A general heuristic for genome rearrangement problems.

In this paper, we present a general heuristic for several problems in the genome rearrangement field. Our heuristic does not solve any problem directly, it is rather used to improve the solutions provided by any non-optimal algorithm that solve them. Therefore, we have implemented several algorithms described in the literature and several algorithms developed by ourselves. As a whole, we implemented 23 algorithms for 9 well known problems in the genome rearrangement field. A total of 13 algorithms were implemented for problems that use the notions of prefix and suffix operations. In addition, we worked on 5 algorithms for the classic problem of sorting by transposition and we conclude the experiments by presenting results for 3 approximation algorithms for the sorting by reversals and transpositions problem and 2 approximation algorithms for the sorting by reversals problem. Another algorithm with better approximation ratio can be found for the last genome rearrangement problem, but it is purely theoretical with no practical implementation. The algorithms we implemented in addition to our heuristic lead to the best practical results in each case. In particular, we were able to improve results on the sorting by transpositions problem, which is a very special case because many efforts have been made to generate algorithms with good results in practice and some of these algorithms provide results that equal the optimum solutions in many cases. Our source codes and benchmarks are freely available upon request from the authors so that it will be easier to compare new approaches against our results.

Novel mutational mechanism in the thyroglobulin gene: imperfect DNA inversion as a cause for hereditary hypothyroidism.

The objective of this study was to perform genetic analysis in three brothers of Turkish origin born from consanguineus parents and affected by congenital hypothyroidism, goiter and low levels of serum TG. The combination of sequencing of DNA, PCR mapping, quantitative real-time PCR, inverse-PCR (I-PCR), multiplex PCR and bioinformatics analysis were used in order to detect TG mutations. We demonstrated that the three affected siblings are homozygous for a DNA inversion of 16,962bp in the TG gene associated with two deleted regions at both sides of the inversion limits. The inversion region includes the first 9bp of exon 48, 1015bp of intron 47, 191bp of exon 47, 1523bp of intron 46, 135bp of exon 46 and the last 14,089bp of intron 45. The proximal deletion corresponds to 27bp of TG intron 45, while the distal deletion spans the last 230bp of TG exon 48 and the first 588bp of intergenic region downstream TG end. The parents were heterozygous carriers of the complex rearrangement. In conclusion, a novel large imperfect DNA inversion within the TG gene was identified by the strategy of I-PCR. This aberration was not detectable by normal sequencing of the exons and exon/intron boundaries. Remarkably, the finding represents the first description of a TG deficiency disease caused by a DNA inversion.