The Experts below are selected from a list of 128364 Experts worldwide ranked by ideXlab platform
Charis Eng - One of the best experts on this subject based on the ideXlab platform.
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association of Germline mutation in the pten tumour suppressor gene and proteus and proteus like syndromes
The Lancet, 2001Co-Authors: Xiao Ping Zhou, Heather Hampel, Hannelore Thiele, Robert J Gorlin, Raoul C M Hennekam, Melissa A Parisi, R M Winter, Charis EngAbstract:Summary The molecular aetiology of Proteus syndrome (PS) remains elusive. Germline mutations in PTEN cause Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, which are hereditary hamartoma syndromes. Some features—eg, macrocephaly, lipomatosis, and vascular malformations—can be seen in all three syndromes. We examined PTEN in patients with PS and undefined Proteus-like syndromes (PS-like) and identified denovo Germline mutations in two of nine patients with PS and three of five patients with PS-like. Germline PTEN mutation analysis should be done in individuals with PS and PS-like because of its association with increased risk of cancer development and potential of Germline-mutation transmission.
Susan Strome - One of the best experts on this subject based on the ideXlab platform.
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Antagonism between MES-4 and Polycomb Repressive Complex 2 Promotes Appropriate Gene Expression in C. elegans Germ Cells
Cell Reports, 2012Co-Authors: Laura J. Gaydos, Thea A. Egelhofer, Andreas Rechtsteiner, Coleen R. Carroll, Susan StromeAbstract:The Caenorhabditis elegans MES proteins are key chromatin regulators of the Germline. MES-2, MES-3, and MES-6 form the C. elegans Polycomb repressive complex 2 and generate repressive H3K27me3. MES-4 generates H3K36me3 on Germline-expressed genes. Transcript profiling of dissected mutant Germlines revealed that MES-2/3/6 and MES-4 cooperate to promote the expression of Germline genes and repress the X chromosomes and somatic genes. Results from genome-wide chromatin immunoprecipitation showed that H3K27me3 and H3K36me3 occupy mutually exclusive domains on the autosomes and that H3K27me3 is enriched on the X. Loss of MES-4 from Germline genes causes H3K27me3 to spread to Germline genes, resulting in reduced H3K27me3 elsewhere on the autosomes and especially on the X. Our findings support a model in which H3K36me3 repels H3K27me3 from Germline genes and concentrates it on other regions of the genome. This antagonism ensures proper patterns of gene expression for germ cells, which includes repression of somatic genes and the X chromosomes.
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Ciba Foundation Symposium 182 - Germline Development - Specification and development of the Germline in Caenorhabditis elegans.
Ciba Foundation symposium, 2007Co-Authors: Susan Strome, Carol Garvin, Janet Paulsen, Elizabeth Capowski, Paula R. Martin, Maureen J. BeananAbstract:: Maternal-effect sterile (mes) genes encode maternal components that are required for establishment and development of the Germline. Five such genes have been identified in the nematode Caenorhabditis elegans. Mutations in one of the genes result in defects in the asymmetric division and cytoplasmic partitioning that generate the primordial germ cell P4 at the 16-24-cell stage of embryogenesis. As a result of these defects, the P4 cell is transformed into a muscle progenitor and mutant embryos develop into sterile adults with extra body muscles. Mutations in the other four mes genes do not affect formation of the Germline during embryogenesis, but result in drastically reduced proliferation of the Germline during post-embryonic stages and in an absence of gametes in adults. The failure to form gametes may reflect a defect in Germline specification or may be a consequence of reduced Germline proliferation. We are currently testing these two possibilities. In addition to the mes gene products, wild-type function of the zygotic gene glp-4 is required for normal post-embryonic proliferation of the Germline. Germ cells in glp-4 mutant worms are arrested in prophase of the mitotic cell cycle and are unable to enter meiosis and form gametes. Thus, following establishment of the germ lineage in the early embryo, both maternal and zygotic gene products work in concert to promote the extensive proliferation of the Germline and to enable germ cells to generate functional gametes.
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Depletion of a novel SET-domain protein enhances the sterility of mes-3 and mes-4 mutants of Caenorhabditis elegans
Genetics, 2001Co-Authors: Lei Xu, Susan StromeAbstract:Four maternal-effect sterile genes, mes-2, mes-3, mes-4, and mes-6, are essential for Germline development in Caenorhabditis elegans. Homozygous mes progeny from heterozygous mothers are themselves fertile but produce sterile progeny with underproliferated and degenerated Germlines. All four mes genes encode chromatin-associated proteins, two of which resemble known regulators of gene expression. To identify additional components in the MES pathway, we used RNA-mediated interference (RNAi) to test candidate genes for enhancement of the Mes mutant phenotype. Enhancement in this assay was induction of sterility a generation earlier, in the otherwise fertile homozygous progeny of heterozygous mothers, which previous results had suggested represent a sensitized genetic background. We tested seven genes predicted to encode regulators of chromatin organization for RNAi-induced enhancement of mes-3 sterility and identified one enhancer, called set-2 after the SET domain encoded by the gene. Depletion of SET-2 also enhances the sterile phenotype of mes-4 but not of mes-2 or mes-6. set-2 encodes two alternatively spliced transcripts, set-2(l) and set-2(s), both of which are enriched in the Germline of adults. In the adult Germline, SET-2(L) protein is localized in mitotic and mid-late-stage meiotic nuclei but is undetectable in early pachytene nuclei. SET-2(L) protein is localized in all nuclei of embryos. The localization of SET-2(L) does not depend on any of the four MES proteins, and none of the MES proteins depend on SET-2 for their normal localization. Our results suggest that SET-2 participates along with the MES proteins in promoting normal Germline development.
