Mapping dystrophin gene recombinants in Greek DMD/BMD families: low recombination frequencies in the STR region

Abstract

A systematic study of 42 Greek DMD/BMD families using 14 polymorphic markers that span the dystrophin gene was performed in order to assess the position and frequency of recombinants in the Greek population and to test whether "hot spots" of recombination and deletions coincide when exclusively studying DMD/BMD families. We report a low percentage of recombination between markers STR44 and STR50; otherwise, the distribution of recombination events in other parts of the gene is largely in agreement with previously published data on Centre d'Etude du Polymorphisme Humaine families. We therefore propose that recombination frequencies and the correlation between recombination and deletion "hot spots" should be evaluated on DMD/BMD families exclusively.

Prenatal diagnosis of Duchenne muscular dystrophy in 131 Chinese families with dystrophinopathy

“…This creates several problems, one of which is the relatively high frequency of recombinations within the DMD gene. Some previous studies have indicated that the frequency of recombination was as high as 10% to 12% . Of the 140 prenatal cases in our study that were successfully analyzed using STR testing, 9 recombination events that occurred near the mutation site were identified, which illustrated the limitation of linkage analysis for the prenatal diagnosis of DMD.…”

“…Some previous studies have indicated that the frequency of recombination was as high as 10% to 12%. [10][11][12] Of the 140 prenatal cases in our study that were successfully analyzed using STR testing, 9 recombination events that occurred near the mutation site were identified, which In each case family, the STR loci analyzed and the peak value are indicated. For example, in case A, the sites STR44/STR45/STR49/STR50 were analyzed, and 180/del/244/239 shows the peak value of each STR loci, in which del indicates the STR was absent at this site.…”

A Larger Spectrum of Intragenic Short Tandem Repeats Improves Linkage Analysis and Localization of Intragenic Recombination Detection in the Dystrophin Gene

“…11,19,20 Furthermore, the use of several STRs with high heterozygosity in the 3Ј region (from intron 50) of the dystrophin gene enabled us to identify about 24% of all the recombinations found in our population. In contrast, a low number of recombinants (4 to 15% of total recombinants) was identified in this region in other populations, 13,14 probably because of the typing of a smaller STR panel.…”

“…8 -11 In recent years, many novel STRs have been identified and mapped in the dystrophin gene (Leiden Muscular Dystrophy, http://www.dmd.nl, accessed January 2006). However, intragenic recombination in the dystrophin gene has been shown to occur with a frequency of 10 to 12%, [12][13][14] which is about four times that expected on the basis of the length of the gene. This high recombination rate is not restricted to families segregating for D/BMD but occurs also in healthy families.…”

Screening for minor changes in the distal part of the human dystrophin gene in Greek DMD/BMD patients

“…Previous studies in the Greek population have also described differences in deletion breakpoints and in recombination events in the STR 44-50 region of the dystrophin gene. 32,33 Moreover, the incidence of the polymorphism C to T at position + 15 of intron 66, in Greek population, is found with a frequency of 15% which is greater than the 5% frequency reported by Lenk et al 15 The three frameshift products that were revealed by cDNA analysis in patient D286 demonstrate the usage of the alternative splicing mechanism. This property of the carboxy terminus of the gene is also evident in the case of BMD patient D320 in whom the DNA defect on exon 74 activates exon skipping and finally restores the frameshift mutation.…”