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"Pierre Zalloua"
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Ancestors
\"In recent years, as companies like 23andMe and Ancestry.com have made genetic testing available across the globe, it has become relatively simple to find out where your ancestors came from. But acclaimed geneticist Pierre Zalloua believes that these test results have led to a dangerous oversimplification of what one's genetic heritage means. People have conflated genetic ancestry with other ways of defining themselves such as \"origin,\" \"ethnicity,\" and even \"race\" but give no attention to the complexities that underlie these concepts. Nowhere is this interplay more important, and more controversial, than in the Levant-an ancient region known as one of the cradles of civilization, and which now includes modern-day Palestine, Israel, Jordan, Lebanon, Syria, and parts of Turkey. Born in Lebanon, Zalloua grew up surrounded by people for whom this question of identity was one of life or death importance. In Ancestors, Zalloua uses the Levant to grapple with what being indigenous really means. He finds that DNA does not determine a culture or an ethnicity, but instead, one must look to their own history to understand their identity. Building on years of research, Zalloua tells a history of the Levant through the framework of genetics that spans from 100,000 years ago, when humans first left Africa, to the 21st century and modern nation-states. World-shifting and accessible, Ancestors will reshape the way you think about where our culture really comes from\"-- Provided by publisher.
BOOK
Genomic Ancestry of North Africans Supports Back-to-Africa Migrations
North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from \"back-to-Africa\" gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa.
Journal Article
Plasma and urine metabolomic analyses in aortic valve stenosis reveal shared and biofluid-specific changes in metabolite levels
Aortic valve stenosis (AVS) is a prevalent condition among the elderly population that eventually requires aortic valve replacement. The lack of reliable biomarkers for AVS poses a challenge for its early diagnosis and the application of preventive measures. Untargeted gas chromatography mass spectrometry (GC-MS) metabolomics was applied in 46 AVS cases and 46 controls to identify plasma and urine metabolites underlying AVS risk. Multivariate data analyses were performed on pre-processed data (e.g. spectral peak alignment), in order to detect changes in metabolite levels in AVS patients and to evaluate their performance in group separation and sensitivity of AVS prediction, followed by regression analyses to test for their association with AVS. Through untargeted analysis of 190 urine and 130 plasma features that could be detected and quantified in the GC-MS spectra, we identified contrasting levels of 22 urine and 21 plasma features between AVS patients and control subjects. Following metabolite assignment, we observed significant changes in the concentration of known metabolites in urine (n = 14) and plasma (n = 15) that distinguish the metabolomic profiles of AVS patients from healthy controls. Associations with AVS were replicated in both plasma and urine for about half of these metabolites. Among these, 2-Oxovaleric acid, elaidic acid, myristic acid, palmitic acid, estrone, myo-inositol showed contrasting trends of regulation in the two biofluids. Only trans-Aconitic acid and 2,4-Di-tert-butylphenol showed consistent patterns of regulation in both plasma and urine. These results illustrate the power of metabolomics in identifying potential disease-associated biomarkers and provide a foundation for further studies towards early diagnostic applications in severe heart conditions that may prevent surgery in the elderly.
Journal Article
Deep Phylogenetic Analysis of Haplogroup G1 Provides Estimates of SNP and STR Mutation Rates on the Human Y-Chromosome and Reveals Migrations of Iranic Speakers
Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of South-West and Central Asia but reaches up to 80% frequency in some populations scattered within this area. We have genotyped the G1-defining marker M285 in 27 Eurasian populations (n= 5,346), analyzed 367 M285-positive samples using 17 Y-STRs, and sequenced ~11 Mb of the Y-chromosome in 20 of these samples to an average coverage of 67X. This allowed detailed phylogenetic reconstruction. We identified five branches, all with high geographical specificity: G1-L1323 in Kazakhs, the closely related G1-GG1 in Mongols, G1-GG265 in Armenians and its distant brother clade G1-GG162 in Bashkirs, and G1-GG362 in West Indians. The haplotype diversity, which decreased from West Iran to Central Asia, allows us to hypothesize that this rare haplogroup could have been carried by the expansion of Iranic speakers northwards to the Eurasian steppe and via founder effects became a predominant genetic component of some populations, including the Argyn tribe of the Kazakhs. The remarkable agreement between genetic and genealogical trees of Argyns allowed us to calibrate the molecular clock using a historical date (1405 AD) of the most recent common genealogical ancestor. The mutation rate for Y-chromosomal sequence data obtained was 0.78×10-9 per bp per year, falling within the range of published rates. The mutation rate for Y-chromosomal STRs was 0.0022 per locus per generation, very close to the so-called genealogical rate. The \"clan-based\" approach to estimating the mutation rate provides a third, middle way between direct farther-to-son comparisons and using archeologically known migrations, whose dates are subject to revision and of uncertain relationship to genetic events.
