Search for Genomic Alterations in Monozygotic Twins Discordant for Cleft Lip and/or Palate
Search for Genomic Alterations in Monozygotic Twins Discordant for Cleft Lip and/or Palate
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DOI：
10.1375/twin.12.5.462
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发表时间：
2009-10-01
影响因子：
0.9
通讯作者：
Murray, Jeffrey C.
中科院分区：
文献类型：
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作者：
Kimani, Jane W.;Yoshiura, Koh-ichiro;Murray, Jeffrey C.
表型不一致的同卵双胞胎提供了通过描绘双胞胎中一个成员的分子异常来发现基因的可能性。一种被提出的不协调机制是由有丝分裂重组和其他体细胞变化引起的合子后发生的基因组变化。检测改变的基因组片段可以揭示候选基因位点，这些基因可以通过额外的分析得到验证。我们使用阵列比较基因组杂交、50K和250K Affymetrix基因芯片(R)SNP阵列和由1,536个SNP组成的Illumina定制阵列来研究这一假设，以扫描具有不协调唇裂和/或腭裂表型的同卵双胞胎样本中的基因组变化。对缺失、扩增和杂合性丢失的配对分析，以及对带有不一致基因呼叫的SNPs的序列验证，没有发现淋巴细胞DNA样本中双胞胎之间的任何基因组不一致。我们的结果表明，合子后基因组改变不是单纯性唇裂和/或腭裂单卵双胞胎不协调的常见原因。然而，不能排除罕见或平衡的基因组改变、组织特异性事件和超出我们实验方法检测水平的微小像差。我们在研究样本中观察到的基因组的稳定性也表明，在其他同卵双胞胎中检测不协调事件将是显着的，具有潜在的疾病意义。
Phenotypically discordant monozygotic twins offer the possibility of gene discovery through delineation of molecular abnormalities in one member of the twin pair. One proposed mechanism of discordance is postzygotically occurring genomic alterations resulting from mitotic recombination and other somatic changes. Detection of altered genomic fragments can reveal candidate gene loci that can be verified through additional analyses. We investigated this hypothesis using array comparative genomic hybridization; the 50K and 250K Affymetrix GeneChip (R) SNP arrays and an Illumina custom array consisting of 1,536 SNPs, to scan for genomic alterations in a sample of monozygotic twin pairs with discordant cleft lip and/or palate phenotypes. Paired analysis for deletions, amplifications and loss of heterozygosity, along with sequence verification of SNPs with discordant genotype calls did not reveal any genomic discordance between twin pairs in lymphocyte DNA samples. Our results demonstrate that postzygotic genomic alterations are not a common cause of monozygotic twin discordance for isolated cleft lip and/or palate. However, rare or balanced genomic alterations, tissue-specific events and small aberrations beyond the detection level of our experimental approach cannot be ruled out. The stability of genomes we observed in our study samples also suggests that detection of discordant events in other monozygotic twin pairs would be remarkable and of potential disease significance.