Distinct Population Groups Research Articles

General-Purpose Genotype or How Epigenetics Extend the Flexibility of a Genotype

This project aims at investigating the link between individual epigenetic variability (not related to genetic variability) and the variation of natural environmental conditions. We studied DNA methylation polymorphisms of individuals belonging to a single genetic lineage of the clonal diploid fish Chrosomus eos-neogaeus sampled in seven geographically distant lakes. In spite of a low number of informative fragments obtained from an MSAP analysis, individuals of a given lake are epigenetically similar, and methylation profiles allow the clustering of individuals in two distinct groups of populations among lakes. More importantly, we observed a significant pH variation that is consistent with the two epigenetic groups. It thus seems that the genotype studied has the potential to respond differentially via epigenetic modifications under variable environmental conditions, making epigenetic processes a relevant molecular mechanism contributing to phenotypic plasticity over variable environments in accordance with the GPG model.

The vigorous core of our nationality: race and regional identity in northeastern Brazil

Vigorous Core of Our Nationality explores conceptualizations of regional identity and a distinct population group known as nordestinos in northeastern Brazil during a crucial historical period. Beginning with the abolition of slavery and ending with the demise of the Estado Novo under Getulio Vargas, Stanley E. Blake offers original perspectives on the paradoxical concept of the nordestino and the importance of these debates to the process of state and nation building. Since colonial times, the Northeast has been an agricultural region based primarily on sugar production. The area s population was composed of former slaves and free men of African descent, indigenous Indians, European whites, and mulattos. The image of the nordestino was, for many years, linked with the predominant ethnic group in the region, the Afro-Brazilian. For political reasons, however, the conception of the nordestino later changed to more closely resemble white Europeans. Blake delves deeply into local archives and determines that politicians, intellectuals, and other urban professionals formulated identities based on theories of science, biomedicine, race, and social Darwinism. While these ideas served political, social, and economic agendas, they also inspired debates over social justice and led to reforms for both the region and the Additionally, Blake shows how debates over northeastern identity and the concept of the nordestino shaped similar arguments about Brazilian national identity and true Brazilian people.

Phylogeography of an Italian endemic salamander (genus Salamandrina): glacial refugia, postglacial expansions, and secondary contact

The Italian endemic genus Salamandrina has been historically regarded as monotypic but, recently, studies based on both mitochondrial and nuclear markers have indicated the existence of two distinct species of spectacled salamanders: Salamandrina perspicillata, in central and northern Italy, and Salamandrina terdigitata, in southern Italy. We analyzed nucleotide variation at mitochondrial and nuclear genes [cytochrome b, 12S and 16S rRNA, recombination activating gene (RAG 1)] in 223 individuals from 56 locations, aiming to investigate their genetic structure and recent evolutionary histories. Phylogenetic and phylogeographical analyses revealed the existence of three and two genetically distinct groups of populations in northern and southern salamander, respectively. Historical demographic analyses led to the inference of range expansion for both species in the late Pleistocene. During the last glacial stage, each salamander survived in a single refugium, namely the southern in Calabria and the northern in central Italy. At the end of this period, both lineages expanded northward and established secondary contact. Spatial distribution of RAG 1 haplotype variation revealed two differentiated population groups corresponding to the major mitochondrial (mt)DNA clades. Nuclear pattern of introgressive hybridization was more extensive than the highly limited introgression of mtDNA markers. From a conservation standpoint, southern Latium and Calabria proved to be the major genetic diversity reservoirs, thus deserving particular conservation efforts.

Population genetic diversity and structure of two rare vernal pool grasses in central California

Vernal pool ecosystems are declining throughout California, with only 10% of historic habitat remaining. This has endangered many specialist endemic plant species, leaving extant populations fragmented, isolated, and threatened or endangered. Recovery plans for the increasing number of endangered vernal pool species require information on their genetic and ecological status to guide conservation and restoration efforts. Federally threatened Neostapfia colusana (Colusa grass) and federally endangered Tuctoria greenei (Greene’s tuctoria) are two endemic vernal pool grasses of high conservation concern in central California. Remaining populations are highly fragmented due to range-wide habitat destruction. Using five polymorphic microsatellite markers for each species, we performed genetic surveys of 240 individuals from eight vernal pools for N. colusana, and 317 individuals from 13 vernal pools for T. greenei. We detected high within-population genetic diversity for both species, with average allelic diversities of 24 alleles/locus (mean Hobs = 0.68, mean Hexp = 0.71) for N. colusana, and 19 alleles/locus (mean Hobs = 0.77, and mean Hexp = 0.79) for T. greenei. Bayesian clustering and AMOVA indicated two genetically distinct population groups for N. colusana (Fst = 0.268, P < 0.0001), and three for T. greenei (Fst = 0.11, P < 0.0001). We found very slight temporal genetic structure at one N. colusana (Fst = 0.013, P < 0.05) and two T. greenei (Fst = 0.015, Fst = 0.018, P < 0.05) pools. These estimates of population genetic diversity and structure are critical measures for both species that will help inform recovery management actions.

