Berrettini W H, Ferraro T N, Goldin L R, Weeks D E, Detera-Wadleigh S, Nurnberger J I, Gershon E S
Department of Psychiatry and Human Behavior, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5918-21. doi: 10.1073/pnas.91.13.5918.
In the course of a systematic genomic survey, 22 manic-depressive (bipolar) families were examined for linkage to 11 chromosome 18 pericentromeric marker loci, under dominant and recessive models. Overall logarithm of odds score analysis for the pedigree series was not significant under either model, but several families yielded logarithm of odds scores consistent with linkage under dominant or recessive models. Affected sibling pair analysis of these data yielded evidence for linkage (P < 0.001) at D18S21. Affected pedigree member analysis also suggests linkage, with multilocus results for five loci giving P < 0.0001 and P = 0.0007 for weighting functions f(p) = 1 and 1/square root p, respectively, where p is the allele frequency. These results imply a susceptibility gene in the pericentromeric region of chromosome 18, with a complex mode of inheritance. Two plausible candidate genes, a corticotropin receptor and the alpha subunit of a GTP binding protein, have been localized to this region.
在一项系统性基因组调查过程中，依据显性和隐性模型，对22个躁郁症（双相情感障碍）家族进行检测，以确定其与11个18号染色体着丝粒周围标记位点的连锁关系。在这两种模型下，对家系系列进行的总体优势对数得分分析均不显著，但有几个家族产生的优势对数得分与显性或隐性模型下的连锁关系相符。对这些数据进行的患病同胞对分析在D18S21处产生了连锁证据（P < 0.001）。患病家系成员分析也表明存在连锁关系，五个位点的多位点结果在加权函数f(p) = 1和1/√p时分别给出P < 0.0001和P = 0.0007，其中p是等位基因频率。这些结果表明18号染色体着丝粒周围区域存在一个易感基因，其遗传模式复杂。两个可能的候选基因，促肾上腺皮质激素受体和一种GTP结合蛋白的α亚基，已定位到该区域。
