Do all hemochromatosis patients have the same origin? An analysis of mitochondrial DNA and Y-DNA.

BACKGROUND

Mitochondrial DNA (mtDNA) and Y-DNA analysis have been widely used to predict ancestral origin. Genetic anthropologists predict that human civilizations may have originated in central Africa one to two million years previously. Primary iron overload is not a common diagnosis among indigenous people of northern Africa, but hereditary hemochromatosis is present in approximately one in 200 people in northern Europe. MtDNA analysis has the potential to determine whether contemporary hemochromatosis patients have an ancient ancestral linkage.

METHODS

DNA was obtained from buccal smears for mtDNA and Y-DNA analysis. Y-DNA analysis included examination of 20 short tandem repeat markers on the Y chromosome. Analysis of mtDNA involved sequencing of the HVR-1 genetic sequence (nucleotides 16001 to 16520) and was compared with the Cambridge Reference Sequence. MtDNA ancestral haplotypes were predicted from the analysis of the HVR-1 sequence.

RESULTS

Twenty-six male C282Y homozygotes were studied. There were 28 polymorphisms present in the HVR-1 sequence of these participants. The most common polymorphism was present at position 16519 in 15 participants and at position 16311 in eight participants. There were 12 different ancestral haplotypes predicted by mtDNA analysis, with the K haplotype being present in five participants. Y-DNA analysis revealed eight different haplotypes, with R1b being found in 11 of the 26 participants.

CONCLUSION

Analysis of mtDNA and Y-DNA in 26 hemochromatosis patients suggested that they did not all originate from the same ancestral tribe in Africa. These findings were consistent with the theory that the original hemochromatosis mutation occurred after migration of these ancestral people to central Europe, possibly 4000 years previously.