EXCLUSION MAPPING OF THE GENE FOR X-LINKED NEURAL-TUBE DEFECTS IN AN ICELANDIC FAMILY

Various polymorphic markers with a random distribution along the X chr omosome were used in a linkage analysis performed on a family with app arently X-linked recessive inheritance of neural tube defects (NTD). T he lod score values were used to generate an exclusion map of the X ch romosome; this showed that the responsible gene was probably not locat ed in the middle part of Xp or in the distal region of Xq. A further r efining of these results was achieved by haplotype analysis, which ind icated that the gene for X-linked NTD was located either within Xp21.1 -pter, distal from the DMD locus, or in the region Xq12-q24 between DX S106 and DXS424. Multipoint linkage analysis revealed that the likelih ood for gene location is highest for the region on Xp. The region Xq26 -q28, which has syntenic homology with the segment of the murine X chr omosome carrying the locus for 'bent tail' (Bn), a mouse model for X-l inked NTD, is excluded as the location for the gene underlying X-linke d NTD in the present family. Thus, the human homologue of the Bn gene and the present defective gene are not identical, suggesting that more than one gene on the X chromosome plays a role in the development of the neural tube.