Evolutionary history and identification of conservation units in the giant otter, Pteronura brasiliensis

The giant otter, Pteronura brasiliensis, occupies a range including the major drainage basins of South America, yet the degree of structure that exists within and among populations inhabiting these drainages is unknown. We sequenced portions of the mitochondrial DNA (mtDNA) cytochrome b (612bp) and control region (383bp) genes in order to determine patterns of genetic variation within the species. We found high levels of mtDNA haplotype diversity (h=0.93 overall) and support for subdivision into four distinct groups of populations, representing important centers of genetic diversity and useful units for prioritizing conservation within the giant otter. We tested these results against the predictions of three hypotheses of Amazonian diversification (Pleistocene Refugia, Paleogeography, and Hydrogeology). While the phylogeographic pattern conformed to the predictions of the Refugia Hypothesis, molecular dating using a relaxed clock revealed the phylogroups diverged from one another between 1.69 and 0.84Ma, ruling out the influence of Late Pleistocene glacial refugia. However, the role of Plio-Pleistocene climate change could not be rejected. While the molecular dating also makes the influence of geological arches according to the Paleogeography Hypothesis extremely unlikely, the recent Pliocene formation of the Fitzcarrald Arch and its effect of subsequently altering drainage pattern could not be rejected. The data presented here support the interactions of both climatic and hydrological changes resulting from geological activity in the Plio-Pleistocene, in shaping the phylogeographic structure of the giant otter.

Treatment of Oropharyngeal Squamous Cell Carcinoma: A SEER Treatment Review

Since most oropharyngeal carcinomas are locally advanced at presentation, patients are often treated with radiation therapy and/or chemotherapy. However, for early stage oropharyngeal carcinoma, national guidelines state that it can be treated by either primary surgery or radiotherapy. This study analyzes national survival rates of oropharyngeal squamous cell carcinoma for surgical and non-surgical treatment modalities. All cases of squamous cell carcinoma of the oropharynx between 1988 and 2007 were selected from the Surveillance, Epidemiology and End Results (SEER) 17 database. The SEER database is a population-based cancer registry that captures 17 distinct population groups in 198 counties in the United States. It represents approximately 26% of the overall United States population and contains information on 6,117,327 cases of cancer diagnosed since 1973. Overall survival was the primary outcome measure. Survival curves were generated using the Kaplan-Meier method and compared using the Mantel-Cox log-rank test. Significance was defined as P < .05. A total of 24,980 patients with squamous cell carcinoma of the oropharynx diagnosed from 1988 to 2007 were analyzed. For Stages I and II post-op RT yielded better survival than pre-op RT (P = 0.0096, hazard ratio = 1.464, 95% CI = 1.097 to 1.954). However, for Stages III and IV there was no difference in survival between the pre-op RT and post-op RT groups (P = .4099; hazard ratio = 0.9518; 95% CI = 0.8464 to 1.070). These data suggest that for early stage oropharyngeal carcinomas, surgery yields better survival rates than radiotherapy alone. Hence, the authors advocate surgery as the first option in these tumors if clear margins can be achieved, allowing radiotherapy to be preserved for locoregional failures or second primary tumors.

