Analysis of Genomic DNA from Medieval Plague Victims Suggests Long-Term Effect of Yersinia pestis on Human Immunity Genes.

Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years, is one of the most devastating recorded in human history. To investigate the potential impact of Y. pestis on human immunity genes, we extracted DNA from 36 plague victims buried in a mass grave in Ellwangen, Germany in the 16th century. We targeted 488 immune-related genes, including HLA, using a novel in-solution hybridization capture approach. In comparison with 50 modern native inhabitants of Ellwangen, we find differences in allele frequencies for variants of the innate immunity proteins Ficolin-2 and NLRP14 at sites involved in determining specificity. We also observed that HLA-DRB1*13 is more than twice as frequent in the modern population, whereas HLA-B alleles encoding an isoleucine at position 80 (I-80+), HLA C*06:02 and HLA-DPB1 alleles encoding histidine at position 9 are half as frequent in the modern population. Simulations show that natural selection has likely driven these allele frequency changes. Thus, our data suggest that allele frequencies of HLA genes involved in innate and adaptive immunity responsible for extracellular and intracellular responses to pathogenic bacteria, such as Y. pestis, could have been affected by the historical epidemics that occurred in Europe.

Origin and Health Status of First-Generation Africans from Early Colonial Mexico.

The forced relocation of several thousand Africans during Mexico's historic period has so far been documented mostly through archival sources, which provide only sparse detail on their origins and lived experience. Here, we employ a bioarchaeological approach to explore the life history of three 16th century Africans from a mass burial at the San José de los Naturales Royal Hospital in Mexico City. Our approach draws together ancient genomic data, osteological analysis, strontium isotope data from tooth enamel, δ13C and δ15N isotope data from dentine, and ethnohistorical information to reveal unprecedented detail on their origins and health. Analyses of skeletal features, radiogenic isotopes, and genetic data from uniparental, genome-wide, and human leukocyte antigen (HLA) markers are consistent with a Sub-Saharan African origin for all three individuals. Complete genomes of Treponema pallidum sub. pertenue (causative agent of yaws) and hepatitis B virus (HBV) recovered from these individuals provide insight into their health as related to infectious disease. Phylogenetic analysis of both pathogens reveals their close relationship to strains circulating in current West African populations, lending support to their origins in this region. The further relationship between the treponemal genome retrieved and a treponemal genome previously typed in an individual from Colonial Mexico highlights the role of the transatlantic slave trade in the introduction and dissemination of pathogens into the New World. Putting together all lines of evidence, we were able to create a biological portrait of three individuals whose life stories have long been silenced by disreputable historical events.

An original Eurasian haplotype, HLA-DRB1*14:54-DQB1*05:03, influences the susceptibility to idiopathic achalasia.

Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (pC<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.

Genetic diversity of the HLA system in human populations from the Sierra (Andean), Oriente (Amazonian) and Costa (Coastal) regions of Ecuador.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in a total of 1101 Ecuadorian individuals from three regions of the country, the Coastal region, the Andean region, and the Amazonian region, to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent HLA haplotypes with significant linkage disequilibrium in those populations are HLA-A*24∼B*35∼DRB1*04∼DQB1*03:02, A*02∼B*35∼DRB1*04∼DQB1*03:02, A*24∼B*35∼DRB1*14∼DQB1*03:01, A*02∼B*35∼DRB1*14∼DQB1*03:01 and A*02∼B*40:02∼DRB1*04∼DQB1*03:02. The only non-Native American haplotype with frequency >1% shared by all groups was A*29∼B*44∼DRB1*07∼DQB1*02. Admixture estimates obtained by a maximum likelihood method using HLA-B as genetic estimator revealed that the main genetic components for this sample of mixed-ancestry Ecuadorians are Native American (ranging from 52.86% to 63.83%) and European (from 28.95% to 46.54%), while an African genetic component was only apparent in the Coastal region (18.19%). Our findings provide a starting point for the study of population immunogenetics of Ecuadorian populations.