Blood group typing in five Afghan populations in the North Hindu-Kush region: implications for blood transfusion practice.

International audienceBACKGROUND AND OBJECTIVES: Blood incompatibility arises from individual and ethnic differences in red blood cell (RBC) antigen profiles. This underlines the importance of documenting RBC antigen variability in various ethnic groups. Central Asia is an area with a long and complex migratory history. The purpose of this article is to describe key antigen frequencies of Afghan ethnic groups in the Hindu-Kush region of Afghanistan as a basis for improving blood transfusion practices in that area. MATERIALS AND METHODS: The key ABO, Rh and Kell antigens were investigated in five Afghan populations. In order to depict accurately the blood group gene diversity in the area, DNA from eight additional Pakistani populations were included, and the entire sample set screened using two multiplex polymerase chain reactions sensitive for 17 alleles in 10 blood group genetic systems (MNS, Kell, Duffy, Kidd, Cartwright, Dombrock, Indian, Colton, Diego and Landsteiner-Wiener). RESULTS: Phenotype and allele frequencies fell within the ranges observed in Western European and East Asian populations. Occurrence of DI*01, IN*01, LW*07 and FY*02N.01 and prevalence of ABO*B were consistent with migratory history as well as with putative environmental adaptation in the subtropical environment Hindu-Kush region. CONCLUSION: These findings expand the current knowledge about key antigen frequencies. Regarding occurrence of viral markers, further blood transfusion in the region requires rigorous typing

Genome-wide analysis of Corsican population reveals a close affinity with Northern and Central Italy

Despite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Corsica may have caused genetic isolation, which, in turn, might be relevant under medical and translational perspectives. Here we analysed genome wide data of 16 Corsicans, and integrated with newly (33 individuals) and previously generated samples from West Eurasia and North Africa. Allele frequency, haplotype-based, and ancient genome analyses suggest that although Sardinia and Corsica may have witnessed similar isolation and migration events, the latter is genetically closer to populations from continental Europe, such as Northern and Central Italians

Y-chromosome phylogeographic analysis of the Greek-Cypriot population reveals elements consistent with Neolithic and Bronze Age settlements

International audienceBackground: The archeological record indicates that the permanent settlement of Cyprus began with pioneering agriculturalists circa 11,000 years before present, (ca. 11,000 y BP). Subsequent colonization events followed, some recognized regionally. Here, we assess the Y-chromosome structure of Cyprus in context to regional populations and correlate it to phases of prehistoric colonization. Results: Analysis of haplotypes from 574 samples showed that island-wide substructure was barely significant in a spatial analysis of molecular variance (SAMOVA). However, analyses of molecular variance (AMOVA) of haplogroups using 92 binary markers genotyped in 629 Cypriots revealed that the proportion of variance among the districts was irregularly distributed. Principal component analysis (PCA) revealed potential genetic associations of Greek-Cypriots with neighbor populations. Contrasting haplogroups in the PCA were used as surrogates of parental populations. Admixture analyses suggested that the majority of G2a-P15 and R1b-M269 components were contributed by Anatolia and Levant sources, respectively, while Greece Balkans supplied the majority of E-V13 and J2a-M67. Haplotype-based expansion times were at historical levels suggestive of recent demography. Conclusions: Analyses of Cypriot haplogroup data are consistent with two stages of prehistoric settlement. E-V13 and E-M34 are widespread, and PCA suggests sourcing them to the Balkans and Levant/Anatolia, respectively. The persistent pre-Greek component is represented by elements of G2-U5(xL30) haplogroups: U5*, PF3147, and L293. J2b-M205 may contribute also to the pre-Greek strata. The majority of R1b-Z2105 lineages occur in both the westernmost and easternmost districts. Distinctively, sub-haplogroup R1b-M589 occurs only in the east. The absence of R1b-M589 lineages in Crete and the Balkans and the presence in Asia Minor are compatible with Late Bronze Age influences from Anatolia rather than from Mycenaean Greeks

Defining KIR and HLA Class I Genotypes at Highest Resolution via High-Throughput Sequencing.

