New polymorphic microsatellite markers place the haemochromatosis gene telomeric to D6S105

Raha-Chowdhury, Ruma; Bowen, Derrick John; Stone, Caroline; Pointon, Jennifer J.; Terwilliger, Joseph D.; Shearman, Jeremy D.; Robson, Kathryn; Bomford, Adrian; Worwood, Mark

doi:10.1093/hmg/4.10.1869

Cited by 78 publications

(42 citation statements)

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“…These and subsequent studies of the strong linkage disequilibrium between HH and various markers in the MHC region all led to the expectation that a putative HH gene would lie within approximately 1 cM of the HLA-A locus (Gasparini et al 1993;Jazwinska et al 1993;Raha-Chowdhury et al 1995;Yaouanq et al 1994). While the HLA association has had profound implications both for the clinical diagnosis and cloning strategies of the HH gene, the possible biological significance of that association is only now becoming evident.…”

Section: Introductionmentioning

confidence: 99%

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Porto

Alves²,

Rodrigues³

et al. 1998

Immunogenetics

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Section: Introductionmentioning

confidence: 99%

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Porto

Alves²,

Rodrigues³

et al. 1998

Immunogenetics

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“…The study of well-dechromosome 6 has been reported. [5][6][7] A candidate gene has fined atypical hemochromatosis families using genetic markbeen described (HFE), 4.5 Mb telomeric to HLA-A. 8 The use ers may increase our understanding of the sensitivity and the of haplotype analysis and the search for recombinations in specificity of genotyping in hemochromatosis.…”

mentioning

confidence: 99%

Clinical and family studies in genetic hemochromatosis: Microsatellite and HFE studies in five atypical families

et al. 1997

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present in 70% of homozygotes, and an extended ancestral A candidate gene (HFE) has been described for hereditary haplotype including HLA-A3 and other DNA markers on hemochromatosis on chromosome 6. The study of well-dechromosome 6 has been reported. [5][6][7] A candidate gene has fined atypical hemochromatosis families using genetic markbeen described (HFE), 4.5 Mb telomeric to HLA-A. 8 The use ers may increase our understanding of the sensitivity and the of haplotype analysis and the search for recombinations in specificity of genotyping in hemochromatosis. One hundred families are considered to be powerful tools for localizing a and thirteen Canadian families with genetic hemochromatosis gene responsible for a disease. However, in hemochromatowere surveyed to find atypical families as possible examples sis, it had been difficult to prove informative genetic recombiof people with genetic recombinations. All families underwent nations for several reasons: 1) the late presentation of the clinical investigations including iron studies and HLA typing.probands in the fifth or sixth decade often means that parenEach individual was typed at three polymorphic microsatellite tal DNA is not available; 2) ascertainment of the phenotypic loci (D6S105, D6S1260, and D6S299) on chromosome 6. Sixstatus may be difficult and may vary between studies; and teen subjects were studied for the two missense mutations 3) lack of heterogeneity with available DNA markers has described for the candidate gene for hemochromatosis reduced the number of informative family studies. In this (C282Y, H63D). There were eight HLA-identical siblings study, 113 Canadian families with genetic hemochromatosis found in four different families (five men, three women; age were reviewed, and DNA studies are presented in 5 atypical range 30-72) with normal transferrin saturation and ferritin families with potential recombinations. levels. There were two patients identified who were homozy- PATIENTS AND METHODS gous for the C282Y mutation without biochemical evidenceA database of 113 Canadian families that had been investigated of iron overload, and two patients with no evidence of the by family studies was reviewed to search for families with potential mutation with significant iron overload. Our conclusions are genetic recombinations. All families were white with European anas follows: 1) finding HLA-identical siblings without iron overcestry. This study included 4 families in which one or more HLAload does not confirm a genetic recombination, 2) difficulties identical sibling was found without phenotypic expression of the in phenotypic definition of disease and the description of new disease, and 1 family in which two putative homozygotes produced iron overload syndromes that may differ from classical genetic an unaffected son. The diagnosis of hemochromatosis was based HC cause complicated genetic studies, and 3) finding iron-on clinical history, physical examination, and elevated serum ferriloaded patients without a C282Y mutation and patients that tin...

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“…D6S306, D6S105, and D6S464, a group of wellcharacterized polymorphic markers, each with one allele in linkage disequilibrium with hemochromatosis (Raha-Chowdhury et al 1995), are located within the left third of y950h11, approximately at the center of the map. D6S1260 (Raha-Chowdhury et al 1995), one of the most telomeric markers reported to be tightly linked to hemochromatosis before the publication by Feder et al (1996), and D6S1016, a tetranucleotide-repeat marker thought to mark the telomeric boundary of the region of linkage disequilibrium with hemochromatosis (Seese et al 1996), are other noteworthy landmarks on this YAC.…”

Section: Yac-contig Mapmentioning

confidence: 99%

“…D6S1260 (Raha-Chowdhury et al 1995), one of the most telomeric markers reported to be tightly linked to hemochromatosis before the publication by Feder et al (1996), and D6S1016, a tetranucleotide-repeat marker thought to mark the telomeric boundary of the region of linkage disequilibrium with hemochromatosis (Seese et al 1996), are other noteworthy landmarks on this YAC. The hemochromatosis gene HLA-H is located in a map segment shared by clones y899g1 and y974a2.…”

Section: Yac-contig Mapmentioning

confidence: 99%

Clone–Contig and STS Maps of the Hereditary Hemochromatosis Region on Human Chromosome 6p21.3–p22

Lauer¹,

Meyer²,

Prass³

et al. 1997

Genome Res.

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YAC-based and bacterial-clone based STS-content maps were constructed that served as the framework physical maps for the positional cloning of a candidate gene for hereditary hemochromatosis. The YAC-based map comprises 43 YACs and 86 STS and spans ∼8 Mb of DNA between the class I region of the major histocompatibility complex on human chromosome 6p21.3 and D6S276 in 6p22. Comparison with published maps revealed a hole in the MIT/Whitehead and CEPH YAC maps that includes the immediate region around the hemochromatosis gene itself. Approximately 3 Mb of DNA was covered by a bacterial clone contig that consists of 38 BACs, 45 PACs, 26 P1 clones and one λ phage. The bacterial clone-based STS map comprises 153 STSs. A contiguous block of 8 STSs could be amplified from both human chromosome 6 and 5. Further characterization of selected STSs and bacterial clones by radiation hybrid mapping and fluorescence in situ hybridization, respectively, revealed the presence of a multicopy DNA segment, more than one bacterial clone length in size, which is duplicated near the chromosome-6 centromere and part of which is present in multiple copies on chromosome 5. Possible implications of the incomplete public YAC–contig map and of the multicopy segment for physical mapping and linkage disequilibrium studies of the hemochromatosis candidate region are discussed.[The sequence data described in this paper have been submitted to GenBank under accession nos. G31205–G31325.]

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New polymorphic microsatellite markers place the haemochromatosis gene telomeric to D6S105

Cited by 78 publications

References 0 publications

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis

Clinical and family studies in genetic hemochromatosis: Microsatellite and HFE studies in five atypical families

Clone–Contig and STS Maps of the Hereditary Hemochromatosis Region on Human Chromosome 6p21.3–p22

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