Groot P C, Moen C J, Dietrich W, Stoye J P, Lander E S, Demant P
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam.
FASEB J. 1992 Jul;6(10):2826-35. doi: 10.1096/fasebj.6.10.1634045.
The genetic control of susceptibility to many common diseases, including cancer, is multigenic both in humans and in animals. This genetic complexity has presented a major obstacle in mapping the relevant genes. As a consequence, most geneticists and molecular biologists presently focus on "single gene" diseases. To make the multigenic diseases accessible to genetic and molecular analysis, we developed a novel genetic tool, the recombinant congenic strains (RCS) in the mouse (4). The RC strains are produced by inbreeding of mice of the second backcross generation between two inbred strains, one of which serves as the "donor" and the other as the "background" strain. A series of RCS consists of approximately 20 strains, each carrying a different set of genes: approximately 12.5% genes from the common donor inbred strain, the remaining 87.5% from the common background inbred strain. As the set of donor strain genes in each RC strain is different, the nonlinked genes of the donor strain involved in the control of a multigenic trait, e.g., cancer susceptibility, become distributed into different RC strains where they can be analyzed one by one. Hence, the RCS system transforms a multigenic trait into a series of single gene traits, where each gene contributing to the multigenic control can be mapped and studied separately. Recently we demonstrated that the RCS system is indeed capable of resolving multigenic traits, which are hardly analyzable otherwise, by mapping four new colon tumor susceptibility loci (8; P. C. Groot, C. J. A. Moen, W. Dietrich, L. F. M. van Zutphen, E. S. Lander, and P. Demant, unpublished results). For successful application of the RCS system, extensive genetic characterization of the individual recombinant congenic strains is essential. In this paper we present detailed information about the genetic composition of three series of RC strains on the basis of typing of 120-180 markers distributed along all autosomes. The data indicate that the relative representation of the donor strain genes in the RC strains does not deviate from the theoretical expectation, and that the RC strains achieved a very high degree of genetic homogeneity and for all practical purposes can be considered inbred strains. The density and distribution of markers reported here permits an effective mapping of unknown genes of donor strain origin at almost all autosomal locations. Much of this information has been obtained using the new class of genetic markers, the simple sequence repeat polymorphisms.(ABSTRACT TRUNCATED AT 400 WORDS)
包括癌症在内的许多常见疾病易感性的遗传控制在人类和动物中都是多基因的。这种遗传复杂性在定位相关基因方面构成了主要障碍。因此，目前大多数遗传学家和分子生物学家都专注于“单基因”疾病。为了使多基因疾病能够进行遗传和分子分析，我们开发了一种新型遗传工具——小鼠重组近交系（RCS）（4）。重组近交系是通过两个近交系之间第二代回交小鼠的近亲繁殖产生的，其中一个作为“供体”，另一个作为“背景”品系。一系列重组近交系大约由20个品系组成，每个品系携带不同的基因组合：约12.5%的基因来自共同的供体近交系，其余87.5%来自共同的背景近交系。由于每个重组近交系中供体品系基因的组合不同，供体品系中参与控制多基因性状（如癌症易感性）的非连锁基因就会分布到不同的重组近交系中，在那里可以逐一进行分析。因此，重组近交系系统将多基因性状转化为一系列单基因性状，其中每个对多基因控制有贡献的基因都可以单独定位和研究。最近我们证明，重组近交系系统确实能够通过定位四个新的结肠癌易感性位点来解析难以用其他方法分析的多基因性状（8；P.C.格鲁特、C.J.A.莫恩、W.迪特里希、L.F.M.范祖芬、E.S.兰德和P.德曼特，未发表的结果）。为了成功应用重组近交系系统，对各个重组近交系进行广泛的遗传特征分析至关重要。在本文中，我们基于沿所有常染色体分布的120 - 180个标记的分型，给出了关于三个系列重组近交系遗传组成的详细信息。数据表明，重组近交系中供体品系基因的相对比例与理论预期没有偏差，并且重组近交系达到了非常高的遗传同质性，实际上可以被视为近交系。本文报道的标记的密度和分布允许在几乎所有常染色体位置有效地定位供体品系来源的未知基因。这些信息大多是使用新型遗传标记——简单序列重复多态性获得的。（摘要截取自400字）