Genetic Differentiation, Structure, and a Transition Zone among Populations of the Pitcher Plant Moth Exyra semicrocea: Implications for Conservation

Pitcher plant bogs, or carnivorous plant wetlands, have experienced extensive habitat loss and fragmentation throughout the southeastern United States Coastal Plain, resulting in an estimated reduction to <3% of their former range. This situation has lead to increased management attention of these habitats and their carnivorous plant species. However, conservation priorities focus primarily on the plants since little information currently exists on other community members, such as their endemic arthropod biota. Here, we investigated the population structure of one of these, the obligate pitcher plant moth Exyra semicrocea (Lepidoptera: Noctuidae), using mitochondrial cytochrome c oxidase subunit I (COI) gene sequences. Examination of 221 individuals from 11 populations across eight southeastern US states identified 51 unique haplotypes. These haplotypes belonged to one of two divergent (∼1.9–3.0%) lineages separated by the Mississippi alluvial plain. Populations of the West Gulf Coastal Plain exhibited significant genetic structure, contrasting with similarly distanced populations east of the Mississippi alluvial plain. In the eastern portion of the Coastal Plain, an apparent transition zone exists between two regionally distinct population groups, with a well-established genetic discontinuity for other organisms coinciding with this zone. The structure of E. semicrocea appears to have been influenced by patchy pitcher plant bog habitats in the West Gulf Coastal Plain as well as impacts of Pleistocene interglacials on the Apalachicola-Chattahoochee-Flint River Basin. These findings, along with potential extirpation of E. semicrocea at four visited, but isolated, sites highlight the need to consider other endemic or associated community members when managing and restoring pitcher plant bog habitats.

SU‐E‐I‐82: CT Protocol Translation in a Multi‐Vendor, Multi‐Hospital Environment

Purpose: To review issues involved with designing CT protocols for achieving consistent standards in a multi‐vendor and multi‐institutional enterprise.Methods: Achieving consistent CT protocols is complicated by a variety of factors. Even in a given institution, CTˈs from different vendors complicate standardizing protocols. An approach based on uniform CTDI values for exam types may meet with resistance due to individual radiologist image preference. The situation is further complicated in multi‐institutional settings where patient demographics, radiologist, and clinician cultures can vary widely. At UT Southwestern, there are three major institutions using CT equipment from different vendors and servicing distinct patient population groups. A childrenˈs hospital, a teaching county hospital, and a university hospital are serviced by a common radiology group. Recent media attention to CT dose, and recommendations by the Conference of Radiation Control Program Directors (CRCPD) have spurred State regulatory bodies to draft requirements for dose management. Examples are given outlining methods to achieve consistent protocols across our facilities, based on experience at UT Southwestern.Results: The approach at UT Southwestern was based on CRCPD recommendations. Further guidance was found in ACR, the Image Gently, and Image Wisely campaigns. A specific result, is given of translating a set of pediatric protocols from the childrenˈs hospital to adult facilities employing CTˈs from different vendors Conclusions: CT protocols can be standardized in multi‐vendor and multi‐ institutional environments. A critical aspect of the process is buy‐in from the radiology staff and further support from management.

Chloroplast DNA polymorphisms in eastern hemlock: range-wide genogeographic analyses and implications for gene conservation

The objective of this study was to determine if the genetic diversity of eastern hemlock ( Tsuga canadensis (L.) Carrière) is uniformly distributed or structured. Such information is relevant to help guide conservation efforts. Individuals were sampled in 60 range-wide populations of T. canadensis and genotyped at seven polymorphic chloroplast DNA loci. All 16 chlorotypes identified in T. canadensis were highly divergent from the unique chlorotype detected in Carolina hemlock ( Tsuga caroliniana Engelm.). Among-population differentiation in T. canadensis was low (GST = 0.020) and the distribution of chlorotypes did not show any strong geographical pattern, which is likely due to the homogenizing effect of pollen gene flow during the Holocene. Nevertheless, a spatial Bayesian approach revealed two distinct groups of populations. Furthermore, an analysis of relative genetic distances indicated that southeastern Appalachian populations harboured greater population differentiation while conserving relatively high allelic richness, which might represent the imprint of an ancient glacial refugium in the region. Thus, these distinctive genetic patterns and the risk of Tsuga decline following climate warming combined with the introduction of the insect Adelges tsugae (Annand) indicate that the southern part of the range should be considered of high priority for ex situ conservation.

