Tybulewicz Victor L J, Fisher Elizabeth M C
Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R103-9. doi: 10.1093/hmg/ddl179.
Aberrations in human chromosome copy number and structure are common and extremely deleterious. Their downstream effects on phenotype are caused by aberrant dosage of sequences in the affected regions. However, we know little about why the abnormal gene copy number causes disease or why specific features result from deficits in specific chromosomes. Mice are the organism of choice to help us try to tease apart the complex relationships between genotype and phenotype in aneuploidy and segmental aneusomy syndromes. As new technologies such as chromosome engineering and the creation of transchromosomic mice become routine, these will help us identify individual dosage-sensitive genes that are causative in specific syndromes and will enable us to produce mouse models to accurately recapitulate human chromosomal disorders.
人类染色体拷贝数和结构的畸变很常见且极其有害。它们对表型的下游影响是由受影响区域序列的异常剂量引起的。然而，我们对异常基因拷贝数为何会导致疾病，或者特定染色体缺陷为何会导致特定特征知之甚少。小鼠是帮助我们试图厘清非整倍体和节段性非整倍体综合征中基因型与表型之间复杂关系的首选生物。随着染色体工程和转基因小鼠创建等新技术变得常规化，这些技术将帮助我们识别在特定综合征中起致病作用的个体剂量敏感基因，并使我们能够制作出准确重现人类染色体疾病的小鼠模型。
