Duchenne/Becker muscular dystrophies (D/BMD) are X-linked recessive disorders resulting from dystrophin gene mutations. Intragenic recombination in the dystrophin gene occurs with a high frequency. Therefore, determination of the location and frequency of recombination improves D/BMD carrier detection and prenatal diagnosis in families in which the disease-causing mutation cannot be detected by most conventional methods. We describe herein a linkage analysis performed using a fast method based on capillary gel electrophoresis of fluorescent-labeled amplified alleles of 15 intragenic short tandem repeats spanning the entire dystrophin gene. On characterization of recombination events in 93 unrelated D/BMD families from southern Italy, we mapped 25 intragenic recombinations out of 273 informative meioses analyzed. The terminal regions of a gene are notoriously challenging for linkage analysis because some recombination events could be missed in case of lack of informativeness of the outermost markers. Many recombination events (10/25) identified in this study were located at the terminal regions of the dystrophin gene, and some were found by typing of several informative short tandem repeats located in these regions. Moreover, about 24% of the recombination events found in this study mapped to the 3 region of the gene, in contrast with the low frequency (4 to 15%) reported by others.

A larger spectrum of intragenic STRs improves linkage analysis and localization of intragenic recombination detection in the dystrophin gene: an analysis of 93 families from Southern Italy. J. Mol. Diagn.

CARSANA, ANTONELLA;FRISSO, GIULIA;SALVATORE, FRANCESCO
2007

Abstract

Duchenne/Becker muscular dystrophies (D/BMD) are X-linked recessive disorders resulting from dystrophin gene mutations. Intragenic recombination in the dystrophin gene occurs with a high frequency. Therefore, determination of the location and frequency of recombination improves D/BMD carrier detection and prenatal diagnosis in families in which the disease-causing mutation cannot be detected by most conventional methods. We describe herein a linkage analysis performed using a fast method based on capillary gel electrophoresis of fluorescent-labeled amplified alleles of 15 intragenic short tandem repeats spanning the entire dystrophin gene. On characterization of recombination events in 93 unrelated D/BMD families from southern Italy, we mapped 25 intragenic recombinations out of 273 informative meioses analyzed. The terminal regions of a gene are notoriously challenging for linkage analysis because some recombination events could be missed in case of lack of informativeness of the outermost markers. Many recombination events (10/25) identified in this study were located at the terminal regions of the dystrophin gene, and some were found by typing of several informative short tandem repeats located in these regions. Moreover, about 24% of the recombination events found in this study mapped to the 3 region of the gene, in contrast with the low frequency (4 to 15%) reported by others.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/333383
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