Multipoint linkage analysis in X-linked Alport syndrome

Abstract

In order to localize the gene for the X-linked form of Alport syndrome (ATS) more precisely, we performed restriction fragment length polymorphism analysis with nine different X-chromosomal DNA markers in 107 members of twelve Danish families segregating for classic ATS or progressive hereditary nephritis without deafness. Two-point linkage analysis confirmed close linkage to the markers DXS17(S21) (zeta max = 4.44 at theta = 0.04), DXS94(pXG-12) (zeta max = 8.07 at theta = 0.04), and DXS101(cX52.5) (zeta max = 6.04 at theta = 0.00), and revealed close linkage to two other markers: DXS88(pG3-1) (zeta max = 6.36 at theta = 0.00) and DXS11(p22-33) (zeta max = 3.45 at theta = 0.00). Multipoint linkage analysis has mapped the gene to the region between the markers DXS17 and DXS94, closely linked to DXS101. By taking into account the consensus map and results from other studies, the most probable order of the loci is: DXYS1(pDP34)-DXS3 (p19-2)-DXS17-(ATS,DXS101)-DXS94-DXS11 -DXS42(p43-15)-DXS51(52A). DXS88 was found to be located between DXS17 and DXS42, but the order in relation to the ATS locus and the other markers used in this study could not be determined.