Damir Marjanović

Y-chromosomal evidence of the cultural diffusion of agriculture in southeast Europe

The debate concerning the mechanisms underlying the prehistoric spread of farming to Southeast Europe is framed around the opposing roles of population movement and cultural diffusion. To investigate the possible involvement of local people during the transition of agriculture in the Balkans, we analysed patterns of Y-chromosome diversity in 1206 subjects from 17 population samples, mainly from Southeast Europe. Evidence from three Y-chromosome lineages, I-M423, E-V13 and J-M241, make it possible to distinguish between Holocene Mesolithic forager and subsequent Neolithic range expansions from the eastern Sahara and the Near East, respectively. In particular, whereas the Balkan microsatellite variation associated to J-M241 correlates with the Neolithic period, those related to E-V13 and I-M423 Balkan Y chromosomes are consistent with a late Mesolithic time frame. In addition, the low frequency and variance associated to I-M423 and E-V13 in Anatolia and the Middle East, support an European Mesolithic origin of these two clades. Thus, these Balkan Mesolithic foragers with their own autochthonous genetic signatures, were destined to become the earliest to adopt farming, when it was subsequently introduced by a cadre of migrating farmers from the Near East. These initial local converted farmers became the principal agents spreading this economy using maritime leapfrog colonization strategies in the Adriatic and transmitting the Neolithic cultural package to other adjacent Mesolithic populations. The ensuing range expansions of E-V13 and I-M423 parallel in space and time the diffusion of Neolithic Impressed Ware, thereby supporting a case of cultural diffusion using genetic evidence.

A recent bottleneck of Y chromosome diversity coincides with a global change in culture

It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

Genomic analyses inform on migration events during the peopling of Eurasia

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.

The peopling of modern Bosnia-Herzegovina: Y-chromosome haplogroups in the three main ethnic groups.

The variation at 28 Y‐chromosome biallelic markers was analysed in 256 males (90 Croats, 81 Serbs and 85 Bosniacs) from Bosnia‐Herzegovina. An important shared feature between the three ethnic groups is the high frequency of the “Palaeolithic” European‐specific haplogroup (Hg) I, a likely signature of a Balkan population re‐expansion after the Last Glacial Maximum. This haplogroup is almost completely represented by the sub‐haplogroup I‐P37 whose frequency is, however, higher in the Croats (∼71%) than in Bosniacs (∼44%) and Serbs (∼31%). Other rather frequent haplogroups are E (∼15%) and J (∼7%), which are considered to have arrived from the Middle East in Neolithic and post‐Neolithic times, and R‐M17 (∼14%), which probably marked several arrivals, at different times, from eastern Eurasia. Hg E, almost exclusively represented by its subclade E‐M78, is more common in the Serbs (∼20%) than in Bosniacs (∼13%) and Croats (∼9%), and Hg J, observed in only one Croat, encompasses ∼9% of the Serbs and ∼12% of the Bosniacs, where it shows its highest diversification. By contrast, Hg R‐M17 displays similar frequencies in all three groups. On the whole, the three main groups of Bosnia‐Herzegovina, in spite of some quantitative differences, share a large fraction of the same ancient gene pool distinctive for the Balkan area.

Prediction of eye and skin color in diverse populations using seven SNPs.

An essential component in identifying human remains is the documentation of the decedents visible characteristics, such as eye, hair and skin color. However, if a decedent is decomposed or only skeletal remains are found, this critical, visibly identifying information is lost. It would be beneficial to use genetic information to reveal these visible characteristics. In this study, seven single nucleotide polymorphisms (SNPs), located in and nearby genes known for their important role in pigmentation, were validated on 554 samples, donated from non-related individuals of various populations. Six SNPs were used in predicting the eye color of an individual, and all seven were used to describe the skin coloration. The outcome revealed that these markers can be applied to all populations with very low error rates. However, the call-rate to determine the skin coloration varied between populations, demonstrating its complexity. Overall, these results prove the importance of these seven SNPs for potential forensic tests.

Non-invasive prenatal paternity testing from maternal blood

Prenatal paternity analysis can be performed only after invasive sampling of chorionic villi or amnionic fluid. Aiming to enable noninvasive paternity testing, we attempted to amplify fetal alleles from maternal plasma. Cell-free DNA was isolated from plasma of 20 pregnant women and amplified with ampFLSTR Identifiler and ampFLSTR Yfiler kits. Unfortunately, autosomal fetal alleles were heavily suppressed by maternal DNA, and the only locus that was reliably amplified with AmpFLSTR Identifiler kit was amelogenin, which revealed only fetal gender. Much better success was obtained with AmpFLSTR Yfiler kit, which, in the case of male fetuses, successfully amplified between six and 16 fetal loci. All amplified fetal alleles matched the alleles of their putative fathers, confirming the tested paternity. To the best of our knowledge, this is a first report of noninvasive prenatal paternity testing.

