Localization of the hemochromatosis gene close to D6S105.
The hemochromatosis (HC) gene is known to be linked to HLA-A (6p21.3); however, its precise location has been difficult to determine because of a lack of additional highly polymorphic markers for this region. The recent identification of short tandem repeat sequences (microsatellites) has now provided this area with a number of markers with similar polymorphic index to the HLA serological polymorphisms. Using four microsatellites--D6S105, D6S109, D6S89, and F13A--together with the HLA class I loci HLA-A and HLA-B in 13 large pedigrees clearly segregating for HC, we have been able to refine the location of the HC gene. We identified no recombination between HC and HLA-A or D6S105, and two-point analyses placed the HC gene within one centimorgan (cM) of HLA-A and D6S105 (HLA-A maximum of the lod score [Zmax] of 9.90 at recombination fraction [theta] of 0.0, and D6S105 Zmax of 8.26 at theta of 0.0). The markers HLA-B, D6S109, D6S89, and F13A were separated from the HC locus by recombination, defining the centromeric and telomeric limits for the HC gene as HLA-B and D6S109, respectively. A multipoint map constructed using HLA-B, HLA-A, and D6S109 indicates that the HC gene is located in a region less than 1 cM proximal to HLA-A and less than 1 cM telomeric of HLA-A. These pedigree data indicate an association between HC and specific alleles at HLA-A and D6S105 (i.e., HLA-A3 and D6S105 allele 8).(ABSTRACT TRUNCATED AT 250 WORDS)
Jazwinska
E C
EC
Liver Unit, Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Australia.
Lee
S C
SC
Webb
S I
SI
Halliday
J W
JW
Powell
L W
LW
D000293:Adolescent; D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D002648:Child; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004276:DNA, Satellite / Q000032:analysis; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008875:Middle Aged; D010375:Pedigree
D004276:DNA, Satellite; D005819:Genetic Markers; D015234:HLA-A Antigens; D015235:HLA-B Antigens