Parolini O, Hejtmancik J F, Allen R C, Belmont J W, Lassiter G L, Henry M J, Barker D F, Conley M E
Department of Pediatrics, University of Tennessee College of Medicine, Memphis.
Genomics. 1993 Feb;15(2):342-9. doi: 10.1006/geno.1993.1066.
The gene for X-linked agammaglobulinemia (XLA) has been mapped to Xq22. No recombinations have been reported between the gene and the probe p212 at DXS178; however, this probe is informative in only 30-40% of women and the reported flanking markers, DXS3 and DXS94, are 10-15 cM apart. To identify additional probes that might be useful in genetic counseling, we examined 11 polymorphisms that have been mapped to the Xq21.3-q22 region in 13 families with XLA. In addition, pulsed-field gel electrophoresis and yeast artificial chromosomes (YACs) were used to further characterize the segment of DNA within which the gene for XLA must lie. The results demonstrated that DXS366 and DXS442, which share a 430-kb pulsed-field fragment, could replace DXS3 as proximal flanking markers. Probes at DXS178 and DXS265 identified the same 145-kb pulsed-field fragment, and both loci were contained within a 200-kb YAC identified with the probe p212. A highly polymorphic CA repeat (DXS178CA) was isolated from one end of this YAC and used in linkage analysis. Probes at DXS101 and DXS328 shared several pulsed-field fragments, the smallest of which was 250 kb. No recombinations were seen between XLA and the DXS178-DXS265-DXS178CA complex, DXS101, DXS328, DXS87, or the gene for proteolipid protein (PLP). Key crossovers, when combined with the linkage data from families with Alport syndrome, suggested the following order of loci: cen-DXS3-DXS366-DXS442-(PLP, DXS101, DXS328, DXS178-DXS265-DXS178CA complex, XLA)-(DXS87, DXS94)-DXS327-(DXS350, DXS362)-tel.(ABSTRACT TRUNCATED AT 250 WORDS)
X连锁无丙种球蛋白血症（XLA）基因已被定位于Xq22。尚未有该基因与DXS178处的探针p212之间发生重组的报道；然而，该探针仅在30% - 40%的女性中具有信息性，且所报道的侧翼标记DXS3和DXS94相距10 - 15厘摩。为了鉴定可能对遗传咨询有用的其他探针，我们在13个患有XLA的家系中检测了11个已被定位于Xq21.3 - q22区域的多态性。此外，脉冲场凝胶电泳和酵母人工染色体（YAC）被用于进一步表征XLA基因必定所在的DNA片段。结果表明，共享一个430 kb脉冲场片段的DXS366和DXS442可替代DXS3作为近端侧翼标记。DXS178和DXS265处的探针鉴定出相同的145 kb脉冲场片段，且两个位点都包含在一个用探针p212鉴定出的200 kb YAC内。从该YAC的一端分离出一个高度多态的CA重复序列（DXS178CA）并用于连锁分析。DXS101和DXS328处的探针共享几个脉冲场片段，其中最小的为250 kb。在XLA与DXS178 - DXS265 - DXS178CA复合体、DXS101、DXS328、DXS87或蛋白脂蛋白（PLP）基因之间未发现重组。关键的交叉，与来自阿尔波特综合征家系的连锁数据相结合，提示了以下位点顺序：着丝粒 - DXS3 - DXS366 - DXS442 - （PLP、DXS101、DXS328、DXS178 - DXS265 - DXS178CA复合体、XLA） - （DXS87、DXS94） - DXS327 - （DXS350、DXS362） - 端粒。（摘要截短于250字）
