Howell Gareth R, Bergstrom Rebecca A, Munroe Robert J, Masse Jessica, Schimenti John C
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Genet Res. 2004 Dec;84(3):153-9. doi: 10.1017/s0016672304007219.
t haplotypes are naturally occurring, variant forms of the t complex on mouse chromosome 17, characterized by the presence of four inversions with respect to wild-type. They harbour mutations causing male sterility, male transmission ratio distortion (TRD) and embryonic lethality. Mice carrying t haplotypes have been found throughout the world, and genetic studies of the lethal mutations have identified at least 16 complementation groups. The embryonic lethal phenotypes of many t haplotypes have been characterized in detail, and are thought to be the consequence of homozygosity for single gene mutations. However, the existence of additional mutations in genes that function at later stages of development would be obscured. Here we investigated the possibility of multiple mutations in t haplotypes by screening the t(w73) haplotype for the presence of novel mutations. Since genetic analysis of t haplotype mutations is hindered by recombination suppression due to the inversions, deletion complexes covering the proximal two-thirds of the t complex were used to uncover the presence of any new lethal alleles. This analysis revealed a novel mutation between D17Jcs41 and D17Mit100, causing mice carrying both t(w73) and selected deletions to die at birth, prior to feeding. The finding of a new, cryptic lethal mutation in t haplotypes is an indication that these recombinationally isolated chromosomes, which already contain at least one lethal mutation that prevents homozygosity, may serve as sinks for the accumulation of additional recessive mutations.
t单倍型是小鼠17号染色体上t复合体的自然存在的变异形式，其特征是相对于野生型存在四处倒位。它们携带导致雄性不育、雄性传递率畸变（TRD）和胚胎致死的突变。携带t单倍型的小鼠在世界各地均有发现，对致死突变的遗传学研究已鉴定出至少16个互补群。许多t单倍型的胚胎致死表型已得到详细表征，被认为是单个基因突变纯合的结果。然而，在发育后期起作用的基因中存在额外突变的情况可能会被掩盖。在这里，我们通过筛选t(w73)单倍型中是否存在新突变来研究t单倍型中存在多个突变的可能性。由于倒位导致的重组抑制阻碍了对t单倍型突变的遗传分析，因此使用覆盖t复合体近端三分之二的缺失复合体来揭示任何新的致死等位基因的存在。该分析揭示了D17Jcs41和D17Mit100之间的一个新突变，导致同时携带t(w73)和选定缺失的小鼠在出生后进食前死亡。在t单倍型中发现一个新的隐性致死突变表明，这些已经包含至少一个阻止纯合的致死突变的重组隔离染色体，可能会成为额外隐性突变积累的汇聚点。
