Mind the gap: analysis of marker-assisted breeding strategies for inbred mouse strains
Mind the gap: analysis of marker-assisted breeding strategies for inbred mouse strains
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DOI：
10.1007/s00335-005-0123-y
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发表时间：
2006-04-01
期刊：
影响因子：
2.5
通讯作者：
Speed, TP
中科院分区：
文献类型：
--
作者：
Armstrong, NJ;Brodnicki, TC;Speed, TP
同类小鼠品系的开发是确认和精细定位数量性状位点以及比较不同近交小鼠品系之间转基因或基因靶向破坏的表型效应的主要方法。传统的育种方案要求在建立同源小鼠品系之前至少进行九次连续回交。最近基因组序列和高通量基因分型的可用性现在允许使用多态性 DNA 标记来减少回交次数，经验数据表明标记辅助育种可能需要少至四次回交。我们使用模拟研究来研究不同标记辅助育种方案的效率，通过检查回交数量、每代产生的小鼠数量以及获得优质同源小鼠品系所需的每只小鼠的基因型数量之间的权衡。已建立的交叉干扰模型也被纳入这些模拟中。通过受体遗传背景中未检测到的杂合性区域（即“间隙”）的概率来评估所产生的菌株的质量，同时保持所需的供体衍生间隔。令人有些惊讶的是，我们发现在建立同源小鼠品系的潜在育种者中存在未被发现的缺口的可能性相对较高。标记辅助育种可能会减少产生同源品系所需的回交代数，但只有额外的回交才能保证减少含有污染供体等位基因的未检测到的间隙的数量和长度。
The development of congenic mouse strains is the principal approach for confirming and fine mapping quantitative trait loci, as well as for comparing the phenotypic effect of a transgene or gene-targeted disruption between different inbred mouse strains. The traditional breeding scheme calls for at least nine consecutive backcrosses before establishing a congenic mouse strain. Recent availability of genome sequence and high-throughput genotyping now permit the use of polymorphic DNA markers to reduce this number of backcrosses, and empirical data suggest that marker-assisted breeding may require as few as four backcrosses. We used simulation studies to investigate the efficiency of different marker-assisted breeding schemes by examining the trade-off between the number of backcrosses, the number of mice produced per generation, and the number of genotypes per mouse required to achieve a quality congenic mouse strain. An established model of crossover interference was also incorporated into these simulations. The quality of the strain produced was assessed by the probability of an undetected region of heterozygosity (i.e., '' gaps '') in the recipient genetic background, while maintaining the desired donor-derived interval. Somewhat surprisingly, we found that there is a relatively high probability for undetected gaps in potential breeders for establishing a congenic mouse strain. Marker-assisted breeding may decrease the number of backcross generations required to generate a congenic strain, but only additional backcrossing will guarantee a reduction in the number and length of undetected gaps harboring contaminating donor alleles.