Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lineage”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,315 records · Page 73Linked to original sources
PubMed2005

Development of a unique system for spatiotemporal and lineage-specific gene expression in mice.

We have developed an advanced method for conditional gene expression in mice that integrates the Cre-mediated and tetracycline-dependent expression systems. An rtTA gene, preceded by a loxP-flanked STOP sequence, was inserted into the ROSA26 locus to create a R26STOPrtTA mouse strain. When the STOP sequence is excised by Cre-mediated recombination, the rtTA is expressed in the Cre-expressing cells and all of their derivatives. Therefore, cell type-, tissue-, or lineage-specific expression of rtTA is achieved by the use of an appropriate Cre transgenic strain. In mice also carrying a target gene under the control of the tetracycline response element, inducible expression of the target gene is temporally regulated by administration of doxycycline. Our results demonstrate that this universal system is uniquely suited for spatiotemporal and lineage-specific gene expression in an inducible fashion. Gene expression can be manipulated in specific cell types and lineages with a flexibility that is difficult to achieve with conventional methods.

Animals↗
PubMed2005

Atherosclerosis quantitative trait loci are sex- and lineage-dependent in an intercross of C57BL/6 and FVB/N low-density lipoprotein receptor-/- mice.

Atherosclerosis is a complex disease that is affected by environmental as well as genetic factors. The aim of the present study was to identify loci of atherosclerosis susceptibility in a cross of atherosclerosis-susceptible C57BL/6 and atherosclerosis-resistant FVB/N mice on the low-density lipoprotein (LDL) receptor (LDLR)-deficient background (LDLR(-/-)) and to test whether these loci are affected by lineage. A total of 459 F(2)s were generated in two ways: In cross "mB6xfFVB," male B6.LDLR(-/-) mice were crossed to female FVB.LDLR(-/-) mice to generate 107 female and 112 male F(2)s. In cross "mFVBxfB6," male FVB.LDLR(-/-) mice were crossed to female B6.LDLR(-/-) mice to generate 120 female and 120 male F(2)s. Animals were phenotyped for cross-sectional atherosclerotic lesion area at the aortic root, and a genome scan was carried out with 192 microsatellite markers. Quantitative trait locus mapping revealed significant loci of atherosclerosis susceptibility on chromosomes 3, 10, and 12. On chromosome 10 maximal logarithm of odds (LOD) scores of 13.1 (D10Mit16, 16 cM) and 5.7 (D10Mit168, 9 cM) were found in female and male mice, respectively. On chromosome 3, a maximal LOD score of 5.1 (D3Mit45, 79 cM) was detected only in females. On proximal chromosome 12 significant LOD scores were lineage-dependent, with maximal LOD scores of 3.9 (D12Mit82, 3 cM) and 4.8 (D12Mit189, 24 cM) present only in female mice of cross mB6xfFVB and male mice of cross mFVBxfB6, respectively. We conclude that, in this intercross, loci of atherosclerosis susceptibility are in part sex- and lineage-dependent. Awareness of these complexities may have major consequences for the identification of atherosclerosis susceptibility genes by quantitative trait locus mapping.

Animals↗
PubMed2003

Lineage-restricted retention of a primitive immunoglobulin heavy chain isotype within the Dipnoi reveals an evolutionary paradox.

The lineage leading to lungfishes is one of the few major jawed vertebrate groups in which Ig heavy chain isotype structure has not been investigated at the genetic level. In this study, we have characterized three different Ig heavy chain isotypes of the African lungfish, Protopterus aethiopicus, including an IgM-type heavy chain and short and long forms of non-IgM heavy chains. Northern blot analysis as well as patterns of V(H) utilization suggest that the IgM and non-IgM isotypes are likely encoded in separate loci. The two non-IgM isotypes identified in Protopterus share structural features with the short and long forms of IgX/W/NARC (referred to hereafter as IgW), which were previously considered to be restricted to the cartilaginous fish. It seems that the IgW isotype has a far broader phylogenetic distribution than considered originally and raises questions with regard to the origin and evolutionary divergence of IgM and IgW. Moreover, its absence in other gnathostome lineages implies paradoxically that the IgW-type genes were lost from teleost and tetrapod lineages.

