Sankila E M, de la Chapelle A, Kärnä J, Forsius H, Frants R, Eriksson A
Clin Genet. 1987 May;31(5):315-22. doi: 10.1111/j.1399-0004.1987.tb02815.x.
Linkage studies using restriction fragment length polymorphisms were conducted in the X-linked disorder, choroideremia, designated TCD for Progressive Tapeto-Choroidal Dystrophy. Previously demonstrated close linkage with locus DXYS1 was confirmed (lod 11.44 at 0 recombination distance). In addition, locus DXYS12 was found to be closely linked with TCD (lod 3.31 at 0 recombination distance). The disease mainly occurs in three large kindreds in remote Northern Finland. While formal genealogical proof is lacking, all presently living (more than 80 affected males and 120 carrier females) probably originate from a common founder couple born in 1644 and 1646, twelve generations ago. All 36 patients and 48 carriers tested from the three kindreds had the same haplotype (TCD/DXYS1, 11kb/DXYS12, 1.6kb). Given that at least 105 female meioses transmitting TCD have occurred since 1650 in these kindreds, extremely close linkage between TCD, DXYS1 and DXYS12 is suggested. The above haplotype is a very useful diagnostic tool in these TCD families. We suggest that our historical-genealogical approach to linkage analysis may be possible elsewhere in similar isolated populations.
利用限制性片段长度多态性进行的连锁研究在X连锁疾病脉络膜骨瘤病（又称进行性毯层脉络膜营养不良，简称TCD）中展开。此前已证实其与DXYS1位点紧密连锁（在重组距离为0时，连锁值为11.44）。此外，还发现DXYS12位点与TCD紧密连锁（在重组距离为0时，连锁值为3.31）。该疾病主要发生在芬兰北部偏远地区的三个大家族中。虽然缺乏正式的系谱证据，但目前所有在世的患者（80多名患病男性和120名携带女性）可能都源自12代之前、出生于1644年和1646年的一对共同祖先夫妇。从这三个家族中检测的所有36名患者和48名携带者都具有相同的单倍型（TCD/DXYS1，11kb/DXYS12，1.6kb）。鉴于自1650年以来这些家族中至少发生了105次传递TCD的女性减数分裂，提示TCD、DXYS1和DXYS12之间存在极其紧密的连锁。上述单倍型在这些TCD家族中是一种非常有用的诊断工具。我们认为，我们这种历史系谱学的连锁分析方法在其他类似的隔离人群中或许也是可行的。