Journal Article
Lies, Gosh Darn Lies, and not enough good statistics: why epidemic model parameter estimation fails
We sought to investigate whether epidemiological parameters that define epidemic models could be determined from the epidemic trajectory of infections, recovery, and hospitalizations prior to peak, and also to evaluate the comparability of data between jurisdictions reporting their statistics. We found that, analytically, the pre-peak growth of an epidemic underdetermines the model variates, and that the rate limiting variables are dominated by the exponentially expanding eigenmode of their equations. The variates quickly converge to the ratio of eigenvector components of the positive growth mode, which determines the doubling time. Without a sound epidemiological study framework, measurements of infection rates and other parameters are highly corrupted by uneven testing rates, uneven counting, and under reporting of relevant values. We argue that structured experiments must be performed to estimate these parameters in order to perform genetic association studies, or to construct viable models accurately predicting critical quantities such as hospitalization loads.
Journal Article
Anatolian genetic ancestry in North Lebanese populations
Lebanon’s rich history as a cultural crossroad spanning millennia has significantly impacted the genetic composition of its population through successive waves of migration and conquests from surrounding regions. Within modern-day Lebanon, the Koura district stands out with its unique cultural foundations, primarily characterized by a notably high concentration of Greek Orthodox Christians compared to the rest of the country. This study investigates whether the prevalence of Greek Orthodoxy in Koura can be attributed to modern Greek heritage or continuous blending resulting from the ongoing influx of refugees and trade interactions with Greece and Anatolia. We analyzed both ancient and modern DNA data from various populations in the region which could have played a role in shaping the current population of Koura using our own and published data. Our findings indicate that the genetic influence stemming directly from modern Greek immigration into the area appears to be limited. While the historical presence of Greek colonies has left its mark on the region’s past, the distinctive character of Koura seems to have been primarily shaped by cultural and political factors, displaying a stronger genetic connection mostly with Anatolia, with affinity to ancient but not modern Greeks.
Journal Article
People from Ibiza: an unexpected isolate in the Western Mediterranean
In this study, we seek to understand and to correlate the genetic patterns observed in the population of the island of Ibiza in the Western Mediterranean basin with past events. Genome-wide genotypes of 189 samples representing 13 of 17 regions in Spain have been analyzed, in addition to 105 samples from the Levant, 157 samples from North Africa, and one ancient sample from the Phoenician Cas Molí site in Ibiza. Before the Catalans conquered the island in 1235 CE, Ibiza (Eivissa) had already been influenced by several cultures, starting with the Phoenicians, then the Carthaginians, followed by the Umayyads. The impact of these various cultures on the genetic structure of the islanders is still unexplored. Our results show a clear distinction between Ibiza and the rest of Spain. To investigate whether this was due to the Phoenician colonization or to more recent events, we compared the genomes of current Ibizans to that of an ancient Phoenician sample from Ibiza and to both modern Levantine and North African genomes. We did not identify any trace of Phoenician ancestry in the current Ibizans. Interestingly, the analysis of runs of homozygosity and changes in the effective population size through time support the idea that drift has shaped the genetic structure of current Ibizans. In addition to the small carrying capacity of the island, Ibiza experienced a series of dramatic demographic changes due to several instances of famine, war, malaria and plague that could have significantly contributed to its current genetic differentiation.
Journal Article
A European Mitochondrial Haplotype Identified in Ancient Phoenician Remains from Carthage, North Africa
While Phoenician culture and trade networks had a significant impact on Western civilizations, we know little about the Phoenicians themselves. In 1994, a Punic burial crypt was discovered on Byrsa Hill, near the entry to the National Museum of Carthage in Tunisia. Inside this crypt were the remains of a young man along with a range of burial goods, all dating to the late 6th century BCE. Here we describe the complete mitochondrial genome recovered from the Young Man of Byrsa and identify that he carried a rare European haplogroup, likely linking his maternal ancestry to Phoenician influenced locations somewhere on the North Mediterranean coast, the islands of the Mediterranean or the Iberian Peninsula. This result not only provides the first direct ancient DNA evidence of a Phoenician individual but the earliest evidence of a European mitochondrial haplogroup, U5b2c1, in North Africa.
Journal Article
Genome-Wide Diversity in the Levant Reveals Recent Structuring by Culture
The Levant is a region in the Near East with an impressive record of continuous human existence and major cultural developments since the Paleolithic period. Genetic and archeological studies present solid evidence placing the Middle East and the Arabian Peninsula as the first stepping-stone outside Africa. There is, however, little understanding of demographic changes in the Middle East, particularly the Levant, after the first Out-of-Africa expansion and how the Levantine peoples relate genetically to each other and to their neighbors. In this study we analyze more than 500,000 genome-wide SNPs in 1,341 new samples from the Levant and compare them to samples from 48 populations worldwide. Our results show recent genetic stratifications in the Levant are driven by the religious affiliations of the populations within the region. Cultural changes within the last two millennia appear to have facilitated/maintained admixture between culturally similar populations from the Levant, Arabian Peninsula, and Africa. The same cultural changes seem to have resulted in genetic isolation of other groups by limiting admixture with culturally different neighboring populations. Consequently, Levant populations today fall into two main groups: one sharing more genetic characteristics with modern-day Europeans and Central Asians, and the other with closer genetic affinities to other Middle Easterners and Africans. Finally, we identify a putative Levantine ancestral component that diverged from other Middle Easterners ∼23,700-15,500 years ago during the last glacial period, and diverged from Europeans ∼15,900-9,100 years ago between the last glacial warming and the start of the Neolithic.
Journal Article
Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions
The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis.
Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries.
Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the
gene was significantly associated with CAD.
Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.
Journal Article