Williamson R, Darling S M
J Pathol. 1983 Nov;141(3):193-200. doi: 10.1002/path.1711410303.
There is much interest in the use of gene-specific probes for the study of dysfunction in human pathology. For the haemoglobinopathies, globin gene recombinants (either prepared from DNA sequences complementary to messenger RNA, or from genomic DNA) are used to determine whether globin genes are present, whether they are expressed in the nucleus, and whether they are correctly processed to give functional mRNAs. This has not only allowed a fuller understanding of the molecular aetiology of the thalassaemias, but also permitted antenatal diagnosis both by direct analysis of the gene lesion, and by linkage analysis using adjacent genes. Similar approaches are being applied to many other single gene defects. There are, however, other possible ways to study human hereditary disease using recombinants. It is now feasible to use random human chromosome-specific sequences to establish a linkage map for the entire human genome. Such a map may then be used either to determine the chromosomal localisation of any "single gene" phenotype by linkage analysis, or to study the contribution of different genes to a complex phenotype determined by several genes, as in multifactorial disease.
人们对使用基因特异性探针来研究人类病理学中的功能障碍有着浓厚兴趣。对于血红蛋白病，珠蛋白基因重组体（要么由与信使核糖核酸互补的DNA序列制备，要么由基因组DNA制备）被用于确定珠蛋白基因是否存在、它们是否在细胞核中表达以及它们是否被正确加工以产生功能性信使核糖核酸。这不仅使人们对地中海贫血的分子病因有了更全面的了解，还通过对基因病变的直接分析以及使用相邻基因的连锁分析实现了产前诊断。类似的方法正在应用于许多其他单基因缺陷。然而，还有其他利用重组体研究人类遗传病的可能途径。现在利用随机的人类染色体特异性序列来建立整个人类基因组的连锁图谱是可行的。这样的图谱随后可用于通过连锁分析确定任何“单基因”表型的染色体定位，或者用于研究不同基因对由多个基因决定的复杂表型的贡献，就像在多因素疾病中那样。
