P111 Five locus high resolution extended haplotypes (eh) in healthy Mexican mestizos from the Highlands of Mexico

Abstract

Aim Continental ancestries are better represented by autosome gene frequencies, such as those of the MHC. In Mexico, Amerindian ancestry is prevalent (51–56%), followed by European (40–45%); the African share being 2–5%, depending on the area. Generation and maintenance of EH has several explanations: it may have been driven to high frequency, over a short period of time by positive selection, or conserved segments are exposed to allele specific recombination suppression, preventing haplotype breakdown. The aim of the study was to sequence a group of Mexican admixed healthy subjects, to determine the EH from unrelated and from family members of certain geographic areas. Methods HLA A ∗ ,C ∗ ,B ∗ ,DRB1 ∗ ,DQB1 ∗ genotyping was performed in 116 Mestizo unrelated controls, 66.4% of the Highlands, Center or North Mexico and 52 (73.1%) family members. DNA was extracted using the Maxwell16 and were sequenced on a 3500 ABI instrument. Allele frequencies (AF) were calculated with the SPSS 12 software and the haplotype (HF) analyses of the unrelated individuals was done with the Arlequin 3.5.1.2 software using the maximum likelihood method. The HF from families was calculated by direct counting. Results The 2 prevalent EH were typically Mexican: A ∗ 02:06-C ∗ 07:02-B ∗ 39:05-DRB1 ∗ 04:07-DQB1 ∗ 03:02, A ∗ 02:01-C ∗ 04:01-B ∗ 35:12-DRB1 ∗ 08:02-DQB1 ∗ 04:02 while the 4th was the cEH A ∗ 01:01-C ∗ 07:01-B ∗ 08:01-DRB1 ∗ 03:01-DQB1 ∗ 02:01. Other ethnic influences and the biological and significance are further discussed. Conclusions Asian EH, from NE China: 11:01-12:02-52:01-15:02:-06:01; Lebanese: 33:01-08:02-14:02-01:02-05:01 and African Bantu, 01:01-12:02-52:01-15:02-06:01, were observed. Some alleles have identical protein sequences but are distinguished at the DNA level by silent substitutions, and many alleles/haplotypes were particular of Mexicans: variants of B39 and B35 like: ∗ 39:05, 39:06, 35:12, 35:14, 35:16, 35:08,35:17, 35:03, 35:28 and 35:17, all of them in distinct EH: these alleles may be ancient or derived from founder ones by gene conversion events. This is true for B locus and it probably happened because the new alleles provided selective advantages, enlarging the peptide binding repertoire of the population, to be able to deal with the particular ecological niche.