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Non-Invasive Sampling of Schistosomes from Humans Requires Correcting for Family Structure

机译：非侵入性人类血吸虫采样需要校正家庭结构

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For ethical and logistical reasons, population-genetic studies of parasites often rely on the non-invasive sampling of offspring shed from their definitive hosts. However, if the sampled offspring are naturally derived from a small number of parents, then the strong family structure can result in biased population-level estimates of genetic parameters, particularly if reproductive output is skewed. Here, we document and correct for the strong family structure present within schistosome offspring (miracidia) that were collected non-invasively from humans in western Kenya. By genotyping 2,424 miracidia from 12 patients at 12 microsatellite loci and using a sibship clustering program, we found that the samples contained large numbers of siblings. Furthermore, reproductive success of the breeding schistosomes was skewed, creating differential representation of each family in the offspring pool. After removing the family structure with an iterative jacknifing procedure, we demonstrated that the presence of relatives led to inflated estimates of genetic differentiation and linkage disequilibrium, and downwardly-biased estimates of inbreeding coefficients (FIS). For example, correcting for family structure yielded estimates of FST among patients that were 27 times lower than estimates from the uncorrected samples. These biased estimates would cause one to draw false conclusions regarding these parameters in the adult population. We also found from our analyses that estimates of the number of full sibling families and other genetic parameters of samples of miracidia were highly intercorrelated but are not correlated with estimates of worm burden obtained via egg counting (Kato-Katz). Whether genetic methods or the traditional Kato-Katz estimator provide a better estimate of actual number of adult worms remains to be seen. This study illustrates that family structure must be explicitly accounted for when using offspring samples to estimate the genetic parameters of adult parasite populations.
机译：由于伦理和后勤方面的原因，寄生虫的种群遗传学研究通常依赖于从其确定宿主寄养的后代的无创采样。但是，如果所采样的后代是自然地从少数父母那里获得的，那么强大的家庭结构可能导致遗传参数在人口水平上的估计偏差，特别是如果生殖输出出现偏差的话。在这里，我们记录并纠正了血吸虫后代（miracidia）中存在的强大的家庭结构，血吸虫后代是从肯尼亚西部的人类以非侵入方式收集的。通过对来自12个微卫星基因座的12位患者的2,424头酸症进行基因分型，并使用同胞关系聚类程序，我们发现样本中包含大量兄弟姐妹。此外，育种血吸虫的生殖成功受到偏倚，在后代池中产生了每个家庭的差异性代表。在通过反复套叠法去除家庭结构后，我们证明了亲戚的存在导致对遗传分化和连锁不平衡的夸大估计，以及近交系数（FIS）的向下偏见。例如，校正家庭结构可得出患者中FST的估计值，其估计值比未校正样本中的估计值低27倍。这些有偏见的估计将使人们对成年人群中的这些参数得出错误的结论。从我们的分析中我们还发现，对全患兄弟病家庭数量的估计值和反刍动物样本的其他遗传参数的估计值高度相关，但与通过卵计数（Kato-Katz）获得的蠕虫负担的估计值不相关。无论是遗传方法还是传统的加藤-卡茨估算器都能更好地估计成虫的实际数量，尚待观察。这项研究表明，在使用后代样本评估成年寄生虫种群的遗传参数时，必须明确考虑家庭结构。

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