Restriction mapping of a YAC contig in the hemochromatosis gene region
- Univ. of Queensland, Brisbane (Australia)
Hemochromatosis is a common inherited disorder of iron metabolism that can lead to cirrhosis, hepatocellular carcinoma, cardiomyopathy, diabetes and anthropathy. We have mapped the hemochromatosis gene to within 1 cM of HLA-A and the microsatellite D6S105, and our allele association studies have shown that D6S105 is the marker most closely associated with the hemochromatosis gene. We are currently constructing a YAC contig and restriction map of this region as part of a positional cloning strategy to identify the hemochromatosis gene. YACs containing HLA-A or D6S105 were selected, and fluorescent-in-situ-hybridization (FISH) was performed to confirm chromosomal location and exclude chimerism. YAC DNA was digested with a panel of rare cutters, separated by pulsed field gel electrophoresis, Southern blotted and probed with the vector arms to create restriction maps. YAC insert terminal ends were isolated using vectorette methodology. A contig extending 600 kb centromeric and 350 kb telomeric of HLA-A has been established. HLA-A, HLA-F and the microsatellite D6S265 have been positioned on this map. The contig does not yet overlap any D6S105 positive YACs but the telomeric end of the contig has been sequenced and is being used to identify additional YACs to bridge this interval. Restriction mapping of three D6S105 YACs has shown the presence of several CpG islands in this region. As these CpG islands are in close proximity to D6S105, they are being used to isolate coding sequences to determine whether any of these mark the position of the hemochromatosis gene.
- OSTI ID:
- 134389
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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BASIC STUDIES
BIOLOGICAL MARKERS
CARCINOMAS
CENTROMERES
CONTIGS
DIABETES MELLITUS
DIGESTIVE SYSTEM DISEASES
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ELECTROPHORESIS
FLUORESCENCE
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOME 6
IRON
METABOLISM
NUCLEOTIDES
PATIENTS
PROBES
TELOMERES
YEASTS