Ewald H, Mors O, Flint T, Friedrich U, Eiberg H, Kruse T A
Department of Psychiatric Demography, Psychiatric Hospital in Aarhus, Denmark.
Am J Med Genet. 1995 Oct 9;60(5):386-92. doi: 10.1002/ajmg.1320600508.
The long arm of chromosome 11 is one of the most interesting regions in the search for major genes involved in the etiology of manic-depressive illness. Several candidate genes have been identified, including the gene encoding the dopamine D2 receptor, the M1 muscarinic receptor, and porfobillinogen deaminase. Furthermore, different families with co-segregation of psychiatric illness and structural chromosome abnormalities involving regions 11q21, 11q22.3, and 11q25 have been reported. Using narrow as well as broad phenotypic models, conservative genetic parameters, models with dominant or recessive modes of inheritance, and various methods to reduce misclassification, the present study did not find evidence for a major gene causing manic-depressive illness on the long arm of chromosome 11. In the broader phenotypic models multi-point analyses excluded at least 11q14 to 11q23.3, approximately 60 cM, even in one large family. Assuming homogeneity close linkage to DRD2 was excluded for all dominant models, and also in the affecteds-only analyses in the large family alone.
在寻找与躁郁症病因相关的主要基因过程中，11号染色体长臂是最有趣的区域之一。已经鉴定出几个候选基因，包括编码多巴胺D2受体、M1毒蕈碱受体和尿卟啉原脱氨酶的基因。此外，还报道了一些精神病与涉及11q21、11q22.3和11q25区域的染色体结构异常共分离的不同家系。本研究采用狭义和广义表型模型、保守的遗传参数、显性或隐性遗传模式的模型以及各种减少错误分类的方法，未发现11号染色体长臂上存在导致躁郁症的主要基因的证据。在更广义的表型模型中，多点分析排除了至少11q14至11q23.3，约60厘摩的区域，即使在一个大家系中也是如此。假设同质性，在所有显性模型中以及仅在这个大家系的患者分析中，均排除了与DRD2的紧密连锁。
