Epilepsy Genetics/Genomics Laboratories, Neurology and Research Services, VA GLAHS-West Los Angeles, CA, USA.
Epilepsy Behav. 2013 Jul;28 Suppl 1:S52-7. doi: 10.1016/j.yebeh.2012.06.033.
Introduced into a specific population, a juvenile myoclonic epilepsy (JME) mutation generates linkage disequilibrium (LD). Linkage disequilibrium is strongest when the JME mutation is of recent origin, still "hitchhiking" alleles surrounding it, as a haplotype into the next thousands of generations. Recombinations decay LD over tens of thousands of generations causing JME alleles to produce smaller genetic displacements, requiring other genes or environment to produce an epilepsy phenotype. Family-based linkage analysis captures rare epilepsy alleles and their "hitchhiking" haplotypes, transmitted as Mendelian traits, supporting the common disease/multiple rare allele model. Genome-wide association studies identify JME alleles whose linkage disequilibrium has decayed through thousands of generations and are sorting out the common disease/common allele versus rare allele models. Five Mendelian JME genes have been identified, namely, CACNB4, CASR, GABRa1, GABRD, and Myoclonin1/EFHC1. Three SNP alleles in BRD2, Cx-36, and ME2 and microdeletions in 15q13.3, 15q11.2, and 16p13.11 also contribute risk to JME.
在特定人群中引入青少年肌阵挛性癫痫（JME）突变会产生连锁不平衡（LD）。当 JME 突变是最近出现的时，LD 最强，仍然“搭便车”围绕它的等位基因，作为单倍型进入下几千代。重组会在数万代中使 LD 衰减，导致 JME 等位基因产生较小的遗传位移，需要其他基因或环境产生癫痫表型。基于家系的连锁分析捕获罕见的癫痫等位基因及其作为孟德尔特征传递的“搭便车”单倍型，支持常见疾病/多个罕见等位基因模型。全基因组关联研究确定了 JME 等位基因，其连锁不平衡已通过数千代衰减，正在梳理常见疾病/常见等位基因与罕见等位基因模型。已经确定了五个孟德尔 JME 基因，即 CACNB4、CASR、GABRa1、GABRD 和 Myoclonin1/EFHC1。BRD2、Cx-36 和 ME2 中的三个 SNP 等位基因以及 15q13.3、15q11.2 和 16p13.11 中的微缺失也会增加 JME 的风险。
