基因组选择及其应用

品种选育在农业生产中占有十分重要的地位,育种值估计是品种选育的核心。随着遗传标记的发展,尤其是高通量的基因分型技术,使得从基因组水平估计育种值成为可能,即基因组选择。文章将基因组选择的方法分为两类:一是基于估计等位基因效应来预测基因组估计育种值(GEBV),如最小二乘法,随机回归-最佳线性无偏预测(RR-BLUP)、Bayes、主成分分析等方法;二是基于遗传关系矩阵来预测GEBV,通过采用高通量标记构建个体间的遗传关系矩阵,然后用线性混合模型来预测育种值,即GBLUP法,并以这两种分类简要介绍了基因组选择各种方法的大致原理。影响基因组选择准确性的因素主要有标记类型和密度、单倍型长度、参考群体大小和标记-数量性状基因座(QTL)连锁不平衡(LD)大小等;在基因组选择的各种方法中,一般说来Bayes方法和GBLUP方法具有较高的准确性,最小二乘法最差;GBLUP计算速度快,能够将标记和系谱结合起来,因而比其他方法更具优势。尽管基因组选择取得了很大进展,但在理论方面还面临着一些挑战,如联合育种、长期选择的遗传进展及如何解析与性状有关和无关的标记等。基因组选择在一些动植物育种上已经开始应用,在人类遗传倾向预测和进化动力学研究中也有潜在的应用前景。基因组选择在个体间亲缘关系的量化上有了突破,比传统方法更加精确,因此,基因组选择将会是动植物育种史上革命性的事件。     

Expected early genetic gain from selection for milk yield in dairy cattle

Summary A matrix program to predict short term genetic gain from single trait selection for milk yield was developed. Rate of genetic gain was calculated as the annual change in the mean breeding value of all producing females. Several parameters sets representing various selection policies were used to examine situations pertinent to dairy populations of the United States. Approach to the asymptotic rates of genetic gain within the model varied with the choice of parameters, but even with consistent selection policies, predicted total genetic gain in the first 10 years was only half of the expected from classical theory. Considerable year to year variation in the rate of gain occurred. Early gains were more dependent on female selection decisions than gains during the steady state. In a two-phase model, the approach to the linear rate of gain in the second phase was accelerated by starting with an ongoing improvement program, but considerable delays still existed. Selection for sex- limited traits such as milk yield, which require pedigree selection and a waiting time for progeny test results reached asymptotic rates more slowly than previously assumed.     

Signatures of selection in five Italian cattle breeds detected by a 54K SNP panel

In this study we used a medium density panel of SNP markers to perform population genetic analysis in five Italian cattle breeds. The BovineSNP50 BeadChip was used to genotype a total of 2,935 bulls of Piedmontese, Marchigiana, Italian Holstein, Italian Brown and Italian Pezzata Rossa breeds. To determine a genome-wide pattern of positive selection we mapped the F _st values against genome location. The highest F _st peaks were obtained on BTA6 and BTA13 where some candidate genes are located. We identified selection signatures peculiar of each breed which suggest selection for genes involved in milk or meat traits. The genetic structure was investigated by using a multidimensional scaling of the genetic distance matrix and a Bayesian approach implemented in the STRUCTURE software. The genotyping data showed a clear partitioning of the cattle genetic diversity into distinct breeds if a number of clusters equal to the number of populations were given. Assuming a lower number of clusters beef breeds group together. Both methods showed all five breeds separated in well defined clusters and the Bayesian approach assigned individuals to the breed of origin. The work is of interest not only because it enriches the knowledge on the process of evolution but also because the results generated could have implications for selective breeding programs.     

