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首页> 美国卫生研究院文献>American Journal of Human Genetics >Indications of Linkage and Association of Gilles de la Tourette Syndrome in Two Independent Family Samples: 17q25 Is a Putative Susceptibility Region
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Indications of Linkage and Association of Gilles de la Tourette Syndrome in Two Independent Family Samples: 17q25 Is a Putative Susceptibility Region

机译：在两个独立的家庭样本中吉列斯·德·图雷特综合症的关联性和关联性指标：25q25是假定的易感性区域

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Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS remains elusive. However, several genomic regions have been implicated. Among them, 17q25 appears to be of special interest, as suggested by various independent investigators. In the present study, we explored the possibility that 17q25 contributes to the genetic component of GTS. The initial scan of chromosome 17 performed on two large pedigrees provided a nonparametric LOD score of 2.41 near D17S928. Fine mapping with 17 additional microsatellite markers increased the peak to 2.61 (P=.002). The original families, as well as two additional pedigrees, were genotyped for 25 single-nucleotide polymorphisms (SNPs), with a focus on three genes in the indicated region that could play a role in the development of GTS, on the basis of their function and expression profile. Multiple three-marker haplotypes spanning all three genes studied provided highly significant association results (P<.001). An independent sample of 96 small families with one or two children affected with GTS was also studied. Of the 25 SNPs, 3 were associated with GTS at a statistically significant level. The transmission/disequilibrium test for a three-site haplotype moving window again provided multiple positive results. The background linkage disequilibrium (LD) of the region was studied in eight populations of European origin. A complicated pattern was revealed, with the pairwise tests producing unexpectedly high LD values at the telomeric TBCD gene. In conclusion, our findings warrant the further investigation of 17q25 as a candidate susceptibility region for GTS.
机译：吉尔斯·德·图雷特综合症（GTS）的特征是多发性运动和声音抽动以及其他神经行为障碍的合并症发生率高。据推测，额叶皮层下途径和复杂的遗传背景与该疾病的发病机理有关。 GTS的遗传基础仍然难以捉摸。然而，已经牵涉到几个基因组区域。在其中，正如各种独立研究人员所建议的那样，《 25qq》似乎特别令人关注。在本研究中，我们探索了17q25有助于GTS遗传成分的可能性。在两个大谱系上进行的17号染色​​体的初始扫描在D17S928附近提供了2.41的非参数LOD评分。使用其他17个微卫星标记进行的精细定位将峰增加至2.61（P = .002）。根据25个单核苷酸多态性（SNP）对原始家族以及另外两个谱系进行了基因分型，并根据其功能重点研究了指定区域中可能在GTS的发育中起作用的三个基因和表达方式。跨越所有研究的三个基因的多个三标记单倍型提供了高度显着的关联结果（P <.001）。还对96个有一个或两个孩子的GTS小家庭的独立样本进行了研究。在25个SNP中，有3个与GTS相关，具有统计学意义。三位单倍型移动窗口的透射/不平衡测试再次提供了多个肯定的结果。在欧洲起源的八个人口中研究了该区域的背景连锁不平衡（LD）。揭示了复杂的模式，配对测试在端粒TBCD基因上产生了意想不到的高LD值。总之，我们的发现值得进一步调查17q25作为GTS的候选药敏区。

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