Great European mountain ranges have acted as barriers to gene flow for resident populations since prehistory and have offered a place for the settlement of small, and sometimes culturally diverse, communities. Therefore, the human groups that have settled in these areas are worth exploring as an important potential source of diversity in the genetic structure of European populations. In this study, we present new high resolution data concerning Y chromosomal variation in three distinct Alpine ethno-linguistic groups, Italian, Ladin and German. Combining unpublished and literature data on Y chromosome and mitochondrial variation, we were able to detect different genetic patterns. In fact, within and among population diversity values observed vary across linguistic groups, with German and Italian speakers at the two extremes, and seem to reflect their different demographic histories. Using simulations we inferred that the joint effect of continued genetic isolation and reduced founding group size may explain the apportionment of genetic diversity observed in all groups. Extending the analysis to other continental populations, we observed that the genetic differentiation of Ladins and German speakers from Europeans is comparable or even greater to that observed for well known outliers like Sardinian and Basques. Finally, we found that in south Tyroleans, the social practice of Geschlossener Hof, a hereditary norm which might have favored male dispersal, coincides with a significant intra-group diversity for mtDNA but not for Y chromosome, a genetic pattern which is opposite to those expected among patrilocal populations. Together with previous evidence regarding the possible effects of “local ethnicity” on the genetic structure of German speakers that have settled in the eastern Italian Alps, this finding suggests that taking socio-cultural factors into account together with geographical variables and linguistic diversity may help unveil some yet to be understood aspects of the genetic structure of European populations.
Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA.
Human settlement and migrations along sides of Bay-of-Bengal have played a vital role in shaping the genetic landscape of Bangladesh, Eastern India and Southeast Asia. Bangladesh and Northeast India form the vital land bridge between the South and Southeast Asia. To reconstruct the population history of this region and to see whether this diverse region geographically acted as a corridor or barrier for human interaction between South Asia and Southeast Asia, we, for the first time analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental autosomal genetic markers among aboriginal Bangladesh tribes currently speaking Tibeto-Burman language. All the three studied populations; Chakma, Marma and Tripura from Bangladesh showed strikingly high homogeneity among themselves and strong affinities to Northeast Indian Tibeto-Burman groups. However, they show substantially higher molecular diversity than Northeast Indian populations. Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both males and females in shaping the Tibeto-Burman expansion in Southern Asia. Moreover, it is noteworthy that in admixture proportion, TB populations of Bangladesh carry substantially higher mainland Indian ancestry component than Northeast Indian Tibeto-Burmans. Largely similar expansion ages of two major paternal haplogroups (O2a and O3a3c), suggested that they arose before the differentiation of any language group and approximately at the same time. Contrary to the scenario proposed for colonization of Northeast India as male founder effect that occurred within the past 4,000 years, we suggest a significantly deep colonization of this region. Overall, our extensive analysis revealed that the population history of South Asian Tibeto-Burman speakers is more complex than it was suggested before.
There are many different studies that contribute to the global picture of the ethnic heterogeneity in Brazilian populations. These studies use different types of genetic markers and are focused on the comparison of populations at different levels. In some of them, each geographical region is treated as a single homogeneous population, whereas other studies create different subdivisions: political (e.g., pooling populations by State), demographic (e.g., urban and rural), or ethnic (e.g., culture, self-declaration, or skin colour). In this study, we performed an enhanced reassessment of the genetic ancestry of ~ 1,300 Brazilians characterised for 46 autosomal Ancestry Informative Markers (AIMs). In addition, 798 individuals from twelve Brazilian populations representing the five geographical macro-regions of Brazil were newly genotyped, including a Native American community and a rural Amazonian community. Following an increasing North to South gradient, European ancestry was the most prevalent in all urban populations (with values up to 74%). The populations in the North consisted of a significant proportion of Native American ancestry that was about two times higher than the African contribution. Conversely, in the Northeast, Center-West and Southeast, African ancestry was the second most prevalent. At an intrapopulation level, all urban populations were highly admixed, and most of the variation in ancestry proportions was observed between individuals within each population rather than among population. Nevertheless, individuals with a high proportion of Native American ancestry are only found in the samples from Terena and Santa Isabel. Our results allowed us to further refine the genetic landscape of Brazilians while establishing the basis for the effective application of an autosomal AIM panel in forensic casework and clinical association studies within the highly admixed Brazilian populations.
