Christian S L, Robinson W P, Huang B, Mutirangura A, Line M R, Nakao M, Surti U, Chakravarti A, Ledbetter D H
Diagnostic Development Branch, National Institutes of Health, Bethesda, MD 20892-0940, USA.
Am J Hum Genet. 1995 Jul;57(1):40-8.
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11-q13. Approximately 70% of these patients have a large deletion of approximately 4 Mb extending from D15S9 (ML34) through D15S12 (IR10). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated from YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542.
普拉德-威利综合征（PWS）和安吉尔曼综合征（AS）是分别由15号染色体q11-q13区域父源和母源缺陷导致的不同的智力发育迟缓综合征。这些患者中约70%存在一个约4 Mb的大片段缺失，该缺失从D15S9（ML34）延伸至D15S12（IR10）。为了进一步确定D15S9近端的缺失断点，开发了三个新的多态性微卫星标记，其观察到的杂合度为60%-87%。D15S541和D15S542是从包含D15S18（IR39）位点的YAC A124A3中分离出来的。D15S543是从一个黏粒中分离出来的，该黏粒是从包含D15S9（ML34）位点的YAC 254B5近端右端克隆而来。利用一组已知减数分裂起源的卵巢畸胎瘤对这些标记进行基因-着丝粒定位，使15号染色体的遗传图谱朝着着丝粒方向扩展了2-3 cM。对53例普拉德-威利综合征和33例安吉尔曼综合征缺失患者中更靠近近端的S541/S542标记进行分析显示出两类患者：44%（35/80）的信息充分的患者在这些标记处发生了缺失（I类），而56%（45/80）未发生缺失（II类），普拉德-威利综合征和安吉尔曼综合征之间无差异。相比之下，在所有信息充分的患者（13/48）中D15S543发生了缺失，或者在35/48的患者中显示存在单个等位基因，这表明该标记在大多数普拉德-威利综合征和安吉尔曼综合征病例中发生了缺失。这些结果证实了普拉德-威利综合征和安吉尔曼综合征中都存在两个常见的近端缺失断点区域，并且与父源和母源缺失由相同的缺失机制导致一致。一个断点区域位于D15S541/S542和D15S543之间，另一个断点区域在D15S541/S542近端。
