Non-Additive Quantitative Traits in Mammals

众所周知，具有不同基因组成的父母杂交的动物往往比他们的父母更有活力和生产力：它们不仅仅是父母的平均水平。这种杂交活力的现象被不同地描述为非加性、杂种优势、越界或显性，这取决于所讨论性状的确切行为。杂交活力在动物育种中非常重要，但在基因组水平上对其原因了解甚少。人们还认为，身体特征通常是由许多基因控制的，这些基因的单独表达倾向于表现出加性。因此，我们的理解存在一个缺口——如果大多数基因表现为加性，我们如何解释杂交活力？在这个项目中，我们的目标是回答这个问题。在这个项目的准备工作中，我们研究了猪、小鼠和大鼠种群的非加性性状的各个方面。我们发现，性状的非加性效应出奇地普遍。其次，当我们试图确定导致这些影响的基因时，我们注意到，通常对身体特征和基因表达都有非加性影响的遗传变异具有显著的特性，即受影响的基因通常位于不同的染色体上。因此，对基因表达的长期影响往往是非加性的，而短期影响是加性的，对杂交活力不起作用。到目前为止，研究主要集中在这些短期效应上，但我们的数据表明，与非加性效应最相关的是长期效应。我们还发现，有时基因的作用取决于它是遗传自母亲还是父亲，这就增加了额外的非加性复杂性。然而，另一个非线性的来源是基因组可能被重新排列，移动基因的位置，有时使它们沉默。在我们的提案中，我们将分析猪、小鼠和大鼠种群的遗传数据，我们也有关于生长和其他性状的大量数据，以寻求预测非加性现象的模式。通过查看许多数据集，我们可以确定我们的结论是可靠的，并且可能推广到其他哺乳动物。

It is well known that animals that are hybrids of parents with differing genetic makeup tend to be more vigorous and productive than their parents: they are not simply the parental average. This phenomenon of hybrid vigor is variously described as non-additive, heterotic, transgressive or dominant, depending on the exact behaviour of the trait in question. Hybrid vigour is very important in animal breeding, but its causes are poorly understood at the level of the genome. It is also accepted that physical traits are often under the control of many genes, and that the expression of these genes individually tend to behave additively. There is thus a gap in our understanding - how do we explain hybrid vigour if most genes behave additively? In this project we aim to answer this question.In preparatory work leading up to this project we have examined aspects of of non-additive traits in populations of pigs, mice and rats. We find that non-additive effects on traits are surprisingly common. Second, when we attempt to identify the genes that are causal for these effects we noticed that often a genetic variant with non-addivive effects on both a physical trait and the expression of a gene have the remarkable property that the affected gene is often on a different chromosome. Thus long-range effects on the expression of a gene tend to be non-additive, in contrast to short-range effects which are additive, and which do not play a role in hybrid vigour. Up to now research has focused on these short-range effects, but our data suggest that it is the long-range effects that are the most relevant to non-additive effects.We have also found that sometimes the effect of a gene depends on whether it is inherited from the mother or father, adding an additional level of non-additive complexity. Yet another source of non-linearity is that genomes may be re-arranged, moving the locations of genes and sometimes silencing them.In our proposal we will analyse genetic data in population of pigs, mice and rats on which we also have extensive data on growth and other traits, to seek patterns that are predictive of non-additive phenomena. By looking across many data sets we can be sure that our conclusions are robust and are likely to generalise to other mammals.