Curtis D, Sherrington R, Brett P, Holmes D S, Kalsi G, Brynjolfsson J, Petursson H, Rifkin L, Murphy P, Moloney E
Academic Department of Psychiatry, St Mary's Hospital Medical School, London, UK.
J R Soc Med. 1993 Sep;86(9):506-10.
Genetic linkage analysis has been used to study five Icelandic pedigrees multiply affected with manic depression. Genetic markers were chosen from regions which had been implicated by other studies or to which candidate genes had been localized. The transmission model used was of a dominant gene with incomplete penetrance and allowing for a large number of phenocopies, especially for unipolar rather than bipolar cases. Multipoint analysis with linked markers enabled information to be gained from regions spanning large distances. Using this approach we have excluded regions of chromosome 11p, 11q, 8q, 5q, 9q and Xq. Candidate genes excluded include those for tyrosine hydroxylase, the dopamine type 2 receptor, proenkephalin, the 5HT1A receptor and dopamine beta hydroxylase. Nevertheless, we remain optimistic that this approach will eventually identify at least some of the genes predisposing to manic depression.
遗传连锁分析已被用于研究五个患有躁郁症的冰岛家系。遗传标记是从其他研究表明有牵连或已定位候选基因的区域中选取的。所采用的遗传传递模型是一个具有不完全外显率且允许大量拟表型存在的显性基因,尤其是在单相而非双相病例中。对连锁标记进行多点分析能够从跨越很长距离的区域获取信息。采用这种方法,我们已经排除了11号染色体短臂、11号染色体长臂、8号染色体长臂、5号染色体长臂、9号染色体长臂和X染色体长臂的区域。被排除的候选基因包括酪氨酸羟化酶、多巴胺2型受体、前脑啡肽、5-羟色胺1A受体和多巴胺β羟化酶的基因。然而,我们仍然乐观地认为,这种方法最终将至少鉴定出一些导致躁郁症的基因。