Mansilla Maria Adela, Kimani Jane, Mitchell Laura E, Christensen Kaare, Boomsma Dorret I, Daack-Hirsch Sandy, Nepomucena Buena, Wyszynski Diego F, Felix Temis M, Martin Nicholas G, Murray Jeffrey C
Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA.
Twin Res Hum Genet. 2005 Feb;8(1):39-46. doi: 10.1375/1832427053435373.
Monozygotic (MZ) twins may be discordant for complex traits due to differential environmental exposure in utero, epigenetic variability in imprinting, X chromosome inactivation, or stochastic effects. Occasionally MZ twins may be discordant for chromosomal and single gene disorders due to somatic mosaicism. For complex traits, which are due to the interactive effects of multiple genes and environmental factors, the affected twin of a discordant MZ pair offers the possibility for identifying somatic mutations in candidate genes. DNA sequencing of candidate genes in discordant MZ twins can identify those rare etiologic mutational events responsible for the different phenotypes since the confounding effects of common single nucleotide polymorphisms are eliminated, as DNA sequences should be identical in MZ pairs. In this report we describe the extensive DNA sequencing of 18 candidate genes in a sample of MZ and dizygotic (DZ) twins with nonsyndromic cleft lip with or without cleft palate. We were unable to identify any somatic differences in approximately 34 Kb of DNA sequenced in 13 MZ pairs, for a total of approximately 900 Kb of sequence comparisons, supporting the hypothesis that nonetiologic posttwinning mutations are rare. While no etiologic variants were identified in this study, sequence comparisons of discordant MZ twins can serve as a tool for identifying etiologic mutations in clefting and other complex traits.
同卵双胞胎（MZ）可能因子宫内环境暴露差异、印记中的表观遗传变异性、X染色体失活或随机效应而在复杂性状上表现不一致。偶尔，同卵双胞胎可能因体细胞镶嵌现象而在染色体和单基因疾病上表现不一致。对于由多个基因和环境因素的相互作用导致的复杂性状，不一致的同卵双胞胎中受影响的一方为识别候选基因中的体细胞突变提供了可能性。对不一致的同卵双胞胎中的候选基因进行DNA测序，可以识别那些导致不同表型的罕见病因性突变事件，因为常见单核苷酸多态性的混杂效应被消除了，因为同卵双胞胎的DNA序列应该是相同的。在本报告中，我们描述了对一组患有或不患有腭裂的非综合征性唇裂的同卵双胞胎和异卵双胞胎（DZ）样本中的18个候选基因进行的广泛DNA测序。在13对同卵双胞胎中，我们对约34 Kb的DNA进行了测序，总共进行了约900 Kb的序列比较，但未能识别出任何体细胞差异，这支持了非病因性孪生后突变罕见的假设。虽然在本研究中未识别出病因性变异，但对不一致的同卵双胞胎进行序列比较可作为识别唇裂和其他复杂性状病因性突变的一种工具。