Spatial genetic structure of Campanula thyrsoides across the European Alps: Indications for glaciation-driven allopatric subspeciation

Abstract Quaternary climate change had profound impacts on the geographical distribution and genetic structure of plant species which is hypothesized to have triggered allopatric speciation due to spatial isolation. However, evidence is scarce despite recent advances that indicate glacial history and substrate requirements as main drivers of spatial genetic structures. Here we built upon these studies to test the role of glaciations on the morphological and ecological differentiation within the calcicolous Campanula thyrsoides across its European Alpine distribution range. We collected samples from 51 populations (1173 plants), used five microsatellite markers, estimated diversity ( N a , H E ) and differentiation ( D est , G ST_est , F ST ) and applied Bayesian clustering analysis and tessellation methods. We found support for four genetically distinct groups of populations, arranged from West to East: (i) France and Western Switzerland, (ii) Central and most of Eastern Switzerland, (iii) parts of Eastern Switzerland and Central Austria, and (iv) Southeastern Austria, Slovenia and Northeastern Italy. Among-subspecies variance was 8.4% and each subspecies was highly differentiated ( C.*thyrsoides : D est = 0.47; C.*carniolica : D est = 0.58). Geographic structuring of within-population diversity was not related to refugia outside of previously-glaciated terrain but to subspecies: the more thermophilic C.*carniolica showed significantly lower levels of within-population diversity and higher numbers of private alleles. The location of the genetic break lines between these four groups of populations corresponds to well-known biogeographic barriers. However, the phylogeographic pattern has elements formerly found in both calcicolous and silicicolous species and thus questions the generality of substrate-related patterns. Within C.*thyrsoides , population admixture upon secondary contact may have led to high genetic diversity across the distribution range. Given the geographic and genetic differences of the subspecies we conclude that differentiation between C.*thyrsoides and C.*carniolica represents a case of glaciation-driven allopatric subspeciation reinforced by missing secondary contact due to incomplete post-glacial recolonization of potential habitats.

Geochemistry and modification of oilfield brines in surface pits in Northern Kuwait

Oilfield brines (produced water) are produced as a waste product daily at the gathering centers (GCs) in Kuwait oilfields. The geochemical evolution of the water produced at the GC (fresh brine) to stagnant pit water (evaporate) has been investigated in the northern fields of Kuwait, and a model is presented showing time-dependent variations. Kuwait oilfield brines are globally similar to others in other large sedimentary basins (USA, Canada), but modifications have occurred due to seawater injection practices performed episodically during the oil extraction process. Brine water chemistry changes from generally average brine chemistry (based on cations and anions) to saturated mixture of seawater, oilfield brine, and anthropogenic chemical pollutants. The objective of this study was to harmonize the database of brine waters in terms of regional identity by comparison with oilfield brines elsewhere, identify water–rock interaction, and statistically treat daily recordings from the pits in order to identify injection peaks and troughs. Laboratory analysis of major and minor cations and anions from the Rawdatayn samples gave the following concentration ranges in parts per million (ppm): (Na+, 11,698–203,977), (Ca2+, 2,216–98,514), (Mg2+, 1,602–28,885), (K+, 1,528–16,573), (Sr2+, 70–502), (Ba2+, 0.01–18.04), (Fe2+, 0.01–8.93), (Li+, 0.09–6.48), (Si2+, 0.00–13.18), (B3+, 0.05–37.45), (SO42+, 330–3100). For the Sabriyah oilfield samples, the major and minor cations and anions concentration ranges in ppm are: (Na+, 9,807–274,947), (Ca2+, 2,555–77,992), (Mg2+, 1,415–28,183), (K+, 764–19,201), (Sr2+, 77.84–641), (Ba2+, 0.15–6.76), (Fe2+, 0.016–38.88), (Li+, 0.05–6.83), (Si2+, 0.0195–16.84), (B3+, 7.17–55.33), (SO42+, 44,812–135,264). The stable isotopic analysis of five samples indicates normal trends in oxygen and hydrogen isotopes that classify the waters as “connate” which follow an evaporation trend. Carbon isotopic signatures are normal for hydrocarbon fields and average out around GC15, δ18O‰ = 1.4, δD‰ = −10, δ13C‰ = −3.6; while for GC23, δ18O‰ = 2.3, δD‰ = −4, δ13C‰ = −2.5; for GC25, δ18O‰ = −2.0, δD‰ = −14, δ13C‰ = −4.6; for pit1, δ18O‰ = 2.3, δD‰ = −5, δ13C‰ = −18.3; and for pit 2, δ18O‰ = 2.5, δD‰ = −4, δ13C‰ = −17.8. Carbon isotope average values for all brine samples from the GCs is = −56 which falls within normal hydrocarbon formation water category. Data spikes coincide with injection periods at the following times (A: May–Jun, 2006), (B: Sep–Oct, 2006), (C: Jan–Feb, 2007), (D: Mar, 2007), (E: May–Jun, 2007), (F: Feb, 2006), (G: Mar–Apr, 2006) and, subsequently the decay to “normal” brine occurs over a period of several weeks. The database was large enough to apply a principal component statistical analysis (PCA). PCA and geo-statistical techniques reveal several distinct population groups. The main chemical groups in the data are as follows: plateau, spike groups, and pit evaporation group. The spike periods correlate closely with seawater injection periods (Jan–Feb, Mar–Apr, May–Jun, and Sep–Oct). The pit chemistry reveals exceptionally high evaporation processes coinciding with summer peak temperature. PCA results show distinct groupings centered around the major elements reminiscent of other oilfields, but with the added evaporation trend strongly enhanced.

