Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

A rapid method of haplotyping HFE mutations and linkage disequilibrium in a Caucasoid population

Mullighan, C.G., Bunce, M., Fanning, G.C., Marshall, S.E. and Welsh, K.I. (1998) A rapid method of haplotyping HFE mutations and linkage disequilibrium in a Caucasoid population. Gut, 42 (4). pp. 566-569.

PDF - Published Version
Download (114kB)
Link to Published Version:
*Subscription may be required


Background—HFE mutations are associated with hereditary haemochromatosis. However, a simple method capable of demonstrating the cis/transarrangement of alleles is lacking, and linkage disequilibrium betweenHFE alleles and classic HLA loci is unknown. These are important issues as the pathogenic role of the mutations is not known.

Aims—To develop a simple method of genotypingHFE mutations suitable for clinical use in addition to large disease studies.

Patients—A total of 330 Caucasoid cadaveric organ donor controls were examined. Ten individuals previouslyHLA-H genotyped by polymerase chain reaction using restriction fragment length polymorphism (PCR-RFLP) were also examined to validate the method.

Methods—A simple polymerase chain reaction using sequence specific primers (PCR-SSP) capable of haplotyping the mutations was developed. HFE allele and haplotype frequencies and linkage disequilibrium with eight HLA class I and II loci were examined in the control population.

Results—27% and 19.7% of patients were positive for the 63D and 282Y alleles, respectively. No chromosome carried both 63D and 282Y. Linkage disequilibrium between 282Y and HLA-A*03 was confirmed, but was not straightforward: some A*03-associated alleles (DRB1*15, DQB1*06), but not all (B*07, Cw*0702), were associated with 282Y.

Conclusions—Linkage disequilibrium data suggest that an HLA-B*07 containing haplotype contains an element affording protection from haemochromatosis and may suggest the timing of the founder 282Y mutation.

Item Type: Journal Article
Publisher: BMJ Publishing Group
Copyright: 1998 BMJ Publishing Group Ltd & British Society of Gastroenterology
Item Control Page Item Control Page


Downloads per month over past year