CYP1A1 Variability In Human Populations

The human cytochrome P4501A1 (CYP1A1) enzyme plays an important role in the metabolism of xenobiotics and endogenous substrates. Because polymorphisms within the CYP1A1 gene have been shown to be associated with various cancer risks and with the predicting clinical efficacy of some chemotherapies in different populations, most studies focus on their clinical significance. We, however, were interested in evaluating whether the polymorphisms could be used to distinguish human populations. Four single nucleotide CYP1A1 polymorphisms (rs4646903/ g.75011641; rs1048943/g.75012985; g.75012235; and rs1799814/ g.75012987) were analysed via PCR-RFLP assay in 1,195 individuals of various human groups from all over the world. In order to gain a more complete view of the genetic variability of the CYP1A1 gene, different statistical analyses were performed upon the populations of the present study and upon the limited data gleaned from previously studied populations. The allele and haplotype frequencies vary among populations: the rs4646903 (C) and rs1048943 (G) have been found to be nearly always linked and were found at the highest frequencies in Native Americans, while the variant associated to the position g.75012235 was only detected in certain African populations. Our work clearly indicates that the CYP1A1 polymorphisms differ among populations and that the prediction of genotypes constitutes an important aspect of precision medicine since some variants were associated with certain cancers and rs1048943 show strong association with optimized chemotherapy. Moreover, the CYP1A1 gene plays an important role in the metabolism of xenobiotics and it is likely that its frequencies could be strongly influenced by environmental factors

Mitochondrial Haplogroup H1 in North Africa: An Early Holocene Arrival from Iberia

The Tuareg of the Fezzan region (Libya) are characterized by an extremely high frequency (61%) of haplogroup H1, a mitochondrial DNA (mtDNA) haplogroup that is common in all Western European populations. To define how and when H1 spread from Europe to North Africa up to the Central Sahara, in Fezzan, we investigated the complete mitochondrial genomes of eleven Libyan Tuareg belonging to H1. Coalescence time estimates suggest an arrival of the European H1 mtDNAs at about 8,000–9,000 years ago, while phylogenetic analyses reveal three novel H1 branches, termed H1v, H1w and H1x, which appear to be specific for North African populations, but whose frequencies can be extremely different even in relatively close Tuareg villages. Overall, these findings support the scenario of an arrival of haplogroup H1 in North Africa from Iberia at the beginning of the Holocene, as a consequence of the improvement in climate conditions after the Younger Dryas cold snap, followed by in situ formation of local H1 sub-haplogroups. This process of autochthonous differentiation continues in the Libyan Tuareg who, probably due to isolation and recent founder events, are characterized by village-specific maternal mtDNA lineages

Studio delle linee mitocondriali in due comunità del centro della Penisola Iberica: Bejar e Vera

Scopo di questo lavoro è stato quello di indagare la storia genetica per via materna di due comunità della Spagna centrale: Bejar e Vera, che secondo i dati archeologici e storici sembrano aver avuto una diversa storia demografica e genetica. Sono state studiate le sequenze dei segmenti HVS-I e HVS-II della regione di controllo del D-loop e alcuni SNPs della zona codificante del DNA mitocondriale in 137 individui (Bejar=71; Vera=66) non imparentati, i cui nonni, materni e paterni, erano nati in queste comunità. Ciascun aplotipo identificato è stato classificato e assegnato a un aplogruppo secondo la classificazione proposta da van Owen e Kaiser. E’ stata condotta l’analisi popolazionistica al fine di evidenziare eventuali affinità genetiche tra le diverse popolazioni della Penisola Iberica. Gli aplotipi appartenenti all’aplogruppo H sono stati ulteriormente classificati saggiando gli SNPs diagnostici. Le linee non attribuibili ad alcun sottoaplogruppo di H sono state sottoposte all’analisi di sequenza dell’intero genoma mitocondriale. Infine, è stato costruito un Median Joining network di tutti gli aplotipi H1 con lo scopo di evidenziare eventuali correlazioni geografiche tra i profili dei campioni da noi analizzati e altri descritti nella letteratura

Principal component analysis (PCA), together with a biplot, of 14 West-African population samples, (a) inclusively and (b) exclusively the Ghanaian C1 population sample, based on the Y-SNP frequencies using the phylogeny given in S3 Fig.

<p>The cumulative proportion of plot (a) is 0.92 for the first two principal components (PC1: 0.83; PC2: 0.09), and of plot (b) is 0.81 for the first two principal components (PC1: 0.45; PC2: 0.36). The nomenclature and the references of the population samples are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141510#pone.0141510.s012" target="_blank">S1 Table</a>. </p

Geographic location of all population samples along the Bight of Benin and the rest of the West-African coast analysed in the study.

<p>The nomenclature and the references of the population samples are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141510#pone.0141510.s012" target="_blank">S1 Table</a>.</p

Principal component analysis (PCA) of ten West-African population samples and the HapMap YRI sample based on the Y-SNP frequencies using the phylogeny given in S2 Fig.

<p>The cumulative proportion of the plot is 0.90 for the first two principal components (PC1: 0.63; PC2: 0.27). In this analysis the Ghanaian C1 population sample was excluded from the analysis. The nomenclature and the references of the population samples are available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141510#pone.0141510.s012" target="_blank">S1 Table</a>.</p