Local sequence determinants of two in-frame triplet deletion/duplication hotspots in the RHD/RHCEgenes
© Chen et al.; licensee Biomed Central Ltd. 2012
Received: 10 May 2012
Accepted: 14 May 2012
Published: 2 August 2012
Different types of human gene mutation can vary in size quite dramatically (e.g., single nucleotide substitutions vs. copy number variations), but what they all have in common is that their occurrence is often closely bound up with specific characteristics of the local DNA sequence environment . Here, we highlight the importance of local sequence features that underlie the two in-frame triplet deletion/duplication hotspots in the cis-linked, highly homologous RHD and RHCE paralogs.
Recently, Pereira and colleagues reported the first in-frame triplet duplication in the RHD gene; this duplication affected the same short region as the aforementioned two deduplications in exon 1 (Figure 1a) . As pointed out by the original authors, this duplication could have resulted from either a duplication of c.74-76TTC or c.75_77TCT. These authors emphasized the importance of a DNA motif (i.e., TTCTC that was identified by analogy to previously reported deletion-predisposing DNA motifs in the RHD gene ) in generating this duplication but did not provide a model to explain how this duplication could have been generated. Given that the sequence tract in question is prone to replication slippage, we surmised that this duplication might also be explicable in terms of such a mechanism. Indeed, as illustrated in Figure 1b, it can be readily explained by the model of serial replication slippage , invoking one step of forward slippage and one step of backward slippage.
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