Admixed populations can make an important contribution to the discovery of disease susceptibility genes if the parental populations exhibit substantial variation in susceptibility. Admixture mapping has been used successfully, but is not designed to cope with populations that have more than two or three ancestral populations. The inference of admixture proportions and local ancestry and the imputation of missing genotypes in admixed populations are crucial in both understanding variation in disease and identifying novel disease loci. These inferences make use of reference populations, and accuracy depends on the choice of ancestral populations. Using an insufficient or inaccurate ancestral panel can result in erroneously inferred ancestry and affect the detection power of GWAS and meta-analysis when using imputation. Current algorithms are inadequate for multi-way admixed populations. To address these challenges we developed PROXYANC, an approach to select the best proxy ancestral populations. From the simulation of a multi-way admixed population we demonstrate the capability and accuracy of PROXYANC and illustrate the importance of the choice of ancestry in both estimating admixture proportions and imputing missing genotypes. We applied this approach to a complex, uniquely admixed South African population. Using genome-wide SNP data from over 764 individuals, we accurately estimate the genetic contributions from the best ancestral populations: isiXhosa , ‡Khomani SAN , European , Indian , and Chinese . We also demonstrate that the ancestral allele frequency differences correlate with increased linkage disequilibrium in the South African population, which originates from admixture events rather than population bottlenecks.
The collective term for people of mixed ancestry in southern Africa is “Coloured,” and this is officially recognized in South Africa as a census term, and for self-classification. Whilst we acknowledge that some cultures may use this term in a derogatory manner, these connotations are not present in South Africa, and are certainly not intended here.
Recent progress in the phylogenetic resolution of the Y-chromosome phylogeny permits the male demographic dynamics and migratory events that occurred in Central and Southern America after the initial human spread into the Americas to be investigated at the regional level. To delve further into this issue, we examined more than 400 Native American Y chromosomes (collected in the region ranging from Mexico to South America) belonging to haplogroup Q – virtually the only branch of the Y phylogeny observed in modern-day Amerindians of Central and South America – together with 27 from Mongolia and Kamchatka. Two main founding lineages, Q1a3a1a-M3 and Q1a3a1-L54(xM3), were detected along with novel sub-clades of younger age and more restricted geographic distributions. The first was also observed in Far East Asia while no Q1a3a1-L54(xM3) Y chromosome was found in Asia except the southern Siberian-specific sub-clade Q1a3a1c-L330. Our data not only confirm a southern Siberian origin of ancestral populations that gave rise to Paleo-Indians and the differentiation of both Native American Q founding lineages in Beringia, but support their concomitant arrival in Mesoamerica, where Mexico acted as recipient for the first wave of migration, followed by a rapid southward migration, along the Pacific coast, into the Andean region. Although Q1a3a1a-M3 and Q1a3a1-L54(xM3) display overlapping general distributions, they show different patterns of evolution in the Mexican plateau and the Andean area, which can be explained by local differentiations due to demographic events triggered by the introduction of agriculture and associated with the flourishing of the Great Empires.
