BACKGROUND: The study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. METHODS: We performed two case-control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. RESULTS: We detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). CONCLUSIONS: These results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.

Alkali silica reaction (ASR), a reaction which occurs between reactive siliceous mineral components in the aggregate and the alkaline pore solution in concrete, is responsible for substantial damage to concrete structures in the U. S. and across the world. Lithium admixtures, including lithium nitrate (LiNO3), have been demonstrated to mitigate ASR damage, and are of particular interest for use in concrete airfield pavement construction, where ASR damage has been recently linked to the use of certain de-icing chemicals. Although the effectiveness of lithium admixtures at ASR-mitigation is well-researched, relatively less is known regarding the potential effects, including negative effects, on overall concrete behavior. The goal of this research is to better understand the influence of LiNO3 admixture on early age concrete behavior, and to determine if a maximum dosage rate for its use exists. Isothermal calorimetry, rheology and bleed water testing, time of setting, chemical shrinkage, autogenous shrinkage, free and restrained concrete shrinkage, and compressive and flexural strength were measured for pastes and concretes prepared with a range of LiNO3 dosages (i.e., 0, 50, 100, 200, and 400% of the recommended dosage). In addition, the interaction of LiNO3 with cement was evaluated by comparing results obtained with six cements of varying alkali and tricalcium aluminate (C3A) contents. Additionally, one of these cements, was examined alone and with 20% by weight Class F fly ash replacement. Results indicate that the hydration of the tricalcium silicate and tricalcium aluminate components of cement are accelerated by the use of LiNO3, and that low alkali cements (typically specified to avoid damage by ASR) may be particularly susceptible to this acceleration. However, inclusion of Class F fly ash at 20% by weight replacement of cement (also common in applications where ASR is a concern) appears to diminish these possibly negative effects of LiNO3 on early age hydration acceleration and heat generation. Dosages higher than the current standard dosage of LiNO3 may have minor effects on fresh concrete workability, causing slight decreases in Bingham yield stress, corresponding to slightly higher slump. Fresh concrete viscosity may also be affected, though more research is necessary to confirm this effect. LiNO3 had no effect on quantity of bleed water in the mixes tested. Generally, LiNO3 had no effect on initial and final setting times, although increasing dosages caused faster set times in the lowest alkali (Na2Oeq = 0.295%) cement examined. In shrinkage testing, higher LiNO3 dosages appeared to cause initial expansion in some sealed paste specimens, but in all cases the highest dosage led to greater autogenous shrinkage after 40 days. In concrete specimens, however, the restraining effect of aggregates diminished shrinkage, and no effect of the LiNO3 was apparent. In no cases, with any dosage of lithium tested, with or without fly ash replacement, did restrained shrinkage specimens show any cracking. Strength testing produced mixed results, with laboratory specimens increasing in 28-day compressive strength, but companion specimens cast in the field and tested by an outside laboratory, exhibited lower 28-day compressive strength, with increasing lithium dosages. Flexural specimens, also cast in the field and tested by an outside laboratory, appeared to show an increase in 28-day flexural strength with increasing lithium dosages. However, because of the conflicting results when comparing the various strength data, further research is necessary for conclusive evidence of LiNO3 effects on concrete strength.

This study reports the findings of an investigation of ten polymorphic autosomal tetranucleotide short tandem repeat loci and Y chromosome haplotype diversity among the genetically diverse populations of UK Leicestershire caucasians, New Zealand Maori and other Polynesian Islanders. The ten autosomal loci were initially isolated and sequenced by the Utah Marker Development group. This present study optimised the methodology for use with unlabelled primers and submarine gel electrophoresis technology. Little or no previous population or forensic genetic research had been carried out incorporating the ten loci presented in this study.

No description available.

Mixture between populations is an evolutionary process that shapes genetic variation. Intermixing between groups of distinct ancestries creates mosaics of chromosomal segments inherited from multiple ancestral populations. Studying populations of mixed ancestry (admixed populations) is of special interest in population genetics as it not only provides insights into the history of admixed groups but also affords an opportunity to reconstruct the history of the ancestral populations, some of whom may no longer exist in unmixed form. Furthermore, it improves our understanding of the impact of population migrations and helps us discover links between genetic and phenotypic variation in structured populations. The majority of research on admixed populations has focused on African Americans and Latinos where the mixture is recent, having occurred within the past 500 years. In this dissertation, I describe several studies that I have led that expand the scope of admixed studies to West Eurasians and South Asians where the mixture is older, and data from ancestral groups is mostly unavailable. First, I introduce a novel method that studies admixture linkage disequilibrium (LD) to infer the time of mixture. I analyze genomewide data from 40 West Eurasian populations and show that all Southern European, Levantine and Jewish groups have inherited sub-Saharan African ancestry in the past 100 generations, likely reflecting events during the Roman Empire and subsequent Arab migrations. Next, I apply a range of methods to study the history of Siddi groups that harbor African, Indian and Portuguese ancestry, and to infer the history of Roma gypsies from Europe. Finally, I develop a novel approach that combines the insights of frequency and LD-based statistics to infer the underlying model of mixture. I apply this method to 73 South Asian groups and infer that major mixture occurred ~2,000-4,000 years ago. In a subset of populations, all the mixture occurred during this period, a time of major change in India marked by the de- urbanization of the Indus valley civilization and recolonization of the Gangetic plateau. Inferences from our analyses provide novel insights into the history of these populations as well as about the broad impact of human migrations.

