A CXCL2 tandem repeat promoter polymorphism is associated with susceptibility to severe sepsis in the Spanish population.

Sepsis describes a complex clinical syndrome resulting from a systemic inflammatory response to bacteria. Functional studies in animal models of sepsis have catalogued CXCL2 as a candidate gene for the development of the disease. We hypothesized that CXCL2 polymorphisms may confer susceptibility to sepsis and performed an association study using 178 severe sepsis patients and 357 population-based controls. We selected two polymorphisms from the promoter of the gene (-437A/G and -665(AC)n), and analyzed whether haplotypes or single loci were associated with disease susceptibility. An overall test of differentiation showed that haplotype distribution was not different between cases and controls (P=0.407). Likewise, -437A/G was not associated with disease susceptibility (heterozygote odds ratio (OR) 0.68 (0.47-1.03), and homozygote OR 0.86 (0.56-1.32); P=0.706). However, for the -665(AC)n, we found that the 24+/-1 repeat alleles were associated with susceptibility (heterozygote OR 2.82 (1.10-7.24), and homozygote OR 3.65 (1.41-9.43); P=0.0006). This association remained significant when using a multiple logistic regression analysis (OR 2.23; 95% confidence intervals (95% CI) 1.22-4.03; P=0.008) and after a genomic control adjustment (P=0.017). Although replicate studies and functional assays are needed, these results suggest that CXCL2 gene variants may contribute to the development of severe sepsis.

A tale of aborigines, conquerors and slaves: Alu insertion polymorphisms and the peopling of Canary Islands.

Classical, mitochondrial DNA (mtDNA) and Y chromosome markers have been used to examine the genetic admixture in present day inhabitants of the Canary Islands. In this study, we report the analysis of ten autosomal Alu insertion polymorphisms in 364 samples from the seven main islands of the Archipelago, and their comparison to continental samples. The detection of population-specific alleles from the Iberian Peninsula and Northwest Africa, as well as their affinities on the basis of genetic distances and principal component analysis, support a clear link between these populations. Coincident with previous results, the Canarian gene pool can be distinguished as being halfway between those of its putative parents, although with a major Iberian contribution (62-78%). Both the substantial Northwest African contribution (23-38%), and the minor sub-Saharan African input (3%), suggest that the genetic legacy from the aborigines and slaves still persists in the Canary Islanders.

Y chromosome and mitochondrial DNA characterization of Pasiegos, a human isolate from Cantabria (Spain).

Mitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non-Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E-M81) with North African assignation, and Y chromosomal (R-SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre-V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south-western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization.

A predominant European ancestry of paternal lineages from Canary Islanders.

We genotyped 24 biallelic sites and 5 microsatellites from the non-recombining portion of the Y chromosome in 652 males from the Canary Islands. The results indicate that, contrary to mtDNA data, paternal lineages of the current population are overwhelmingly (>90%) of European origin, arguing for a highly asymmetric pattern of mating after European occupation. However, the presence of lineages of indisputable African assignation demonstrates that an aboriginal background still persists (<10%). On the basis of distribution and dating of some of these lineages we derived a genetic perspective of settlement processes of the archipelago in two stages, congruent with anthropological, archaeological and linguistic findings.

Major genomic mitochondrial lineages delineate early human expansions.

BACKGROUND: The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA) sequences from 42 human lineages, representing major clades with known geographic assignation. RESULTS: We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. CONCLUSIONS: The first detectable expansion occurred around 59,000-69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000-52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

The peopling of the Canary Islands: a CD4/Alu microsatellite haplotype perspective.

A new CD4 microsatellite allele with three TTTTC complete repetitions, previously described only in hominoids, has been found in this screening. The number of haplotypes and heterozygosities in the Canary Islands (15 and 0.746+/-0.007) is more similar to Iberian (14 and 0.748+/-0.015) than to North African (18 and 0.827+/-0.009) values. However, in some islands, with less European migratory impact, haplotypes with major African assignation (90[+] and 130[+]) reach frequencies similar to African populations. There is a significant negative correlation between geographic distances to Africa and insular heterozygosity values, which suggests a main aborigine colonization from East to West still detectable today.

Y-chromosome differentiation in Northwest Africa.

Variation of seven Y-chromosomal DNA polymorphisms, one microsatellite (DYS19), and six biallelic markers (DYS287, DYS271, SRY-2627, SRY-1532, 92R7, and M9), were studied in males from Northwest Africa. To evaluate the degree of differentiation in this region, males from neighboring areas such as the Iberian Peninsula and sub-Saharan Africa were also typed. The results show a large number of paternal lineages of Northwest African origin (over 75%), supporting a long-term population continuity in the area. When the analysis of molecular variance (AMOVA) was performed both on the microsatellite and biallelic marker combinations or haplogroups, a large degree of differentiation among areas was revealed. In spite of these geographic differences, some gene flow between areas was detected by the presence of haplogroups with other geographical origins.

Northwest African distribution of the CD4/Alu microsatellite haplotypes.

We have analysed a linked microsatellite/Alu polymorphism at the CD4 locus (CD4/Alu) in 666 chromosomes from samples of the Iberian Peninsula, Northwest Africa, and West sub-Saharan Africa. The Iberian Peninsula differs from other European populations by its higher levels of haplotype diversity (0.75), and weaker association between the microsatellite allele 90 and Alu(-) chromosomes. These results are explainable by a substantial gene flow from Northwest Africa. Significant geographic clines for the five major haplotypes suggest a south to north migration from sub-Saharan Africa into Northwest Africa. In spite of this, the consistent presence of haplotype 110(-) in this area is congruent with an ancient and autochthonous human presence in Northwest Africa.