Amino Acid Sequence↗
PubMed2006

A deletion defining a common Asian lineage of Mycobacterium tuberculosis associates with immune subversion.

Six major lineages of Mycobacterium tuberculosis appear preferentially transmitted amongst distinct ethnic groups. We identified a deletion affecting Rv1519 in CH, a strain isolated from a large outbreak in Leicester U.K., that coincidentally defines the East African-Indian lineage matching a major ethnic group in this city. In broth media, CH grew less rapidly and was less acidic and H2O2-tolerant than reference sequenced strains (CDC1551 and H37Rv). Nevertheless, CH was not impaired in its ability to grow in human monocyte-derived macrophages. When compared with CDC1551 and H37Rv, CH induced less protective IL-12p40 and more antiinflammatory IL-10 and IL-6 gene transcription and secretion from monocyte-derived macrophages. It thus appears that CH compensates microbiological attenuation by skewing the innate response toward phagocyte deactivation. Complementation of Rv1519, but none of nine additional genes absent from CH compared with the type strain, H37Rv, reversed the capacity of CH to elicit antiinflammatory IL-10 production by macrophages. The Rv1519 polymorphism in M. tuberculosis confers an immune subverting phenotype that contributes to the persistence and outbreak potential of this lineage.

Asia↗
PubMed2006

Ameiotic recombination in asexual lineages of Daphnia.

Despite the enormous theoretical attention given to the evolutionary consequences of sexual reproduction, the validity of the key assumptions on which the theory depends rarely has been evaluated. It is often argued that a reduced ability to purge deleterious mutations condemns asexual lineages to an early extinction. However, most well characterized asexual lineages fail to exhibit the high levels of neutral allelic divergence expected in the absence of recombination. With purely descriptive data, it is difficult to evaluate whether this pattern is a consequence of the rapid demise of asexual lineages, an unusual degree of mutational stability, or recombination. Here, we show in mutation-accumulation lines of asexual Daphnia that the rate of loss of nucleotide heterozygosity by ameiotic recombination is substantially greater than the rate of introduction of new variation by mutation. This suggests that the evolutionary potential of asexual diploid species is not only a matter of mutation accumulation and reduced efficiency of selection, and [corrected] it underscores the limited utility of using neutral allelic divergence as an indicator of ancient asexuality.

Animals↗
PubMed2000

Gene genealogies reveal global phylogeographic structure and reproductive isolation among lineages of Fusarium graminearum, the fungus causing wheat scab.

During the past decade, the plant disease called scab or Fusarium head blight of wheat and barley has reached epidemic proportions in North America and elsewhere in the world. Scab is an economically devastating plant disease, not only because it causes significant reduction in seed yields and quality, but also because infested seeds are often contaminated with trichothecene and estrogenic mycotoxins that pose a serious threat to animal health and food safety. To test whether the primary etiological agent of scab, the fungus Fusarium graminearum, is panmictic throughout its range, allelic genealogies were constructed from six single-copy nuclear genes from strains selected to represent the global genetic diversity of this pathogen. Excluding one hybrid strain, all six genealogies recovered the same seven biogeographically structured lineages, suggesting that they represent phylogenetically distinct species among which gene flow has been very limited during their evolutionary history. Parsimony analysis of the combined data set comprising 7,120 aligned nucleotide characters resolved most relationships among the seven lineages of the F. graminearum clade and related fusaria included in the study. Phylogenetic evidence is also presented for introgressive hybridization and intragenic recombination among lineages of the F. graminearum clade in nature.

Biological Evolution↗
PubMed2003

The complexity of alternative splicing of hagoromo mRNAs is increased in an explosively speciated lineage in East African cichlids.

The adaptive radiation of cichlid fishes in the lakes of East Africa is a prime example of speciation. The choice of cichlid mates on the basis of a variety of coloration represents a potential basis for speciation that led to adaptive radiation. Here, we characterize the cichlid homolog of the zebrafish hagoromo (hag) gene that was recently cloned and characterized from a pigmentation mutant. Although only one hag mRNA was reported in zebrafish, cichlids express nine different hag mRNAs resulting from alternative splicing. The hag mRNAs are expressed between the myotome and the epidermis where pigment cells are located, suggesting the cichlid hag gene is involved in pigmentation. The hag mRNA splicing pattern does not fluctuate among individuals from each of two species, suggesting that alternative splice site choice is fixed within species. Furthermore, cichlids in lineages that underwent explosive speciation expressed a greater variety of hag mRNAs than those in lineages that did not undergo such a degree of speciation, suggesting that species in the explosively speciated lineage acquired a complex regulatory mechanism of alternative splicing over a very short evolutionary period. Here, we provide an example in which alternative splicing may play a role in mate choice, leading to cichlid speciation through diversification of gene function by production of multiple mRNAs from a single gene.

