利用 Tir1 主要基因座固定易感等位基因的 F12 高级互交系对锥虫病抗性基因 Tir2 和 Tir3 进行高分辨率定位。

High resolution mapping of trypanosomosis resistance loci Tir2 and Tir3 using F12 advanced intercross lines with major locus Tir1 fixed for the susceptible allele.

机构信息

International Livestock Research Institute, PO Box 30709, Nairobi, Kenya.

出版信息

BMC Genomics. 2010 Jun 22;11:394. doi: 10.1186/1471-2164-11-394.

DOI:10.1186/1471-2164-11-394

PMID:20569426

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2898758/

Abstract

BACKGROUND

Trypanosomosis is the most economically important disease constraint to livestock productivity in Africa. A number of trypanotolerant cattle breeds are found in West Africa, and identification of the genes conferring trypanotolerance could lead to effective means of genetic selection for trypanotolerance. In this context, high resolution mapping in mouse models are a promising approach to identifying the genes associated with trypanotolerance. In previous studies, using F2 C57BL/6J x A/J and C57BL/6J x BALB/cJ mouse resource populations, trypanotolerance QTL were mapped within a large genomic intervals of 20-40 cM to chromosomes MMU17, 5 and 1, and denoted Tir1, Tir2 and Tir3 respectively. Subsequently, using F6 C57BL/6J x A/J and C57BL/6J x BALB/cJ F6 advanced intercross lines (AIL), Tir1 was fine mapped to a confidence interval (CI) of less than 1 cM, while Tir2 and Tir3, were mapped within 5-12 cM. Tir1 represents the major trypanotolerance QTL.

RESULTS

In order to improve map resolutions of Tir2 and Tir3, an F12 C57BL/6J x A/J AIL population fixed for the susceptible alleles at Tir1 QTL was generated. An F12 C57BL/6J x A/J AIL population, fixed for the resistant alleles at Tir1 QTL was also generated to provide an additional estimate of the gene effect of Tir1. The AIL populations homozygous for the resistant and susceptible Tir1 alleles and the parental controls were challenged with T. congolense and followed for survival times over 180 days. Mice from the two survival extremes of the F12 AIL population fixed for the susceptible alleles at Tir1 were genotyped with a dense panel of microsatellite markers spanning the Tir2 and Tir3 genomic regions and QTL mapping was performed. Tir2 was fine mapped to less than 1 cM CI while Tir3 was mapped to three intervals named Tir3a, Tir3b and Tir3c with 95% confidence intervals (CI) of 6, 7.2 and 2.2 cM, respectively.

CONCLUSIONS

The mapped QTL regions encompass genes that are vital to innate immune response and can be potential candidate genes for the underlying QTL.

摘要

背景

锥虫病是非洲畜牧业生产力最具经济重要性的疾病制约因素。在西非发现了一些抗锥虫病的牛品种，鉴定赋予抗锥虫病能力的基因可能会导致有效的遗传选择抗锥虫病的方法。在这种情况下，在小鼠模型中进行高分辨率图谱绘制是识别与抗锥虫病相关的基因的有前途的方法。在以前的研究中，使用 F2 C57BL/6J x A/J 和 C57BL/6J x BALB/cJ 小鼠资源群体，将抗锥虫病 QTL 映射到 MMU17、5 和 1 染色体的 20-40cM 大基因组区间内，分别命名为 Tir1、Tir2 和 Tir3。随后，使用 F6 C57BL/6J x A/J 和 C57BL/6J x BALB/cJ F6 高级交叉系（AIL），将 Tir1 精细映射到置信区间（CI）小于 1cM，而 Tir2 和 Tir3 则映射到 5-12cM 内。Tir1 代表主要的抗锥虫病 QTL。

结果

为了提高 Tir2 和 Tir3 的图谱分辨率，生成了固定在 Tir1 QTL 易感等位基因的 F12 C57BL/6J x A/J AIL 群体。还生成了固定在 Tir1 QTL 抗性等位基因的 F12 C57BL/6J x A/J AIL 群体，以提供 Tir1 基因效应的额外估计。来自 F12 AIL 群体的两个生存极端的纯合抗性和易感 Tir1 等位基因的个体和亲本对照用 T. congolense 进行了挑战，并在 180 天以上的时间内进行了存活时间的跟踪。用 Tir2 和 Tir3 基因组区域跨越的密集微卫星标记对来自 Tir1 固定在易感等位基因的 F12 AIL 群体的两个生存极端的个体进行了基因型分析，并进行了 QTL 映射。将 Tir2 精细映射到小于 1cM CI，而将 Tir3 映射到三个区间，分别命名为 Tir3a、Tir3b 和 Tir3c，置信区间（CI）分别为 6、7.2 和 2.2cM。