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  • 1
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    Differential microRNA regulation of HLA-C expression and its association with HIV control (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-04-19
    Description: The HLA-C locus is distinct relative to the other classical HLA class I loci in that it has relatively limited polymorphism, lower expression on the cell surface, and more extensive ligand-receptor interactions with killer-cell immunoglobulin-like receptors. A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV, and with levels of HLA-C messenger RNA transcripts and cell-surface expression, but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C. Here we show that variation within the 3' untranslated region (UTR) of HLA-C regulates binding of the microRNA hsa-miR-148 to its target site, resulting in relatively low surface expression of alleles that bind this microRNA and high expression of HLA-C alleles that escape post-transcriptional regulation. The 3' UTR variant associates strongly with control of HIV, potentially adding to the effects of genetic variation encoding the peptide-binding region of the HLA class I loci. Variation in HLA-C expression adds another layer of diversity to this highly polymorphic locus that must be considered when deciphering the function of these molecules in health and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084326/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084326/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kulkarni, Smita -- Savan, Ram -- Qi, Ying -- Gao, Xiaojiang -- Yuki, Yuko -- Bass, Sara E -- Martin, Maureen P -- Hunt, Peter -- Deeks, Steven G -- Telenti, Amalio -- Pereyra, Florencia -- Goldstein, David -- Wolinsky, Steven -- Walker, Bruce -- Young, Howard A -- Carrington, Mary -- 5-M01-RR-00722/RR/NCRR NIH HHS/ -- HHSN261200800001E/CO/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- N02-CP-55504/CP/NCI NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- R01-DA04334/DA/NIDA NIH HHS/ -- R01-DA12568/DA/NIDA NIH HHS/ -- U01-AI-35039/AI/NIAID NIH HHS/ -- U01-AI-35040/AI/NIAID NIH HHS/ -- U01-AI-35041/AI/NIAID NIH HHS/ -- U01-AI-35042/AI/NIAID NIH HHS/ -- U01-AI-35043/AI/NIAID NIH HHS/ -- U01-AI-37613/AI/NIAID NIH HHS/ -- U01-AI-37984/AI/NIAID NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Apr 28;472(7344):495-8. doi: 10.1038/nature09914. Epub 2011 Apr 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21499264" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Alleles ; Base Sequence ; Cell Line ; *Gene Expression Regulation/genetics/immunology ; Genes, Reporter/genetics ; HIV/*immunology ; HIV Infections/*genetics/*immunology/therapy ; HLA-C Antigens/*genetics ; Humans ; MicroRNAs/*genetics ; Polymorphism, Single Nucleotide/genetics ; Viral Load
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Cardiac malformation in neonatal mice lacking connexin43 (1995)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1995-03-24
    Description: Gap junctions are made up of connexin proteins, which comprise a multigene family in mammals. Targeted mutagenesis of connexin43 (Cx43), one of the most prevalent connexin proteins, showed that its absence was compatible with survival of mouse embryos to term, even though mutant cell lines showed reduced dye coupling in vitro. However, mutant embryos died at birth, as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract from the heart. This finding suggests that Cx43 plays an essential role in heart development but that there is functional compensation among connexins in other parts of the developing fetus.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reaume, A G -- de Sousa, P A -- Kulkarni, S -- Langille, B L -- Zhu, D -- Davies, T C -- Juneja, S C -- Kidder, G M -- Rossant, J -- New York, N.Y. -- Science. 1995 Mar 24;267(5205):1831-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7892609" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Connexin 43/*genetics/*physiology ; Embryo, Mammalian/cytology ; Heart Defects, Congenital/*genetics/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Respiratory Transport/genetics ; Stem Cells ; Ventricular Outflow Obstruction/congenital/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    The shaping of modern human immune systems by multiregional admixture with archaic humans (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-08-27
    Description: Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677943/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677943/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abi-Rached, Laurent -- Jobin, Matthew J -- Kulkarni, Subhash -- McWhinnie, Alasdair -- Dalva, Klara -- Gragert, Loren -- Babrzadeh, Farbod -- Gharizadeh, Baback -- Luo, Ma -- Plummer, Francis A -- Kimani, Joshua -- Carrington, Mary -- Middleton, Derek -- Rajalingam, Raja -- Beksac, Meral -- Marsh, Steven G E -- Maiers, Martin -- Guethlein, Lisbeth A -- Tavoularis, Sofia -- Little, Ann-Margaret -- Green, Richard E -- Norman, Paul J -- Parham, Peter -- AI031168/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- R01 AI031168/AI/NIAID NIH HHS/ -- RR000165/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Oct 7;334(6052):89-94. doi: 10.1126/science.1209202. Epub 2011 Aug 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21868630" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; African Continental Ancestry Group/genetics ; Alleles ; Animals ; Asian Continental Ancestry Group/genetics ; Continental Population Groups/*genetics ; European Continental Ancestry Group/genetics ; Evolution, Molecular ; *Genes, MHC Class I ; Genetic Variation ; HLA-A Antigens/*genetics/immunology/metabolism ; HLA-B Antigens/*genetics/immunology/metabolism ; HLA-C Antigens/*genetics/immunology ; Haplotypes ; Hominidae/*genetics/*immunology ; Humans ; *Hybridization, Genetic ; Killer Cells, Natural/immunology ; Ligands ; Linkage Disequilibrium ; Molecular Sequence Data ; Oceanic Ancestry Group/genetics ; Receptors, KIR/immunology/metabolism ; Selection, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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