Africa, Eastern↗
PubMed2003

Encephalization and allometric trajectories in the genus Homo: evidence from the Neandertal and modern lineages.

The term "encephalization" is commonly used to describe an enlargement in brain size, considered as either absolute endocranial volumes or relative values in relation to body size. It is widely recognized that a considerable endocranial expansion occurred throughout the evolution of the genus Homo. This article aims to evaluate whether this phenomenon was the outcome of distinct evolutionary lineages, reaching similar brain expansions but through different trajectories. Endocranial morphology was studied in a sample of fossil hominines by multivariate approaches using both traditional metrics and geometric morphometrics. The analysis was focused on the transition from a generalized archaic pattern within the genus Homo to the modern morphology and compared with changes that occurred along the Neandertal lineage. The main result was the identification of two different evolutionary trajectories, in which a similar expansion in endocranial size has been reached by different changes in shape. Along the Neandertal lineage we observed maintenance of an "archaic" endocranial model, in which a large amount of variability is based on a single allometric trend. By contrast, when modern endocasts were compared with nonmodern ones, we found important differences apparently led by a parietal expansion. In this light, the origin of our species may have represented the opportunity to surpass the constraints imposed on encephalization by the ontogenetic pattern shared by nonmodern Homo representatives.

Animals↗
PubMed2001

Bazooka is required for localization of determinants and controlling proliferation in the sensory organ precursor cell lineage in Drosophila.

Asymmetric divisions with two different division orientations follow different polarity cues for the asymmetric segregation of determinants in the sensory organ precursor (SOP) lineage. The first asymmetric division depends on frizzled function and has the mitotic spindle of the pI cell in the epithelium oriented along the anterior-posterior axis, giving rise to pIIa and pIIb, which divide in different orientations. Only the pIIb division resembles neuroblast division in daughter-size asymmetry, spindle orientation along the apical-basal axis, basal Numb localization, and requirement for inscuteable function. Because the PDZ domain protein Bazooka is required for spindle orientation and basal localization of Numb in neuroblasts, we wondered whether Bazooka plays a similar role in the pIIb in the SOP lineage. Surprisingly, Bazooka controls asymmetric localization of the Numb-anchoring protein Pon, but not spindle orientation, in pI and all subsequent divisions. Bazooka also regulates cell proliferation in the SOP lineage; loss of bazooka function results in supernumerary cell divisions and apoptotic cell death.

Animals↗
PubMed1982

Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows.

Two mitochondrial genotypes are shown to exist within one Holstein cow maternal lineage. They were detected by the appearance of an extra Hae III recognition site in one genotype. The nucleotide sequence of this region has been determined and the genotypes are distinguished by an adenine/guanine base transition which creates the new Hae III site. This point mutation occurs within an open reading frame at the third position of a glycine codon and therefore does not alter the amino acid sequence. The present pattern of genotypes within the lineage demands that multiple shifts between genotypes must have occurred within the past 20 years with the most rapid shift taking place in no more than 4 years and indicates that mitochondrial DNA polymorphism can occur between maternally related mammals. The process that gave rise to different genotypes in one lineage is clearly of fundamental importance in understanding intraspecific mitochondrial polymorphism and evolution in mammals. Several potential mechanisms for rapid mitochondrial DNA variation are discussed in light of these results.

Animals↗
PubMed1984

Long-term cultured B lymphocytes and their precursors reconstitute the B-lymphocyte lineage in vivo.

