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Loss of Major DNase I Hypersensitive Sites in Duplicatedglobin Gene Cluster Incompletely Silences HBB Gene Expression

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00472091" target="_blank" >RIV/68378050:_____/16:00472091 - isvavai.cz</a>

  • Alternative codes found

    RIV/61989592:15110/16:33162128 RIV/00216224:14110/16:00124600

  • Result on the web

    <a href="http://dx.doi.org/10.1002/humu.23061" target="_blank" >http://dx.doi.org/10.1002/humu.23061</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1002/humu.23061" target="_blank" >10.1002/humu.23061</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Loss of Major DNase I Hypersensitive Sites in Duplicatedglobin Gene Cluster Incompletely Silences HBB Gene Expression

  • Original language description

    We report an infant with sickle cell disease phenotype by biochemical analysis whoseglobin gene (HBB) sequencing showed sickle cell mutation (HBBS) heterozygosity. The proband has a unique head-to-tail duplication of theglobin gene cluster having wild-type (HBBA) and HBBS alleles inherited from her father; constituting her HBBS/HBBS-HBBA genotype. Further analyses revealed that proband's duplicatedglobin gene cluster (approximate to 650kb) encompassing HBBA does not include the immediate upstream locus control region (LCR) or 3 DNase I hypersensitivity (HS) element. The LCR interacts withglobin gene cluster involving long range DNA interactions mediated by various transcription factors to drive the regulation of globin genes expression. However, a low level of HBBA transcript was clearly detected by digital PCR. In this patient, the observed transcription from the duplicated, distally displaced HBBA cluster demonstrates that the loss of LCR and flanking 3HS sites do not lead to complete silencing of HBB transcription.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    EB - Genetics and molecular biology

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/LH15223" target="_blank" >LH15223: Molecular pathophysiology of erythroid disorders</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Human Mutation

  • ISSN

    1059-7794

  • e-ISSN

  • Volume of the periodical

    37

  • Issue of the periodical within the volume

    11

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    4

  • Pages from-to

    1153-1156

  • UT code for WoS article

    000385804100005

  • EID of the result in the Scopus database