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Università Degli Studi Di Milano Scuola Di Dottorato in Medicina Molecolare
| Content Provider | Semantic Scholar |
|---|---|
| Author | Xxvii, Ciclo Accademico, Anno Forni, Diego Comi, Giacomo Pietro Clerici, Mario |
| Copyright Year | 2010 |
| Abstract | INTRODUCTION Genetic diversity is generated by a combination of different evolutionary processes, including mutation, genetic drift, migration, and natural selection.It is well known that natural selection acts on a specific locus\variant, whereas demographic effects act on all loci in the same way; also the selection is expected to be focused on genomic positions that have a functional role. Importantly, the selected variants targeted by selection may not only have a functional role but can correlate with predisposition or protection to some specific diseases. They can therefore be prioritized in screenings for association with diseases and infections; indeed, genetic variants that are advantageous tend to increase in frequency in the population, while deleterious mutations tend to be eliminated. To identify selection, intra and inter species approaches are usually applied; comparing orthologous genes among different species is a successful approach to detect positive selection acting over long evolutionary timescales; on the other hand, comparing genetic variation within human populations may underline more recent adaptive events. Genes related to immune system are among the most studied genes from an evolutionary point of view: it is now established that infections have been acting as a major selective pressure on humans and, most likely, on all living organisms. Thus, the interactions between hosts and pathogens have shaped the genetic diversity over time on both sides: moreover the continuous arm race between hosts and pathogens creates a competition of co-evolving genes that develop adaptations and counter-adaptations against each other. Therefore, it is important to evaluate the level of genetic variation that determines advantageous phenotypic traits to identify genomic regions/positions underlying diversity and adaptation. My first study was focused on molecules involved in the regulation of T-cell activation. The activation of T lymphocytes is a complex phenomenon that is mediated by the interaction of a number of proteins expressed on the surface of T lymphocytes and antigen presenting cells (APC).Several pathogens have evolved strategies that specifically target these genes to either invade the host or to reduce the response of the immune system. Thus, on one hand,these genes have been engaged in a constant conflict with a large number of pathogens and play a fundamental role during infections; on the other hand, genetic variation at these loci has a potential impact on the development of autoimmune and inflammatory conditions. In the second study I focused on molecules involved in the antigen processing and presentation pathway (APP).Whatever the nature of the presenting molecule, the limited dimension of its cleft makes it impossible for macro molecules to be presented: only fragments (antigens) derived from the lysis of such molecules can be nested in the cleft. This antigenic repertoire is generated by the antigen processing and presentation pathway. Another study focused on the contact system and the molecules involved in this pathway. In particular this pathway represents a link between the coagulation and inflammatory responses, two systems central to host survival in the face of tissue damage and infection. Finally, the last molecules analyzed were the proteins responsible for nucleic acids |
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| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/231162/300443/phd_unimi_R09212.pdf |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/217438/262803/phd_unimi_R08697.pdf |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/401417/616875/phd_unimi_R10203.pdf |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/231157/299635/phd_unimi_R08143.pdf |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/150064/128867/phd_unimi_R07687.pdf |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/279118/396679/phd_unimi_R09723.pdf |
| Alternate Webpage(s) | https://air.unimi.it/retrieve/handle/2434/348007/504674/phd_unimi_R10173.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
