Hästbacka J, Kaitila I, Sistonen P, de la Chapelle A
Department of Medical Genetics, University of Helsinki, Finland.
Proc Natl Acad Sci U S A. 1990 Oct;87(20):8056-9. doi: 10.1073/pnas.87.20.8056.
We have used polymorphic DNA markers to map the gene for a clinically well-characterized form of osteochondrodysplasia, diastrophic dysplasia (DD), an autosomal recessive disorder of unknown pathogenesis. Linkage was analyzed in 13 families with two or three affected sibs comprising a total of 84 individuals. Positive two-point logarithm-of-odds (lod) scores were obtained between the DD locus and three polymorphic markers on chromosome 5. The highest pairwise lod score estimate of 7.37 with zero recombination to locus D5S72 suggests very tight linkage. There was no evidence of heterogeneity. Multipoint linkage analysis against the published order of the three loci gave the result centromere-D5S84-(DD, D5S72)-D5S61-terminus with a four-point lod score of 9.11. The present findings place the DD locus distal to the gene for adenomatous polyposis coli on the distal part of the long arm of chromosome 5. Our results provide a basis for refining the map position of the DD locus followed by physical localization, isolation, and characterization of the gene.
我们利用多态性DNA标记,对一种临床特征明确的骨软骨发育不良——畸形性发育不良(DD)的基因进行定位,DD是一种常染色体隐性疾病,发病机制不明。我们对13个家庭进行了连锁分析,这些家庭中有两到三个患病同胞,共计84人。在DD基因座与5号染色体上的三个多态性标记之间获得了正向两点对数优势(lod)分数。与基因座D5S72零重组时,最高的成对lod分数估计值为7.37,表明连锁非常紧密。没有异质性的证据。针对已公布的三个基因座顺序进行的多点连锁分析结果为:着丝粒-D5S84-(DD,D5S72)-D5S61-末端,四点lod分数为9.11。目前的研究结果表明,DD基因座位于5号染色体长臂远端的腺瘤性息肉病基因的远端。我们的结果为进一步精确DD基因座的图谱位置奠定了基础,随后可对该基因进行物理定位、分离和特征分析。