Marc Haber

• PhD
• Wellcome Sanger Institute

Understanding human genetic diversity in Africa is important for interpreting the evolution of all humans, yet vast regions in Africa, such as Chad, remain genetically poorly investigated. Here, we use genotype data from 480 samples from Chad, the Near East, and southern Europe, as well as whole-genome sequencing from 19 of them, to show that many...

Ancient DNA research is revealing a human history far more complex than that inferred from parsimonious models based on modern DNA. Here, we review some of the key events in the peopling of the world in the light of the findings of work on ancient DNA.

The Armenians are a culturally isolated population who historically inhabited a region in the Near East bounded by the Mediterranean and Black seas and the Caucasus, but remain under-represented in genetic studies and have a complex history including a major geographic displacement during World War I. Here, we analyse genome-wide variation in 173 A...

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 o...

High-altitude environments pose substantial challenges for human survival and reproduction, attracting considerable attention to the demographic and adaptive histories of high-altitude populations. Previous work focused mainly on Tibetans, establishing their genetic relatedness to East Asians and their genetic adaptation to high altitude, especiall...

The Middle East region is important to understand human evolution and migrations but is underrepresented in genomic studies. Here, we generated 137 high-coverage physically phased genome sequences from eight Middle Eastern populations using linked-read sequencing. We found no genetic traces of early expansions out-of-Africa in present-day populatio...

Human Y chromosome haplogroup J1-M267 is a common male lineage in West Asia. One high-frequency region—encompassing the Arabian Peninsula, southern Mesopotamia, and the southern Levant—resides ~ 2000 km away from the other one found in the Caucasus. The region between them, although has a lower frequency, nevertheless demonstrates high genetic dive...

The Middle East is an important region to understand human evolution and migrations, but is underrepresented in genetic studies. We generated and analysed 137 high-coverage physically-phased genome sequences from eight Middle Eastern populations using linked-read sequencing. We found no genetic traces of early expansions out-of-Africa in present-da...

The Iron and Classical Ages in the Near East were marked by population expansions carrying cultural transformations that shaped human history, but the genetic impact of these events on the people who lived through them is little-known. Here, we sequenced the whole genomes of 19 individuals who each lived during one of four time periods between 800...

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scal...

We report high coverage whole genome sequencing data from 46 Yemeni individuals as well as genome wide genotyping data from 169 Yemenis from diverse locations. We use this dataset to define the genetic diversity in Yemen and how it relates to people elsewhere in the Near East. Yemen is a vast region with substantial cultural and geographic diversit...

Humans expanded out of Africa 50,000-70,000 years ago, but many details of this migration are poorly understood. Here, Haber et al. sequence Y chromosomes belonging to a rare African lineage and analyze... Present-day humans outside Africa descend mainly from a single expansion out ∼50,000–70,000 years ago, but many details of this expansion remain...

During the medieval period, hundreds of thousands of Europeans migrated to the Near East to take part in the Crusades, and many of them settled in the newly established Christian states along the Eastern Mediterranean coast. Here, we present a genetic snapshot of these events and their aftermath by sequencing the whole genomes of 13 individuals who...

We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India, or Tibet at over 500,000 SNPs, and analyzed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resemb...

Founder effects in modern populations The genomes of ancient humans can reveal patterns of early human migration (see the Perspective by Achilli et al. ). Iceland has a genetically distinct population, despite relatively recent settlement (∼1100 years ago). Ebenesersdóttir et al. examined the genomes of ancient Icelandic people, dating to near the...

Little is known regarding the first people to enter the Americas and their genetic legacy.Genomic analysis of the oldest human remains from the Americas showed a direct relationship between a Clovis-related ancestral population and all modern Central and South Americans as well as a deep split separating them from North Americans in Canada.We prese...

The Canaanites inhabited the Levant region during the Bronze Age and established a culture that became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain unc...

The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-...

The Canaanites inhabited the Levant region during the Bronze Age and established a culture which became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain un...

Aboriginal Australians represent one of the oldest continuous cultures outside Africa, with evidence indicating that their ancestors arrived in the ancient landmass of Sahul (present-day New Guinea and Australia) ~55 thousand years ago. Genetic studies, though limited, have demonstrated both the uniqueness and antiquity of Aboriginal Australian gen...

Archaeological, palaeontological and geological evidence shows that post-glacial warming released human populations from their various climate-bound refugia. Yet specific connections between these refugia and the timing and routes of post-glacial migrations that ultimately established modern patterns of genetic variation remain elusive. Here, we us...

Aboriginal Australians are one of the more poorly studied populations from the standpoint of human evolution and genetic diversity. Thus, to investigate their genetic diversity, the possible date of their ancestors’ arrival and their relationships with neighboring populations, we analyzed mitochondrial DNA (mtDNA) diversity in a large sample of Abo...

Figure S2. Population relationships from genome-wide haplotypes. Each tip of the tree corresponds to an individual; numbers of individuals are shown next to their population name at the tip of the branches. Numbers on branches show partition posterior probability. Armenians are shown in blue, forming two major clusters in a Near Eastern branch.

