Identification and time dependence of quantitative trait loci for basal locomotor activity in the BXD recombinant inbred series and a B6D2 F2 intercross

Identification and time dependence of quantitative trait loci for basal locomotor activity in the BXD recombinant inbred series and a B6D2 F2 intercross
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DOI:
10.1023/a:1001963906258
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发表时间:
2000-05-01
期刊:
影响因子:
2.6
通讯作者:
Hitzemann, R
Hitzemann, R
中科院分区:
医学3区
文献类型:
--
作者:
Koyner, J;Demarest, K;Hitzemann, R

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使用互补的两阶段策略来检测和绘制与对盐水挑战(10ml/kg)的基础运动反应相关的数量性状基因座(QTL)。在第 1 阶段,通过分析 B x D 重组自交系系列的 25 个品系的品系平均值,鉴定了 p < 0.01 或更好的显着 QTL。在 1、3、5、9、10、16 和 18 号染色体上鉴定出 QTL。其中一些 QTL 在整个实验期间(0-20 分钟)检测到,而其他 QTL 则与特定的 5 分钟块相关。对 1800 只 C57BL/6J (B6) x DBA/2J (D2) F-2 杂交动物进行基础运动反应表型分析,其中 500 至 700 只伪随机选择的个体用于全基因组扫描,以确认 RI 生成的 QTL 并检测新的 QTL。没有检测到新的 QTL,但在 p < 10(-5) 至 p < 10(-9) 处确认了 1 号染色体上的 QTL,具体取决于时间间隔。此外,第 5 号和第 9 号染色体上的 QTL 得到确认,p < 0.001,提供的组合概率 (RI + F-2) 超过了显着关联的阈值。研究了另外两种表现出显着 RI 菌株差异的表型——适应和趋触性。适应映射到 9 号染色体的同一区域,触动性映射到 1 号染色体的同一区域,作为远行 QTL。总体而言,这里和其他地方提供的数据(Flint 等,1995;Gershenfeld 等,1997)表明基础活性的 QTL 既稳健又可靠。
A complimentary two-phase strategy was used to detect and map quantitative trait loci (QTLs) associated with the basal locomotor response to a saline challenge (10 ml/kg). In phase 1, putative QTLs, significant at p < 0.01 or better, were identified by analysis of the strain means for 25 strains of the B x D recombinant inbred series. QTLs were identified on chromosomes 1, 3, 5, 9, 10, 16, and 18. Some of these QTLs were detected across the entire experimental period (0-20 min), while others were associated with specific 5-min blocks. Eighteen hundred C57BL/6J (B6) x DBA/2J (D2) F-2 intercross animals were phenotyped for the basal locomotor response, and of this group, 500 to 700 individuals, psuedo-randomly selected, were used for a genomewide scan to confirm the RI-generated QTLs and to detect new QTLs. No new QTLs were detected but the QTLs on chromosome 1 were confirmed at p < 10(-5) to p < 10(-9), depending on the time interval. In addition, the QTLs on chromosomes 5 and 9 were confirmed at p < 0.001, providing a combined probability (RI + F-2) which exceeds the threshold for a significant association. Two additional phenotypes which showed significant RI strain differences were examined-adaptation and thigmotaxis. Adaptation mapped to the same region of chromosome 9 and thigmotaxis to the same region of chromosome 1 as the distance-traveled QTL. Overall, the data presented here and elsewhere (Flint et al., 1995; Gershenfeld et al., 1997) illustrate that QTLs for basal activity are both robust and reliable.