Essential oils composition in two Rosmarinus officinalis L. varieties and incidence for antimicrobial and antioxidant activities

The essential oil composition of Rosmarinus officinalis var. typicus and var. troglodytorum endemic to Tunisia, and growing wild in different bioclimates, was determined by GC and GC–MS. Oils were assessed for their antimicrobial and antioxidant activity. A variation of the chemical composition attributed to varieties rather than to bioclimates was revealed. 1.8-Cineole (47.2–27.5%) and camphor (12.9–27.9%) were identified as the main constituents of var. typicus and var. troglodytorum, respectively. The principal component analysis performed on oil constituents for all the populations allowed the distinction of two distinct population groups in accordance to the varietal subdivision. Based on the determination of the diameter of inhibition and the determination of the minimum inhibitory concentration, a low to moderate antimicrobial activity according to oils was revealed against eight bacteria tested. However, oils from var. troglodytorum showed higher bactericidal effect than those from var. typicus. The oils’ antioxidant activity, determined by 1,1-diphenyl-1-picrylhydrazyl (DPPH) assay, ferric reducing (FRAP) assay and β-carotene bleaching test, was relatively high. The highest activity was found in oils from var. troglodytorum and in one population of var. typicus from the upper semi-arid bioclimate.

Genetic structure of coastal and inland populations of Spergularia media (L.) C. Presl (Caryophyllaceae) in Central Europe

In Central Europe, salt-influenced habitats are restricted mainly to the coastlines of the North Sea and the Baltic Sea. The few natural inland salt sites suffer from size reduction and loss in biodiversity, while anthropogenic salt sites around potash mining dumps experienced recent and massive de novo colonization by numerous halophytes. Our study aimed to elucidate the general patterns of gene flow among coastal and inland salt habitats. We used amplified fragment length polymorphisms to assess the genetic diversity and genetic structure of 18 European populations of the halophyte Spergularia media (Caryophyllaceae), sampled from inland and coastal salt sites of Germany, the Netherlands, Denmark, Austria, France and Italy. Estimates of genetic diversity on the population level were generally low, especially within inland salt habitats. Analyses of molecular variance showed comparatively strong differentiation among populations. Multivariate ordination (principal coordinate analysis) and a NeighborNet analysis revealed four distinct groups of populations that showed good correspondence to their geographic origins. A Bayesian analysis performed with the program Structure as well as high pairwise Φ ST values supported the results of the phenetic analyses. The observed patterns of diversity and differentiation among inland populations of S. media are best explained by the isolated nature of suitable salt habitats, with concomitant reduction of gene flow to and among these sites. Our data support the hypothesis that the colonization of anthropogenic salt sites by S. media originated from natural inland habitats.

Phylogeography of the Italian vairone (Telestes muticellus, Bonaparte 1837) inferred by microsatellite markers: evolutionary history of a freshwater fish species with a restricted and fragmented distribution