The ADAM33 gene is associated with the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD) and atherosclerosis. In this study we investigated all-cause, COPD and cardiovascular mortality, in relation to single nucleotide polymorphisms (SNPs) in ADAM33 (Q_1, S_1, S_2, T_1 and T_2) that were genotyped in 1,390 subjects from the Vlagtwedde/Vlaardingen cohort. Participants were examined at entry in 1989/1990 and followed up till evaluation of the vital status on December 31st, 2008. Using Cox proportional hazards regression we estimated the risk of the SNPs in relation to mortality, adjusting for gender, age, FEV1, height, place of residence and packyears of smoking. Additionally, we performed stratified analyses according to gender and smoking habits. After 18 years, 284 (20.4%) subjects had died (107 due to cardiovascular disease and 20 due to COPD). Individuals homozygous for the minor allele of SNP T_2 had an increased risk of all-cause and cardiovascular mortality compared to wild types: hazard ratio 3.6 (95% confidence interval 2.0 to 6.7) and 3.4 (1.2 to 9.5) respectively. Individuals homozygous for the minor allele of S_1, S_2, T_2 or Q_1 had a significantly increased risk of COPD mortality. In stratified analyses the risk of all-cause mortality associated with SNP T_2 did not change: females 3.5 (1.5 to 8.3), males 3.1 (1.2 to 7.6), never smokers 3.8 (0.9 to 16.3), ever smokers 3.6 (1.8 to 7.2). This study shows for the first time that ADAM33 is a pleiotropic gene that is associated with all-cause, COPD and cardiovascular mortality, independent of potential confounders.
The Tagaeri Taromenane People are two indigenous groups belonging to the Waorani first nation living in voluntary isolation within the Napo region of the western Amazon rainforest. To protect their territory the Ecuadorean State has declared and geographically defined, by Decrees, the Zona Intangible Tagaeri Taromenane (ZITT). This zone is located within the UNESCO Yasuní Biosphere Reserve (1989), one of the most biodiverse areas in the world. Due to several hydrocarbon reserve exploitation projects running in the area and the advancing of a large-scale deforestation front, the survival of these groups is presently at risk. The general aim was to validate the ZITT boundary using the geographical references included in the Decree 2187 (2007) by analyzing the geomorphological characteristics of the area. Remote sensing data such as Digital Elevation Models (DEM), Landsat imagery, topographic cartography of IGM-Ecuador, and fieldwork geographical data have been integrated and processed by Geographical Information System (GIS). The ZITT presents two levels of geographic inconsistencies. The first dimension is about the serious cartographical weaknesses in the perimeter delimitation related to the impossibility of linking two rivers belonging to different basins while the second deals with the perimeter line not respecting the hydrographic network. The GIS analysis results clearly show that ZITT boundary is cartographically nonsense due to the impossibility of mapping out the perimeter. Furthermore, GIS analysis of anthropological data shows presence of Tagaeri Taromenane clans outside the ZITT perimeter, within oil production areas and in nearby farmer settlements, reflecting the limits of protection policies for non-contacted indigenous territory. The delimitation of the ZITT followed a traditional pattern of geometric boundary not taking into account the nomadic characteristic of Tagaeri Taromenane: it is necessary to adopt geographical approaches to recognize the indigenous right to their liveable territories in the complex territorialities enacted by different stakeholders.
For years, studies of founder populations and genetic isolates represented the mainstream of genetic mapping in the effort to target genetic defects causing Mendelian disorders. The genetic homogeneity of such populations as well as relatively homogeneous environmental exposures were also seen as primary advantages in studies of genetic susceptibility loci that underlie complex diseases. European colonization of the St-Lawrence Valley by a small number of settlers, mainly from France, resulted in a founder effect reflected by the appearance of a number of population-specific disease-causing mutations in Quebec. The purported genetic homogeneity of this population was recently challenged by genealogical and genetic analyses. We studied one of the contributing factors to genetic heterogeneity, early Native American admixture that was never investigated in this population before. Consistent admixture estimates, in the order of one per cent, were obtained from genome-wide autosomal data using the ADMIXTURE and HAPMIX software, as well as with the fastIBD software evaluating the degree of the identity-by-descent between Quebec individuals and Native American populations. These genomic results correlated well with the genealogical estimates. Correlations are imperfect most likely because of incomplete records of Native founders’ origin in genealogical data. Although the overall degree of admixture is modest, it contributed to the enrichment of the population diversity and to its demographic stratification. Because admixture greatly varies among regions of Quebec and among individuals, it could have significantly affected the homogeneity of the population, which is of importance in mapping studies, especially when rare genetic susceptibility variants are in play.
