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      Multilocus microsatellite typing of Leishmania and clinical applications: a review Translated title: Typage microsatellite multilocus des Leishmania et applications cliniques : une synthèse

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          Microsatellite markers have been used for Leishmania genetic studies worldwide, giving useful insight into leishmaniasis epidemiology. Understanding the geographic distribution, dynamics of Leishmania populations, and disease epidemiology improved markedly with this tool. In endemic foci, the origins of antimony-resistant strains and multidrug treatment failures were explored with multilocus microsatellite typing (MLMT). High genetic variability was detected but no association between parasite genotypes and drug resistance was established. An association between MLMT profiles and clinical disease manifestations was highlighted in only three studies and this data needs further confirmation. At the individual level, MLMT provided information on relapse and reinfection when multiple leishmaniasis episodes occurred. This information could improve knowledge of epidemiology and guide therapeutic choices for active chronic visceral leishmaniasis, the disease form in some HIV-positive patients.

          Translated abstract

          Les marqueurs microsatellites ont été utilisés pour les études génétiques de Leishmania dans le monde et ont procuré un aperçu utile de l’épidémiologie des leishmanioses. La compréhension de la répartition géographique, de la dynamique des populations de Leishmania et de l’épidémiologie de la maladie est nettement améliorée avec cet outil. Dans les foyers d’endémie, les origines des souches résistantes à l’antimoine et des échecs de traitement avec plusieurs médicaments ont été explorées par typage microsatellite multilocus (MLMT). Une grande variabilité génétique a été détectée, mais aucune association entre les génotypes parasitaires et la résistance aux médicaments n’a été prouvée. Une association entre les profils MLMT et les manifestations cliniques de la maladie a été mise en évidence dans seulement trois études et ces données nécessitent d’être confirmées. Au niveau individuel, le MLMT fournit des informations sur la rechute et la réinfection lorsque plusieurs épisodes de leishmaniose ont eu lieu. Cette information pourrait améliorer la connaissance de l’épidémiologie et guider le choix thérapeutique pour la leishmaniose viscérale chronique active, la forme de la maladie chez certains patients VIH-positifs.

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          Most cited references 54

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          The relationship between leishmaniasis and AIDS: the second 10 years.

          To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.
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            Evolutionary dynamics of microsatellite DNA.

            Within the past decade microsatellites have developed into one of the most popular genetic markers. Despite the widespread use of microsatellite analysis, an integral picture of the mutational dynamics of microsatellite DNA is just beginning to emerge. Here, I review both generally agreed and controversial results about the mutational dynamics of microsatellite DNA. Microsatellites are short DNA sequence stretches in which a motif of one to six bases is tandemly repeated. It has been known for some time that these sequences can differ in repeat number among individuals. With the advent of polymerase chain reaction (PCR) technology this property of microsatellite DNA was converted into a highly versatile genetic marker (Litt and Luty 1989; Tautz 1989; Weber and May 1989). Polymerase chain reaction products of different length can be amplified with primers flanking the variable microsatellite region. Due to the availability of high-throughput capillary sequencers or mass spectrography the sizing of alleles is no longer a bottleneck in microsatellite analysis. The almost random distribution of microsatellites and their high level of polymorphism greatly facilitated the construction of genetic maps (Dietrich et al. 1994; Dib et al. 1996) and enabled subsequent positional cloning of several genes. Almost at the same time, microsatellites were established as the marker of choice for the identification of individuals and paternity testing. The high sensitivity of PCR-based microsatellite analysis was not only of great benefit for forensics, but opened completely new research areas, such as the analysis of samples with limited DNA amounts (e.g., many social insects) or degraded DNA (e.g., feces, museum material) (Schlötterer and Pemberton 1998). More recently, microsatellite analysis has also been employed in population genetics (Goldstein and Schlötterer 1999). Compared with allozymes, microsatellites offer the advantage that, in principle, several thousand potentially polymorphic markers are available. Nevertheless, the application of microsatellites to population genetic questions requires a more detailed understanding of the mutation processes of microsatellite DNA as the evolutionary time frames covered in population genetics are often too long to allow novel microsatellite mutations to be ignored. Additional interest in the evolution of microsatellite DNA comes from the discovery that trinucleotide repeats, a special class of microsatellites, are involved in human neurodegenerative diseases (e.g., fragile X and Huntington's disease). A detailed understanding of the processes underlying microsatellite instability is therefore an important contribution toward a better understanding of these human neurodegenerative diseases.
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              Microsatellite mutations in the germline: implications for evolutionary inference.

               H. Ellegren (2000)
              Microsatellite DNA sequences mutate at rates several orders of magnitude higher than that of the bulk of DNA. Such high rates mean that spontaneous mutations that form new-length variants can realistically be seen in pedigree analysis. Data on observed mutation events from various organisms are now accumulating, allowing inferences on DNA sequence evolution to be made through an unusually direct approach. Here I discuss and integrate microsatellite mutation data in an evolutionary context. A striking feature of the mutation process is that it seems highly heterogeneous, with distinct differences between species, repeat types, loci and alleles. Age and sex also affect the mutation rate. Within genomes at equilibrium, the microsatellite-length distribution is a delicate balance between biased mutation processes and point mutations acting towards the decay of repetitive DNA. Indeed, simple repeats do not evolve simply.

                Author and article information

                EDP Sciences
                05 May 2015
                : 22
                : ( publisher-idID: parasite/2015/01 )
                [1 ] Aix-Marseille Université Marseille France
                [2 ] INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la Relation Hôte Pathogènes 06204 Nice Cedex 3 France
                [3 ] UMR MIVEGEC IRD 224-CNRS 5290, Universités Montpellier 1 et 2 Montpellier France
                [4 ] Université de Nice Sophia Antipolis, Faculté de Médecine 06107 Nice Cedex 2 France
                [5 ] Parasitologie-Mycologie, Centre Hospitalier Universitaire l’Archet CS 23079 06202 Nice Cedex 3 France
                Author notes
                [* ]Corresponding author: pomares.c@ 123456chu-nice.fr
                parasite140122 10.1051/parasite/2015016
                © S. Aluru et al., published by EDP Sciences, 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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