Schimenti J C
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Mamm Genome. 1999 Oct;10(10):969-76. doi: 10.1007/s003359901142.
Mouse t haplotypes exhibit transmission ratio distortion (TRD), whereby heterozygous males (+/t) transmit the t chromosome to nearly all offspring. TRD is mediated by the t complex responder locus (Tcr), whose transmission is elevated above Mendelian levels by additive contribution of several t haplotype-encoded quantitative trait loci (QTLs) called t complex distorters (Tcd1-Tcd5). The entire genetically defined Tcr interval has been cloned and consists of under 200 kb. This interval is one of three large duplication units in t haplotypes that retain high levels of similarity. The cis-active nature of Tcr raises the possibility that it is not a protein-encoding gene, but another anomaly such as a structural anomaly of chromatin. To further investigate the Tcr-critical interval, a 30-kb region upstream of the Tcp10b(t) gene (a testis-expressed former candidate for Tcr) was sequenced, along with the duplicated paralogous region associated with Tcp10c(t), which lies immediately adjacent but outside the Tcr interval. Several genes or transcriptional units were identified, including the 3' end of ribosomal s6 kinase (Rsk3); two apparently intronless and ORF-less genes; and Gpr31, an intronless, putative G-protein coupled receptor. While the 30-kb regions were 98% identical, the Gpr31 paralog from the Tcr-critical region (Gpr31b(t)) contained an in-frame 210-bp deletion that disrupted two of the seven predicted transmembrane domains. Furthermore, an intronless and ORFless gene from this interval, Trex1b(t), contained a 4-bp deletion that distinguished it from all other homologs in t haplotypes and wild-type chromosomes. Although it is unknown whether any of these genes are involved in TRD, their discovery raises new possibilities regarding the nature of Tcr, including a model whereby it might function as an RNA rather than a protein or chromatin anomaly.
小鼠t单倍型表现出传递比失真（TRD），即杂合雄性（+/t）将t染色体传递给几乎所有后代。TRD由t复合反应位点（Tcr）介导，通过几个t单倍型编码的数量性状位点（QTL）（称为t复合畸变基因（Tcd1 - Tcd5））的累加贡献，其传递率高于孟德尔水平。整个遗传定义的Tcr区间已被克隆，长度不到200 kb。该区间是t单倍型中保留高度相似性的三个大的重复单元之一。Tcr的顺式激活性质增加了一种可能性，即它不是一个蛋白质编码基因，而是另一种异常，如染色质的结构异常。为了进一步研究Tcr关键区间，对Tcp10b(t)基因（一个先前作为Tcr候选的睾丸表达基因）上游30 kb的区域进行了测序，以及与Tcp10c(t)相关的重复旁系区域，Tcp10c(t)紧邻Tcr区间但在其外部。鉴定出了几个基因或转录单元，包括核糖体s6激酶（Rsk3）的3'端；两个明显无内含子且无开放阅读框的基因；以及Gpr31，一个无内含子的假定G蛋白偶联受体。虽然这两个30 kb的区域有98%的同一性，但来自Tcr关键区域的Gpr31旁系同源物（Gpr31b(t)）包含一个读框内210 bp的缺失，该缺失破坏了七个预测跨膜结构域中的两个。此外，来自该区间的一个无内含子且无开放阅读框的基因Trex1b(t)，包含一个4 bp的缺失，使其与t单倍型和野生型染色体中的所有其他同源物区分开来。虽然尚不清楚这些基因中是否有任何一个参与TRD，但它们的发现为Tcr的性质提出了新的可能性，包括一种模型，即它可能作为一种RNA发挥作用，而不是作为蛋白质或染色质异常。