Oral history and oral genealogies are mechanisms of collective memory and a main cultural heritage of many populations without a writing system. In the effort to analytically address the correspondence between genetic data and historical genealogies, anthropologists hypothesised that genealogies evolve through time, ultimately containing three parts: literal – where the most recent ancestry is truthfully represented; intended – where ancestry is inferred and reflects political relations among groups; and mythical – that does not represent current social reality. While numerous studies discuss oral genealogies, to our knowledge no genetic studies have been able to investigate to what extent genetic relatedness corresponds to the literal and intended parts of oral genealogies. We report on the correspondence between genetic data and oral genealogies among Bimoba males in a single village in North-Eastern Ghana. We compared the pairwise mismatch distribution of Y chromosome short tandem repeat (Y-STR) haplotypes among all lineages present in this village to the self-reported (oral) relatedness. We found that Bimoba are able to correctly identify unrelated individuals in 92% of the cases. In contrast, they are able to correctly identify related individuals only in 38% of the cases, which can be explained by three processes: (1) the compression of genealogies, leading to increasing inaccuracy with increasing genealogical distance, (2) inclusions into the lineage from intended relations such as clan co-option or adoptions, and (3) false paternities, which in this study were found to have a minor effect on the correspondence between genetic data and oral genealogies. In addition, we observed that 70% of unrelated pairs have from six to eight Y-STR differences, a diversification peak which we attribute to an ancient West African expansion dating around 9454 years ago. We conclude that, despite all caveats, oral genealogies are reflecting ancient lineages more accurately than previously thought.
Human mortality exhibits a strong seasonal pattern with deaths in winter far exceeding those in the summer. While the pattern itself is clear, there have been very few studies examining whether the magnitude or timing of seasonal mortality varies considerably across space. Thus, the goal of this study is to conduct a comprehensive geographic analysis of seasonal mortality across the United States and to uncover systematic regional differences in such mortality. Unique seasonal mortality curves were created for 28 metropolitan statistical areas across the United States, and the amplitude and timing of mortality peaks were determined. The findings here indicate that the seasonality of mortality exhibits strong spatial variation with the largest seasonal mortality amplitudes found in the southwestern United States and the smallest in the North, along with South Florida. In addition, there were strong intra-regional similarities that exist among the examined cities, implying that environmental factors are more important than social factors in determining seasonal mortality response. This work begins to fill a large gap within the scientific literature concerning the geographic variation and underlying causes of seasonal mortality across the United States.
Proteins not present in normal cells, i.e., cancer cells, may elicit a host immune response that leads to the generation of antibodies that might react with these tumor-associated proteins. In recent years, a growing number of reports have showed that autoantibody profiling may provide an alternative approach for the detection of cancer. However, most studies of antigen-autoantibody reactivity have relied on recombinant proteins. Recombinant proteins lack the proper post-translational modifications present in native proteins. Because of this limitation, native or natural protein antigen microarrays are gaining popularity for profiling antibody responses.
1) to illustrate some examples of autoantibodies as signatures for early stage cancer; 2) to briefly outline the various protein antigen microarray platforms; 3) to illustrate the use of native or natural protein microarrays in the discovery of potential biomarkers; and, 4) to discuss the advantages of native protein antigen microarrays over other approaches.
The nature of protein microarray platforms is conducive to multiplexing, which amplifies the potential for uncovering effective biomarkers for many significant diseases. However, the major challenge will be in integrating microarray platforms into multiplexed clinical diagnostic tools, as the main drawback is the reproducibility and coefficient of variation of the results from array to array, and the transportability of the array platform to a more automatable platform.
Autoantibody profiling; Antigen microarray; Biomarker; Cancer diagnostic; Humoral response; Native antigen microarray; Natural antigen microarray; Protein microarray; Reverse capture microarray; Serologic detection
Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA.
To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined.
Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity).
Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA.
autoantibodies; biomarkers; immunomics; prostate cancer; prostate specific antigen; protein microarray
This study aimed to compare self-reported weight and body mass index (BMI) in order to determine discrepancies between subjective and objective obesity-related markers, and possible explanatory factors of overweight and obesity underestimation, in urban, rural and migrant populations.