No Evidence from Genome-wide Data of a Khazar Origin for the Ashkenazi Jews

Abstract The origin and history of the Ashkenazi Jewish population have long been of great interest, and advances in high-throughput genetic analysis have recently provided a new approach for investigating these topics. We and others have argued on the basis of genome-wide data that the Ashkenazi Jewish population derives its ancestry from a combination of sources tracing to both Europe and the Middle East. It has been claimed, however, through a reanalysis of some of our data, that a large part of the ancestry of the Ashkenazi population originates with the Khazars, a Turkic-speaking group that lived to the north of the Caucasus region ∼1,000 years ago. Because the Khazar population has left no obvious modern descendants that could enable a clear test for a contribution to Ashkenazi Jewish ancestry, the Khazar hypothesis has been difficult to examine using genetics. Furthermore, because only limited genetic data have been available from the Caucasus region, and because these data have been concentrated in populations that are genetically close to populations from the Middle East, the attribution of any signal of Ashkenazi-Caucasus genetic similarity to Khazar ancestry rather than shared ancestral Middle Eastern ancestry has been problematic. Here, through integration of genotypes from newly collected samples with data from several of our past studies, we have assembled the largest data set available to date for assessment of Ashkenazi Jewish genetic origins. This data set contains genome-wide single-nucleotide polymorphisms in 1,774 samples from 106 Jewish and non-Jewish populations that span the possible regions of potential Ashkenazi ancestry: Europe, the Middle East, and the region historically associated with the Khazar Khaganate. The data set includes 261 samples from 15 populations from the Caucasus region and the region directly to its north, samples that have not previously been included alongside Ashkenazi Jewish samples in genomic studies. Employing a variety of standard techniques for the analysis of population-genetic structure, we found that Ashkenazi Jews share the greatest genetic ancestry with other Jewish populations and, among non-Jewish populations, with groups from Europe and the Middle East. No particular similarity of Ashkenazi Jews to populations from the Caucasus is evident, particularly populations that most closely represent the Khazar region. Thus, analysis of Ashkenazi Jews together with a large sample from the region of the Khazar Khaganate corroborates the earlier results that Ashkenazi Jews derive their ancestry primarily from populations of the Middle East and Europe, that they possess considerable shared ancestry with other Jewish populations, and that there is no indication of a significant genetic contribution either from within or from north of the Caucasus region.

Genetic Heritage of the Balto-Slavic Speaking Populations: A Synthesis of Autosomal, Mitochondrial and Y-Chromosomal Data

The Slavic branch of the Balto-Slavic sub-family of Indo-European languages underwent rapid divergence as a result of the spatial expansion of its speakers from Central-East Europe, in early medieval times. This expansion–mainly to East Europe and the northern Balkans–resulted in the incorporation of genetic components from numerous autochthonous populations into the Slavic gene pools. Here, we characterize genetic variation in all extant ethnic groups speaking Balto-Slavic languages by analyzing mitochondrial DNA (n = 6,876), Y-chromosomes (n = 6,079) and genome-wide SNP profiles (n = 296), within the context of other European populations. We also reassess the phylogeny of Slavic languages within the Balto-Slavic branch of Indo-European. We find that genetic distances among Balto-Slavic populations, based on autosomal and Y-chromosomal loci, show a high correlation (0.9) both with each other and with geography, but a slightly lower correlation (0.7) with mitochondrial DNA and linguistic affiliation. The data suggest that genetic diversity of the present-day Slavs was predominantly shaped in situ, and we detect two different substrata: ‘central-east European’ for West and East Slavs, and ‘south-east European’ for South Slavs. A pattern of distribution of segments identical by descent between groups of East-West and South Slavs suggests shared ancestry or a modest gene flow between those two groups, which might derive from the historic spread of Slavic people.

Population Data for the Twelve Y-chromosome Short Tandem Repeat Loci from the Sample of Multinational Population in Bosnia and Herzegovina

POPULATION: We have analyzed the distribution of allele frequencies at 12 Y-chromosornal short tandem repeats loci (DYS 19, DYS385a, DYS385b. DYS389I. DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439) in the representative sample of Bosnian and Herzegovinians. A total of 100 unrelated male individuals (Caucasians) from different regions of Bosnia and Herzegovina have been sampled for the analysis. Samples were collected with a respect to the approximate proportional participation of three main ethnic groups in Bosnia and Herzegovina [Bosniacs-Muslim (35). Serbs (31), Croats (34)].

Classification of asthma using artificial neural network

This paper presents a system for classification of asthma based on artificial neural network. A total of 1800 Medical Reports were used for neural network training. The system was subsequently tested through the use of 1250 Medical Reports established by physicians from hospital Sarajevo. Out of the aforementioned Medical Reports, 728 were diagnoses of asthma, while 522 were healthy subjects. Out of the 728 asthmatics, 97.11% were correctly classified, and the healthy subjects were classified with an accuracy of 98.85%. Sensitivity and specificity were assessed, as well, which were 97.11% and 98.85%, respectively. Our system for classification of asthma is based on a combination of spirometry (SPIR) and Impulse Oscillometry System (IOS) test results, whose measurement results were inputs to artificial neural network. Artificial neural network is implemented to obtain both static and dynamic assessment of the patients respiratory system.