Oudet C, Heilig R, Hanauer A, Mandel J L
Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Am J Hum Genet. 1991 Aug;49(2):311-9.
Indirect tracking of mutation by DNA polymorphisms is still essential for carrier and prenatal diagnosis of Duchenne/Becker muscular dystrophy, at least in the families where no deletion can be detected. Because of the relatively high level of intragenic recombination, informative and easily testable markers at both ends of the gene are necessary for efficient and accurate diagnosis. We report the characterization of two polymorphic microsatellite sequences (TG repeats) at the 5' end of the dystrophin gene, within 40 kb of the muscle-specific promoter. The most useful one (5' DYS MSA) has 10 alleles with a 57% heterozygosity and can be tested on small polyacrylamide gels in a nonradioactive PCR-based assay. Despite its large number of alleles, this microsatellite shows strong linkage disequilibrium with a two-allele polymorphism reported by Roberts et al., an indication of the stability of this type of sequences. We have used the new microsatellites at the 5' end, along with one we reported previously for the 3' end, to type the families in the CEPH (Centre d'Etude du Polymorphisme Humain) panel. While the number of informative families has increased by a factor of about two with respect to the study of Abbs et al., the estimates of the recombination fractions are in good agreement with this previous report, suggesting a 11% recombination across the gene (3% between the 5' end and the pERT87 region, 8% between pERT87 and the 3' end), which is about fivefold more than expected. However, these estimates still have wide confidence limits.
通过DNA多态性间接追踪突变对于杜兴/贝克型肌营养不良症的携带者及产前诊断仍然至关重要，至少在那些未检测到缺失的家系中是如此。由于基因内重组水平相对较高，为了进行高效准确的诊断，在基因两端具有信息性且易于检测的标记是必要的。我们报告了肌营养不良蛋白基因5'端、肌肉特异性启动子40 kb范围内两个多态性微卫星序列（TG重复序列）的特征。最有用的一个（5' DYS MSA）有10个等位基因，杂合度为57%，可在基于非放射性PCR的检测中于小型聚丙烯酰胺凝胶上进行检测。尽管该微卫星有大量等位基因，但它与Roberts等人报道的一个双等位基因多态性显示出强连锁不平衡，这表明这类序列具有稳定性。我们使用了5'端的新微卫星以及我们之前报道的3'端的一个微卫星，对CEPH（人类多态性研究中心）家系进行分型。与Abbs等人的研究相比，信息性家系的数量增加了约两倍，而重组率的估计与之前的报告高度一致，表明整个基因的重组率为11%（5'端与pERT87区域之间为3%，pERT87与3'端之间为8%），这比预期高出约五倍。然而，这些估计的置信区间仍然很宽。
