实验动物,遗传学 z-bo 2020-07-24 763

　　1. Basic concepts

　　Closedcolony is a group of animals with different genotypes, also known as inbred species. This refers to a group of experimental animals that are reproduced and produced by hybrids without introducing new animals from outside. Individual circumstances. It breeds continuously for at least four generations.

In the 　　 closed group, the degree of individual differences mainly depends on the origin of the ancestors. When the ancestors are from common hybrids, the individual differences are even greater. If the ancestors are from the same inbred strain, the difference is even greater. small. Inbred groups of ancestral inbred lines are also called inbreds and random crosses. A closed group is a group of animals that have been isolated from the outside world for a long time. Male and female individuals can mate randomly. Its genetic composition is relatively close to the animal population structure under natural conditions. From the perspective of the overall population, the state of the closed population and random mating make the gene frequency of the population basically stable, but due to the genetic heterozygosity between individuals in the inbred population, there are great differences. Relatively stable genetic characteristics maintained within a certain range. The key to a closed group is that animals cannot introduce new genes from outside, avoid inbreeding, mate randomly, prevent gene loss in the population, and achieve a certain heterozygosity in the population. Is to keep. Certain closed populations have individual mutant genes called mutations. These mutations can be homozygous or heterozygous in the population. In addition to checking the genetic composition of closed populations, breeders also need to pay more attention to the preservation and inheritance of mutant genes in closed populations and their application value. 2. The characteristics of the experimental animals in the closed group The animals in the closed group have heterozygous characteristics and avoid inbreeding, thereby avoiding the appearance of inbreeding. Its lifespan and fecundity are stronger than inbred lines, and its reproduction rate is high. Because of its strong disease resistance, it can produce blocking groups in large quantities and have sufficient supply. Closed groups have not introduced new blood relatives on the whole, and their genetic and other response characteristics are relatively stable, but as far as individuals in the group are concerned, heterozygosity can cause interpersonal responses to gender differences. Due to the rapid response of individuals, some individuals are weak, so the repeatability and consistency between individuals is not as good as inbred animals. These characteristics make closed group animals generally suitable for drug screening, toxicological safety testing and educational applications. Currently, common closed group animals include KM mice (Kunming mice), LACA mice, NIH mice, Wistar rats, white rabbits (Japanese white rabbits), New Zealand rabbits (New Zealand white rabbits), etc. It is the most commonly used animal in our country. The ancestor may be a Swiss mouse. It was introduced to Kunming from India in 1946 and is called "Kunming Rat" because it has been distributed to various regions of China.

　　 3. Breeding

　　 Closed groups usually use random mating and breeding. In other words, in a group of breeders, each individual has the same opportunity to breed with individuals of other sexes. This mating method is random because it does not consider the parental origin or genetic relationship. Its purpose is to prevent inbreeding without separating independent lineages from offspring. There is no reduction in inbred lines, because random mating can maintain genetic heterogeneity. The greater the number of parents, the further the average relationship between random mating pairs. Therefore, in order to minimize inbreeding, aliens should keep as many parents as possible. If you want to keep the original species indefinitely, you should keep the growth rate of the inbreeding coefficient below 1% per generation. The following describes how to calculate the inbreeding coefficient of a random mating population without a pedigree record.

　　 As mentioned above, inbreeding refers to the mating and reproduction of related individuals. In sexually reproductive species, everyone has two parent birds, four ancestors and eight grandparents. As early as the nth generation, we had 2n ancestors. In a limited number of groups, even if mating is completely random, mating between relatives is inevitable. The smaller the group, the more likely two individuals randomly selected from the group will be related. Chances increase. Close relatives have the same ancestry than non-close relatives and are more likely to carry the same genes. The proportion of inbred lines in minority groups is very high, increasing the number of homozygotes but reducing the number of heterozygotes. This affects the frequency of genotypes in the population. When recessive genes become homozygous, their recessive traits will be affected by natural selection, which will further affect the frequency of these genes and their related genes in the population.

The degree of inbreeding in the 　　 group can be measured by the inbreeding coefficient. The inbreeding coefficient refers to the probability that an individual in a population will inherit two homologous alleles (genes from a common ancestor). Generally represented by F. Suppose you have a group of IV individuals that can produce 2N gametes. In the next generation, the probability that two gametes of the same person will come together to form a zygote is 1/2N. In other words, the inbreeding coefficient increases as follows.

