Identification of duplication downstream of BMP2 in a Chinese family with brachydactyly type A2 (BDA2).
Identification of duplication downstream of BMP2 in a Chinese family with brachydactyly type A2 (BDA2).
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中国 A2 型短指 (BDA2) 家系中 BMP2 下游重复的鉴定
DOI：
10.1371/journal.pone.0094201
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Liu X;Gao L;Zhao A;Zhang R;Ji B;Wang L;Zheng Y;Zeng B;Valenzuela RK;He L;Ma J
A2型短指畸形（BDA2，MIM 112600）的特征是食指和第二脚趾的中指骨偏离和缩短。利用中国 BDA2 家族的全基因组连锁分析，我们将 BDA2 的最大候选区间映射到染色体 20p12.3 内 D20S194 和 D20S115 之间约 1.5 Mb 的区域，并发现标记 D20S156 的比值得分的成对对数最高（Zmax = 6.09，θ = 0）。基于功能和位置的角度，骨形态发生蛋白 2 (BMP2) 基因被确定为该区域 BDA2 的致病基因，尽管在 BMP2 中未检测到点突变。通过进一步研究，我们发现了 BMP2 下游的 4,671 bp（Chr20：6,809,218–6,813,888）基因组重复。这种重复位于相关区域内，与该家族中的 BDA2 表型共分离，并且在未受影响的家族成员和不相关的对照个体中未发现。与之前报道的重复相比，该家族中的重复具有不同的断点，两侧是微同源序列GATCA，并且长度略有不同。在重复区域中还发现了一些其他微同源核苷酸。总之，我们的研究结果支持这样的结论：BMP2是BDA2的致病基因，对应于重复区域的基因组位置容易发生与手指畸形相关的结构变化，并且这种趋势可能是由该区域中丰富的微同源序列引起的。
Brachydactyly type A2 (BDA2, MIM 112600) is characterized by the deviation and shortening of the middle phalange of the index finger and the second toe. Using genome-wide linkage analysis in a Chinese BDA2 family, we mapped the maximum candidate interval of BDA2 to a ∼1.5 Mb region between D20S194 and D20S115 within chromosome 20p12.3 and found that the pairwise logarithm of the odds score was highest for marker D20S156 (Zmax = 6.09 at θ = 0). Based on functional and positional perspectives, the bone morphogenetic protein 2 (BMP2) gene was identified as the causal gene for BDA2 in this region, even though no point mutation was detected in BMP2. Through further investigation, we identified a 4,671 bp (Chr20: 6,809,218–6,813,888) genomic duplication downstream of BMP2. This duplication was located within the linked region, co-segregated with the BDA2 phenotype in this family, and was not found in the unaffected family members and the unrelated control individuals. Compared with the previously reported duplications, the duplication in this family has a different breakpoint flanked by the microhomologous sequence GATCA and a slightly different length. Some other microhomologous nucleotides were also found in the duplicated region. In summary, our findings support the conclusions that BMP2 is the causing gene for BDA2, that the genomic location corresponding to the duplication region is prone to structural changes associated with malformation of the digits, and that this tendency is probably caused by the abundance of microhomologous sequences in the region.
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影响因子：
4.8
作者：
KAWABATA, M;CHYTIL, A;MOSES, HL
通讯作者：
MOSES, HL
影响因子：
4
作者：
Armour, CM;McCready, ME;Bulman, DE
通讯作者：
Bulman, DE
DOI：
10.1073/pnas.0602558103
发表时间：
2006-05-16
影响因子：
11.1
作者：
Allendorph, George P.;Vale, Wylie W.;Choe, Senyon
通讯作者：
Choe, Senyon
影响因子：
4
作者：
Kjaer, KW;Eiberg, H;Mundlos, S
通讯作者：
Mundlos, S
影响因子：
4
作者：
FITCH, N
通讯作者：
FITCH, N