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The genomic region (~4 Mb) of the human major histocompatibility complex (MHC) on chromosome 6p21 is a prime model for the study and understanding of conserved polymorphic sequences (CPSs) and structural diversity of ancestral haplotypes (AHs)/conserved extended haplotypes (CEHs). The aim of this study was to use a set of 95 MHC genomic sequences downloaded from a publicly available BioProject database at NCBI to identify and characterise polymorphic human leukocyte antigen (HLA) class I genes and pseudogenes,  MICA  and  MICB , and retroelement indels as haplotypic lineage markers, and single-nucleotide polymorphism (SNP) crossover loci in DNA sequence alignments of different haplotypes across the  Olfactory Receptor  ( OR ) gene region (~1.2 Mb) and the MHC class I region (~1.8 Mb) from the  GPX5  to the  MICB  gene. Our comparative sequence analyses confirmed the identity of 12 haplotypic retroelement markers and revealed that they partitioned the  HLA-A/B/C  haplotypes into distinct evolutionary lineages. Crossovers between SNP-poor and SNP-rich regions defined the sequence range of haplotype blocks, and many of these crossover junctions occurred within particular transposable elements, lncRNA,  OR12D2, MUC21, MUC22, PSORS1A3, HLA-C, HLA-B , and  MICA . In a comparison of more than 250 paired sequence alignments, at least 38 SNP-density crossover sites were mapped across various regions from  GPX5  to  MICB . In a homology comparison of 16 different haplotypes, seven CEH/AH ( 7.1, 8.1, 18.2, 51.x, 57.1, 62.x , and  62.1 ) had no detectable SNP-density crossover junctions and were SNP poor across the entire ~2.8 Mb of sequence alignments. Of the analyses between different recombinant haplotypes, more than half of them had SNP crossovers within 10 kb of  LTR16B/ERV3-16A3_I, MLT1, Charlie , and/or  THE1  sequences and were in close vicinity to structurally polymorphic  Alu  and  SVA  insertion sites. These studies demonstrate that (1) SNP-density crossovers are associated with putative ancestral recombination sites that are widely spread across the MHC class I genomic region from at least the telomeric  OR12D2  gene to the centromeric  MICB  gene and (2) the genomic sequences of MHC homozygous cell lines are useful for analysing haplotype blocks, ancestral haplotypic landscapes and markers, CPSs, and SNP-density crossover junctions.

SNP-Density Crossover Maps of Polymorphic Transposable Elements and HLA Genes Within MHC Class I Haplotype Blocks and Junction