Xiao Ping Zhou - One of the best experts on this subject based on the ideXlab platform.
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association of Germline mutation in the pten tumour suppressor gene and proteus and proteus like syndromes
The Lancet, 2001Co-Authors: Xiao Ping Zhou, Heather Hampel, Hannelore Thiele, Robert J Gorlin, Raoul C M Hennekam, Melissa A Parisi, R M Winter, Charis EngAbstract:Summary The molecular aetiology of Proteus syndrome (PS) remains elusive. Germline mutations in PTEN cause Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, which are hereditary hamartoma syndromes. Some features—eg, macrocephaly, lipomatosis, and vascular malformations—can be seen in all three syndromes. We examined PTEN in patients with PS and undefined Proteus-like syndromes (PS-like) and identified denovo Germline mutations in two of nine patients with PS and three of five patients with PS-like. Germline PTEN mutation analysis should be done in individuals with PS and PS-like because of its association with increased risk of cancer development and potential of Germline-mutation transmission.
Jarad Niemi - One of the best experts on this subject based on the ideXlab platform.
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a hobo transgene that encodes the p element transposase in drosophila melanogaster autoregulation and cytotype control of transposase activity
Genetics, 2002Co-Authors: Michael J Simmons, Kevin J Haley, Craig D Grimes, John D Raymond, Jarad NiemiAbstract:Drosophila were genetically transformed with a hobo transgene that contains a terminally truncated but otherwise complete P element fused to the promoter from the Drosophila hsp70 gene. Insertions of this H(hsp/CP) transgene on either of the major autosomes produced the P transposase in both the male and female Germlines, but not in the soma. Heat-shock treatments significantly increased transposase activity in the female Germline; in the male Germline, these treatments had little effect. The transposase activity of two insertions of the H(hsp/CP) transgene was not significantly greater than their separate activities, and one insertion of this transgene reduced the transposase activity of P(ry(+), Delta2-3)99B, a stable P transgene, in the Germline as well as in the soma. These observations suggest that, through alternate splicing, the H(hsp/CP) transgene produces a repressor that feeds back negatively to regulate transposase expression or function in both the somatic and Germline tissues. The H(hsp/CP) transgenes are able to induce gonadal dysgenesis when the transposase they encode has P-element targets to attack. However, this ability and the ability to induce P-element excisions are repressed by the P cytotype, a chromosomal/cytoplasmic state that regulates P elements in the Germline.
Mats Ohlin - One of the best experts on this subject based on the ideXlab platform.
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parallel antibody Germline gene and haplotype analyses support the validity of immunoglobulin Germline gene inference and discovery
Molecular Immunology, 2017Co-Authors: Ufuk Kirik, Lennart Greiff, Fredrik Levander, Mats OhlinAbstract:Analysis of antibody repertoire development and specific antibody responses important for e.g. autoimmune conditions, allergy, and protection against disease is supported by high throughput sequencing and associated bioinformatics pipelines that describe the diversity of the encoded antibody variable domains. Proper assignment of sequences to Germline genes are important for many such processes, for instance in the analysis of somatic hypermutation. Germline gene inference from antibody-encoding transcriptomes, by using tools such as TIgGER or IgDiscover, has a potential to enhance the quality of such analyses. These tools may also be used to identify Germline genes not previously known. In this study, we exploited such software for Germline gene inference and define aspects of analysis settings and pre-existing knowledge of Germline genes that affect the outcome of gene inference. Furthermore, we demonstrate the capacity of IGHJ and IGHD haplotype inference, whenever subjects are heterozygous with respect to such genes, to lend support to IGHV gene inference in general, and to the identification of novel alleles presently not recognized by Germline gene reference directories. We propose that such haplotype analysis shall, whenever possible, be used in future best practice to support the outcome of Germline gene inference. IGHJ-directed haplotype inference was also used to identify haplotypes not expressing some IGHV Germline genes. In particular, we identified a haplotype that did not express several major Germline genes such as IGHV1-8, IGHV3-9, IGHV3-15, IGHV1-18, IGHV3-21, and IGHV3-23. We envisage that haplotype analysis will provide an efficient approach to identify subjects for further studies of the link between the available immunoglobulin repertoire and outcomes of immune responses.