Growth hormone gene polymorphism associated with selection for milk fat production in lines of cattle

Summary
Fifty-eight calves of both sexes from lines of Red Danish dairy breed selected for high ( n = 36) and low ( n = 22) milk fat production, and 32 heifers from lines of Norwegian Red dairy breed selected for high ( n = 16) and low ( n = 16) milk fat yield were typed for two previously reported restriction fragment length polymorphisms (RFLPs) in the growth hormone gene. The RFLPs are consistent with: (1) an insertion(I)/deletion(D) of approximately 0.9kb in the 3'-region of the growth hormone gene and (2) a polymorphic Msp I(+/−) site in the third intron. A traditional RFLP procedure was used for typing the I/D polymorphism and a polymerase chain reaction (PCR) procedure was developed for typing the Mspl polymorphism. Only the I-MspI(+) and D- Msp I(-) haplotypes were found. In the Red Danish lines the frequency of D- Msp I(-) haplo-type was 0.28 in high line and 0.05 in low line calves, this difference was significant ( P <0.01). The corresponding frequencies in the Norwegian Red lines were 0.09 in the high line and 0.0 in the low line. Attempts to screen for RFLPs in the growth hormone receptor gene and in the insulin-like growth factor-I gene were unsuccessful.     

Genomic analysis of the major bovine milk protein genes.

The genomic arrangement of the major bovine milk protein genes has been determined using a combination of physical mapping techniques. The major milk proteins consist of the four caseins, alpha s1 (CASAS1), alpha s2 (CASAS2), beta (CASB), and kappa (CASK), as well as the two major whey proteins, alpha-lactalbumin (LALBA) and beta-lactoglobulin (LGB). A panel of bovine X hamster hybrid somatic cells analyzed for the presence or absence of bovine specific restriction fragments revealed the genes coding for the major milk proteins to reside on three chromosomes. The four caseins were assigned to syntenic group U15 and localized to bovine chromosome 6 at q31-33 by in situ hybridization. LALBA segregated with syntenic group U3, while LGB segregated with U16. Pulsed-field gel electrophoresis confirmed genetic mapping results indicating tight linkage of the casein genes. The four genes reside on less than 200 kb of DNA in the order CASAS1-CASB-CASAS2-CASK. Multiple restriction fragment length polymorphisms were also found at the six loci in three breeds of cattle.     

Genomic selection as a possible accelerator of traditional selection

Selection using single nucleotide polymorphism (SNP) markers scattered throughout the genome or genomic selection (GS) is considered. This approach permits simultaneous selection of most quantitative trait loci (QTLs) determining the selected trait. According to expert assessment, GS makes it possible to save 92% of the funds spent on traditional selection and is twice as efficient as the latter.     

Genomic stability over 9 years of an isoniazid resistant Mycobacterium tuberculosis outbreak strain in Sweden

In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.     

Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study.

OBJECTIVE: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population. DESIGN: Longitudinal cohort study followed up annually by a house to house census and medical survey. SETTING: Rural population in south west Uganda. SUBJECTS: About 10,000 people from 15 villages who were enrolled in 1989-90 or later. MAIN OUTCOME MEASURES: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection. RESULTS: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative. CONCLUSIONS: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.     

The theoretical basis and practical application of a new method of selection for determining water deficiency in plants

Summary 1. On the basis of new theoretical considerations developed by us a new and reliable method has been elaborated for the rapid determination of water deficit in plant cultures. 2. In paper-chromatograms of plants optimally supplied with water free proline is shown to be present in very small amounts, usually only as traces. Comparative experiments showed that in cases of water shortage the proline content of the leaves of the plant strikingly increases. This commonly occurs in every phase of development of mono- and dicotyledons. 3. Drought-resistant plants synthetize more proline than varieties less resistant to water deficit when equally water deficient. 4. By a method which does not require chromatography the procedure of tests has been accelerated so that leaf extract containing amino acid mixture was dropped onto a chromatogram paper and immediately treated with isatine. In this test the effect of slight, permanent or medium water deficit upon proline content is so great that extracts react with isatine to give an intense dark blue colour which suppresses the reddish-brown colour of other amino acids. 5. To avoid the necessity of preparing isatine reagent frequently, because it loses its amino acid sensitivity very rapidly, a new isatine solution has been formulated. Our isatine-paper indicator prepared with this solution keeps its reactivity with amino acids 5 to 6 months. 6. An unusually high proline concentration occurs also if the salt content of irrigation water or also of the soil is high. The increase of the proline level indicates therefore physiological dryness.