Diversity of HLA Class I and Class II blocks and conserved extended haplotypes in Lacandon Mayans.

Here we studied HLA blocks and haplotypes in a group of 218 Lacandon Maya Native American using a high-resolution next generation sequencing (NGS) method. We assessed the genetic diversity of HLA class I and class II in this population, and determined the most probable ancestry of Lacandon Maya HLA class I and class II haplotypes. Importantly, this Native American group showed a high degree of both HLA homozygosity and linkage disequilibrium across the HLA region and also lower class II HLA allelic diversity than most previously reported populations (including other Native American groups). Distinctive alleles present in the Lacandon population include HLA-A*24:14 and HLA-B*40:08. Furthermore, in Lacandons we observed a high frequency of haplotypes containing the allele HLA-DRB1*04:11, a relatively frequent allele in comparison with other neighboring indigenous groups. The specific demographic history of the Lacandon population including inbreeding, as well as pathogen selection, may have elevated the frequencies of a small number of HLA class II alleles and DNA blocks. To assess the possible role of different selective pressures in determining Native American HLA diversity, we evaluated the relationship between genetic diversity at HLA-A, HLA-B and HLA-DRB1 and pathogen richness for a global dataset and for Native American populations alone. In keeping with previous studies of such relationships we included distance from Africa as a covariate. After correction for multiple comparisons we did not find any significant relationship between pathogen diversity and HLA genetic diversity (as measured by polymorphism information content) in either our global dataset or the Native American subset of the dataset. We found the expected negative relationship between genetic diversity and distance from Africa in the global dataset, but no relationship between HLA genetic diversity and distance from Africa when Native American populations were considered alone

The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ’≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Admixture estimates obtained by a maximum likelihood method using HLA-A/-B/-DRB1 as genetic estimators revealed that the main genetic components in Mexico as a whole are Native American (ranging from 37.8% in the northern part of the country to 81.5% in the southeastern region) and European (ranging from 11.5% in the southeast to 62.6% in northern Mexico). African admixture ranged from 0.0 to 12.7% not following any specific pattern. We were able to detect three major immunogenetic clusters correlating with genetic diversity and differential admixture within Mexico: North, Central and Southeast, which is in accordance with previous reports using genome-wide data. Our findings provide insights into the population immunogenetic substructure of the whole country and add to the knowledge of mixed ancestry Latin American population genetics, important for disease association studies, detection of demographic signatures on population variation and improved allocation of public health resources.Fil: Barquera, Rodrigo. Max Planck Institute For The Science Of Human History; Alemania. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Hernández Zaragoza, Diana Iraíz. Técnicas Genéticas Aplicadas A la Clínica (tgac); México. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Bravo Acevedo, Alicia. Instituto Mexicano del Seguro Social; MéxicoFil: Arrieta Bolaños, Esteban. Universitat Essen; AlemaniaFil: Clayton, Stephen. Max Planck Institute For The Science Of Human History; AlemaniaFil: Acuña Alonzo, Víctor. Instituto Nacional de Antropología E Historia, Mexico; MéxicoFil: Martínez Álvarez, Julio César. Instituto Mexicano del Seguro Social; MéxicoFil: López Gil, Concepción. Instituto Mexicano del Seguro Social; MéxicoFil: Adalid Sáinz, Carmen. Instituto Mexicano del Seguro Social; MéxicoFil: Vega Martínez, María del Rosario. Hospital Central Sur de Alta Especialidad; MéxicoFil: Escobedo Ruíz, Araceli. Instituto Mexicano del Seguro Social; MéxicoFil: Juárez Cortés, Eva Dolores. Instituto Mexicano del Seguro Social; MéxicoFil: Immel, Alexander. Max Planck Institute For The Science Of Human History; Alemania. Christian Albrechts Universitat Zu Kiel; AlemaniaFil: Pacheco Ubaldo, Hanna. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: González Medina, Liliana. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Lona Sánchez, Abraham. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Lara Riegos, Julio. Universidad Autónoma de Yucatán; MéxicoFil: Sánchez Fernández, María Guadalupe de Jesús. Instituto Mexicano del Seguro Social; MéxicoFil: Díaz López, Rosario. Hospital Central Militar, Mexico City; MéxicoFil: Guizar López, Gregorio Ulises. Hospital Central Militar, Mexico City; MéxicoFil: Medina Escobedo, Carolina Elizabeth. Instituto Mexicano del Seguro Social; MéxicoFil: Arrazola García, María Araceli. Instituto Mexicano del Seguro Social; MéxicoFil: Montiel Hernández, Gustavo Daniel. Instituto Nacional de Antropología E Historia. Escuela Nacional de Antropología E Historia; MéxicoFil: Hernández Hernández, Ofelia. Técnicas Genéticas Aplicadas a la Clínica ; MéxicoFil: Ramos de la Cruz, Flor del Rocío. Instituto Mexicano del Seguro Social; MéxicoFil: Juárez Nicolás, Francisco. Instituto Nacional de Pediatría; MéxicoFil: Pantoja Torres, Jorge Arturo. Instituto Mexicano del Seguro Social; MéxicoFil: Rodríguez Munguía, Tirzo Jesús. Hospital General Norberto Treviño Zapata; MéxicoFil: Juárez Barreto, Vicencio. Hospital Infantil de Mexico Federico Gomez; MéxicoFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentin

Genetic diversity of HLA system in four populations from Baja California, Mexico: Mexicali, La Paz, Tijuana and rural Baja California

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 250 Mexicans from the states of Baja California Norte and Baja California Sur living in Mexicali (N = 100), La Paz (N = 75), Tijuana (N = 25) and rural communities (N = 50) to obtain information regarding allelic and haplotypic frequencies. The most frequent haplotypes for the Baja California region include nine Native American and five European haplotypes. Admixture estimates revealed that the main genetic components are European (50.45 ± 1.84% by ML; 42.03% of European haplotypes) and Native American (43.72 ± 2.36% by ML; 40.24% of Native American haplotypes), while the African genetic component was less apparent (5.83 ± 0.98% by ML; 9.36% of African haplotypes)

Historic Treponema pallidum genomes from Colonial Mexico retrieved from archaeological remains.

