Mapping of human X-linked hypophosphataemic rickets by multilocus linkage analysis

Area of Science:

• Human Genetics
• Molecular Biology
• X-linked Disorders

Background:

• X-linked dominant hypophosphataemic rickets (HPDR) is a genetic disorder affecting phosphate metabolism.
• Previous studies have localized some genetic loci on the X chromosome, but the precise location of HPDR remained elusive.

Purpose of the Study:

• To determine the chromosomal location of the gene responsible for X-linked dominant hypophosphataemic rickets (HPDR).
• To investigate the relationship between human and mouse X chromosome organization for the HPDR locus.

Main Methods:

• Genetic linkage analysis was performed in eleven families affected with HPDR.
• A series of X chromosome markers, including probe 99.6 (DXS41), were used for typing.
• Multilocus linkage analysis was employed to refine the mapping.

Main Results:

• Significant linkage was established between HPDR and probe 99.6 (DXS41) with a peak lod score of 4.82.
• Multilocus analysis indicated that the HPDR locus maps distal to the DXS41 marker on the X chromosome (Xp22.31-p21.3).
• The determined location in humans is consistent with the known mapping of the hypophosphataemia (Hyp) locus in mice, suggesting conserved synteny.

Conclusions:

• The gene for X-linked dominant hypophosphataemic rickets is located on the distal region of the X chromosome, distal to DXS41.
• The conserved location with the mouse homolog (Hyp) supports evolutionary relationships between human and mouse X chromosomes.
• Further studies are needed to identify the specific gene and mutations responsible for HPDR.