Materials and Methods
Data from the PERU MIGRANT study, a cross-sectional study, in low-income settings, of urban, migrant (rural-to-urban), and rural groups, including BMI, self-reported weight and socio-demographic indicators were analyzed. Percentage of concurrences between BMI and self-reported weight and Kappa coefficients for inter-rater agreement were calculated. Univariate and standardized descriptive analyses were performed to identify potential explanatory variables for weight underestimation in only overweight and obese individuals, using established BMI and waist circumference cut offs.
983 Participants–199 urban, 583 migrants and 201 rural–were analyzed. Based on BMI, overall prevalence of obesity was 20.1% (95% CI 17.6%–22.6%), and overweight was 38.3% (95% CI 35.2%–41.2%), with differences between study groups (p<0.001). Only 43% of the whole sample had matching self-reported weight and BMI status, whereas 54% underestimated and 3% overestimated their BMI category. Kappa coefficient, between BMI and self-reported weight, for the entire sample was 0.16, rural residents had the lowest coefficient (0.01) and the most underestimation, especially in the overweight category. In overweight and obese individuals, deprivation index (p = 0.016), age (p = 0.014) and waist circumference (p<0.001) were associated with weight underestimation.
Overall, high levels of overweight, obesity, and underestimation of BMI status were found, with poor agreement between BMI and self-reported weight, showing the unawareness of weight status severity in this low-income setting.
The human populations of the Iberian Peninsula are the varied result of a complex mixture of cultures throughout history, and are separated by clear social, cultural, linguistic or geographic barriers. The stronger genetic differences between closely related populations occur in the northern third of Spain, a phenomenon commonly known as “micro-differentiation”. It has been argued and discussed how this form of genetic structuring can be related to both the rugged landscape and the ancient societies of Northern Iberia, but this is difficult to test in most regions due to the intense human mobility of previous centuries. Nevertheless, the Spanish autonomous community of Asturias shows a complex history which hints of a certain isolation of its population. This, joined together with a difficult terrain full of deep valleys and steep mountains, makes it suitable for performing a study of genetic structure, based on mitochondrial DNA and Y-Chromosome markers. Our analyses do not only show that there are micro-differentiation patterns inside the Asturian territory, but that these patterns are strikingly similar between both uniparental markers. The inference of barriers to gene flow also indicates that Asturian populations from the coastal north and the mountainous south seem to be relatively isolated from the rest of the territory. These findings are discussed in light of historic and geographic data and, coupled with previous evidence, show that the origin of the current genetic patterning might indeed lie in Roman and Pre-Roman sociopolitical divisions.
In the majority of countries, surnames represent a ubiquitous cultural attribute inherited from an individual's ancestors and predominantly only altered through marriage. This paper utilises an innovative method, taken from economics, to offer unprecedented insights into the “surname space” of the Czech Republic. We construct this space as a network based on the pairwise probabilities of co-occurrence of surnames and find that the network representation has clear parallels with various ethno-cultural boundaries in the country. Our inductive approach therefore formalizes a simple assumption that the more frequently the bearers of two surnames concentrate in the same locations the higher the probability that these two surnames can be related (considering ethno-cultural relatedness, common co-ancestry or genetic relatedness, or some other type of relatedness). Using the Czech Republic as a case study this paper offers a fresh perspective on surnames as a quantitative data source and provides a methodology that can be easily incorporated within wider cultural, ethnic, geographic and population genetics studies already utilizing surnames.
European lactose tolerance genotype (LCT -13910 C>T, rs4988234) has been positively associated to body mass indexes (BMI) in a meta-analysis of 31,720 individuals of northern and central European descent. A strong association of lactase persistence (LP) with BMI and obesity has also been traced in a Spanish Mediterranean population. The aim of this study was to analyze a potential association of LP compared to lactase non-persistence (LNP) with BMI in inhabitants of the Canary Islands of Spain using Mendelian randomization.
A representative, randomly sampled population of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain, aged 18–75 years (n = 551), was genotyped for the LCT – 13910 C>T polymorphism. Milk consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured. WHO classification of BMI was used.