BackgroundOwing to its independence from the main Central European drainage systems, the Italian freshwater fauna is characterized by a high degree of endemicity. Three main ichthyogeographic districts have been proposed in Italy. Yet, the validity of these regions has not been confirmed by phylogenetic and population genetic analyses and a phylogeographic scenario for Italy's primary freshwater fish fauna is still lacking. Here, we investigate the phylogeography of the Italian vairone (Telestes muticellus).ResultsWe sampled 38 populations representing the species' entire distribution range and covering all relevant drainage systems, and genotyped 509 individuals at eight variable microsatellite loci. Applying various population genetic analyses, we identify five distinct groups of populations that are only partly in agreement with the proposed ichthyogeographic districts. Our group I, which is formed by specimens from Veneto and the Po River system draining into the Adriatic Sea, corresponds to the Padano-Venetian ichthyogeographic district (PV), except for two Middle Adriatic drainages, which we identify as a separate group (III). The Tuscano-Latium district (TL) is equivalent to our group V. A more complex picture emerges for the Ligurian drainages: populations from Central Liguria belong to group I, while populations from West (group II) and East Liguria (group IV) form their own groups, albeit with affinities to PV and TL, respectively.ConclusionsWe propose a phylogeographic scenario for T. muticellus in which an initial T. muticellus stock became isolated from the 'Alpine' clade and survived the various glaciation cycles in several refugia. These were situated in the Upper Adriatic (groups I and II), the Middle Adriatic (group III), (East) Liguria (group IV) and Tuscano-Latium (group V). The population structure in the vairone is, in principal, in agreement with the two main ichthyogeographic districts (PV and TL), except for the two populations in the Middle Adriatic, which we identify as additional major "district".

Analysis of human hair cross sections from two different population groups by Nuclear Microscopy

Trace element analysis of hair is used as a screening technique to assess body-nutrient levels and/or toxicity due to environmental pollutants. With the aim to compare element content and spatial distribution within scalp hair-shaft cross sections of two distinct human population groups, and to assess possible similarities and/or differences, hair samples from Sudan and South Africa were collected. Proton backscattering and Micro-PIXE were used to determine the matrix composition and content of light and middle transition elements, with beam energies of 1.5 and 3.0 MeV. Mapping analysis showed a relatively similar content distribution for S, Cl, K and Ca within each group. However significant differences, particularly for heavier metals, such as Fe and Zn were also found. Correspondence Analysis of the data showed a clear separation between the two groups when the total content over the hair cross section was considered.

Comprehensive Sequence Analysis of the Human IL23A Gene Defines New Variation Content and High Rate of Evolutionary Conservation

A newly described heterodimeric cytokine, interleukin-23 (IL-23) is emerging as a key player in both the innate and the adaptive T helper (Th)17 driven immune response as well as an initiator of several autoimmune diseases. The rate-limiting element of IL-23 production is believed to be driven by expression of the unique p19 subunit encoded by IL23A. We set out to perform comprehensive DNA sequencing of this previously under-studied gene in 96 individuals from two evolutionary distinct human population groups, Southern African Bantu and European. We observed a total of 33 different DNA variants within these two groups, 22 (67%) of which are currently not reported in any available database. We further demonstrate both inter-population and intra-species sequence conservation within the coding and known regulatory regions of IL23A, supporting a critical physiological role for IL-23. We conclude that IL23A may have undergone positive selection pressure directed towards conservation, suggesting that functional genetic variants within IL23A will have a significant impact on the host immune response.

Genetic diversity in Tunisian Crataegus azarolus L. var. aronia L. populations assessed using RAPD markers

• The genetic diversity of nine wild Tunisian Crataegus azarolus var. aronia L. populations from different bioclimates was assessed using RAPD markers.• Eight selected primers generated a total of 105 bands, 81 of which were polymorphic. Shannon’s index (H ′) ranged from 0.222 to 0.278 according to a population with an average of 0.245. The genetic variation within the species (H SP = 0.423) was relatively low. A high differentiation (G ST = 0.421) among populations coupled with a low level of gene flow (N m = 0.472) were observed. The analysis of molecular variance (AMOVA) revealed also significant differentiation among populations (ΦST = 0.371), even at a low scale space. The majority of variation occurred within populations (63.31%). The Mantel test performed on genetic (ΦST ) and geographic distance matrices among population pairs did not reveal an isolation by distance.• Interpretation of Neighbour-joining tree based on Nei’s and Li’s genetic distance among individuals showed distinct population groupings. The UPGMA dendrogram based on ΦST values revealed two population sub-clusters, each including populations from different bioclimates and/or geographic regions.• The low level of genetic diversity and the high genetic structure of populations resulted from genetic drift caused both by habitat fragmentation and the low size of populations.• The high differentiation among populations and the similar low level of diversity within populations suggest that in situ conservation should interest all populations. The ex situ conservation should be based on the collection of seeds rather within than among populations because of the maximum of variation was revealed within populations.

