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Rapid publication: Flanking markers define the X‐linked hypophosphatemic rickets gene locus
Author(s) -
Econs Michael J.,
Fain Pamela R.,
Norman Michael,
Speer Marcy C.,
PericakVance Margaret A.,
Becker Peggy A.,
Barker David F.,
Taylor Arlene,
Drezner Marc K.
Publication year - 1993
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650080916
Subject(s) - hypophosphatemic rickets , locus (genetics) , hypophosphatemia , positional cloning , biology , genetics , genetic linkage , gene , gene mapping , rickets , endocrinology , vitamin d and neurology , chromosome
X‐linked hypophosphatemic rickets (HYP) is an X‐linked dominant disorder characterized by decreased renal tubular phosphate reabsorption and consequent hypophosphatemia. The defect in tubular phosphate reabsorption is probably secondary to an unidentified humoral factor. Identification of the humoral factor and a full understanding of the pathophysiology of the disease await the identification of the HYP gene. Previously we demonstrated that DXS257 and DXS41 are flanking markers for the HYP gene. Two markers, DXS365 and DXS274, are tightly linked to the HYP gene, but investigators have been unable to determine whether they are centromeric or telomeric to the disease gene. Since tightly linked flanking markers are necessary prerequisites to obtain the gene by positional cloning techniques, we sought to determine the relative positions of these markers to the HYP gene by expanding our data base for linkage studies. We also investigated a new polymorphic probe for linkage to HYP to construct a more detailed genetic map around the HYP locus. Our data indicate that the markers DXS365, DXS274, and DXS92 are tightly linked to the HYP locus and suggest a locus order of Xtel‐(DXS444/DXS315)‐DXS43‐(DXS257/DXS365)‐HYP‐(DXS274/DXS41/DXS92)‐DXS451‐DXS319‐Xcen. These results will facilitate attempts further to localize and clone the HYP gene.