Expression of Robo receptor molecules is important for axon guidance across the midline of the mammalian central nervous system. Here we describe novel isoform a of human ROBO2, which is initially strongly expressed in the fetal human brain but thereafter only weakly expressed in adult brain and a few other tissues. The known isoform b of ROBO2 shows a more or less ubiquitous expression pattern, suggesting diverse functional roles. The genomic structure and distinct expression patterns of Robo2a and Robo2b have been conserved in the mouse, but in contrast to human ROBO2a mouse Robo2a is also abundant in adult brain. Exons 1 and 2 of human ROBO2a lie in an inherently unstable DNA segment at human chromosome 3p12.3 that is associated with segmental duplications, independent chromosome rearrangements during primate evolution, and homozygous deletion and loss of heterozygosity in various human cancers. The 5' end of mouse Robo2a lies in a <150-kb DNA segment of break in synteny between mouse chromosome 16C3.1 and the human genome.

Summary T‐box transcription factor T (TBXT), encoding the brachyury protein, is an embryonic nuclear transcription factor involved in mesoderm formation and differentiation. Previous studies indicate that TBXT mutations are responsible for the tailless or short‐tailed phenotype of many vertebrates. To verify whether the tailless phenotype in fat‐rumped sheep is associated with TBXT mutations, exon 2 of the TBXT gene for 301 individuals belonging to 13 Chinese and Iranian sheep breeds was directly sequenced. Meanwhile, 380 samples were used to detect the genotypes of the candidate variations by mapping to their reads databases in the Sequence Read Archive repository of GenBank. The results showed that one missense mutation, c.334G>T (GGG>TGG) with a completely linked synonymous variant c.333G>C (CCG>CCC) was found to be associated with the ‘tailless’ characteristic in typical fat‐rumped sheep breeds. The c.334G>T transversion led to the conversion of glycine to tryptophan at the 112th amino acid in the T‐box domain of the brachyury protein. In addition, crossbreeding experiments for long‐tailed and tailless sheep showed that CT/CT allele of nucleotides (nt) 333 and 334, a recessive mutation, would cause sheep tails to be shorter, suggesting that these two linked variants at nucleotides 333 and 334 in TBXT are probably causative mutations responsible for the tailless phenotype in sheep.

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We have applied FISH with fully integrated BACs and BAC subfragments assessed in the human genome sequence to a de novo t(7;10)(q33;q23) translocation in a patient with developmental delay and macrocephaly. The translocation breakpoints disrupt the SEC8L1 gene on chromosome 7 and the PTEN gene on chromosome 10. RT-PCR demonstrated chimeric transcripts containing the first 11 exons of SEC8L1 fused to exon 3 of PTEN. In addition to the balanced translocation, we found a 7-Mb deletion in the translocated part of chromosome 7 at 4-Mb distance of the translocation breakpoint. This microdeletion, which disrupts the PTN and TPK1 genes and deletes 29 bonafide genes and the T-cell receptor beta locus, arose in the paternal germline. The patient's phenotype may be caused by a dominant-negative effect of the SEC8L1-PTEN fusion protein and/or haploinsufficiency of the disrupted or deleted genes. Our study demonstrates that de novo translocations can be associated with microdeletions outside the breakpoint region(s), rendering the study and risk estimation of such breakpoints more complicated than previously assumed.