INVESTIGADORES
RAMALLO Virginia
congresos y reuniones científicas
Título:
TP53 AND MDM2: GENETIC VARIATION IN NATIVE AMERICANS
Autor/es:
JACOVAS, VC; BORTOLINI, MC; DE AZEVEDO, S; SALZANO, FM; RAMALLO V
Reunión:
Congreso; 59 Congresso Brasileiro de Genética; 2013
Resumen:
TP53 is a tumor suppressor gene and the corresponding protein p53, whose activity is regulated by post-transcriptional systems, is a transcription factor, involved in many cellular functions (DNA repair, cell senescence, and apoptosis). Two human-speci c polymorphisms a ect the p53 stress response pathway: p53 codon 72 (rs1042522, a C-G transversion in exon 4 which leads to a Pro/Arg aminoacid change); and MDM2 SNP309 (rs2279744, a T-G transversion which creates a binding site for the transcription factor SP1 MIM 189906). Allele frequencies are di erent ethnically and geographically, supporting the hypothesis of selective pressure from environmental variables. e distribution would be dependent on latitude, winter temperature or UV radiation. With the aim of better understanding the distribution of these polymorphisms in America, we genotyped these two SNPs in 65 unrelated individuals from 4 Amerindian populations (Aymara (N=17); Quechua (N=17); Guaraní-Ñandeva (N=15); and Guaraní-Kaiowa (N=16)). We also included data from the literature, in a total of 415 samples and 15 Amerindian populations, and tested for correlations with altitude and seven climate-related environmental variables (precipitation rates, minimum, maximum and mean temperatures of warmest and coldest seasons). Pearsons correlation coeficient and Spearmans rho correlation coe cient were computed to evaluate the relationship between SNP allele frequencies and each environmental variable. For the P-values, two tailed tests were performed. Analysis was conducted with SPSS20.0. Hardy-Weinberg was tested by the Web program (http://www.oege.org/software/hwe-mr-calc.shtml), and the statistical signi cance was assessed by Fishers exact test. Both SNPs distributions were in HWE in all populations. For the p53-Arg allele, the most high frequencies were reported in Brazilian Amerindian populations (especially high in Guaraní samples); while MDM2 309G showed high frequencies in Bolivian samples. Generally, there were no correlations between allele frequencies and precipitation rates, but there is a trend for the MDM2 309G frequencies to increase with altitude (rho=0.711 p<0.05) which had lower mean temperatures in winter (rho=-0,723, p<0.05). Since only this correlation was found and both genes in uence the same metabolic pathway, it is premature correlate it to this environmental stress. e occupation of the American continent was the last major expansion of modern humans. e Amerindian populations have a particular pattern of diversity/divergence, derived from demographic and historical processes. However, signals of natural selection have also been identified. Our results indicated that the allele frequency distributions across populations are di erent from those in other regions of the world, but the factors involved in these di erences remain to be identified.