Genetic and phyisological regulation of KIR2DL4 expression

基因突变经常发生，但大多数是有害的，并从种群中消失。选择有利的突变，并最终取代原始基因。然而，一些突变在一种情况下是有利的，在另一种情况下是不利的。这些突变通常在人群中达到很高的频率，并与原始基因一起保持不变。这种情况的一个例子是引起镰状细胞性贫血的血红蛋白基因突变。突变基因的单一拷贝可以预防疟疾(有益)，但双倍剂量的基因会导致镰状细胞性贫血，这是致命的。突变基因和原始基因都保留在种群中，因为死于镰状细胞性贫血的人数少于如果没有突变基因就会死于疟疾的人数。这种现象被称为平衡选择。有许多平衡选择的例子，每一个例子通常都有一个与双倍剂量的突变基因相关的医学条件。我们发现了一个在免疫系统使用的一种基因中平衡选择的新例子。人们对这种基因的功能知之甚少。事实上，关于这种基因的文献中有很多相互矛盾的发现。我们发现突变基因在人群中出现的频率非常高，这有助于解释这些相互矛盾的发现，并将我们置于非常有利的地位，以实现对该基因功能的更好理解。我们建议调查该基因的基本生物学以及它如何在免疫系统中使用，以获得关于这种突变可能与哪种医学状况相关的线索。

Genetic mutations occur frequently but most are deleterious and are lost from the population. Advantageous mutations are selected for and eventually replace the original gene. However, some mutations are advantageous under one set of circumstances and disadvantageous under others. These mutations often reach a high frequency in the population and are maintained along with the original gene. An example of this situation is the mutation in the haemoglobin gene that causes sickle cell anaemia. A single copy of the mutant gene protects against malaria (advantageous) but a double dose of the gene results in sickle cell anaemia, which is fatal. Both the mutant and original gene are maintained in the population as the number of people dying from sickle cell anaemia is less than the number who would die from malaria if the mutant gene did not exist. This phenomenon is known as balancing selection. There are many examples of balancing selection and for each example there is usually a medical condition associated with a double dose of the mutant gene. We have discovered a new example of balancing selection in one of the genes used by the immune system. Very little is known about the function of this gene. In fact the literature abounds with contradictory findings concerning this gene. Our discovery that a mutant gene is present at very high frequency in the population helps explain these contradictory findings and places us in a very strong position to achieve a much better understanding of the function of this gene. We propose to investigate the basic biology of this gene and how it used in the immune system in order to obtain clues as to which medical condition this mutation may be relevant to.