the overall importance of genetic variation in stroke, the key to developing new treatment strategies is to identify the specific genetic variants (mutations) that modify an individual’s risk of stroke. Genetic association studies (GWAS) seek to identify these variants and link them to specific genes, which, in turn, point to specific cellular processes to become therapeutic targets for drug development. In addition, newly discovered genetic risk loci can be used to improve existing phenotyping systems, enhance prediction tools aimed to identify high-risk patients, and aid in establishing causality for associations involving nongenetic exposures. Successfully identifying the range of genetic variants that cause stroke and leveraging these discoveries to reduce the suffering caused by this condition requires overcoming several key challenges. First, stroke is the final result of multiple different pathological processes and must, therefore, be accurately subtyped to identify underlying biology. Second, because large number of cases and controls are required to identify the culprit genetic variants, tens (even hundreds) of thousands of cases must be studied, requiring the collaboration of multiple centers, many of which use different ascertainment methods and criteria. Third, because genetic variation differs across the globe, representative populations from all ethnicities must be studied. Finally, all these data must be shared rapidly and widely to ensure the most expedited progress in research and enable investigators with the brightest ideas to utilize these data provided by patients to …

Unexplained cholestasis in adults and adolescents: diagnostic benefit of genetic examination

Objectives: A few adult and adolescent patients with even severe cholestatic liver disease remain unexplained after standard diagnostic work-up. We studied the value of genetic examination in such patients and developed a panel of eight genes with known cholestatic associations.Materials and methods: Thirty-three patients with unexplained cholestasis despite a thorough clinical work-up were examined for sequence variations in the coding regions of the ABCB4, ABCB11, ABCC2, ABCG5, ATP8B1, JAG1, NOTCH2, and UGT1A1 genes and the promoter region of UGT1A1 by massive parallel sequencing of DNA extracted from whole blood. Hepatologists and clinical geneticists evaluated the causal potential of genetic variants.Results: In 9/33 patients (27%), we identified genetic variants as a certain causal factor and in further 9/33 (27%) variants as a possible contributing factor. In most cases, a detailed family history was necessary to establish the importance of genetic variants. Genetic causes were identified in 6/13 women (46%) with intrahepatic cholestasis during pregnancy and persisting abnormal biochemistry after delivery.Conclusions: Our study suggests that a small number of well-known genetic variants are involved in at least 27–54% of patients with unexplained cholestasis. An expanded panel will likely explain more cases. This motivates genetic testing of these patients. Genetic testing, however, cannot stand alone but should be combined with a clinical genetic work-up in collaboration between hepatologists and clinical geneticists.

Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia.

Two single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia. Structural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain. Individuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, p adj = 0.01) and left (up to 45%, p adj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles. Our findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition.

Current status of pathway analysis in genome-wide association study.

Since the first publication in 2005, the genome-wide association study (GWAS) strategy has contributed significantly to the understanding of the mechanisms of human genetic diseases. Integrations of statistical methods and systematic biology are important means to explore the GWAS data. Pathway analysis establishes the importance of genetic variants from GWAS and provides insights into their biological significance. It is conducive in correlating the genetic variants, which have only small but interactive changes, to their importance in the biological pathways. At present, pathway analysis has been widely applied to studies of GWAS data, with relatively good results. In the meantime, various analytical methods are being developed and adapted for research on more types of complex data. In this review, we summarize the statistical methods of pathway analysis on GWAS data, and divide them into non-kernel methods and kernel methods. The non-kernel methods include gene set enrichment analysis (GSEA) and hierarchical Bayes prioritization (HBP) analysis, while kernel methods include linear kernel (LIN), identity-by-status kernel (IBS) and powered exponential kernel. We have summarized the calculation principles and features of these statistical methods to provide insights for further developments of new algorithms in GWAS research.

Genetic diversity of bovine diarrhea and mucosal disease virus

Abstract Bovine viral diarrhea virus (BVDV) is classified as a member of the Pestivirus genus of the Flaviviridae family. BVDV is one of the most important viral pathogens of ruminants worldwide, causing severe economic losses. Infection results in a wide range of clinical manifestations, ranging from mild respiratory disease to fetal death and mucosal disease. The virus particles are small and contain a singlestranded, positive-sense RNA molecule of approximately 12.3 kb with one large open reading frame flanked by two untranslated regions (5’UTR and 3’UTR). The polyprotein is proteolytically cleaved by viral and host proteases resulting in the formation of mature viral proteins. It is well established that BVDV strains show considerable genetic diversity. BVD viruses are classified as two species: BVDV-1 and BVDV-2. Quite recently, a new putative species, BVDV-3, was detected. The viruses exist as one of two biotypes: cytopathic or non- cytopathic, based on their activity in cell cultures. The phylogenetic analysis of the 5’UTR and Npro region has revealed at least 21 distinct subtypes of BVDV-1 and 4 subtypes of BVDV-2. Genetic diversity of BVD viruses has serious clinical implications such as immune evasion, increase of virulence, host range alteration and also affects the efficacy of vaccination programmes and diagnostic methods. 1. Introduction. 2. Characteristics of BVD virus. 3. Genetic diversity. 4. The importance of genetic variation. 5. Conclusion

Assessing hatching rates and the timing of hatching from plankton resting stages-an accurate and cost effective high throughput approach

Hatching rates and the timing of diapause termination are traits of high relevance in ecology and evolution of diapausing organisms. The analysis of hatching from dormant stages of planktonic organisms is an active area of research, which has been extensively studied in the context of phenology adjustment over latitude. Research on populations from temporary ponds has revealed temporal hatching profiles consisting of various hatching peaks, which is considered a risk-spreading strategy. Studies on outstanding scientific questions such as the evolution of risk-spreading strategies, the importance of genetic variation in hatching in an eco-evolutionary context, and the genomic underpinning of hatching phenotypes all require very large sample sizes. We therefore developed a high throughput approach for the assessment of hatching rates and temporal hatching profiles of resting stages from crustacean zooplankton. Our method consists in the photographic monitoring of resting stages hatching assays and the detection of hatchlings using free software for the automation of biological image analysis. We compared the performance of our new method with data obtained by traditional visual assessment of hatching. Our results indicate that our approach is highly accurate (>95%) and raises efficiency by a factor of 10 compared to non-automated visual assessment. Our new high throughput approach therefore allows to upscale the analysis of temporal hatching profiles and hatching success to sample sizes that will enable large-scale genomic studies or massive phenotyping and monitoring of these highly relevant traits in the future.

