Mechanisms of ring chromosome formation, ring instability and clinical consequences.
Mechanisms of ring chromosome formation, ring instability and clinical consequences.
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DOI：
10.1186/1471-2350-12-171
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发表时间：
2011-12-21
影响因子：
--
通讯作者：
Melaragno MI
中科院分区：
文献类型：
--
作者：
Guilherme RS;Meloni VF;Kim CA;Pellegrino R;Takeno SS;Spinner NB;Conlin LK;Christofolini DM;Kulikowski LD;Melaragno MI
对14例患者环状染色体断裂点及其形成机制进行了研究和定位。进行了几种技术，如全基因组阵列，MLPA（多重连接依赖性探针扩增）和FISH（荧光原位杂交）。确定患者I至XIV的环状染色体分别为：（3）（p26.1q29），r（4）（p16.3q35.2），r（10）（p15.3q26.2），r（10）（p15.3q26.13），r（13）（p13q31.1），r（13）（p13q34），r（14）（p13q32.33）、r（15）（p13q26.2）、r（18）（p11.32q22.2）、r（18）（p11.32q21.33）、r（18）（p11.21q23）、r（22）（p13q13.33）、r（22）（p13q13.2）和r（22）（p13q13.2）。这些环被发现是由不同的机制形成的，例如：两条染色体臂断裂，然后端对端重新结合（患者IV、VIII、IX、XI、XIII和XIV）;一条染色体臂断裂，随后与另一条染色体的亚端粒区融合（患者I和II）;一条染色体臂断裂，随后与相对的端粒区域融合（患者III和X）;两个亚端粒区域的融合（患者VII）;和端粒-端粒融合（患者XII）。因此，r（14）和一个r（22）可以被认为是完整的环，因为没有丢失相关的遗传物质。两名r（13）患者（V和VI）显示重复沿着13 q末端缺失，其中一名被证明是倒位的，这种机制被称为inv-dup-del。环不稳定性检测环损失和继发性畸变，但在所有三名患者，谁提出了稳定的环形染色体（II，XIII和XIV）。结论：环状染色体患者的临床表型可能与多种因素有关，包括基因单倍性不足、基因重复和环不稳定。由于环状染色体的环状结构引起的表观遗传因素也必须考虑，因为即使是完整的环状染色体也会导致表型改变，正如我们在完全r（14）和r（22）患者中观察到的那样。
The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization). The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV). We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).
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影响因子：
30.8
作者：
Gunderson, KL;Steemers, FJ;Chee, MS
通讯作者：
Chee, MS
影响因子：
4
作者：
Conlin, Laura K.;Kramer, Whitney;Spinner, Nancy B.
通讯作者：
Spinner, Nancy B.
影响因子：
5.3
作者：
KOSZTOLANYI, G
通讯作者：
KOSZTOLANYI, G
DOI：
10.1007/bf00272478
发表时间：
1975-01-01
期刊：
HUMANGENETIK
影响因子：
--
作者：
NISS, R;PASSARGE, E
通讯作者：
PASSARGE, E
影响因子：
0.4
作者：
Sodre, C. P.;Guilherme, R. S.;Melaragno, M. I.
通讯作者：
Melaragno, M. I.