Crawford Allan M, Paterson Korena A, Dodds Ken G, Diez Tascon Cristina, Williamson Penny A, Roberts Thomson Meredith, Bisset Stewart A, Beattie Anne E, Greer Gordon J, Green Richard S, Wheeler Roger, Shaw Richard J, Knowler Kevin, McEwan John C
AgResearch, Invermay Agricultural Centre, Private Bag 50034, Mosgiel, New Zealand.
BMC Genomics. 2006 Jul 18;7:178. doi: 10.1186/1471-2164-7-178.
Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes.
Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23.
Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion.
目前,大多数牧民依靠驱虫剂来控制绵羊胃肠道寄生线虫。线虫群体对驱虫剂的抗性正在迅速增加,以至于在一些农场,现在没有一种驱虫剂家族是完全有效的。众所周知,宿主对线虫感染的抗性是一种中度可遗传的性状。本研究旨在确定基因组中包含影响抗寄生线虫基因的区域,即数量性状基因座(QTL)。
从抗线虫寄生虫和易感选择系杂交获得的公羊用于衍生五个大型半同胞家系,每个父系的后代数量在348至101之间。总后代包括940只羔羊。对所有后代进行了一系列寄生虫负荷和免疫功能性状的广泛测量,从而可以对每个家系中的每只羔羊对线虫寄生虫的相对抗性进行排名。最初,每个家系中最具抗性的22只后代和最易感的22只后代用于基因组扫描,该扫描使用了分布在所有绵羊常染色体上的203个微卫星标记。这项研究确定了9条染色体上的区域,这些区域显示出足够的连锁性,值得对所有后代进行基因分型。在用覆盖第1、3、4、5、8、12、13、22和23号染色体的标记对所有后代进行基因分型后,第8号染色体的端粒末端被确定为具有一个显著的抗寄生虫QTL,该QTL通过第二次寄生虫攻击结束时皱胃和小肠中毛圆线虫成虫的数量来衡量。在第23号染色体上还确定了另外两个与第二次寄生虫攻击结束时总血清IgE和结肠毛圆线虫特异性血清IgG的相关免疫功能性状有关的QTL。
尽管寄生虫抗性是一种中度可遗传的性状,但这项大型研究仅能确定一个与之相关联的显著QTL。该QTL与羔羊约6个月大时第二次寄生虫攻击结束时的成虫寄生虫负荷有关。我们未能发现更多QTL表明,控制该性状的大多数基因的影响相对较小。发现的大量暗示性QTL(每个家系每个性状发现的QTL数量多于偶然预期)也支持这一结论。