Haplotypic Associations and Differentiation of MHC Class II Polymorphic Alu Insertions at Five Loci With HLA-DRB1 Alleles in 12 Minority Ethnic Populations in China

The analysis of polymorphic variations in the human major histocompatibility complex (MHC) class II genomic region on the short-arm of chromosome 6 is a scientific enquiry to better understand the diversity in population structure and the effects of evolutionary processes such as recombination, mutation, genetic drift, demographic history, and natural selection. In order to investigate associations between the polymorphisms of HLA-DRB1 gene and recent Alu insertions (POALINs) in the HLA class II region, we genotyped HLA-DRB1 and five Alu loci (AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10), and determined their allele frequencies and haplotypic associations in 12 minority ethnic populations in China. There were 42 different HLA-DRB1 alleles for ethnic Chinese ranging from 12 alleles in the Jinuo to 28 in the Yugur with only DRB1∗08:03, DRB1∗09:01, DRB1∗12:02, DRB1∗14:01, DRB1∗15:01, and DRB1∗15:02 present in all ethnic groups. The POALINs varied in frequency between 0.279 and 0.514 for AluDPB2, 0 and 0.127 for AluDQA2, 0.777 and 0.995 for AluDQA1, 0.1 and 0.455 for AluDRB1 and 0.084 and 0.368 for AluORF10. By comparing the data of the five-loci POALIN in 13 Chinese ethnic populations (including Han-Yunnan published data) against Japanese and Caucasian published data, marked differences were observed between the populations at the allelic or haplotypic levels. Five POALIN loci were in significant linkage disequilibrium with HLA-DRB1 in different populations and AluDQA1 had the highest percentage association with most of the HLA-DRB1 alleles, whereas the nearby AluDRB1 indel was strongly haplotypic for only DRB1∗01, DRB1∗10, DRB1∗15 and DRB1∗16. There were 30 five-locus POALIN haplotypes inferred in all populations with H5 (no Alu insertions except for AluDQA1) and H21 (only AluDPB2 and AluDQA1 insertions) as the two predominant haplotypes. Neighbor joining trees and principal component analyses of the Alu and HLA-DRB1 polymorphisms showed that genetic diversity of these genomic markers is associated strongly with the population characteristics of language family, migration and sociality. This comparative study of HLA-DRB1 alleles and multilocus, lineage POALIN frequencies of Chinese ethnic populations confirmed that POALINs whether investigated alone or together with the HLA class II alleles are informative genetic and evolutionary markers for the identification of allele and haplotype lineages and genetic variations within the same and/or different populations.

TypeTE: a tool to genotype mobile element insertions from whole genome resequencing data

Alu retrotransposons account for more than 10% of the human genome, and insertions of these elements create structural variants segregating in human populations. Such polymorphic Alus are powerful markers to understand population structure, and they represent variants that can greatly impact genome function, including gene expression. Accurate genotyping of Alus and other mobile elements has been challenging. Indeed, we found that Alu genotypes previously called for the 1000 Genomes Project are sometimes erroneous, which poses significant problems for phasing these insertions with other variants that comprise the haplotype. To ameliorate this issue, we introduce a new pipeline – TypeTE – which genotypes Alu insertions from whole-genome sequencing data. Starting from a list of polymorphic Alus, TypeTE identifies the hallmarks (poly-A tail and target site duplication) and orientation of Alu insertions using local re-assembly to reconstruct presence and absence alleles. Genotype likelihoods are then computed after re-mapping sequencing reads to the reconstructed alleles. Using a high-quality set of PCR-based genotyping of >200 loci, we show that TypeTE improves genotype accuracy from 83% to 92% in the 1000 Genomes dataset. TypeTE can be readily adapted to other retrotransposon families and brings a valuable toolbox addition for population genomics.

Determination of genetic heterogeneity in humans by Alu insertions in Lorica-Córdoba-Colombia

El objetivo de la presente investigación fue evaluar la diversidad genética de la población humana de Lorica-Córdoba. utilizando marcadores Alu. El estudio se realizó con una muestra de 46 individuos no emparentadas, a los cuales, se les determinó la presencia o ausencia de las 5 inserciones Alu: FXIII, ACE, D1, APO, PV92. Todos los marcadores Alu evaluados resultaron polimórficos, con frecuencias que oscilaron desde 0,109 (PV92) hasta 0,707 (APO), se detectó una heterocigosidad observada de 0.066 y una heterocigosidad esperada de 0.334, también se determinó ausencia de equilibrio Hardy-Weinberg para todos los marcadores utilizados y se encontró que la población de Lorica se agrupó con poblaciones afrocolombianas, ibéricas y norteafricanas. Los resultados obtenidos en este estudio nos permiten concluir que la población humana de Lorica presenta bajos niveles de heterocigosidad. Palabras clave: Diversidad genética Heterocigosidad, Marcadores, Población,