Bouchra Douaihy

Large scale association analysis identifies three susceptibility loci for coronary artery disease.

Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

Y-Chromosome and mtDNA Genetics Reveal Significant Contrasts in Affinities of Modern Middle Eastern Populations with European and African Populations

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 have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of FSTs, RSTs, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanons mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

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 understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10−5). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10−6), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10−10). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD.

Afghanistan's ethnic groups share a y-chromosomal heritage structured by historical events

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. Afghanistans location, history, and diverse ethnic groups present a unique opportunity to explore how nations and ethnic groups emerged, and how major cultural evolutions and technological developments in human history have influenced modern population structures. In this study we have analyzed, for the first time, the four major ethnic groups in present-day Afghanistan: Hazara, Pashtun, Tajik, and Uzbek, using 52 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y-chromosome. A total of 204 Afghan samples were investigated along with more than 8,500 samples from surrounding populations important to Afghanistans history through migrations and conquests, including Iranians, Greeks, Indians, Middle Easterners, East Europeans, and East Asians. Our results suggest that all current Afghans largely share a heritage derived from a common unstructured ancestral population that could have emerged during the Neolithic revolution and the formation of the first farming communities. Our results also indicate that inter-Afghan differentiation started during the Bronze Age, probably driven by the formation of the first civilizations in the region. Later migrations and invasions into the region have been assimilated differentially among the ethnic groups, increasing inter-population genetic differences, and giving the Afghans a unique genetic diversity in Central Asia.

High genetic diversity with moderate differentiation in Juniperus excelsa from Lebanon and the eastern Mediterranean region

Juniperus excelsa constitutes a precious woody species of high ecological value able to grow up to Mountain treeline around the Mediterranean. Nuclear microsatellites were used to shed light on genetic diversity and differentiation of different Mediterranean populations. This information is essential in planning conservation strategies and reforestation programs.

Nuclear DNA C-values for biodiversity screening: Case of the Lebanese flora

The geographic position of Lebanon in the Mediterranean basin at the transition of two major landmasses, Eurasia and Africa, has contributed to its high plant diversity and makes its flora particularly interesting to study. This paper contributes to the plant DNA C-value database of native Lebanese taxa. These data should reinforce biodiversity evaluation, systematic and evolution studies involving processes of speciation such as polyploidisation. C-values have been estimated by flow cytometry using propidium iodide as intercalary fluorochrome stain. Each sample comprised at least five individuals. Where possible, several populations were measured for each species. This study presents C-values for 225 taxa belonging to 55 families and 141 genera. C-values are novel for 193 taxa including 126 plants endemic to the Eastern Mediterranean region. These are the first values for 50 genera. In this panel, genome size ranged from 1C = 0.28 pg in Hypericum thymifolium to 54.69 pg in Fritillaria alfredae. The life growth form and life cycle type are analysed according to the genome size class. Cases of polyploidy are reported for some species usually considered as only diploid. Examination of C-value variation through flow cytometry constitutes a powerful tool to screen taxonomic heterogeneity, opening further investigations.

Morphological versus molecular markers to describe variability in Juniperus excelsa subsp. excelsa (Cupressaceae)

This is a large scale investigation of morphological diversity in Juniperus excelsa excelsa. It offers complementary results to those obtained for the same populations using molecular markers. These two approaches are complementary and should be considered together in order to obtain a comprehensive view of the variability of J. excelsa excelsa.

Mapping post-glacial expansions: the peopling of Southwest Asia

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 use Y-chromosome markers combined with autosomal data to reconstruct population expansions from regional refugia in Southwest Asia. Populations from three regions in particular possess distinctive autosomal genetic signatures indicative of likely refugia: one, in the north, centered around the eastern coast of the Black Sea, the second, with a more Levantine focus, and the third in the southern Arabian Peninsula. Modern populations from these three regions carry the widest diversity and may indeed represent the most likely descendants of the populations responsible for the Neolithic cultures of Southwest Asia. We reveal the distinct and datable expansion routes of populations from these three refugia throughout Southwest Asia and into Europe and North Africa and discuss the possible correlations of these migrations to various cultural and climatic events evident in the archaeological record of the past 15,000 years.

Unlocking the Karyological and Cytogenetic Diversity of Iris from Lebanon: Oncocyclus Section Shows a Distinctive Profile and Relative Stasis during Its Continental Radiation

Despite being an important target of conservation concern and horticultural interest, Lebanese irises yet have a confusing taxonomic history and species’ delimitation is often considered problematic, more especially among royal irises (Iris section Oncocyclus). Indeed, these irises of exceptionally large and spectacular flowers have radiated across Caucasus and eastern Mediterranean giving rise to a number of strict endemic taxa, many of them being considered under threat. Whilst efforts have mostly focused on clarifying the evolutionary relationships in the group based on morphological and molecular data, karyological and cytogenetic characters have been comparatively overlooked. In this study, we established for the first time the physical mapping of 35S rDNA loci and heterochromatin, and obtained karyo-morphological data for ten Lebanese Iris species belonging to four sections (Iris, Limniris, Oncocyclus and Scorpiris). Our results evidenced distinctive genomic profiles for each one of the sections, where Oncocyclus irises, while having the lowest chromosome numbers, exhibit both the highest number of 35S loci and CMA3+ sites. The continental radiation of royal irises has been accompanied by a relative karyological and cytogenetic stasis, even though some changes were observed regarding karyotype formula and asymmetry indexes. In addition to that, our results enabled taxonomic differentiation between I. germanica and I. mesopotamica–two taxa currently considered as synonyms–and highlighted the need for further studies on populations of I. persica and I. wallasiae in the Eastern Mediterranean Region.