Identification of a Closely Linked DNA Marker, DXS178, to Further
Refine the X-linked Agammaglobulinemia Locus
S-P. Kwan, J. Terwilliger, R. Parmley, G. Raghu, L.A. Sandkuyl,
J. Ott, H. Ochs, R. Wedgwood, F. Rosen
Genomics , 6(2), 238--242 (1990 Feb)
Abstract
X-linked agammaglobulinemia (XLA) is an inherited recessive disorder
in which the primary defect is not known and the gene product has
yet to be identified. Utilizing genetic linkage analysis, we
previously localized the XLA gene to the map region of Xq21.3-Xq22
with DNA markers DXS3 and DXS17. In this study, further mapping was
performed with two additional DNA probes, DXS94 and DXS178, by means
of multipoint analysis of 20 families in which XLA is segregating.
Thirteen of these families had been previously analyzed with DXS3
and DXS17. Three crossovers were detected with DXS94 and no
recombinations were found between DXS178 and the XLA locus in 9
informative families. Our results show that XLA is closely linked to
DXS178 with a two-point lod score of 4.82 and a multipoint lod score
of 10.24. Thus, the most likely gene order is
DXS3-(XLA,DXS178)-DXS94-DXS17, with the confidence interval for
location of XLA lying entirely between DXS3 and DXS94. In 2 of these
families, we identified recombinants with DXS17, a locus with which
recombination had not previously been detected by others in as many
as 40 meiotic events. Furthermore, DXS178 is informative in both of
these families and does not show recombination with the disease
locus. Therefore, our results indicate that DXS178 is linked tightly
to the XLA gene.
