Structural analysis of the HLA-A/HLA-F subregion: Precise localization of two new multigene families closely associated with the HLA class I sequences
- CNRS, Rennes (France); and others
Positional cloning strategies for the hemochromatosis gene have previously concentrated on a target area restricted to a maximum genomic expanse of 400 kb around the HLA-A and HLA-F loci. Recently, the candidate region has been extended to 2-3 Mb on the distal side of the MHC. In this study, 10 coding sequences [hemochromatosis candidate genes (HCG) I to X] were isolated by cDNA selection using YACs covering the HLA-A/HLA-F subregion. Two of these (HCG II and HCG IV) belong to multigene families, as well as other sequences already described in this region, i.e., P5, pMC 6.7, and HLA class I. Fingerprinting of the four YACSs overlapping the region was performed and allowed partial localization of the different multigene family sequences on each YAC without defining their exact positions. Fingerprinting on cosmids isolated from the ICRF chromosome 6-specific cosmid library allowed more precise localization of the redundant sequences in all of the multigene families and revealed their apparent organization in clusters. Further examination of these intertwined sequences demonstrated that this structural organization resulted from a succession of complex phenomena, including duplications and contractions. This study presents a precise description of the structural organization of the HLA-A/HLA-F region and a determination of the sequences involved in the megabase size polymorphism observed among the A3, A24, and A31 haplotypes. 29 refs., 2 figs., 2 tabs.
- OSTI ID:
- 466597
- Journal Information:
- Genomics, Vol. 32, Issue 2; Other Information: PBD: 1 Mar 1996
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
HUMAN CHROMOSOMES
GENETIC MAPPING
GENES
GENE MUTATIONS
DNA-CLONING
DNA SEQUENCING
STRUCTURE-ACTIVITY RELATIONSHIPS
BIOLOGICAL EVOLUTION
HISTOCOMPATIBILITY COMPLEX
IRON
METABOLISM
MAN
HEREDITARY DISEASES
METABOLIC DISEASES
COSMIDS
ELECTROPHORESIS
PROBES
DNA HYBRIDIZATION