Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families
Clustered 11q23 and 22q11 breakpoints and 3:1 meiotic malsegregation in multiple unrelated t(11;22) families
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DOI：
10.1086/302666
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发表时间：
1999-12-01
影响因子：
9.8
通讯作者：
Emanuel, BS
中科院分区：
文献类型：
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作者：
Shaikh, TH;Budarf, ML;Emanuel, BS
t（11;22）是唯一已知的复发性非罗伯逊体质易位。我们分析了t（11;（22）对多个无关家系的平衡易位携带者进行FISH检测，以定位11号和22号染色体上的t（11;22）断裂点。在23个无关的平衡易位携带者中，断裂点位于22 q11上D22 S788（N41）和ZNF 74之间的400 kb间隔内。此外，这23名携带者中的13名使用来自11号染色体的探针进行了测试，并且在每个携带者中，断裂点位于11 q23上的D11 S1340和APOA 1之间小于或等于185 kb的区域。因此，11号染色体和22号染色体上的断裂点聚集在多个不相关的家族中。由于der（22）基因的分离不良，额外der（22）t（11; 22）综合征可发生在平衡t（11;22）携带者的后代中。人们一直在猜测这种不公平隔离的发生机制。为了阐明这一机制，我们分析了16个t（11;22）家族，使用11号和22号染色体上的短串联重复多态性标记。在所有提供信息的病例中，先证者从t（11;22）携带者父母那里获得了三个等位基因中的两个，即22号染色体断裂点上方和11号染色体断裂点下方的标记。这些数据有力地表明，在所有16个家系中，t（11;22）平衡易位携带者亲本中的3：1减数分裂I异常分离是机制。总之，这些结果表明，大多数t（11;22）易位发生在相同的基因组间隔内，大多数supernumeraryder（22）后代是由平衡易位携带者的3：1减数分裂I异常分离引起的。
The t(11;22) is the only known recurrent, non-Robertsonian constitutional translocation. We have analyzed t(11;22) balanced-translocation carriers from multiple unrelated families by FISH, to localize the t(11;22) breakpoints on both chromosome 11 and chromosome 22. In 23 unrelated balanced-translocation carriers, the breakpoint was localized within a 400-kb interval between D22S788 (N41) and ZNF74, on 22q11. Also, 13 of these 23 carriers were tested with probes from chromosome 11, and, in each, the breakpoint was localized between D11S1340 and APOA1, on 11q23, to a region less than or equal to 185 kb. Thus, the breakpoints on both chromosome 11 and chromosome 22 are clustered in multiple unrelated families. Supernumerary-der(22)t(11;22) syndrome can occur in the progeny of balanced-t(11;22) carriers, because of malsegregation of the der(22). There has been speculation regarding the mechanism by which the malsegregation occurs. To elucidate this mechanism, we have analyzed 16 of the t(11;22) families, using short tandem-repeat-polymorphism markers on both chromosome 11 and chromosome 22. In all informative cases the proband received two of three alleles, for markers above the breakpoint on chromosome 22 and below the breakpoint on chromosome 11, from the t(11;22)carrier parent. These data strongly suggest that 3:1 meiosis I malsegregation in the t(11;22) balanced-translocation-carrier parent is the mechanism in all 16 families. Taken together, these results establish that the majority of t(11;22) translocations occur within the same genomic intervals and that the majority of supernumeraryder(22) offspring result from a 3:1 meiosis I malsegregation in the balanced-translocation carrier.