Guerrini Irene, Cook Christopher C H, Kest Wendy, Devitgh Audrey, McQuillin Andrew, Curtis David, Gurling Hugh M D
Molecular Psychiatry Laboratory, Windeyer Institute for Medical Sciences, Department of Mental Health Sciences, Royal Free and University College London Medical School, 46 Cleveland Street, London, W1T 4JF, UK.
BMC Genet. 2005 Mar 1;6:11. doi: 10.1186/1471-2156-6-11.
In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study.
DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD) where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA) 3. Alcohol Dependence Syndrome (ADS) as defined by Edwards and Gross (1976) and now incorporated into ICD10 and DSMIV.
Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1) for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model.
These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA) study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.
为了证实先前关于1号染色体与酒精中毒存在连锁关系的研究结果，我们开展了一项基因连锁研究。
选取了18个受酒精中毒严重影响的家庭的DNA，用于对一组多态性微卫星标记进行基因分型，这些标记位于1号染色体短臂和部分长臂上，间隔约10厘摩。使用经典对数优势计分法和无模型方法进行连锁分析。定义了三种不同的患病状态，分别为：1. 重度饮酒（HD），即受影响的受试者饮酒量超过皇家精神科医学院推荐的每周饮酒量。2. 酒精中毒研究诊断标准（RDCA）。3. 爱德华兹和格罗斯（1976年）定义的酒精依赖综合征（ADS），现已纳入ICD10和DSMIV。
对于酒精中毒的RDCA定义，使用覆盖细胞遗传学区域1p22.1 - 11.2的标记D1S1588、D1S2134、D1S1675进行连锁分析，均得到了阳性的两点和多点对数优势计分，在D1S1588（1p22.1）处的最大对数优势计分为1.8。使用HD患病模型，在1q21.3 - 24.2区域的D1S1653处发现了另一个对数优势计分为1.8的结果。
这些结果既支持了1p22.1 - 11.2区域存在连锁关系，这一区域先前已被美国酒精中毒遗传学协作研究（COGA）研究证实，同时也表明在1q21.3 - 24.2处存在另一个易感基因座。
