In large-scale population genomic data sets, individual chromosomes are likely to share extended regions of haplotype identity with others in the sample. Patterns of local haplotype sharing can be highly informative about many processes including historical demography, selection and recombination. However, in outbred diploid populations, the identification of extended shared haplotypes is not straightforward, particularly in the presence of low levels of genotyping error. Here, we introduce a model-based method for accurately detecting extended haplotype sharing between sets of individuals from unphased data. We describe two implementations of the algorithm that can be applied to data sets consisting of thousands of samples. The method leads naturally to an approach for statistical haplotype estimation, which is shown to be comparable in accuracy to current methods. By applying the method to genome-wide SNP data from over 5,000 samples from the UK we show that the N50 maximal haplotype sharing between unrelated samples is typically 2cM, consistent with a population history of rapid exponential growth that started approx. 125 generations ago. In contrast, within two Greek population isolates of approx. 700 individuals the N50 for maximal haplotype sharing is 12.5cM, while for an unrelated Greek sample of the same size the N50 is 1.3cM. By assessing the size and geographical distribution of maximal haplotype sharing within and between all Greek cohorts, we make inference on the extent of isolatedness of each cohort and on recent migration. We additionally date recent coancestry to about 10 generations for the isolates and 90 generations for the unrelated sample, and finnally attempt to date the time of divergence between them.

The aim of the present study was to evaluate the power of discrimination and genetic (diversity) parameters in the Y chromosome extended haploytpe markers in populations of Tanzania for forensic and populations studies. Eleven Y chromosome extended haplotype markers were selected for this study, these includes Minimal haplotypes markers i.e. DYS19, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS389I/II and two additional markers DYS438 and DYS439. Six populations of Tanzania were investigated under this study. These populations were selected based on the language family categories / Niger Congo (Kuria and Sukuma), Nilo Saharan (Luo and Maasai) and Afro Asiatic (Iraqw and Alagwa).

The aim of the present study was to evaluate the power of discrimination and genetic (diversity) parameters in the Y chromosome extended haploytpe markers in populations of Tanzania for forensic and populations studies. Eleven Y chromosome extended haplotype markers were selected for this study, these includes Minimal haplotypes markers i.e. DYS19, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS389I/II and two additional markers DYS438 and DYS439. Six populations of Tanzania were investigated under this study. These populations were selected based on the language family categories / Niger Congo (Kuria and Sukuma), Nilo Saharan (Luo and Maasai) and Afro Asiatic (Iraqw and Alagwa).

The aim of the present study was to evaluate the power of discrimination and genetic(diversity) parameters in the Y chromosome extended haploytpe markers in populations of Tanzania for forensic and populations studies. Eleven Y chromosome extended haplotype markers were selected for this study, these includes Minimal haplotypes markers i.e. DYS19, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS389I/II and two additional markers DYS438 and DYS439. Six populations of Tanzania were investigated under this study. These populations were selected based on the language family categories; Niger Congo (Kuria and Sukuma), Nilo Saharan (Luo and Maasai) and Afro Asiatic (Iraqw and Alagwa).Buccal swabs were collected from unrelated males from Mwanza province (Sukuma),Mara (Kuria and Luo), Arusha (Maasai and Iraqw) and Dodoma province (Alagwa).Samples were typed using ABI 377 Genetic Analyser (Applied Biosystem) followed by analysis using softwares Gelprocessor, GeneScan 3.0.0 (Applied Biosystems) and Genotyper 3.7 (Applied Biosystems). The data obtained were analysed by GenePop 4.0,Arlequin 3.11 and Genetix v.4.05.2 software packages. Analyses such as AMOVA, Fst population pairwise comparison, Factorial component Analysis were used to obtain Allele frequency, haplotype frequency, gene diversities among various loci and levels of gene flow between populations.For the overall individuals, the highest Gene Diversity value was 0.8251 (DYS385) and the lowest was 0.2723 (DYS392). The overall Haplotype Diversity was 0.9984 and Discrimination capacity resulted 84.27%. A total of 225 distinct haplotypes were identified in 267 individuals, 28 were shared, the most frequent haplotype was present in 5 individuals. The levels of genetic diversity for the haplotypes per group as revealed by haplotype diversities confirmed that the most diverse group being Sukuma, Kuria,Iraqw, Maasai, Luo and Alagwa being the least diverse. The Discrimination capacity of these set of markers showed the highest value in Sukuma population (100%) subsequently followed by Iraqw, Luo, Maasai, Kuria and Alagwa (78.38%) being the lowest. Analysis of Molecular Variance showed a significant differentiation among populations, 93.96% of variance was found within population and 6.04% among population. Population pairwise results between all population pairs (except Sukuma and kuria and Alagwa and Luo) showed significant results (P < 0.05). Genetic heterogeneity that was found among Tanzanian populations could not be attributed to language barriers but was largely being contributed by a limited level of gene flow between these populations due to different ethnical, social, cultural and historical backgrounds between them. All Y chromosome extended haplotype loci used in this study (except DYS392 and DYS391 which showed the lowest level of polymorphism) were found to be likely useful for forensic application in Tanzania. Furthermore the extended haplotype markers used in this study may be useful in the establishment of the National DNA database following the enactment of the Human DNA Legislation in Tanzania (http://www.parliament.go.tz). / Magister Scientiae - MSc

