Genetic linkage analysis identifies new proximal and distal flanking markers for the X-linked agammaglobulinemia gene locus, refining its localization in Xq22

Abstract

Genetic linkage analysis has been instrumental in mapping the gene for X-linked agammaglobulinemia (XLA) to the proximal long arm of the human X chromosome, to Xq22. Due to the relative rarity of this disease the localization of the gene within Xq22 has remained imprecise. We have investigated twenty-nine families affected by XLA and have found no recombinants with the DXS178 locus in over 30 informative meioses. DXS178 is now the most reliable and informative locus for use in pre-natal diagnosis and carrier detection of XLA. In addition, we have identified new closely linked proximal and distal flanking markers for XLA, DXS442 and DXS101, respectively. These loci are separated by 2cM, considerably reducing the extent of DNA within which the XLA locus can be contained. This will open up the way for more directed positional cloning efforts for the isolation of the XLA gene.