Treponema pallidum infections occur worldwide causing, among other diseases, syphilis and yaws. In particular sexually transmitted syphilis is regarded as a re-emerging infectious disease with millions of new infections annually. Here we present three historic T. pallidum genomes (two from T. pallidum ssp. pallidum and one from T. pallidum ssp. pertenue) that have been reconstructed from skeletons recovered from the Convent of Santa Isabel in Mexico City, operational between the 17th and 19th century. Our analyses indicate that different T. pallidum subspecies caused similar diagnostic presentations that are normally associated with syphilis in infants, and potential evidence of a congenital infection of T. pallidum ssp. pertenue, the causative agent of yaws. This first reconstruction of T. pallidum genomes from archaeological material opens the possibility of studying its evolutionary history at a resolution previously assumed to be out of reach

Historic <i>Treponema pallidum</i> genomes from Colonial Mexico retrieved from archaeological remains

<div><p><i>Treponema pallidum</i> infections occur worldwide causing, among other diseases, syphilis and yaws. In particular sexually transmitted syphilis is regarded as a re-emerging infectious disease with millions of new infections annually. Here we present three historic <i>T</i>. <i>pallidum</i> genomes (two from <i>T</i>. <i>pallidum</i> ssp. <i>pallidum</i> and one from <i>T</i>. <i>pallidum</i> ssp. <i>pertenue</i>) that have been reconstructed from skeletons recovered from the Convent of Santa Isabel in Mexico City, operational between the 17^th and 19^th century. Our analyses indicate that different <i>T</i>. <i>pallidum</i> subspecies caused similar diagnostic presentations that are normally associated with syphilis in infants, and potential evidence of a congenital infection of <i>T</i>. <i>pallidum</i> ssp. <i>pertenue</i>, the causative agent of yaws. This first reconstruction of <i>T</i>. <i>pallidum</i> genomes from archaeological material opens the possibility of studying its evolutionary history at a resolution previously assumed to be out of reach.</p></div

Examples for bone lesions for the three positive individuals.

<p>(A) The right tibia of individual 94A displays reactive periosteal bone on the anterior aspect of the diaphysis accompanied by progressive layering of the reactive bone. (B) The <i>pars basilaris</i> portion of the cranium of individual 94A showing pathological reactive bone in the endocranial surface, active at time of death. (C) An unidentified long bone from individual 94B displays fulminating periosteal reaction involving the whole of the diaphysis fragment. (D) The left femur of individual 133 presenting periosteal bone formation and expansion with cortical resorption characteristic of treponemal diseases. Source of the pictures: skeletal collection from Santa Isabel Convent, Mexico City, in custody of the Laboratory of Osteology, Post Graduate Studies Division, National School of Anthropology and History (ENAH), Mexico.</p

Phylogenetic trees and Circos plot [90] of the three ancient strains in comparison to modern strains.

<p>(A) Maximum Likelihood tree with bootstrap support for 39 modern strains and the three ancient strains. The strains 94A (magenta) and 94B (orange) branch with the syphilis SS14 clade while strain 133 (brown) branches with Fribourg-Blanc and other yaws strains. The scale represents the mean number of substitutions per site according to the GTR+GAMMA. Colored bars highlight the three subspecies <i>Treponema pallidum</i> ssp <i>pallidum</i> (TPA), <i>pertenue</i> (TPE) and <i>endemicum</i> (TEN). Strains of subspecies <i>pallidum</i> cause syphilis, subspecies <i>pertenue</i> cause yaws and subspecies <i>endemicum</i> causes bejel. (B) Bayesian trees visualized in Densitree overlaying phylogenetic trees based on the most probable topologies. Blue colored trees represent the most probable topology followed by red colored trees. For the ancient strains 94A and 94B two conflicting topologies are visible. The bars represent the 95% highest probability density intervals of the heights of the clades. The support value given at each clade is the fraction of trees in the tree-set that contain the clade. (C) Circos plot showing the shared SNP positions with specific clades and the coverage of the three ancient strains. From outer circle to the inner circle regions of possible recombination detected by ClonalFrameML are denoted on the outermost circle (purple). ‘ORI’ refers to the origin of replication. The genome coverages of the ancient strains 94B, 94A and 133 are represented in orange magenta and brown respectively from outward to inwards. Based on the SNPs that are specifically shared with different clades, colored bars are shown for strains 94B and 94A respectively in the innermost circles. Red bars highlight the SNP positions specifically shared with Fribourg-Blanc (supporting a phylogenetic position ancestral to the two syphilis clades). The green bars highlight the SNP positions shared with the SS14 clade while the blue bars highlight the SNP positions shared with the Nichols clade.</p

Summary statistics of the three positive historic samples.

<p>Summary statistics of the three positive historic samples.</p