LP individuals were significantly more obese than LNP subjects (χ2 = 10.59; p<0.005). LP showed in a multivariate linear regression analysis showed a positive association of LP with BMI compared to LNP, (β = 0.96; 95% CI: 0.08–1.85, p = 0.033). In a multinomial logistic regression analysis normal range weight LP subjects showed an odds ratio for obesity of 2.41; 95%CI 1.39–418, (p = 0.002) compared to LNP.
The T-13910 of the allele LCT-13910 C>T polymorphism is positively associated with BMI. LP increases significantly the risk to develop obesity in the studied population. The LCT-13910 C>T polymorphism stands proxy for the lifetime exposure pattern, milk intake, that may increase susceptibility to obesity and to obesity related pathologies.
Characterization of population genetic variation and structure can be used as tools for research in human genetics and population isolates are of great interest. The aim of the present study was to characterize the genetic structure of Xavante Indians and compare it with other populations. The Xavante, an indigenous population living in Brazilian Central Plateau, is one of the largest native groups in Brazil. A subset of 53 unrelated subjects was selected from the initial sample of 300 Xavante Indians. Using 86,197 markers, Xavante were compared with all populations of HapMap Phase III and HGDP-CEPH projects and with a Southeast Brazilian population sample to establish its population structure. Principal Components Analysis showed that the Xavante Indians are concentrated in the Amerindian axis near other populations of known Amerindian ancestry such as Karitiana, Pima, Surui and Maya and a low degree of genetic admixture was observed. This is consistent with the historical records of bottlenecks experience and cultural isolation. By calculating pair-wise Fst statistics we characterized the genetic differentiation between Xavante Indians and representative populations of the HapMap and from HGDP-CEPH project. We found that the genetic differentiation between Xavante Indians and populations of Ameridian, Asian, European, and African ancestry increased progressively. Our results indicate that the Xavante is a population that remained genetically isolated over the past decades and can offer advantages for genome-wide mapping studies of inherited disorders.
Evolutionary accounts of human traits are often based on proxies for genetic fitness (e.g., number of sex partners, facial attractiveness). Instead of using proxies, actual differences in reproductive success is a more direct measure of Darwinian fitness. Certain voice acoustics such as fundamental frequency and measures of health such as handgrip strength correlate with proxies of fitness, yet there are few studies showing the relation of these traits to reproduction. Here, we explore whether the fundamental frequency of the voice and handgrip strength account for differences in actual reproduction among a population of natural fertility humans. Our results show that both fundamental frequency and handgrip strength predict several measures of reproductive success among a group of indigenous Namibian females, particularly amongst the elderly, with weight also predicting reproductive outcomes among males. These findings demonstrate that both hormonally regulated and phenotypic quality markers can be used as measures of Darwinian fitness among humans living under conditions that resemble the evolutionary environment of Homo sapiens. We also argue that these findings provide support for the Grandmother Hypothesis.
Data from morphology, linguistics, history, and archaeology have all been used to trace the dispersal of chickens from Asian domestication centers to their current global distribution. Each provides a unique perspective which can aid in the reconstruction of prehistory. This study expands on previous investigations by adding a temporal component from ancient DNA and, in some cases, direct dating of bones of individual chickens from a variety of sites in Europe, the Pacific, and the Americas. The results from the ancient DNA analyses of forty-eight archaeologically derived chicken bones provide support for archaeological hypotheses about the prehistoric human transport of chickens. Haplogroup E mtDNA signatures have been amplified from directly dated samples originating in Europe at 1000 B.P. and in the Pacific at 3000 B.P. indicating multiple prehistoric dispersals from a single Asian centre. These two dispersal pathways converged in the Americas where chickens were introduced both by Polynesians and later by Europeans. The results of this study also highlight the inappropriate application of the small stretch of D-loop, traditionally amplified for use in phylogenetic studies, to understanding discrete episodes of chicken translocation in the past. The results of this study lead to the proposal of four hypotheses which will require further scrutiny and rigorous future testing.
