Sequence analysis of the MHC class I region reveals the basis of the genomic matching technique

Genesis of ancestral haplotypes: RNA modifications and reverse transcription–mediated polymorphisms

“…The concept has been extended to the conserved polymorphic blocks of functionally related genes on other chromosomes, such as the genes encoding the proteins regulating complement activation in the RCA complex on chromosome 1 [9,10 ] as well as other mammalian species, such as the dog MHC [11]. In the 1990s these studies led to the development of the Genomic Matching Technique (GMT) to match donor and recipients at the MHC in bone marrow transplantation [12,13]. The GMT allowed successful matching of potential donors and recipients at the DNA sequence level in the MHC generating characteristic PCR fragment DNA profiles for polymorphic blocks within the MHC that do not undergo recombination.…”

“…The GMT is based on priming multiple sites within the block amplifying polymorphic complex sequences providing haplospecific and haplotypic signatures of the entire block rather than individual loci. Extended DNA sequences covering many exonic and intronic regions can be exactly matched by the technique without resorting to DNA sequencing [13].…”

“…Here we offer an outline of a plausible hypothesis which has been arrived at by merging two different molecular approaches to genetics: (1) The work of Dawkins and associates [5,12,13,24,25] at the genomic level concerning the particular genetic features, and thus questions on the origin of, Polymorphic…”

Use of the genomic matching technique to complement multiplex STR profiling reduces DNA profiling costs in high volume crimes and intelligence led screens

“…The technique generates characteristic DNA profiles for polymorphic genomic blocks in the MHC that do not undergo www.elsevier.com/locate/forsciint Forensic Science International 151 (2005) 249-257 recombination and are inherited as a 'frozen block' of sequence (also termed polymorphic frozen blocks) ( Fig. 1) [2][3][4]. The genomic blocks in the MHC can include up to 200-300 kb of sequence and have become relatively fixed over time.…”

“…Recombination occurs between blocks but rarely, if ever, within blocks, so they are inherited as a complete unit of sequence. Highly polymorphic and duplicated sequences are observed within the MHC blocks and these stable sequences are targeted in the GMT [4]. The polymorphisms include indels (insertion and deletions) and single nucleotide polymorphisms (SNPs), and are far more frequent within blocks than flanking sequences [5].…”