Human populations evolved throughout the Old World for over 1 million years. However, anatomical characteristics of modern humans are thought to have evolved only in Africa in the last 200 thousand years. To this day, the extent to which archaic human populations contributed to the modern human gene pool is largely unknown. This work explores the evidence of genetic contribution from archaic populations at two loci in chromosome 12. Two different archaic humans, Neandertal and Denisova, living respectively in West Eurasia and in East Asia, have been indicated as potential contributors to anatomically modern human populations outside of Africa. This research shows the presence in non-Africans of two distinct introgressive alleles from archaic populations at the immune genes OAS1 and STAT2. In addition to the detection of patterns of genetic variation previously proposed as indicators of genetic introgression from archaic populations, it was possible to use the sequence of archaic individuals to infer a recent common ancestry between the introgressive modern allele and the archaic sequences. The analysis of genetic variation at the genomic region containing the gene STAT2 shows the presence of introgressive Neandertal-like and Denisova-like haplotypes. The elevated frequency in Melanesian populations of the haplotype introgressive from Neandertals suggests that this haplotype has been adaptive in Melanesians (APPENDIX B). A haplotype of the gene OAS1, nearly restricted to Melanesian populations, provides evidence of introgression from a population with genetic affinities to Denisova. The introgressive haplotype carries non-synonymous variants predicted to have functional significance and a block of very deep divergence with the remaining modern sequences (APPENDIX A). A second haplotype, observed mostly in Eurasian populations, shows evidence of having introgressed recently from Neandertals. The Neandertal-like haplotype also contains a block with very deep divergence with the remaining modern sequences (APPENDIX C). Blocks of very deep divergence within introgressive haplotypes suggest an important role of ancient population structure in the evolution of humans.

The history of North Africa is extremely complex, and it has been difficult to assess from genetic and archeological data whether early populations were replaced by later migrations or if there has been continuous settlement of the region. To resolve the history of human origin and migrations in North Africa, I have used two main forms of genetic data, the maternally inherited mtDNA and 730,000 genome-wide SNPs from a genotype array in a sample set representative of the region. I have discovered that North Africa is a mosaic of an autochthonous component dating back to the Paleolithic and at least four other ancestries, two recent ancestries from sub-Saharan Africa and the others from Europe and the Near East. We have also discovered extensive North African gene flow to the Iberian Peninsula, and minor proportions in the rest of the Europe. / La història del Nord d’Àfrica és extremadament complexa, i fins ara ha estat molt difícil determinar a partir de la genètica o l’arqueologia si els primers pobladors van ser reempleçats per migracions posteriors, o si el poblament de la regió ha estat continuat al llarg del temps. Per tal d’investigar els orígens i les migracions de l’home al Nord d’Àfrica he fet servir dos marcadors genètics en un grup de poblacions representatives de la regio, el marcador heretat per via materna, el DNA mitocondrial (mtDNA), i 730,000 SNPs de tot el genoma genotipats amb un xip. He descobert que el Nord d’Àfrica és un mosaic format per un component autòcton amb origens en el Paleolític i un mínim de quatre components més, dos d’ells recents d’origen sub-Saharià i els altres Europeu i d’Orient Proper. També hem descobert un flux genic recent d’origen Nord Africà molt elevat a la Península Ibèrica, i en menor quantitat a Europa.

The genus Vitis (the grapevine) is a group of highly diverse, diploid woody perennial vines consisting of approximately 60 species from across the northern hemisphere. To gain insights into the use of wild Vitis species during the past century of interspecific grape breeding and to provide a foundation for marker- assisted breeding programmes, we present a principal components analysis based ancestry estimation method to calculate admixture proportions of hybrid grapes in the United States Department of Agriculture grape germplasm collection using genome-wide polymorphism data. We find that grape breeders have backcrossed to both the domesticated V. vinifera and wild Vitis species and that reasonably accurate genome-wide ancestry estimation can be performed on interspecific Vitis hybrids using a panel of fewer than 50 ancestry informative genetic markers.

