Fine-mapping chromosome 20 in 230 systemic lupus erythematosus sib pair and multiplex families: Evidence for genetic epistasis with chromosome 16q12
Fine-mapping chromosome 20 in 230 systemic lupus erythematosus sib pair and multiplex families: Evidence for genetic epistasis with chromosome 16q12
复制标题
DOI：
10.1086/503686
复制
发表时间：
2006-05-01
影响因子：
9.8
通讯作者：
Behrens, TW
中科院分区：
文献类型：
--
作者：
Gaffney, PM;Langefeld, CD;Behrens, TW
系统性红斑狼疮（SLE）易感基因的存在，染色体20上的遗传连锁的观察，在几个独立的系统性红斑狼疮（SLE）家族收藏建议。为了进一步定位遗传效应，我们在两个最佳区域中对59个微卫星进行了分型，如基因组筛选所定义的。在一组230个SLE家系中，通过非参数连锁方法、基于家族的关联检验（传递/不平衡和系谱不平衡检验）和单倍型共享统计（单倍型游程检验）的组合，分析基因型与SLE的统计学连锁和/或关联。在白色家系中，与SLE连锁的最大证据是20 p12（LOD = 2.84）和20 q13.1（LOD = 1.64）。根据与16 q12连锁的证据对家族进行亚组化显著提高了20号染色体两个位置的LOD分数（20 p12 LOD = 5.06和20 q13），与上位性一致。然后，我们在20q13.1上的1.3 Mb候选区域中对162个单核苷酸多态性标记LOD = 3.65进行了分型，并确定了几个SNP，这些SNP证明了相关性的重要证据。这些数据为SLE与20 p12和20q13.1的联系和关联提供了额外的支持，并进一步细化了感兴趣的区间。这些数据进一步表明SLE家系中20 q12、20 q13和16 q12区域内的基因座之间存在上位关系的可能性。
The presence of systemic lupus erythematosus (SLE) susceptibility genes on chromosome 20 is suggested by the observation of genetic linkage in several independent SLE family collections. To further localize the genetic effects, we typed 59 microsatellites in the two best regions, as defined by genome screens. Genotypes were analyzed for statistical linkage and/or association with SLE, by use of a combination of nonparametric linkage methods, family-based tests of association (transmission/disequilibrium and pedigree disequilibrium tests), and haplotype-sharing statistics (haplotype runs test), in a set of 230 SLE pedigrees. Maximal evidence for linkage to SLE was to 20p12 (LOD = 2.84) and 20q13.1 (LOD = 1.64) in the white pedigrees. Subsetting families on the basis of evidence for linkage to 16q12 significantly improved the LOD scores at both chromosome 20 locations (20p12 LOD = 5.06 and 20q13), consistent with epistasis. We then typed 162 single-nucleotide polymorphism markers LOD = 3.65 across a 1.3-Mb candidate region on 20q13.1 and identified several SNPs that demonstrated significant evidence for association. These data provide additional support for linkage and association to 20p12 and 20q13.1 in SLE and further refine the intervals of interest. These data further suggest the possibility of epistatic relationships among loci within the 20q12, 20q13, and 16q12 regions in SLE families.