The “thrifty genotype” hypothesis proposes that the high prevalence of type 2 diabetes (T2D) in Native Americans and admixed Latin Americans has a genetic basis and reflects an evolutionary adaptation to a past low calorie/high exercise lifestyle. However, identification of the gene variants underpinning this hypothesis remains elusive. Here we assessed the role of Native American ancestry, socioeconomic status (SES) and 21 candidate gene loci in susceptibility to T2D in a sample of 876 T2D cases and 399 controls from Antioquia (Colombia). Although mean Native American ancestry is significantly higher in T2D cases than in controls (32% v 29%), this difference is confounded by the correlation of ancestry with SES, which is a stronger predictor of disease status. Nominally significant association (P<0.05) was observed for markers in: TCF7L2, RBMS1, CDKAL1, ZNF239, KCNQ1 and TCF1 and a significant bias (P<0.05) towards OR>1 was observed for markers selected from previous T2D genome-wide association studies, consistent with a role for Old World variants in susceptibility to T2D in Latin Americans. No association was found to the only known Native American-specific gene variant previously associated with T2D in a Mexican sample (rs9282541 in ABCA1). An admixture mapping scan with 1,536 ancestry informative markers (AIMs) did not identify genome regions with significant deviation of ancestry in Antioquia. Exclusion analysis indicates that this scan rules out ∼95% of the genome as harboring loci with ancestry risk ratios >1.22 (at P < 0.05).
Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.
Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.
Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered “no” to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.
Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
Genetic association studies are now routinely used to identify single nucleotide polymorphisms (SNPs) linked with human diseases or traits through single SNP-single trait tests. Here we introduced partial least squares path modeling (PLSPM) for association between single or multiple SNPs and a latent trait that can involve single or multiple correlated measurement(s). Furthermore, the framework naturally provides estimators of polygenic effect by appropriately weighting trait-attributing alleles. We conducted computer simulations to assess the performance via multiple SNPs and human obesity-related traits as measured by body mass index (BMI), waist and hip circumferences. Our results showed that the associate statistics had type I error rates close to nominal level and were powerful for a range of effect and sample sizes. When applied to 12 candidate regions in data (N = 2,417) from the European Prospective Investigation of Cancer (EPIC)-Norfolk study, a region in FTO was found to have stronger association (rs7204609∼rs9939881 at the first intron P = 4.29×10−7) than single SNP analysis (all with P>10−4) and a latent quantitative phenotype was obtained using a subset sample of EPIC-Norfolk (N = 12,559). We believe our method is appropriate for assessment of regional association and polygenic effect on a single or multiple traits.
Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9×10−8) for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5×10−4 and 2.9×10−5 in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7×10−5) for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening.
Studies examining human and nonhuman primates have supported the hypothesis that the recent increase in the occurrence of misalignment of teeth and/or incorrect relation of dental arches, named dental malocclusion, is mainly attributed to the availability of a more processed diet and the reduced need for powerful masticatory action. For the first time on live human populations, genetic and tooth wear influences on occlusal variation were examined in a split indigenous population. The Arara-Iriri people are descendants of a single couple expelled from a larger village. In the resultant village, expansion occurred through the mating of close relatives, resulting in marked genetic cohesion with substantial genetic differences.
Dental malocclusion, tooth wear and inbreeding coefficient were evaluated. The sample examined was composed of 176 individuals from both villages. Prevalence Ratio and descriptive differences in the outcomes frequency for each developmental stage of the dentition were considered. Statistical differences between the villages were examined using the chi-square test or Fisher's exact statistic. Tooth wear and the inbreeding coefficient (F) between the villages was tested with Mann-Whitney statistics. All the statistics were performed using two-tailed distribution at p≤0.05. The coefficient inbreeding (F) confirmed the frequent incestuous unions among the Arara-Iriri indigenous group. Despite the tooth wear similarities, we found a striking difference in occlusal patterns between the two Arara villages. In the original village, dental malocclusion was present in about one third of the population; whilst in the resultant village, the occurrence was almost doubled. Furthermore, the morphological characteristics of malocclusion were strongly different between the groups.
Our findings downplay the widespread influence of tooth wear, a direct evidence of what an individual ate in the past, on occlusal variation of living human populations. They also suggest that genetics plays the most important role on dental malocclusion etiology.