Figure S1. Genetic structure in Armenians. MCLUST classifies Armenians into three clusters. Cluster 1 (blue) includes 95% of the Armenians that trace their origin to Western Armenia (East Turkey) (labelled W). Cluster 1 also includes 33% of the general Armenians (recruited from modern Armenia). Cluster 2 includes 57% of the general Armenians. Clust...

Figure S3. Shared genetic drift between worldwide populations and the Tylorean Iceman, a 5,300 year old European.

To the editor: In our paper “The Kalash Genetic Isolate: Ancient Divergence, Drift, and Selection,” we reported that the Kalash people of present-day Pakistan experienced no detectable gene flow from their geographic neighbors in Pakistan, or from the other extant western Eurasian populations tested, since their split from a common ancestor.1 It is...

Cultural, dietary, and lifestyle factors are the main modulators of type 2 diabetes mellitus (T2DM) disease risk. Coffee is one of the most popular worldwide beverages, and recent epidemiological studies have showed that coffee consumption is associated with a lower risk of T2DM. This study investigates the impact of coffee intake on T2DM risk and...

Background: More evidence is emerging on the strong association between chronic kidney disease (CKD) and cardiovascular disease. We assessed the relationship between coronary artery disease (CAD) and renal dysfunction level (RDL) in a group of Lebanese patients. Methods: A total of 1268 patients undergoing cardiac catheterization were sequential...

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of [sim]185,000 CAD cases and controls, interrogating 6.7 million common (minor allele fre...

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of [sim]185,000 CAD cases and controls, interrogating 6.7 million common (minor allele fre...

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequen...

The predominantly African origin of all modern human populations is well established, but the route taken out of Africa is still unclear. Two alternative routes, via Egypt and Sinai or across the Bab el Mandeb strait into Arabia, have traditionally been proposed as feasible gateways in light of geographic, paleoclimatic, archaeological, and genetic...

The Kalash represent an enigmatic isolated population of Indo-European speakers who have been living for centuries in the Hindu Kush mountain ranges of present-day Pakistan. Previous Y chromosome and mitochondrial DNA markers provided no support for their claimed Greek descent following Alexander III of Macedon's invasion of this region, and analys...

The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis. The aim of this study is to investigate the effect of "selected" genetic variants within the...

Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of SouthWest 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...

The Armenians are a culturally isolated population who historically inhabited a region in the Near East bounded by the Mediterranean and Black seas and the Caucasus, but remain underrepresented in genetic studies and have a complex history including a major geographic displacement during World War One. Here, we analyse genome-wide variation in 173...

Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are crucial to the understanding of Type 2 Diabetes Mellitus (T2DM) pathophysiology. We report a GWAS on the genetic basis of T2DM in a 3,286 Lebanese participants. More than 5,000,000 SNPs were directly genotyped or imputed using the 1...

Supplementary Info

The peopling of Europe and the nature of the Neolithic agricultural migration as a primary issue in the modern human colonization of the globe is still widely debated. At present, much uncertainty is associated with the reconstruction of the routes of migration for the first farmers from the Near East. In this context, hospitable climatic condition...

The burden of diabetes in Lebanon requires well-targeted interventions for screening type 2 diabetes mellitus (T2DM) and prediabetes and prevention of risk factors. Newly recruited 998 Lebanese individuals, in addition to 7,292 already available, were studied to investigate the prevalence of diabetes, prediabetes and their associated risk factors....

A main underlying pathology of coronary artery disease is the deposition of cholesterol in the arteries supplying blood to the heart that leads to stenosis and myocardial infarction. We tested if dyslipidemia is a risk factor for coronary artery disease in the Lebanese population, and studied the role of the total cholesterol/HDL cholesterol (TC/HD...

The search for a method that utilizes biological information to predict humans' place of origin has occupied scientists for millennia. Over the past four decades, scientists have employed genetic data in an effort to achieve this goal but with limited success. While biogeographical algorithms using next-generation sequencing data have achieved an a...

The human mitochondrial haplogroup C1 has a broad global distribution but is extremely rare in Europe today. Recent ancient DNA evidence has demonstrated its presence in European Mesolithic individuals. Three individuals from the 7,500 year old Mesolithic site of Yuzhnyy Oleni Ostrov, Western Russia, could be assigned to haplogroup C1 based on mito...

Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better apprecia...

The geostrategic location of North Africa as a crossroad between three continents and as a stepping-stone outside Africa has evoked anthropological and genetic interest in this region. Numerous studies have described the genetic landscape of the human population in North Africa employing paternal, maternal, and biparental molecular markers. However...

Located in the center of the Mediterranean landscape and with an extensive coastal line, the territory of what is today Italy has played an important role in the history of human settlements and movements of Southern Europe and the Mediterranean Basin. Populated since Paleolithic times, the complexity of human movements during the Neolithic, the Me...

