Huntington disease: linkage analysis with age-of-onset corrections.
Huntington disease: linkage analysis with age-of-onset corrections.
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亨廷顿病：与发病年龄校正的连锁分析。
DOI：
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发表时间：
1980
期刊：
影响因子：
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通讯作者：
S. Tideman
中科院分区：
文献类型：
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作者：
Susan E. Hodge;M. Spence;Barbara F. Crandall;Robert S. Sparkes;M. Sparkes;M. Crist;S. Tideman
对11个分离常染色体显性遗传亨廷顿病（HD）的扩展家系进行了15个基因标记的连锁分析。使用了直线年龄校正（STLN），大致拟合已发表的发病年龄数据，但不包括最老和最年轻的年龄。结果未能证实Brackenridge et al [1978]报告的HD和触珠蛋白（Hp）之间的阳性lod评分;我们的lod评分（单独使用）将排除这种联系。在我们的研究中没有lod得分超过0.40。三个信息标记，腺苷脱氨酶（ADA），Hp，和MNS，被用来比较通过采用不同的年龄校正在LOD评分计算得到的结果。除STLN外，还使用了最小二乘线（LSQR）和累积正态曲线（CSQN）。由于它与数据的拟合程度最接近，因此被认为是最准确的。为了进行比较，还检查了两种不涉及年龄校正的方法：一种是所有未受影响的人统一分配50%的风险率（NONE），另一种是所有年轻的风险人群从分析中删除（REMV）。NONE和REMV在某些情况下显著扭曲了lod评分。更重要的是，他们有时也会对重组分数的估计产生偏差。相比之下，STLN和LSQR给出的结果通常与使用CORN发现的结果非常相似。因此，得出的结论是，使用的年龄校正的确切形状是不关键的连锁分析，但不使用任何校正可能会导致不可接受的结果。
Eleven extended pedigrees segregating autosomal dominant Huntington disease (HD) were analyzed for linkage with 15 gene markers. A straight-line age correction (STLN), fitted roughly to published age-of-onset data but excluding the oldest and youngest ages, was used. The results failed to confirm a positive lod score reported by Brackenridge et al [1978] between HD and haptoglobin (Hp); our lod scores, taken alone, would rule out this linkage. No lod score in our study exceeded 0.40. Three informative markers, adenosine deaminase (ADA), Hp, and MNSs, were used to compare results obtained by employing different age corrections during lod score calculation. In addition to STLN, a least-squares line (LSQR) and a cumulative normal curve (CUMN) were used. CUMN was assumed to be the most accurate, since it fitted the data most closely. For comparison, two methods involving no age correction were also examined: one in which all unaffected persons were uniformly assigned a 50% penetrance (NONE) and one in which all younger at-risk persons were removed from the analysis (REMV). NONE and REMV distorted lod scores, in some cases strikingly. More importantly, they also sometimes biased the estimate of the recombination fraction. In contrast, STLN and LSQR gave results generally very similar to those found using CUMN. Thus, it was concluded that the exact shape of the age correction used is not critical to linkage analyses, but that failure to use any correction may lead to unacceptable results.