Angel Charity for Children-Wings for Genetic Research, Steele Children's Research Center, Section of Medical and Molecular Genetics, Department of Pediatrics and Molecular and Cellular Biology, University of Arizona College of Medicine, 1501 N. Campbell Avenue, PO Box 245073, University of Arizona, Tucson, AZ 85724-5073, USA.
Mutat Res. 2010 Oct;705(2):96-106. doi: 10.1016/j.mrrev.2010.04.002. Epub 2010 Apr 24.
Somatic mosaicism is well known in disorders where the manifestations are readily seen, e.g. the skin in neurofibromatosis I. In single gene disorders of higher frequency, especially X-linked ones, the frequency of combined germ-line and somatic mosaicism is increasingly being appreciated, e.g. Duchenne Muscular Dystrophy. Cell separation techniques; such as the fluorescence-activated cell sorter (FACS) also detect much somatic mosaicism among blood cells in disorders such as paroxysmal nocturnal hemoglobinuria. Depending on the disorder and the class of mutation, in genes for which there are sufficient numbers of patients studied, 6-20% of cases are due to somatic mutation. This update of my previous review is stimulated by the rapid application of new technologies for the study of DNA variation in disease. The results of these studies implicate somatic mutation in a greater variety of genetic diseases and a wider spectrum of tissues than have previously been shown, including heart and kidney. The classes of mutation have also expanded beyond base pair changes, insertions/deletion (indels), and short tandem repeat mutations to include copy number variants and transposon-mediated mutations. I also briefly discuss previously well-known mosaicism for chromosomal mutations. Genomic sequencing, performed on DNA from blood, shows many mutations which are conclusively somatic in origin. It is still too early to see if there is a different pattern of somatic mutation compared to germ-line mutation. Though the parameters to allow careful quantification are not yet available, it seems that the frequency of gene mutation in embryonic cells is not markedly different than that in the germ line.
体细胞嵌合现象在表现明显的疾病中广为人知，例如神经纤维瘤病 I 中的皮肤。在频率较高的单基因疾病中，尤其是 X 连锁疾病中，生殖细胞和体细胞嵌合的频率越来越受到重视，例如杜氏肌营养不良症。细胞分离技术，如荧光激活细胞分选仪（FACS），也在阵发性夜间血红蛋白尿等疾病的血细胞中检测到大量体细胞嵌合。根据疾病和突变类别，在有足够数量患者进行研究的基因中，有 6-20%的病例是由于体细胞突变引起的。由于新技术在疾病中 DNA 变异研究中的快速应用，促使我更新了之前的综述。这些研究结果表明，体细胞突变涉及到比以前更多样的遗传疾病和更广泛的组织，包括心脏和肾脏。突变类别也已扩展到碱基对变化、插入/缺失（indels）和短串联重复突变之外，还包括拷贝数变异和转座子介导的突变。我还简要讨论了以前已知的染色体突变嵌合体。对血液中的 DNA 进行基因组测序，显示出许多明确来源于体细胞的突变。目前还为时过早，无法确定与生殖细胞突变相比，体细胞突变是否存在不同的模式。尽管还没有可用于仔细量化的参数，但胚胎细胞中的基因突变频率似乎与生殖系中的基因突变频率没有明显差异。
