112 research outputs found

    The Human Chromogranin A Gene: Chromosome Assignment and RFLP Analysis.

    Get PDF
    Chromogranin A/secretory protein I (CgA) is a glycoprotein that is stored and released along with peptide hormones and neurotransmitters from several tissues, although its exact function is not known. A cDNA (gene symbol CHGA) clone was used as a probe in Southern blot analyses of human-rodent somatic cell hybrid DNAs. Discordancy analysis allowed confirmation of the assignment of the gene to chromosome 14. These results were extended using in situ chromosome hybridization, and a signal was found at 14q32. BglII digestion of genomic DNA from 28 unrelated Caucasian individuals probed with CHGA detected a two-allele RFLP with allelic frequencies of .34 and .66

    Chromosomal Localization of Nucleic Acid-Binding Proteins by Affinity Mapping: Assignment of the IRE-Binding Protein Gene to Human Chromosome 9

    Get PDF
    Three human mRNAs are regulated post-transcriptionally by iron via iron-responsive elements (IREs) contained in each mRNA. A cytoplasmic protein (IRE-BP) binds to these cis-acting elements and mediates the translational regulation of ferritin H- and L-chain mRNA and the iron-dependent stability of transferrin receptor (TfR) mRNA. We have taken advantage of the different mobilities of the human and rodent IRE/IRE-BP complexes on non-denaturing polyacrylamide gels to determine the chromosomal localization of the gene encoding the IRE-BP. Utilizing a panel of 34 different human/rodent hybrid cell lines we have assigned the IRE-BP gene to human chromosome 9. This new technique based on nucleic acid/protein interaction may allow determination of the chromosomal localization of other RNA- or DNA-binding proteins

    A Molecular Phylogeny of Living Primates

    Get PDF
    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (~8 Mb) from 186 primates representing 61 (~90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species

    Polymorphisms in the α4 Integrin of Neotropical Primates: Insights for Binding of Natural Ligands and HIV-1 gp120 to the Human α4β7

    Get PDF
    The α4 integrin subunit associates with β7 and β1 and plays important roles in immune function and cell trafficking. The gut-homing receptor α4β7 has been recently described as a new receptor for HIV. Here, we describe polymorphisms of ITGA4 gene in New World primates (NWP), and tested their impact on the binding to monoclonal antibodies, natural ligands (MAdCAM and VCAM), and several gp120 HIV-1 envelope proteins. Genomic DNA of NWP specimens comprising all genera of the group had their exons 5 and 6 (encoding the region of binding to the ligands studied) analyzed. The polymorphisms found were introduced into an ITGA4 cDNA clone encoding the human α4 subunit. Mutant α4 proteins were co-expressed with β7 and were tested for binding of mAbs, MAdCAM, VCAM and gp120 of HIV-1, which was compared to the wild-type (human) α4. Mutant α4 proteins harboring the K201E/I/N substitution had reduced binding of all ligands tested, including HIV-1 gp120 envelopes. The mAbs found with reduced biding included one from which a clinically-approved drug for the treatment of neurological disorders has been derived. α4 polymorphisms in other primate species may influence outcomes in the development and treatment of infectious and autoimmune diseases in humans and in non-human primates

    Sperm Length Variation as a Predictor of Extrapair Paternity in Passerine Birds

    Get PDF
    The rate of extrapair paternity is a commonly used index for the risk of sperm competition in birds, but paternity data exist for only a few percent of the approximately 10400 extant species. As paternity analyses require extensive field sampling and costly lab work, species coverage in this field will probably not improve much in the foreseeable future. Recent findings from passerine birds, which constitute the largest avian order (∼5,900 species), suggest that sperm phenotypes carry a signature of sperm competition. Here we examine how well standardized measures of sperm length variation can predict the rate of extrapair paternity in passerine birds.We collected sperm samples from 55 passerine species in Canada and Europe for which extrapair paternity rates were already available from either the same (n = 24) or a different (n = 31) study population. We measured the total length of individual spermatozoa and found that both the coefficient of between-male variation (CV(bm)) and within-male variation (CV(wm)) in sperm length were strong predictors of the rate of extrapair paternity, explaining as much as 65% and 58%, respectively, of the variation in extrapair paternity among species. However, only the CV(bm) predictor was independent of phylogeny, which implies that it can readily be converted into a currency of extrapair paternity without the need for phylogenetic correction.We propose the CV(bm) index as an alternative measure to extrapair paternity for passerine birds. Given the ease of sperm extraction from male birds in breeding condition, and a modest number of sampled males required for a robust estimate, this new index holds a great potential for mapping the risk of sperm competition across a wide range of passerine birds

