Anaya J.-M.,El Rosario University
Autoimmunity Reviews | Year: 2014
Autoimmune diseases (ADs) are chronic and heterogeneous conditions that affect specific target organs or multiple organ systems. The chronic nature of these diseases places a significant burden on the utilization of medical care, direct and indirect economic costs, and quality of life. ADs are observed in genetically susceptible individuals in whom their clinical expression is modified by permissive and protective environments occurring over time. These are complex traits, meaning that their inheritance does not follow a single-gene dominant or single-gene recessive Mendelian law, and thus that they are polygenic. ADs are often diagnosed according to classification criteria, however they share similar subphenotypes including signs and symptoms, non-specific autoantibodies and other immune changes, which are prone to taxonomic problems. Polyautoimmunity is defined as the presence of more than one AD in a single patient. When three or more ADs coexist, this condition is called multiple autoimmune syndrome (MAS), which represents the best example of polyautoimmunity as well as the effect of a single genotype on diverse autoimmune phenotypes. Its study will provide important clues to elucidate the common mechanisms of ADs (i.e., the autoimmune tautology). © 2014 Elsevier B.V.
Laissue P.,El Rosario University
Molecular and Cellular Endocrinology | Year: 2015
Premature ovarian failure (POF) is a frequent pathology affecting 1-1.5% of women under 40 years old. Despite advances in diagnosing and treating human infertility, POF is still classified as being idiopathic in 50-80% of cases, strongly suggesting a genetic origin for the disease. Different types of autosomal and X-linked genetic anomalies can originate the phenotype in syndromic and non-syndromic POF cases. Particular interest has been focused on research into non-syndromic POF causative coding variants during the past two decades. This has been based on the assumption that amino acid substitutions might modify the intrinsic physicochemical properties of functional proteins, thereby inducing pathological phenotypes. In this case, a restricted number of mutations might originate the disease. However, like other complex pathologies, POF might result from synergistic/compensatory effects caused by several low-to-mildly drastic mutations which have frequently been classified as non-functional SNPs. Indeed, reproductive phenotypes can be considered as quantitative traits resulting from the subtle interaction of many genes. Although numerous sequencing projects have involved candidate genes, only a few coding mutations explaining a low percentage of cases have been described. Such apparent failure to identify aetiological coding sequence variations might have been due to the inherent molecular complexity of mammalian reproduction and to the difficulty of simultaneously analysing large genomic regions by Sanger sequencing.The purpose of this review is to present the molecular and cellular effects caused by non-synonymous mutations which have been formally associated, by functional tests, with the aetiology of hypergonadotropic non-syndromic POF. Considerations have also been included regarding the polygenic nature of reproduction and POF, as well as future approaches for identifying novel aetiological genes based on next generation sequencing (NGS). © 2015 The Author.
Anaya J.-M.,El Rosario University
Autoimmunity Reviews | Year: 2012
The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed. © 2012 Elsevier B.V.
Montoya-Ortiz G.,El Rosario University
Autoimmune Diseases | Year: 2013
Senescence is a normal biological process that occurs in all organisms and involves a decline in cell functions. This process is caused by molecular regulatory machinery alterations, and it is closely related to telomere erosion in chromosomes. In the context of the immune system, this phenomenon is known as immunosenescence and refers to the immune function deregulation. Therefore, functions of several cells involved in the innate and adaptive immune responses are severely compromised with age progression (e.g., changes in lymphocyte subsets, decreased proliferative responses, chronic inflammatory states, etc.). These alterations make elderly individuals prone to not only infectious diseases but also to malignancy and autoimmunity. This review will explore the molecular aspects of processes related to cell aging, their importance in the context of the immune system, and their participation in elderly SLE patients. © 2013 Gladis Montoya-Ortiz.
Bocarejo D.,El Rosario University
Antipode | Year: 2012
The focus of this article is a paradox inherent in the political effects of spatial claims undertaken by multicultural policies in many nation states: though territory is considered as one of the primary means of achieving autonomy and self-determination, it is at the same time a mechanism that encloses difference. Through a combination of archival and ethnographic research I study the political effects of binding indigenous people's minority rights with indigenous reservations in Colombia. I focus on analyzing the legal ways in which an "ethnic indigenous type" has been attached to an "ethnic indigenous rural topos" in the jurisprudence of the Colombian Constitutional Court. I also examine how ethnic groups in the capital city of Bogotá have questioned the multicultural ideals of indigeneity and the romantic desires of what an indigenous place should look like. Ultimately, my intention is to draw attention both analytically and politically, to the necessity of more thorough analyses of the consequences of strict forms of spatializing ethnicity. © 2011 The Author Antipode © 2011 Antipode Foundation Ltd.