The nucleotide sequence of a HindIII‐EcoRI DNA fragment, 8 kbp long, of a lambda recombinant containing the whole human c‐myc gene has been deduced by the method of Maxam and Gilbert. This fragment encodes the complex c‐myc locus and the sequence provides information relative to the 2.7 kb long c‐myc transcript. It appears that although exons 2 and 3 would code for a 48‐K protein homologous to the myc domain of the viral p110 gag‐myc protein, the first exon, which has a large open reading frame ending with a stop codon just upstream from the donor splice site, could code on its own for a 20‐K protein. Speculations about the role of that putative protein on the regulation of the expression of exons 2 and 3 are made.

BackgroundBalanced chromosomal rearrangements associated with abnormal phenotype are rare events, but may be challenging for genetic counselling, since molecular characterisation of breakpoints is not performed routinely. We used next-generation sequencing to characterise breakpoints of balanced chromosomal rearrangements at the molecular level in patients with intellectual disability and/or congenital anomalies.MethodsBreakpoints were characterised by a paired-end low depth whole genome sequencing (WGS) strategy and validated by Sanger sequencing. Expression study of disrupted and neighbouring genes was performed by RT-qPCR from blood or lymphoblastoid cell line RNA.ResultsAmong the 55 patients included (41 reciprocal translocations, 4 inversions, 2 insertions and 8 complex chromosomal rearrangements), we were able to detect 89% of chromosomal rearrangements (49/55). Molecular signatures at the breakpoints suggested that DNA breaks arose randomly and that there was no major influence of repeated elements. Non-homologous end-joining appeared as the main mechanism of repair (55% of rearrangements). A diagnosis could be established in 22/49 patients (44.8%), 15 by gene disruption (KANSL1, FOXP1, SPRED1, TLK2, MBD5, DMD, AUTS2, MEIS2, MEF2C, NRXN1, NFIX, SYNGAP1, GHR, ZMIZ1) and 7 by position effect (DLX5, MEF2C, BCL11B, SATB2, ZMIZ1). In addition, 16 new candidate genes were identified. Systematic gene expression studies further supported these results. We also showed the contribution of topologically associated domain maps to WGS data interpretation.ConclusionPaired-end WGS is a valid strategy and may be used for structural variation characterisation in a clinical setting.