The major genetic determinants of HIV-1 control affect HLA class I peptide presentation     

International HIV Controllers Study  Pereyra F  Jia X  McLaren PJ  Telenti A  de Bakker PI  Walker BD  Ripke S  Brumme CJ  Pulit SL  Carrington M  Kadie CM  Carlson JM  Heckerman D  Graham RR  Plenge RM  Deeks SG  Gianniny L  Crawford G  Sullivan J  Gonzalez E  Davies L  Camargo A  Moore JM  Beattie N  Gupta S  Crenshaw A  Burtt NP  Guiducci C  Gupta N  Gao X  Qi Y  Yuki Y  Piechocka-Trocha A  Cutrell E  Rosenberg R  Moss KL  Lemay P  O'Leary J  Schaefer T  Verma P  Toth I  Block B  Baker B  Rothchild A  Lian J  Proudfoot J  Alvino DM 《Science (New York, N.Y.)》2010,330(6010):1551-1557

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.  相似文献   

A whole-genome association study of major determinants for host control of HIV-1     

Fellay J  Shianna KV  Ge D  Colombo S  Ledergerber B  Weale M  Zhang K  Gumbs C  Castagna A  Cossarizza A  Cozzi-Lepri A  De Luca A  Easterbrook P  Francioli P  Mallal S  Martinez-Picado J  Miro JM  Obel N  Smith JP  Wyniger J  Descombes P  Antonarakis SE  Letvin NL  McMichael AJ  Haynes BF  Telenti A  Goldstein DB 《Science (New York, N.Y.)》2007,317(5840):944-947

Understanding why some people establish and maintain effective control of HIV-1 and others do not is a priority in the effort to develop new treatments for HIV/AIDS. Using a whole-genome association strategy, we identified polymorphisms that explain nearly 15% of the variation among individuals in viral load during the asymptomatic set-point period of infection. One of these is found within an endogenous retroviral element and is associated with major histocompatibility allele human leukocyte antigen (HLA)-B*5701, whereas a second is located near the HLA-C gene. An additional analysis of the time to HIV disease progression implicated two genes, one of which encodes an RNA polymerase I subunit. These findings emphasize the importance of studying human genetic variation as a guide to combating infectious agents.  相似文献   

A restricted selection index method based on eigenanalysis     

J. Jesús Cerón-Rojas  Jaime Sahagún-Castellanos  Fernando Castillo-González  Amalio Santacruz-Varela  José Crossa 《Journal of Agricultural, Biological & Environmental Statistics》2008,13(4):440-457

Selection indices, used in animal and plant breeding to select the best individuals for the next breeding cycle, are based on phenotypic observations of traits recorded in candidate individuals. The restrictive selection index (RSI) facilitates maximizing the genetic progress of some characters, while leaving others unchanged. Recently a selection index (SI) was proposed based on the eigen analysis method (ESIM), in which the first eigenvector (from the largest eigenvalue) is used as the SI criterion, and its elements determine the proportion of the trait that contributes to the SI. However, the current ESIM, which has two main limitations, is based on the assumption that the vector of coefficients of the index is equal to the genotypic variance-covariance matrix among the traits multiplied by the vector of economic weights, and does not allow one to restrict the number of traits. In this study, we develop a more general ESIM that has two main features, namely, it makes no assumption concerning the coefficients of the index and it can be generalized to a restrictive ESIM (RESIM). We use two datasets to illustrate the theoretical results and practical use of ESIM and RESIM, and to compare them with standard unrestrictive and restrictive selection indices. The main advantages of RESIM over traditional unrestrictive and restrictive SIs are that its statistical sampling properties are known; its selection responses are equal to or greater than those estimated from the traditional restrictive SI; and it does not require economic weights and thus can be used in practical applications when all or some of the traits need to be improved simultaneously (traditional SIs cannot improve several traits simultaneously if economic weights are not available). Finally, we prove that the coefficients of the traditional RSI belong to the space generated by the eigenvectors of RESIM.  相似文献   

Altitudinal genetic variation in Pinus hartwegii Lindl. I: Height growth,shoot phenology,and frost damage in seedlings     

Héctor Viveros-Viveros  Cuauhtémoc Sáenz-Romero  J. Jesús Vargas-Hernández  Javier López-Upton  Gustavo Ramírez-Valverde  Amalio Santacruz-Varela 《Forest Ecology and Management》2009

The altitudinal pattern of genetic variation in Pinus hartwegii Lindl. populations was explored for seedling height growth, frost damage, grass-stage, and phenological stage of the terminal shoot. A provenance test was conducted with open-pollinated seed from 13 populations collected along an altitudinal transect (3000–3600 m) at the National Park Pico de Tancítaro, Michoacán, center-west Mexico. Height growth of seedlings in a nursery was assessed at seven and 18 months of age. Frost damage at −15 °C was evaluated in laboratory at 18 months of age; proportion of plants that had left grass-stage and stage of shoot development was assessed at the age of 22 months. Significant differences among provenances (P < 0.0001) were detected for all of the evaluated characters. The variation among populations was structured as a moderate altitudinal cline, with populations from lower altitudes showing larger height growth in seedlings, larger proportion of frost damages, fewer seedlings in grass-stage and more seedlings with developed shoot, whereas in populations from higher altitudes, seedlings exhibiting shorter plant height, lower percentages of frost damage, more seedlings with unbroken grass-stage, and fewer seedlings with advanced shoot development were displayed. Options for seed and seedling movement along the altitudinal gradient are discussed under the scope of reforestation, aiming at ecological restoration, conservation of forest genetic resources, and assisted migration considering global warming. We suggest delineation of two altitudinal seed zones (Zone I: 3000–3350 m; Zone II: 3350–3700 m).  相似文献