This study examined the amount of European genetic admixture in the enslaved African population from Newton Plantation, Barbados. Newton Plantation was a British sugar plantation from the 17th to 19th centuries. Approximately 150 individuals were recovered from an unmarked slave cemetery during archaeological investigations in the 1970s and 1990s. Using maximum mesiodistal and buccolingual tooth measurements of the available teeth from the individuals in the cemetery, Newton was compared to nineteen comparative samples of African, European, African American and European American populations that date from the time of British colonization to the 20th century. Previous European admixture estimations in the Newton Plantation cemetery sample were 5-10% (Corruccini et al., 1982; Ritter, 1991); this study found similar rates of admixture in the population (5.38-10.25%). Because of social practices in the Caribbean during the time of slavery, European admixture could have resulted in preferential treatment of slaves with such genetic background.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-08-29T21:26:52Z No. of bitstreams: 1 Taisa Manuela Bonfim Machado. Ancestralidade em Salvador - BA.pdf: 1157160 bytes, checksum: b3800dd208ac4ea86750232d8ab8ef3d (MD5) / Made available in DSpace on 2012-08-29T21:26:52Z (GMT). No. of bitstreams: 1 Taisa Manuela Bonfim Machado. Ancestralidade em Salvador - BA.pdf: 1157160 bytes, checksum: b3800dd208ac4ea86750232d8ab8ef3d (MD5) Previous issue date: 2008 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / Os ameríndios, africanos e europeus foram identificados como principais formadores da população brasileira e conseqüentemente da população de Salvador. A população brasileira considerada a mais heterogênea do mundo é resultado de 500 anos de miscigenação. Contudo a distribuição dos grupos étnicos ancestrais ao longo do território brasileiro não ocorreu de forma homogênea, diferindo significativamente a depender da região geográfica. Além disso, houve um forte direcionamento entre os casamentos, sendo mais freqüentes as uniões entre homens europeus e mulheres ameríndias e africanas. Dados do IBGE 2000 mostram que em Salvador o percentual de afrodescendentes, por autodenominação é de 79,8%. Para estimarmos a contribuição dos grupos ancestrais nesta população foram analisados 1.286 indivíduos, provenientes da população de Salvador, para os alelos específicos de população AT3-I/D, APO, SB19.3, PV92, FYnull, LPL, CKMM, GC e CYP3A4 que apresentam alto diferencial de freqüência entre os grupos ancestrais. Para estimar a origem africana dos indivíduos também foi avaliada a presença de sobrenome de conotação religiosa. Foram identificados 287 sobrenomes nesta população A freqüência de sobrenomes de conotação religiosa foi de 54,9% na população de Salvador e avaliando as regiões presentes no estudo observamos uma relação inversa entre a classe sócio-econômica e a presença deste tipo de sobrenome. Estes dados foram confirmados por uma maior ancestralidade genômica africana (53,1%) entre indivíduos que apresentam sobrenomes de conotação religiosa. A miscigenação da população de Salvador foi confirmada pela diferença das freqüências desta população com as ancestrais. Assim como pela estimativa de mistura populacional, com contribuição africana de 49,2%; 36,3% européia e 14,5% ameríndia e também pelas análises de heterozigose média (0,397) e estrutura populacional. Foi calculada a estatística F (0,005) que demonstrou que as regiões da cidade de Salvador são diferentes, porém em pequenas proporções. Ao compararmos a estimativa da contribuição africana do IBGE, 2000, por autodenominação com os dados de sobrenome e moleculares deste trabalho concluímos que a autodenominação é um critério impreciso na avaliação da contribuição parental dentro desta população. Este tipo de trabalho pode auxiliar estudos de associação entre fatores de saúde com a heterogeneidade ancestral para melhoria e/ou implantação de programas de saúde pública que considerem a composição parental desta população. / Native American, Africans and Europeans are the major founder populations of Brazil and of Salvador city. Brazilian population is considered as the most heterogeneous in the world, resulting from 5 centuries of miscegenation. However, ethnic ancestral groups were not distributed equally in the different Brazilian regions. In addition, a strong bias occurred originated by more frequent unions among European men and Amerindians and Africans women. Results from IBGE 2000 show that in Salvador the percent of selfclassification afrodescending, is 79.8 %. To estimate the contribution of ancestral groups in these populations we analyzed some population specific alleles: AT3-I/D, APO, SB19.3, PV92, FYnull, LPL, CKMM, GC and CYP3A4 from 1,286 subjects of Salvador that presents large frequency differential among ancestry groups. To estimate the African origin of the subjects we also analyzed the religious connotation surnames. We identified 287 surnames in these populations. In Salvador population, the frequency of religious connotation surnames was 54. 9% and we observed an inverse relation between socioeconomic status and the presence of this type of surname. These data were confirmed for a major African genomic ancestry (53. 1%) between individuals that present religious connotation surname. The miscegenation of Salvador was confirmed by the frequencies differences in this population with the ancestry, such as the population admixture esteemed, with African contribution of 49.2%; 36.3% European and 14.5% Amerindian and also by heterozygosis mediam analyses (0,397) and populational structure. F statistic (0,005) was calculated and showed differences between regions in the city, but in little proportions, confirming the admixture estimated in these regions. When we compared IBGE- 2000 African contribution esteemed, by autodenomination, with the surnames and molecular data of this work we concluded that autodenomination is an inaccurate criterion to evaluate the parental contribution into this population. This kind of work can support association studies among health factors with ancestry heterogeneity to improve and/or to implement public health programs that consider the parental composition of this population.