Homogeneous Proto-Slavic genetic substrate and/or extensive mixing after World War II were suggested to explain homogeneity of contemporary Polish paternal lineages. Alternatively, Polish local populations might have displayed pre-war genetic heterogeneity owing to genetic drift and/or gene flow with neighbouring populations. Although sharp genetic...

Raw coancestry matrix shows relationships between the Levantines and the world populations. A) Intensity of the colors reflects the number of haplotype chunks donated to the Levantines. The vertical line is a visual aid to reflect the Levantine split observed in the tree. Horizontal lines distinguish the major geographic regions. B) coancestry matr...

World population structure inferred by ADMIXTURE analysis of >240K autosomal SNPs. A) Each horizontal line represents ancestry probabilities of an individual in 2–10 constructed ancestral populations. Levantine population names are shown in blue. B) Cross-validation plot for the world dataset. (TIF)

Ancestry probabilities of individuals considering 10 ancestral populations. Highlighted cells indicate individuals have >60% of one component. Standard errors were estimated using 200 bootstrap replicates. (XLS)

Description of the ROLLOFF analysis. (PDF)

Stratified random sampling of 75 Lebanese samples. A) 25 samples from each of the three main religion groups in Lebanon were randomly chosen from the 1,341 samples illustrated in Figure 1. B) Map of Lebanon showing the distribution of the samples. (TIF)

Principle component analysis generated with fineSTRUCTURE using ChromoPainter's coancestry matrix showing the top two components. A) Plot shows global diversity using 50 populations. B) Magnification of West Asia region showing the Levantine populations in their regional and religion context. (TIF)

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies ha...

Fisher exact tests for haplogroup frequencies vs. population within the Middle East. (XLS)

Populations comparison based on Y haplogroups a) Principal Component Analysis of relative frequencies of Y haplogroups within populations, b) with mean-linkage (UPGMA) dendrogram determined from Euclidean distances. (TIF)

mtDNA FST distances between populations. (XLS)

Y STR RST distances between populations. (XLS)

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies ha...

North East Europe harbors a high diversity of cultures and languages, suggesting a complex genetic history. Archaeological, anthropological, and genetic research has revealed a series of influences from Western and Eastern Eurasia in the past. While genetic data from modern-day populations is commonly used to make inferences about their origins and...

The Genographic Project is an international effort using genetic data to chart human migratory history. The project is non-profit and non-medical, and through its Legacy Fund supports locally led efforts to preserve indigenous and traditional cultures. In its second phase, the project is focusing on markers from across the entire genome to obtain a...

Previous studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that...

Vlad III The Impaler, also known as Dracula, descended from the dynasty of Basarab, the first rulers of independent Wallachia, in present Romania. Whether this dynasty is of Cuman (an admixed Turkic people that reached Wallachia from the East in the 11th century) or of local Romanian (Vlach) origin is debated among historians. Earlier studies have...

The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understand...

For decades, the peopling of the Americas has been explored through the analysis of uniparentally inherited genetic systems in Native American populations and the comparison of these genetic data with current linguistic groupings. In northern North America, two language families predominate: Eskimo-Aleut and Na-Dene. Although the genetic evidence f...

Afghanistan has held a strategic position throughout history. It has been inhabited since the Paleolithic and later became a crossroad for expanding civilizations and empires. Afghanistan's location, history, and diverse ethnic groups present a unique opportunity to explore how nations and ethnic groups emerged, and how major cultural evolutions an...

Suggested origins of the main ethnic groups in Afghanistan. (DOC)

Populations selected for this study. (XLS)

AMOVA results. Comparing populations grouped according to their country or region of origin with populations grouped according to Barrier structures. (DOC)

Y-chromosome haplogroups frequencies in Afghanistan's ethnic groups. (XLS)

BATWING topologies and dates with 95% confidence intervals of population splits derived from multiple combinations of population subsets. (XLS)

Reduced median networks. (A) C-M130, (B) R1a1a-M17, (C) E1b1b1-M35, and (D) B-M60 showing STR haplotype distributions among populations; area is proportional to haplotype frequency, and color indicates populations. Connecting lines represent putative phylogenetic relationships between haplotypes. (TIF)

Y-chromosome haplogroups and haplotypes in 204 unrelated individuals from Afghanistan. (XLS)

Basque people have received considerable attention from anthropologists, geneticists, and linguists during the last century due to the singularity of their language and to other cultural and biological characteristics. Despite the multidisciplinary efforts performed to address the questions of the origin, uniqueness, and heterogeneity of Basques, t...

Elevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease. The rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine. A total...

Afghanistan has held a strategic position throughout history. It has been inhabited since the Paleolithic and later became a crossroad for expanding civilizations and empires. Afghanistan's location, history, and diverse ethnic groups present a unique opportunity to explore how nations and ethnic groups emerged, and how major cultural evolutions an...

Population origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and r...

Variants' imputed genotype probabilities. Imputed genotype probabilities for variants in 88 candidate genes with +/- 50Kb on each side. The test was considered significant when P<0.01, relative information >0.4 and minor allele frequency >5%. (DOC)