　　ΣF= 1/2N After one generation, the probability of individuals without homologous genes in the population is 1-1/2N. In the second generation, the third generation... After t generation, the probability of individuals without homologous genes in the population is (1-1/2N)2, (1-1/2N)3...( In the case of (1-1/2N)t, the probability that an individual with a homologous gene appears after t is produced, that is, the inbreeding coefficient F is as follows. When in

　　 When there is no influence of factors such as exercise and choice over age, the inbreeding coefficient of this group continues to increase, and the smaller the group, the faster the inbreeding coefficient increases. The principle of breeding closed group animals is to keep the genetic heterogeneity and polymorphism of closed group animals as close as possible so that the inbreeding coefficient will not increase sharply with the increase of breeding generations. According to the approximate formula σF= 1/2 used to calculate the increase in inbreeding coefficient, the number of animals introduced in each generation (mainly closed small rodent groups) is usually 25 pairs. It can be calculated as above. However, based on the random genetic drift in actual sampling, there are still 25 pairs of individuals susceptible to changes in gene frequency, so it is necessary to keep as many breeders as possible.

　　4. Establish a closed population genetic quality control method to reduce genetic drift

　　 Closed group animals are widely used for drug testing and biologic identification. However, the current closed population regeneration system is difficult to keep the genetic characteristics of the closed population stable. As a result, the reproducibility of experimental results using a closed animal group is poor. Therefore, various factors affecting the quantitative traits of animals should be controlled as much as possible. The standardization of environmental factors is mainly achieved by controlling the microclimate of the animal house, fixed feed formula and specific microbial background (GF, SPF, etc.). So far, the genetic quality standards for laboratory animals are for inbred lines. The established closed population reproductive system may reduce the incidence of genetic homozygotes, but it is still not enough to maintain the stability of the genetic traits of the closed population. The coefficient of inbreeding in many groups has increased.

The control of genetic traits of closed herd animals is mainly aimed at two aspects: ①Maintain large genetic trait differences between individuals within the population; ②If the relative frequency of all genes is large enough and lacks selectivity, the genetic characteristics of the population are almost will not change. However, not all offspring actually participate in the mating and reproduction of the next generation. In order to provide effective genetic control in a closed population, Rapp collects and uses population reproductive characteristics, bone characteristics, isoenzymes and hematology data of each breeding pair in the closed population. Choose to breed offspring. Since these offspring have the same trait ratio as their parents, population stability is maintained at these corresponding positions.

　　Increase rate of inbreeding, you can use maximum inbreeding, regular mating or random mating to avoid inbreeding of breeding units in closed groups. Although these mating methods can effectively control the rate of increase of the inbreeding coefficient, they will not affect the stability of maintaining the genetic traits of the closed population and the control of genetic drift. Many scholars believe that in addition to adopting appropriate methods of reproduction and mating, it is also necessary to monitor and control the various biological characteristics of enclosed animal groups. These biological characteristics include hair color genes, immune sites, biochemical sites and bone measurements. Characteristics (hematology data, reproductive ability, etc.), Hedrich believes that it is not suitable for routine monitoring of animals with closed immune sites. However, it was not until Lap proposed "secondary optimization" in the mid-1980s that the results of biological monitoring were successfully used to guide the selection of closed populations.

　　 The original distribution of the genotypes of the closed population, we first collect the various trait data of the closed population, establish the normal population value for the animals in the closed population, and then use this standard. Choose the next generation based on. The selected attributes should be as diverse as possible, and convenient, fast and accurate measurement methods must be used. The cost should be as low as possible, and the genetic variation or heritability of quantitative traits should be as high as possible. All biomarkers must be expressed in multiple locations in the population. Table 1-1 shows various biological characteristics commonly used when selecting species using the "secondary optimization method".

　　 The normal value of the population is represented by the mean and variance of each biological characteristic. The normal population value should be obtained from data accumulated over many years, not from the current population.

　　 When selecting a new breeding group, one should choose the one with the mean and variance of each biological characteristic closest to the normal value of the group. This will enable the new breeding group to best maintain the genetic characteristics of the group.