Magister Scientiae - MSc / The aim of the present study was to evaluate the power of discrimination and genetic (diversity) parameters in the Y chromosome extended haploytpe markers in populations of Tanzania for forensic and populations studies. Eleven Y chromosome extended haplotype markers were selected for this study, these includes Minimal haplotypes markers i.e. DYS19, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS389I/II and two additional markers DYS438 and DYS439. Six populations of Tanzania were investigated under this study. These populations were selected based on the language family categories; Niger Congo (Kuria and Sukuma), Nilo Saharan (Luo and Maasai) and Afro Asiatic (Iraqw and Alagwa). / South Africa

Erythrocytes infected by mature forms of the Plasmodium falciparum parasite adhere to other components of the vascular space, a behavior considered critical to the pathogenesis of severe malaria. Adhesion is mediated by the P. falciparum erythrocyte membrane protein 1 (PfEMP1), a highly variant antigen expressed by the parasite and subject to switching during the course of an infection. The host ligands of PfEMP1 include CD36, ICAM-1 and the ABO antigens. By employing a series of population- and family-based association studies from multiple African populations, we examined whether variation in the genes underlying these molecules affects susceptibility to severe malaria. Our results suggest that a common frameshift mutation in the ABO glycosyltransferase, responsible for blood group O, is associated with protection from severe malarial phenotypes (P=2x10⁻⁷), particularly severe malarial anaemia. However, we found no significant disease associations with variation in either the ICAM1 or CD36 genes. We focused on two particular functional polymorphisms, the missense ICAM-1Kilifi and the CD36 nonsense mutation T1264G. We genotyped both markers in around 10,000 individuals, but neither demonstrated an association with severe malarial phenotypes. Malaria has been a profound selection pressure shaping human genetic diversity. The last decade has seen the development of several haplotype-based methods to detect signatures of recent positive evolutionary selection. These techniques are potentially invaluable tools in our hunt for genetic variants that protect from life threatening malaria. We used simulations and empirical data from the International HapMap Project to demonstrate the validity of searching for long regions of haplotype homozygosity, as an approach to finding alleles undergoing selective sweeps. We analysed genetic data from a range of populations, particularly those utilized by HapMap, to investigate whether our candidate genes were associated with signals of recent positive selection. We characterized the distribution of a selection event associated with the CD36 1264G allele, focused in Central-West Africa, and demonstrated a novel signal of low population differentiation at the ABO gene, suggestive of longstanding balancing selection. Our work confirms that variation in the host ligands of PfEMP1 modulates severe malaria susceptibility, and highlights the value of using signals of selection, along with functional experiments and genetic association studies, to dissect the biology of severe malaria.