Kwan S P, Terwilliger J, Parmley R, Raghu G, Sandkuyl L A, Ott J, Ochs H, Wedgwood R, Rosen F
Department of Immunology, Rush Medical School, Chicago, Illinois 60612.
Genomics. 1990 Feb;6(2):238-42. doi: 10.1016/0888-7543(90)90562-9.
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.
X连锁无丙种球蛋白血症（XLA）是一种遗传性隐性疾病，其主要缺陷尚不清楚，基因产物也有待确定。利用遗传连锁分析，我们先前已通过DNA标记DXS3和DXS17将XLA基因定位到Xq21.3 - Xq22的图谱区域。在本研究中，通过对20个XLA正在分离的家系进行多点分析，使用另外两个DNA探针DXS94和DXS178进行了进一步的图谱绘制。其中13个家系先前已用DXS3和DXS17进行过分析。在9个信息丰富的家系中，检测到与DXS94有3次交换，而在DXS178与XLA基因座之间未发现重组。我们的结果表明，XLA与DXS178紧密连锁，两点连锁值为4.82，多点连锁值为10.24。因此，最可能的基因顺序是DXS3 -（XLA，DXS178）- DXS94 - DXS17，XLA定位的置信区间完全位于DXS3和DXS94之间。在其中2个家系中，我们鉴定出与DXS17的重组体，此前在多达40次减数分裂事件中其他人未检测到与该位点的重组。此外，DXS178在这两个家系中均具有信息性，且未显示与疾病位点的重组。因此，我们的结果表明DXS178与XLA基因紧密连锁。