    The germline mutational landscape of BRCA1 and BRCA2 in Brazil

    Get PDF
    The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio

    Chromosomes and spermatozoa of the great apes and man

    Get PDF
    The chromosome complement of four species phylogenetically related to man, the chimpanzee (Pan troglodytes), the pygmy chimpanzee (Pan paniscus), the gorilla (Gorilla gorilla), and the orangutan (Pongo pygmaeus) have been analysed with chromosome banding techniques and compared to the human chromosome comple¬ ment. This has shown remarkable homologies between species, and presumed mechanisms of chromosome evolution have been proposed. Chromosome heteromorphisms in the great apes have been compared to those found in human populations, and most of them affected the distribution or the amount of constitutive heterochromatin and/or brilliantly fluorescent material, a situation comparable to man where such variations have been established as chromosome polymorphisms. However, a balanced polymorphic structural rearrangement involving large segments of euchromatic material has been found in two populations of orangutan. This rearrangement consisted of two pericentric inversions, one inside the other, comprising an unusual kind of chromosome polymorphism in mammalian populations. Moreover, it showed that pericentric inversions, the most probable chromosome rearrangements in the phylogeny of the chromosomes of man and the great apes, might not necessarily be restricted by infertility barriers, but may spread successfully in the population. The patterns of late replication of the chromosomes of the great apes and man have been compared, using BUdr as a thymidine substitute in the cell cycle. This has shown remarkable similarities in the patterns of late replication between species, and, as in the human chromosomes, most regions of late replication in the chromosomes of the great apes corresponded to areas of positive G-banding. Q-, C- and G-banding as methods of demonstrating chromosome homologies between these species have been analysed in relation to the content of highly repeated satellite DNAs in man and homologous sequences in the great apes. This has shown that the banding patterns are not informative about these sequences, and that they must reflect a degree of chromosome organization due to DNA packaging rather than DNA composition. Finally, the phylogeny of the chromosomes of man and the great apes has been reconstructed in view of the findings presented in this work and of previous data in the literature. In this study, man and gorilla resembled each other more closely than to any of the other species studied, a finding that is contrary to the generally held view that man and the chimpanzee are the two most closely related species. Comparative studies of the spermatozoa of the great apes and man were undertaken and showed that man was not unique in producing pleiomorphic spermatozoa, since this feature was also present in the gorilla. Moreover, the morphology of human and gorilla spermatozoa resembled each other so closely that on morphological grounds it was impossible to distinguish the spermiogram of these two species. Fluorescent ("f") bodies were detected in the spermatozoa of the African apes, although the distribution of such bodies did not resemble that of human spermatozoa, where the Y chromosome is usually visible. An analysis of the haploid DNA content of the great apes and man w®3 undertaken by estimating the total dry mass of the sperm head in these species. Man showed the lowest DNA content, whilst the gorilla showed the highest; this latter latter species also showed a higher variability in the haploid DNA content than all other species, including man. Diploid spermatozoa were also detected in the gorilla, in proportions similar to those found in man. These findings on spermatozoa are indicative of a closer relationship between man and gorilla than between man and the other hominoid apes. Moreover, the heteromorphism of spermatozoa in both human and gorilla semen samples makes it unlikely that clothing induced hyperthermia is the cause of pleiomorphic spermatozoa in man
    corecore