Frequent and Efficient Use of the Sister Chromatid for DNA Double-Strand Break Repair during Budding Yeast Meiosis

Studies of DNA double-strand break repair during meiosis reveal that a substantial fraction of recombination occurs between sister chromatids

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

Polymorphism in the circumsporozoite protein of the human malaria parasite Plasmodium vivax

Centers for Disease Control, Public Health Services. U.S. Department of Health and Human Services. Division of Parasitic Diseases, National Center for Infectious Diseases. Malaria Branch. Atlanta GA, USA.Centers for Disease Control, Public Health Services. U.S. Department of Health and Human Services. Division of Parasitic Diseases, National Center for Infectious Diseases. Malaria Branch. Atlanta GA, USA.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Governo do Estado de São Paulo. Superintendência de Controle de Endemias. Malaria Department. São Paulo, SP, Brazil.Papua New Guinea Institute of Medical Research. Goroka, PNG.The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B- and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein, in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have led to the emergence of the variant CS repeat sequence ANGA(G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P. vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-depth study of parasite population dynamics is required before field trials for vaccine formulations based on polymorphic immunodominant determinants are conducted

Wide distribution of the variant form of the human malaria parasite Plasmodium vivax

Center for Infectious Diseases. Centers for Disease Control, Public Health Service. Department of Health and Human Service. Division of Parasitic Diseases. Malaria Branch. Atlanta, GA, USA.Center for Infectious Diseases. Centers for Disease Control, Public Health Service. Department of Health and Human Service. Division of Parasitic Diseases. Malaria Branch. Atlanta, GA, USA.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Papua New Guinea Institute of Medical Research. Madang, PNG.Center for Infectious Diseases. Centers for Disease Control, Public Health Service. Department of Health and Human Service. Division of Parasitic Diseases. Malaria Branch. Atlanta, GA, USA.We have found polymorphism in the repetitive and nonrepetitive regions of the sporozoite vaccine antigen, the circumsporozoite (CS) protein, in Plasmodium vivax malaria parasites from two geographically distant malaria endemic regions of the world. Like the recently described variant repeat sequence of P. vivax from Thailand, the CS protein repeat sequence of the variant P. vivax parasites from Papua New Guinea and Brazil is ANGA(G/D)(N/D)QPG, which differs from the previously identified CS repeat sequence, GDRA(D/A)GQPA, of P. vivax parasites from South America, Central America, and North Korea. Comparison of the P. vivax CS protein outside the repeat region revealed restricted polymorphism in regions that have exhibited T-cell immune function and sequence heterogeneity in the CS protein of Plasmodium falciparum. Our results show that P. vivax malaria parasites with the variant CS repeat sequences are widespread in nature and that the polymorphism in the CS protein of P. vivax is also present in the nonrepeat region

A new polymerase chain reaction/restriction fragment length polymorphism protocol for Plasmodium vivax circumsporozoite protein genotype (VK210, VK247, and P. vivax-like) determination

Universidade Estadual Paulista Júlio de Mesquita Filho. São José do Rio Preto, SP, Brasil / Faculdade de Medicina de São José do Rio Preto. Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias. Centro de Investigação de Microrganismos. São José do Rio Preto, SP, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Centers for Disease Control and Prevention. Atlanta , GA, USA.Faculdade de Medicina de São José do Rio Preto. Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias. Centro de Investigação de Microrganismos. São José do Rio Preto, SP, Brasil.Faculdade de Medicina de São José do Rio Preto. Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias. Centro de Investigação de Microrganismos. São José do Rio Preto, SP, Brasil / Fundação Faculdade de Medicina de São José do Rio Preto. São José do Rio Preto, SP, Brasil.Faculdade de Medicina de São José do Rio Preto. Departamento de Doenças Dermatológicas, Infecciosas e Parasitárias. Centro de Investigação de Microrganismos. São José do Rio Preto, SP, Brasil / Fundação Faculdade de Medicina de São José do Rio Preto. São José do Rio Preto, SP, Brasil.For the molecular diagnosis of Plasmodium vivax variants (VK210, VK247, and P. vivax-like) using DNA amplification procedures in the laboratory, the choice of rapid and inexpensive identification products of the 3 different genotypes is an important prerequisite. We report here the standardization of a new polymerase chain reaction/restriction fragment length polymorphism technique to identify the 3 described P. vivax circumsporozoite protein (CSP) variants using amplification of the central immunodominant region of the CSP gene of this protozoan. The simplicity, specificity, and sensitivity of the system described here is important to determine the prevalence and the distribution of infection with these P. vivax genotypes in endemic and nonendemic malaria areas, enabling a better understanding of their phylogeny

Use of glass beads and CF 11 cellulose for removal of leukocytes from malaria-infected human blood in field settings

Public Health Services. Centers for Disease Control. National Center for Infectious Diseases. Division of Parasitic Diseases. Malaria Branch. Atlanta GA, USA.Public Health Services. Centers for Disease Control. National Center for Infectious Diseases. Division of Parasitic Diseases. Malaria Branch. Atlanta GA, USA.Public Health Services. Centers for Disease Control. National Center for Infectious Diseases. Division of Parasitic Diseases. Malaria Branch. Atlanta GA, USA.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Public Health Services. Centers for Disease Control. National Center for Infectious Diseases. Division of Parasitic Diseases. Malaria Branch. Atlanta GA, USA.Public Health Services. Centers for Disease Control. National Center for Infectious Diseases. Division of Parasitic Diseases. Malaria Branch. Atlanta GA, USA.Passage of malaria-infected blood through a two-layered column composed of acid-washed glass beads and CF 11 cellulose removes white cells from parasitized blood. However, because use of glass beads and CF 11 cellulose requires filtration of infected blood separately through these two resins and the addition of ADP, the procedure is time-consuming and may be inappropriate for use in the field, especially when large numbers of blood samples are to be treated. Our modification of this process yields parasitized cells free of contaminating leukocytes, and because of its operational simplicity, large numbers of blood samples can be processed. Our procedure also compares well with those using expensive commercial Sepacell resins in its ability to separate leukocytes from whole blood. As a test of usefulness in molecular biologic investigations, the parasites obtained from the blood of malaria-infected patients using the modified procedure yield genomic DNA whose single copy gene, the circumsporozoite gene, efficiently amplifies by polymerase chain reaction