Mapping and characterization of non-HLA multigene assemblages in the human MHC class I region.

Abstract:

:The major histocompatibility complex (MHC) class I region has been shown to be associated with a variety of immune and nonimmune disorders. In an effort to initiate steps designed to identify the idiopathic hemochromatosis disease gene (HFE), we have cloned and mapped two expressed messages using probes from the HLA-H subregion that lie immediately distal to the HLA-A9 breakpoint. Although the cDNA clones identify distinct multifragment families that are dispersed throughout the MHC, the gene sequences from which the two cDNA clones derive map centromeric to the HLA-B locus and are absent from the genomes of higher nonhuman primates. This suggests that a syntenic coding segment arose within a highly polymorphic region (TNF to HLA-B interval) as the result of an insertion event following the emergence of Homo sapiens. An additional syntenic cluster exists within a peak of linkage disequilibrium with the HFE gene and may define coding sequences that underlie the defect in genetic iron overload. These data generally support the concept that the class I region is potentially gene-rich and further highlight the possibility that these new coding sequences may play a role in the development of a variety of HLA-linked diseases. The observations presented suggest that interlocus exchanges have played a structural role in the genesis of the human class I region.

journal_name

Genomics

journal_title

Genomics

authors

Venditti CP,Harris JM,Geraghty DE,Chorney MJ

doi

10.1006/geno.1994.1382

subject

Has Abstract

pub_date

1994-07-15 00:00:00

pages

257-66

issue

2

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(84)71382-6

journal_volume

22

pub_type

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