Refining the genetic map for the region flanking the X-linked hypophosphataemic rickets locus (Xp22.1-22.2)

• Published in: Human genetics 1994-03, Vol.93 (3), p.291-294
• Main Authors: ROWE, P. S. N, GOULDING, J, O'RIORDAN, J. L. H, READ, A, LEHRACH, H, FRANCIS, F, HANAUER, A, OUDET, C, BIANCALANA, V, KOOH, S. W, DAVIES, K. E
• Format: Article
• Language: English
• Subjects: Base Sequence; Biochemistry, Molecular Biology; Biological and medical sciences; Chromosome Mapping; Cloning, Molecular; Diseases of the osteoarticular system; DNA, Satellite; Female; Genetic Markers; Humans; Hypophosphatemia, Familial - genetics; Life Sciences; Lod Score; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Molecular Sequence Data; Polymerase Chain Reaction; X Chromosome
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/BF00212025

We have screened fourteen kindreds with X-linked hypophosphataemic rickets with four microsatellite markers, viz AFM163yh2, DXS999 (AFM234yf12), DXS443 and DXS365, in order to refine the genetic map flanking the gene, and to define a close flanking interval for the construction of a yeast artificial chromosome (YAC) and cosmid contig. The genetic data were enhanced after the isolation of a large 1.2-megabase YAC derived from AFM163yh2, in which marker DXS274 was present but not DXS365 or DXS443. Against HYP, DXS365, AFM163yh2 and DXS443 showed no recombinants (Zmax = 18.1, Zmax = 9.9, and Zmax = 16.0 respectively). DXS999 gave Zmax = 9.6 at 4% recombination and lies distal to HYP but proximal to DXS197 and DXS43. The disease gene and markers AFM163yh2 and DXS365 are flanked by DXS443 and DXS274. Combining the genetic and physical data, we are able to propose the following gene marker order: Xptel-DXS43-DXS197-DXS999-DXS443-[(DXS3 65-AFM163yh2), HYP]-DXS274-DXS41-Xcen.