Demographic History of Indigenous Populations in Mesoamerica Based on mtDNA Sequence Data

The genetic characterization of Native American groups provides insights into their history and demographic events. We sequenced the mitochondrial D-loop region (control region) of 520 samples from eight Mexican indigenous groups. In addition to an analysis of the genetic diversity, structure and genetic relationship between 28 Native American populations, we applied Bayesian skyline methodology for a deeper insight into the history of Mesoamerica. AMOVA tests applying cultural, linguistic and geographic criteria were performed. MDS plots showed a central cluster of Oaxaca and Maya populations, whereas those from the North and West were located on the periphery. Demographic reconstruction indicates higher values of the effective number of breeding females (Nef) in Central Mesoamerica during the Preclassic period, whereas this pattern moves toward the Classic period for groups in the North and West. Conversely, Nef minimum values are distributed either in the Lithic period (i.e. founder effects) or in recent periods (i.e. population declines). The Mesomerican regions showed differences in population fluctuation as indicated by the maximum Inter-Generational Rate (IGRmax): i) Center-South from the lithic period until the Preclassic; ii) West from the beginning of the Preclassic period until early Classic; iii) North characterized by a wide range of temporal variation from the Lithic to the Preclassic. Our findings are consistent with the genetic variations observed between central, South and Southeast Mesoamerica and the North-West region that are related to differences in genetic drift, structure, and temporal survival strategies (agriculture versus hunter-gathering, respectively). Interestingly, although the European contact had a major negative demographic impact, we detect a previous decline in Mesoamerica that had begun a few hundred years before

Influence of the Osteogenomic Profile in Response to Alendronate Therapy in Postmenopausal Women with Osteoporosis: A Retrospective Cohort Study

Background: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. Aim: The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. Methods: A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. Results: A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). Conclusions: Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis

Hgs frequencies (%) for the eight Native Mexican populations according to the complete mtDNA control region.

<p>Hgs frequencies (%) for the eight Native Mexican populations according to the complete mtDNA control region.</p

Skyline plot for the 28 populations grouped in the five cultural regions.

<p>North, West, Central, Oaxaca and Maya.</p

Geographical and cultural information from the 28 Native American populations included in this study.

<p>Geographical and cultural information from the 28 Native American populations included in this study.</p

Time distribution (bottom) of the maximum (green points) and minimum IGR values (red points) by Mesoamerican periods (top) for populations clustered in cultural areas.

<p>The vertical red stripe indicates periods before 8,000 ybp.</p

Geographical location of the 28 populations included in the study.

<p>Quadrants represent the regions zoomed in the supplementary information based on the cultural areas of Mesoamerica. Populations studied in this paper appear in bold. For abbreviations please check <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131791#pone.0131791.t001" target="_blank">Table 1</a>.</p

MDS plot representing Fst distances between Native American groups based on mtDNA D-loop region.

<p>Bold letters denote the indigenous groups studied herein. a) MDS plot for eight Native Mexican groups; b) MDS plot for 28 Native American groups. Colors indicate the cultural regions to which the populations belong: green, Maya region; blue, North; red, West; yellow, Center; and purple, Oaxaca. Bold letters indicate Mexican indigenous groups included in this study.</p

Time distribution (bottom) of the maximum (green points) and minimum Nef values (red points) by Mesoamerican periods (top) for populations clustered in cultural areas.

<p>The vertical red stripe indicates periods before 8,000 ybp.</p

Diversity parameters based on mtDNA control region sequences for the eight Native Mexican populations included in this study.

<p>n, sample size; k, number of different haplotypes; S, polymorphic sites; H, haplotype diversity; π, nucleotide diversity;</p><p>θ, mean number of pairwise differences between sequences. D, Tajima’s D; FS, Fu’s FS test (sd, standard deviation).</p><p>Diversity parameters based on mtDNA control region sequences for the eight Native Mexican populations included in this study.</p