Theisen Aaron, Shaffer Lisa G
Signature Genomic Laboratories, Spokane, WA, USA.
Appl Clin Genet. 2010 Dec 10;3:159-74. doi: 10.2147/TACG.S8884. Print 2010.
Many human genetic disorders result from unbalanced chromosome abnormalities, in which there is a net gain or loss of genetic material. Such imbalances often disrupt large numbers of dosage-sensitive, developmentally important genes and result in specific and complex phenotypes. Alternately, some chromosomal syndromes may be caused by a deletion or duplication of a single gene with pleiotropic effects. Traditionally, chromosome abnormalities were identified by visual inspection of the chromosomes under a microscope. The use of molecular cytogenetic technologies, such as fluorescence in situ hybridization and microarrays, has allowed for the identification of cryptic or submicroscopic imbalances, which are not visible under the light microscope. Microarrays have allowed for the identification of numerous new syndromes through a genotype-first approach in which patients with the same or overlapping genomic alterations are identified and then the phenotypes are described. Because many chromosomal alterations are large and encompass numerous genes, the ascertainment of individuals with overlapping deletions and varying clinical features may allow researchers to narrow the region in which to search for candidate genes.
许多人类遗传疾病是由染色体不平衡异常引起的，即存在遗传物质的净增加或减少。这种失衡常常会扰乱大量对剂量敏感的、在发育中起重要作用的基因，并导致特定而复杂的表型。另外，一些染色体综合征可能是由具有多效性的单个基因的缺失或重复引起的。传统上，染色体异常是通过在显微镜下目视检查染色体来识别的。荧光原位杂交和微阵列等分子细胞遗传学技术的应用，使得隐匿的或亚显微水平的失衡得以识别，这些失衡在光学显微镜下是不可见的。微阵列通过“基因型优先”的方法，使得众多新综合征得以识别，即先识别具有相同或重叠基因组改变的患者，然后描述其表型。由于许多染色体改变很大，包含众多基因，确定具有重叠缺失和不同临床特征的个体，可能使研究人员缩小寻找候选基因的区域。
