HLA‐C molecular characterization of a Lebanese population and genetic structure of 39 populations from Europe to India–Pakistan

Abstract

Lebanon is located at a continental crossroad between Europe, Africa, and Asia. This region has been the center of wide-scale movements of populations as well as the theater of genetic and cultural trade off among neighboring populations. In this study, HLA-C alleles were characterized by a PCR-SSOP (sequence-specific oligonucleotide probes) hybridization protocol in a sample of 97 Lebanese. A total of 23 alleles were identified with four predominant, Cw*0401, Cw*0602, Cw*0701/06, and Cw*1203, accounting for almost 60% of HLA-C allele frequencies. We included the Lebanese data into a broad analysis of the HLA-C genetic structure of a large set of populations located in Europe, the Middle East, and the Indian subcontinent. Our results indicate that Lebanese exhibit an intermediate genetic profile among the populations from the Middle East, which constitute a rather homogeneous genetic group. In Europe, a high correlation coefficient is found between genetic and geographic distances. In this continent, we also identified a significant genetic frontier following a north-east to south-west axis. This frontier cuts through the Alps and the Pyrenees, thus separating the north-western European populations from those located in the eastern and Mediterranean areas. Finally, the populations from India - Pakistan are very heterogeneous, particularly the Dravidians. Their differentiation has probably been caused by rapid genetic drift under complex influences of cultural, linguistic, and/or religious barriers. Overall, the results show that the HLA-C genetic patterns of these three geographic regions, i.e., the Middle East, Europe, and India-Pakistan, have been shaped by very different genetic histories.

The Heterogeneous HLA Genetic Makeup of the Swiss Population

“…While encompassing a restricted geographic area, Switzerland is a region of great interest in Europe from a genetic point of view, as it is centrally located and embraces two very distinct environments, north/north-western lowlands (the Central Plateau) and south/south-eastern highlands (the Alps), in addition to another softly mountainous region in the north (the Jura). Therefore, this country may lie at the boundary of an abrupt genetic variation of HLA frequencies previously observed between north-western and south-eastern Europe, and tentatively explained by the presence of the Alps as a geographic barrier to gene flow [26], [29]. Moreover, Switzerland is characterized by an important cultural diversity, with three main languages spoken, French, German and Italian, and a fourth minor national language, Romansh.…”

“…In this study, the Swiss Blood Stem Cells (SBSC) registry has been used to explore in detail the HLA genetic variation throughout Switzerland, for which few results have been published until now [26], [27], [28]. While encompassing a restricted geographic area, Switzerland is a region of great interest in Europe from a genetic point of view, as it is centrally located and embraces two very distinct environments, north/north-western lowlands (the Central Plateau) and south/south-eastern highlands (the Alps), in addition to another softly mountainous region in the north (the Jura).…”

HLA DNA Sequence Variation among Human Populations: Molecular Signatures of Demographic and Selective Events

“…transplantation) purposes, but it has seldom been used to study the genetic variation among populations. Many studies have shown that the HLA polymorphism is very informative to reconstruct past human migration events [19], [20], [21], [22], [23], [24], [25]. However, these works are based on the interpretation of allelic frequency distributions, with all alleles being considered as equidistant molecular units in each population; the main reason being that there is still a lot of uncertainty associated to HLA molecular typings due to the extreme level of polymorphism at these loci.…”

A New HLA Map of Europe: Regional Genetic Variation and Its Implication for Peopling History, Disease-Association Studies and Tissue Transplantation

“…1 ), may have resulted from reduced gene flow across the Alps. Indeed, a significant genetic boundary has previously been detected in this region through HLA comparisons, both at the continental scale [36] and at the country level [i.e. Switzerland, 66 ].…”

“…The total number of individuals per locus varied between 1,582 and 125,889 (also depending on the resolution level considered). This database includes data from the 12th, 13th, 15th and 16th International Histocompatibility workshops [22][23][24][25]34] , the 'HLA-NET' project [35] and other published sources [36][37][38][39] (online suppl. table S1 and suppl.…”