The physiological functions of natural killer (NK) cells in human immunity and reproduction depend upon diverse interactions between killer cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands: HLA-A, HLA-B, and HLA-C. The genomic regions containing the KIR and HLA class I genes are unlinked, structurally complex, and highly polymorphic. They are also strongly associated with a wide spectrum of diseases, including infections, autoimmune disorders, cancers, and pregnancy disorders, as well as the efficacy of transplantation and other immunotherapies. To facilitate study of these extraordinary genes, we developed a method that captures, sequences, and analyzes the 13 KIR genes and HLA-A, HLA-B, and HLA-C from genomic DNA. We also devised a bioinformatics pipeline that attributes sequencing reads to specific KIR genes, determines copy number by read depth, and calls high-resolution genotypes for each KIR gene. We validated this method by using DNA from well-characterized cell lines, comparing it to established methods of HLA and KIR genotyping, and determining KIR genotypes from 1000 Genomes sequence data. This identified 116 previously uncharacterized KIR alleles, which were all demonstrated to be authentic by sequencing from source DNA via standard methods. Analysis of just two KIR genes showed that 22% of the 1000 Genomes individuals have a previously uncharacterized allele or a structural variant. The method we describe is suited to the large-scale analyses that are needed for characterizing human populations and defining the precise HLA and KIR factors associated with disease. The methods are applicable to other highly polymorphic genes.This study was supported by U.S. National Institutes of Health grants U01 AI090905, R01 20 GM109030, R01 AI17892 and U19 AI119350. Authors Steven Norberg and Mostafa Ronaghi are 21 employees of Illumina Inc.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Elsevier

An efficient multiplex genotyping approach for detecting the major worldwide human Y-chromosome haplogroups

The Y chromosome is paternally inherited and therefore serves as an evolutionary marker of patrilineal descent. Worldwide DNA variation within the non-recombining portion of the Y chromosome can be represented as a monophyletic phylogenetic tree in which the branches (haplogroups) are defined by at least one SNP. Previous human population genetics research has produced a wealth of knowledge about the worldwide distribution of Y-SNP haplogroups. Here, we apply previous and very recent knowledge on the Y-SNP phylogeny and Y-haplogroup distribution by introducing two multiplex genotyping assays that allow for the hierarchical detection of 28 Y-SNPs defining the major worldwide Y haplogroups. PCR amplicons were kept small to make the method sensitive and thereby applicable to DNA of limited amount and/or quality such as in forensic settings. These Y-SNP assays thus form a valuable tool for researchers in the fields of forensic genetics and genetic anthropology to infer a man's patrilineal bio-geographic ancestry from DNA

Genetics and the Archaeology of Ancient Israel

This paper is a call for DNA testing on ancient skeletal materials from the southern Levant to begin to database genetic information of the inhabitants of this crossroads region. Archaeologists and biblical historians view the earliest presence in the region of a group that called itself Israel in the Iron I period, traditionally dated to ca. 1200-1000 BCE. These were in villages in the varied hill countries of the region, contemporary with urban settlements in the coastal plains, inland valleys, and central Hill Country attributed to varied indigenous groups collectively called Canaanite. The remnants of Egyptian imperial presence in the region lasted until around 1150 BCE, postdating the arrival of an immigrant group from the Aegean called the Philistines ca. 1175 BCE. The period that follows the Iron I in the southern Levant is marked by the development of territorial states throughout the region, ca. 1000-800 BCE. These patrimonial kingdoms, including the United Kingdom of Israel and the divided kingdoms of northern Israel and Judah, coalesced varied peoples under central leadership and newly founded administrative and religious bureaucracies. Ancient DNA testing will give us a further refined understanding of the individuals who peopled the region of the southern Levant throughout its varied archaeological and historic periods, and put forward scientific data that will support, refute, or nuance our socio-historic reconstruction of ancient group identities. These social identities may or may not map onto genetic data, and without sampling of ancient DNA we may never know. A database of ancient DNA will also allow for comparisons with modern DNA samples collected throughout the greater region and the Mediterranean littoral, giving a more robust understanding of the long historical trajectories of regional human genetics and the genetics of varied ancestral groups of today’s Jewish populations and other cultural groups in the modern Middle East and Mediterranean

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

Genes flow by the channels of culture: the genetic imprint of matrilocality in Ngazidja, Comoros Islands

International audienc

Environmental and genetic determinants of two Vitamin D metabolites in healthy Australian children

Background: Vitamin D deficiency has been associated with adverse health outcomes. We examined genetic and environmental determinants of serum 25(OH)D3 and 1,25(OH)2D3 in childhood.Methods: The study sample consisted of 322 healthy Australian children (predominantly Caucasians) who provided a venous blood sample. A parental interview was conducted and skin phototype and anthropometry measures were assessed. Concentrations of 25(OH)D3 and 1,25(OH)2D3 were measured by selective solid-phase extraction-capillary liquid chromatography-tandem mass spectrometry. These concentrations were deseasonalised where relevant to remove the effect of month of sampling.Results: Deseasonalised log 25(OH)D3 and 1,25(OH)2D3 concentrations were only moderately correlated (r=0.42, pConclusions: Environmental factors and genetic factors contributed to both vitamin D metabolite concentrations. The intriguing finding that the higher ambient UVR contributed to higher 1,25(OH)2D3 after accounting for 25(OH)D3 concentrations requires further evaluation