ORFless, intronless, and mutant transcription units in the mouse t complexresponder (Tcr) locus

Mouse t haplotypes exhibit transmission ratio distortion (TRD), whereby het erozygous males (+/t) transmit the t chromosome to nearly all offspring. TR D is mediated by the t complex responder locus (Tcr), whose transmission is elevated above Mendelian levels by additive contribution of several t hapl otype-encoded quantitative trait loci (QTLs) called t complex distorters (T cd1-Tcd5). The entire genetically defined Tcr interval has been cloned and consists of under 200 kb. This interval is one of three large duplication u nits 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 Tcp1 0b(t) gene (a testis-expressed former candidate for Tcr) was sequenced, alo ng with the duplicated paralogous region associated with Tcp10c(t), which l ies immediately adjacent but outside the Tcr interval. Several genes or tra nscriptional units were identified, including the 3' end of ribosomal s6 ki nase (Rsk3); two apparently intronless and ORF-less genes; and Gpr31, an in tronless, 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 predi cted transmembrane domains. Furthermore, an intronless and ORFless gene fro m this interval, Trex1b(t), contained a 4-bp deletion that distinguished it from all other homologs in t haplotypes and wildtype chromosomes. Although it is unknown whether any of these genes are involved in TRD, their discov ery raises new possibilities regarding the nature of Tcr, including a model whereby it might function as an RNA rather than a protein or chromatin ano maly.