Bergstrom David E, Bergstrom Rebecca A, Munroe Robert J, Lee Barbara K, Browning Victoria L, You Yun, Eicher Eva M, Schimenti John C
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Mamm Genome. 2003 Dec;14(12):817-29. doi: 10.1007/s00335-003-2298-4.
Chromosome deletion complexes in model organisms serve as valuable genetic tools for the functional and physical annotation of complex genomes. Among their many roles, deletions can serve as mapping tools for simple or quantitative trait loci (QTLs), genetic reagents for regional mutagenesis experiments, and, in the case of mice, models of human contiguous gene deletion syndromes. Deletions also are uniquely suited for identifying regions of the genome containing haploinsufficient or imprinted loci. Here we describe the creation of new deletions at the proximal end of mouse Chromosome (Chr) 17 by using the technique of ES cell irradiation and the extensive molecular characterization of these and previously isolated deletions that, in total, cover much of the mouse t complex. The deletions are arranged in five overlapping complexes that collectively span about 25 Mbp. Furthermore, we have integrated each of the deletion complexes with physical data from public and private mouse genome sequences, and our own genetic data, to resolve some discrepancies. These deletions will be useful for characterizing several phenomena related to the t complex and t haplotypes, including transmission ratio distortion, male infertility, and the collection of t haplotype embryonic lethal mutations. The deletions will also be useful for mapping other loci of interest on proximal Chr 17, including T-associated sex reversal ( Tas) and head-tilt ( het). The new deletions have thus far been used to localize the recently identified t haplolethal ( Thl1) locus to an approximately 1.3-Mbp interval.
模式生物中的染色体缺失复合体是对复杂基因组进行功能和物理注释的重要遗传工具。在它们众多的作用中,缺失可作为简单或数量性状基因座(QTL)的定位工具、区域诱变实验的遗传试剂,在小鼠中还可作为人类相邻基因缺失综合征的模型。缺失也特别适合用于鉴定基因组中包含单倍剂量不足或印记基因座的区域。在此,我们描述了利用胚胎干细胞辐射技术在小鼠17号染色体(Chr)近端创建新的缺失,以及对这些缺失和先前分离的缺失进行广泛的分子特征分析,这些缺失总共覆盖了小鼠t复合体的大部分区域。这些缺失被排列成五个重叠复合体,共同跨越约25兆碱基对。此外,我们已将每个缺失复合体与来自公共和私人小鼠基因组序列的物理数据以及我们自己的遗传数据整合起来,以解决一些差异。这些缺失将有助于表征与t复合体和t单倍型相关的几种现象,包括传递比率畸变、雄性不育以及t单倍型胚胎致死突变的收集。这些缺失也将有助于在17号染色体近端定位其他感兴趣的基因座,包括T相关性别反转(Tas)和头部倾斜(het)。到目前为止,新的缺失已被用于将最近鉴定的t单倍体致死(Thl1)基因座定位到一个约1.3兆碱基对的区间。