Long-term in vitro cultured B lymphocytes and their precursors were tested for their ability to reconstitute a functional B-cell lineage in vivo. Continuous in vitro production of cells representing early stages of the B-lymphocyte lineage originates from a bone marrow cell type that can be distinguished from a multipotential hematopoietic stem cell. Progenitors of the long-term cultured B-lymphoid cells are recoverable in vitro after in vivo passage into lethally irradiated mice. Long-term cultured B-lymphoid cells and their progenitors reconstituted the B-lymphocyte lineage and restored normal humoral immunity in genetically defective mice. Cultured B-lymphoid cells did not cause lymphoid tumors in vivo in irradiated syngeneic mice. These findings indicate that multipotential hematopoietic stem cells are not directly required for the continued production of functionally competent B lymphocytes in vitro, and they suggest the existence of a B lymphoid progenitor cell with in vitro, and possibly in vivo, stem cell-like qualities.

Animals↗
PubMed1985

T-cell receptor gene rearrangements as markers of lineage and clonality in T-cell neoplasms.

Ig gene rearrangements represent markers of lineage, clonality, and differentiation of B cells, allowing a molecular diagnosis and immunogenotypic classification of B-cell neoplasms. We sought to apply a similar approach to the study of T-cell populations by analyzing rearrangements of the T-cell receptor beta-chain (T beta) gene. Our analysis, by Southern blotting hybridization using T beta-specific probes of DNAs from polyclonal T cells and from 12 T-cell tumors, indicates that T beta gene rearrangement patterns can be used as markers of (i) lineage, allowing the identification of polyclonal T-cell populations, and (ii) clonality, allowing the detection of monoclonal T-cell tumors. In addition, our data indicate that T beta gene rearrangements represent early and general markers of T-cell differentiation since they are detectable in histologically different tumors at all stages of T-cell development. The ability to determine lineage, clonality, and stage of differentiation has significant implications for future experimental and clinical studies on normal and neoplastic T cells.

Cell Differentiation↗
PubMed1986

Developmental origins of skeletal muscle fibers: clonal analysis of myogenic cell lineages based on expression of fast and slow myosin heavy chains.

A clonal analysis was used to show that skeletal muscle myoblasts are committed to distinct cell lineages during development. Myoblasts taken from embryonic chicken hindlimb muscles of different ages were cultured at clonal density. The content of fast and slow classes of the myosin heavy chain isoforms in the myotubes of the resulting muscle colonies was determined immunocytochemically with specific monoclonal antibodies that served as markers for the different fiber types. The muscle colonies formed by cloning myoblasts from early hindlimbs (days 4-6 in ovo) were of three types: the most numerous type, in which all myotubes in a colony contained only the fast class of myosin heavy chain; a less numerous type, in which all myotubes in a colony contained both the fast and slow classes of myosin heavy chain isoforms; and a rare type, in which all myotubes in a colony contained only the slow class of myosin heavy chain. The muscle colonies formed by cloning myoblasts from later hindlimbs (days 10-12 in ovo) were, however, all of one type, in which every myotube in a colony contained only fast myosin heavy chain. Thus, myoblasts in the early embryo (days 4-6 in ovo) were a heterogeneous population committed to three myogenic lineages: fast, mixed fast/slow, and slow, whereas myoblasts from the later embryo (days 10-12 in ovo) were only in the fast myogenic lineage. These results suggest that muscle fiber formation is rooted in two developmental phases--an early phase in which diverse fiber types are formed from intrinsically diverse populations of myoblasts and a later phase in which fibers are formed from a single population of myoblasts.

Age Factors↗
PubMed1986

Lineage-related polypeptide markers in acute lymphoblastic leukemia detected by two-dimensional gel electrophoresis.

We have utilized two-dimensional polyacrylamide gel electrophoresis, coupled with ultrasensitive silver staining, to identify lineage-related polypeptide markers in lymphoblasts from children with acute lymphoblastic leukemia. Twelve polypeptides were detected that could distinguish between the major subgroups of acute lymphoblastic leukemia. These included a new marker for common acute lymphoblastic leukemia and markers for cells of B and T lineages. Analysis of the two-dimensional patterns also allowed the tentative identification of T-cell lineage in two cases with an otherwise undifferentiated non-T-cell non-B-cell phenotype. Two-dimensional electrophoresis thus provides a powerful tool for the delineation of the cell of origin in leukemia.

B-Lymphocytes↗
PubMed1987

Cloned murine T200 (Ly-5) cDNA reveals multiple transcripts within B- and T-lymphocyte lineages.

