Estimation of heritability from limited family data using genome-wide identity-by-descent sharing
Estimation of heritability from limited family data using genome-wide identity-by-descent sharing
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DOI：
10.1186/1297-9686-44-16
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发表时间：
2012-05-08
影响因子：
4.1
通讯作者：
Meuwissen, Theo H. E.
中科院分区：
文献类型：
--
作者：
Odegard, Jorgen;Meuwissen, Theo H. E.
背景：在经典的系谱分析中，加性遗传方差是从家系间的变异中估计出来的，这需要存在更大的表型和家系群体，涉及许多家庭(父母)。然而，估计常常因为遗传和环境家庭影响的混淆而变得复杂，后者通常发生在全同胞中。出于这个原因，遗传方差通常是基于较远亲属之间的协方差来推断的，这降低了分析的能力。这项模拟研究表明，近亲之间的全基因组血统认同共享可以仅使用极小的家庭样本数据来量化家庭内变异的加性遗传差异。方法：假设基因组大小与人类相似(有效座位数类似于80个)，模拟全同胞之间的血统认同关系。遗传差异是根据表型数据估计的，假设通过血统的基因组身份关系可以使用来自全基因组标记的信息准确地重建。结果：对于一个多基因性状和给定数量的表型，最准确的遗传方差估计仅基于单个大型全同胞家系的数据。与传统的系谱分析方法相比，该方法对亲本间的选择以及环境和遗传效应的混杂具有更强的稳健性。此外，在某些情况下，即使使用不太理想的数据结构，也可以获得令人满意的结果，例如，对于选择性的基因分型数据和遗传方差在很大程度上受几个主基因控制的性状。结论：利用基因组血统关系估计遗传方差对于旨在估计高繁殖力物种的加性遗传方差的研究特别有用，使用的数据来自谱系信息有限的小群体和/或可用亲本很少的数据，即来自非血统甚至野生群体的亲本。
Background: In classical pedigree-based analysis, additive genetic variance is estimated from between-family variation, which requires the existence of larger phenotyped and pedigreed populations involving numerous families (parents). However, estimation is often complicated by confounding of genetic and environmental family effects, with the latter typically occurring among full-sibs. For this reason, genetic variance is often inferred based on covariance among more distant relatives, which reduces the power of the analysis. This simulation study shows that genome-wide identity-by-descent sharing among close relatives can be used to quantify additive genetic variance solely from within-family variation using data on extremely small family samples.Methods: Identity-by-descent relationships among full-sibs were simulated assuming a genome size similar to that of humans (effective number of loci similar to 80). Genetic variance was estimated from phenotypic data assuming that genomic identity-by-descent relationships could be accurately re-created using information from genome-wide markers. The results were compared with standard pedigree-based genetic analysis.Results: For a polygenic trait and a given number of phenotypes, the most accurate estimates of genetic variance were based on data from a single large full-sib family only. Compared with classical pedigree-based analysis, the proposed method is more robust to selection among parents and for confounding of environmental and genetic effects. Furthermore, in some cases, satisfactory results can be achieved even with less ideal data structures, i.e., for selectively genotyped data and for traits for which the genetic variance is largely under the control of a few major genes.Conclusions: Estimation of genetic variance using genomic identity-by-descent relationships is especially useful for studies aiming at estimating additive genetic variance of highly fecund species, using data from small populations with limited pedigree information and/or few available parents, i.e., parents originating from non-pedigreed or even wild populations.