Genotypic richness predicts phenotypic variation in an endangered clonal plant.

Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species. However, the strong link between genotypic and phenotypic variation suggests that a range of genotypes is still the best case scenario for adaptation to and recovery from predicted environmental change.

Population genetic structure and ancestry of steelhead/rainbow trout (Oncorhynchus mykiss) at the extreme southern edge of their range in North America

Steelhead (Oncorhynchus mykiss) populations have declined dramatically in many parts of their range in North America, most critically in Southern California, where these anadromous trout are now classified as ‘Endangered’ under the United States Endangered Species Act. The widespread introduction of hatchery rainbow trout, the domesticated freshwater resident form of the species O. mykiss, is one factor threatening the long-term persistence of native steelhead and other trout populations. To identify where native fish of coastal steelhead lineage remained, we performed a population genetic analysis of microsatellite and SNP genotypes from O. mykiss populations at the extreme southern end of their range in Southern California, USA and Baja California, Mexico. In the northern part of this region, nearly all populations appeared to be primarily descendants of native coastal steelhead. However, in the southern, more urbanized part of this region, the majority of the sampled populations were derived primarily from hatchery trout, indicating either complete replacement of native fish or a strong signal of introgression overlaying native ancestry. Nevertheless, these genetically introgressed populations represent potentially critical genetic resources for the continued persistence of viable networks of O. mykiss populations, given the limited native ancestry uncovered in this region and the importance of genetic variation in adaptation. This study elucidates the geographic distribution of native trout populations in this region, and serves as a baseline for evaluating the impacts of hatchery trout on native O. mykiss populations and the success of steelhead conservation and recovery efforts.

Genotyping of non-human primate models: perspectives and challenges for the implementation of the &amp;quot;three R's&amp;quot;

Abstract. Although non-human primates (NHPs) represent only a minor fraction of all animals used in biomedical research, there is a continuous effort to further reduce, refine and replace research with NHPs in accordance with the principles of the three R's. Most of the NHP model species are genetically highly diverse, and significant variation occurs among populations of different geographic origins, particularly in macaques. Since such differences can considerably affect the outcome of biomedical experiments, genotyping represents a promising tool to refine research approaches and to reduce the number of NHPs in biomedical research. Accordingly, the European Primate Network (EUPRIM-Net) developed an anonymous online survey to evaluate possibilities and potential hindrances for the application of genotyping in NHP research. On the one hand, our results point to the importance of genetic variation in NHPs and the need to consider the genetic background for future research approaches. On the other hand, our survey identified several hindrances and limiting factors for the application of genotyping and its incorporation in research, primate husbandry and breeding. We provide some fundamental recommendations on how to meet these challenges and how genotyping can be efficiently used to refine NHP research and to reduce the number of NHPs in biomedical research in the long term.

Gene Pathway Analyses For Multiple Sclerosis Point To Cellular Adhesion Molecules As Susceptibility Factors

Evaluation of: Damotte V, Guillot-Noel L, Patsopoulos NA et al. A gene pathway analysis highlights the role of cellular adhesion molecules in multiple sclerosis susceptibility. Genes Immun. 15(2), 126–132 (2014). This study represents a gene pathway analysis focusing on the role of cellular adhesion molecules (CAMs) for susceptibility to multiple sclerosis (MS). The authors focused on CAM genes, since CAMs play an important role in the disruption of the blood–brain barrier, an early important mechanism in MS pathogenesis. Data from eight genome-wide association studies (GWAS) were analyzed together with protein interaction network data, and hereby a total of 70 genes involved in the CAM pathway were investigated. The authors identified five subnetworks in which significantly associated CAM genes were over-represented, including among others ITGA4, coding for the target of natalizumab. Thus, the importance of genetic variation in CAM genes for MS pathogenesis and therapy was further underlined. However, it may take some time before these genetic results can become clinically relevant.

Properties and action mechanisms of intravenous gammaglobulin

Intravenous immunoglobulins (IVIG) preparations have been used as a substitutive therapy for primary and secondary immunodeficiencies for many years; now it is well know that IVIG can have two other important and opposite functions: pro and anti-inflammatory, depending on its concentration. Low doses of IVIG exert proinflammatory activities, that require complement activation or binding via Fc fragment of IgG to IgG Fcγ specific receptors present on effector cells of innate immunity. On the other hand, administration of high IVIG doses has anti-inflammatory activity. This manuscript presents a revision of how IVIG IgG mediated this effects, how and upon which cells from the immune system acts, their capacity to scavenging complement fragments, the recently demonstrated anti-inflammatory activity of variable minor sialylated portion of IgG molecules and finally, the importance of genetic variation and expression of Fcγ receptors. To comprehend the mechanism of action of IVIG is fundamental, not only to obtain further improvements on therapeutic effectiveness, but also to discover new and unexpected capacities of this biological bomb known as IVIG.