The murine T200 family of cell-surface glycoproteins is expressed on hematopoietic lineage cell types in a developmentally regulated manner with different lymphocyte subpopulations expressing cross-reactive but structurally distinct forms. To investigate the differences between these forms and the regulation of these differences, murine T200 cDNA clones were isolated by using a probe obtained by subtractive hybridization. This procedure made use of a T200+ L-cell transfectant and the parent Ltk- cell line. The 1.9-kilobase (kb) cDNA clone was sequenced and found to contain the coding region of the COOH-terminal 331 amino acids and 0.9 kb of 3' untranslated region. Where the sequence overlapped with the rat sequence, 80-90% homology was observed. RNA blot analysis revealed that B-lineage cell lines express either a 5.6-kb or a 6.5-kb mRNA correlating to the size difference of the T200 glycoprotein synthesized. Similarly, in the T-cell lineage a helper T-cell clone and a cytotoxic T-cell clone express T200 transcripts of 5.6 kb and 5.9 kb, respectively, which correlate with the distinct sizes of their T200 glycoproteins. A T200-negative mutant of a T-cell line was found to express full-length T200 mRNA, although at a diminished level.

Amino Acid Sequence↗
PubMed1992

Diversification of the Wnt gene family on the ancestral lineage of vertebrates.

Diversification of the Wnt genes, a family of powerful developmental regulator molecules, is inferred by molecular evolutionary analyses. Fifty-five recently determined partial sequences from a variety of vertebrates and invertebrates, together with 17 published sequences, mostly from the mouse and Drosophila melanogaster, are analyzed. Wnt-1 through -7 originated before the last common ancestor of arthropods and deuterostomes lived. Another round of gene duplication, involving Wnt-3, -5, -7, and -10, occurred after the echinoderm lineage arose, on the ancestral lineage of jawed vertebrates. Increased constraints were imposed on the Wnt genes when jawed vertebrates originated, as indicated by an overall 4-fold lower rate of amino acid replacements in jawed vertebrates compared with invertebrates and jawless vertebrates. The Wnt genes are thus inferred to have undergone a disproportionately high amount of structural and functional evolution in the relatively short time (approximately 100 million years) between the origin of the echinoderm lineage and the first diversification of jawed vertebrates. A model is presented for the relationship of functional diversification of developmental regulators and their rates of amino acid replacement.

Amino Acid Sequence↗
PubMed1992

Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors.

The programmed activation/repression of transcription factors in early hematopoietic differentiation has not yet been explored. The DNA-binding protein GATA-1 is required for normal erythroid development and regulates erythroid-expressed genes in maturing erythroblasts. We analyzed GATA-1 expression in early human adult hematopoiesis by using an in vitro system in which "pure" early hematopoietic progenitors are induced to gradual and synchronized differentiation selectively along the erythroid or granulocyte-macrophage pathway by differential treatment with hematopoietic growth factors. The GATA-1 gene, though virtually silent in quiescent progenitors, is activated after entrance into the cell cycle upon stimulation with hematopoietic growth factors. Subsequently, increasing expression along the erythroid pathway contrasts with an abrupt downregulation in the granulocyte-macrophage lineage. These results suggest a microenvironment-directed, two-step model for GATA-1 expression in differentiating hematopoietic progenitors that involves (i) cycle-dependent initiation and (ii) lineage-dependent maintenance or suppression. Hypothetically, on/off switches of lineage-restricted transactivators may underlie the binary fate decisions of hematopoietic progenitors.

Antigens, Surface↗
PubMed1992

Differential development of progenitor activity for three B-cell lineages.

Cell-transfer studies presented here distinguish three murine B cell lineages: conventional B cells, which develop late and are continually replenished from progenitors in adult bone marrow; Ly-1 B cells (B-1a), which develop early and maintain their numbers by self-replenishment; and Ly-1B "sister" (B-1b) cells, which share many of the properties of Ly-1 B cells, including self-replenishment and feedback regulation of development but can also readily develop from progenitors in adult bone marrow. The sequential emergence of these lineages, the time at which their progenitors function during ontogeny, and the distinctions among their repertoires and functions suggest that evolution has created a layered immune system in which the immune response potential of each successive lineage is adapted to its particular niche.

Animals↗