O papel da seleção induzida por protozoários em modelar a variabilidade genética humana

terça-feira, fevereiro 23, 2010

Trends in Genetics, Volume 26, Issue 3, 95-99, 25 January 2010

doi:10.1016/j.tig.2009.12.010

Update

The role of protozoa-driven selection in shaping human genetic variability

Uberto Pozzoli1, Matteo Fumagalli1, 2, Rachele Cagliani1, Giacomo P. Comi3, Nereo Bresolin1, 3, Mario Clerici4, 5 and Manuela Sironi1,

1 Scientific Institute IRCCS E. Medea, Bioinformatic Laboratory, Via don L. Monza 20, 23842 Bosisio Parini (LC), Italy

2 Bioengineering Department, Politecnico di Milano, P.zza L. da Vinci, 32, 20133 Milan, Italy

3 Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, Via F. Sforza 35, 20100 Milan, Italy

4 Department of Biomedical Sciences and Technologies LITA Segrate, University of Milan, Via F.lli Cervi 93, 20090 Milan, Italy

5 Don C. Gnocchi ONLUS Foundation IRCCS, Via Capecelatro 66, 20148 Milan, Italy

Abstract

Protozoa exert a strong selective pressure in humans. The selection signatures left by these pathogens can be exploited to identify genetic modulators of infection susceptibility. We show that protozoa diversity in different geographic locations is a good measure of protozoa-driven selective pressure; protozoa diversity captured selection signatures at known malaria resistance loci and identified several selected single nucleotide polymorphisms in immune and hemolytic anemia genes. A genome-wide search enabled us to identify 5180 variants mapping to 1145 genes that are subjected to protozoa-driven selective pressure. We provide a genome-wide estimate of protozoa-driven selective pressure and identify candidate susceptibility genes for protozoa-borne diseases.

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