Genetic structure of a unique admixed population: implications for medical research

STATEMENT: In naming population groups, we think a chief aim is to use terms that the group members use themselves, or find familiar and comfortable. The terms used in this manuscript to describe populations are as historically correct as possible and are chosen so as not to offend any population group. Two of the authors (DCP and REvdR) belong to the Coloured population, with one of the authors (REvdR) having contributed extensively to current literature on the history of the Coloured people of South Africa and served as Vice-President of the South African Institute of Race Relations. According to the 2001 South African census (http://www.statssa.gov.za/census01/HTML/CInBrief/CIB2001.pdf), "Statistics South Africa continues to classify people by population group, in order to monitor progress in moving away from the apartheid-based discrimination of the past. However, membership of a population group is now based on self-perception and self-classification, not on a legal definition. Five options were provided on the questionnaire, Black African, Coloured, Indian or Asian, White and Other. Responses in the category 'Other' were very few and were therefore imputed". We have elected to use the term Bushmen rather than San to refer to the hunter-gatherer people of Southern Africa. Although they have no collective name for themselves, this decision was based on the term Bushmen (or Bossiesman) being the more familiar to the communities themselves, while the term San is the more accepted academic classification. Understanding human genetic structure has fundamental implications for understanding the evolution and impact of human diseases. In this study, we describe the complex genetic substructure of a unique and recently admixed population arising approximately 350 years ago as a direct result of European settlement in South Africa. Analysis was performed using over 900 000 genome-wide single nucleotide polymorphisms in 20 unrelated ancestry-informative marker selected Coloured individuals and made comparisons with historically predicted founder populations. We show that there is substantial genetic contribution from at least four distinct population groups: Europeans, South Asians, Indonesians and a population genetically close to the isiXhosa sub-Saharan Bantu. This is in good accord with the historical record. We briefly examine the implications of determining the genetic diversity of this population, not only for furthering understanding of human evolution out of Africa, but also for genome-wide association studies using admixture mapping. In conclusion, we define the genetic structure of a uniquely admixed population that holds great potential to advance genetic-based medical research.

Functional impact of sequence variation in the promoter region of TGFB1

Pathological deregulation of the transforming growth factor, beta 1 (TGFB1) pathway has been implicated in the development of several major diseases, including cancers. Regulatory variation in the TGFB1 gene may lead to altered TGFB1 expression and activity, and thus, modulate an individual's susceptibility to disease. Here, we performed a study of the functional relevance of cis-acting regulatory variation in the proximal promoter region of the TGFB1 gene. In a previous study, 9 promoter polymorphisms were identified in the 2kb region upstream of the transcription start site and 9 distinct promoter haplotypes were inferred from a panel of individuals from 5 distinct continental population groups. Following experimental validation, we found that the 2 major haplotypes significantly influenced TGFB1 transcriptional activity in an allele-specific manner and that 3 of the SNPs (-1886G>A, -509C>T and -1550DEL/AGG) altered DNA-protein complex formation. Though the biological relevance of these findings remains to be verified, our study suggests that polymorphisms in the TGFB1 promoter could indeed influence gene expression and potentially contribute to the pathogenesis of TGFB1 related diseases.

Revisiting MSUD in Portuguese Gypsies: Evidence for a Founder Mutation and for a Mutational Hotspot within the BCKDHA Gene

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder of branched-chain amino acid metabolism. In the context of the wide mutational spectrum known for this disease, a few common mutations have been described in populations where founder effects played a major role in modeling diversities. In Portugal, for instance, a high proportion of patients are of Gypsy origin and all share the same mutation (c.117delC-alpha; p.R40GfsX23), causing the neonatal severe form of MSUD. In this study, we used four microsatellite markers closely flanking the BCKDHA gene (E1alpha protein) to demonstrate that c.117delC-alpha is a founder mutation responsible for the high incidence of the disorder among Portuguese Gypsies. These results are of medical relevance since carrier tests and prenatal diagnosis can be offered to families at risk, particularly because the carrier frequency of c.117delC-alpha was estimated at 1.4% among the healthy Portuguese Gypsies from the South of the country. Finally we present evidence that the genomic region of the BCKDHA gene where c.117delC-alpha is located is likely a mutational hotspot, since recurrence of c.117delC-alpha was observed in two distinct population groups.