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@article{772608,
author = {van Zelm, Menno. C and Geertsema, Corinne and Nieuwenhuis, Nicole and de Ridder, Dick and Conley, Mary Ellen and Schiff, Claudie and Tezcan, Ilhan and Bernatowska, Ewa and Hartwig, Nico G. and Sanders, Elisabeth A.M. and Litzman, jiří and Kondratenko, Irina and van Dongen, Jacques J.M. and van der Burg, Mirjam},
article_location = {University of Chicago Press},
article_number = {2},
keywords = {BTK; Artemis IGHM; gross deletion; immunodefeicncy},
language = {eng},
issn = {0002-9297},
journal = {Genetická a funkční charakterizace rozsáhlých delecí gentů IGHM, BTK a Artemis u pacientů s vrozenou agamaglobulinenmií.},
title = {Gross deletions involving IGHM, BTK, or Artemis: a model for genomic lesions mediated by transposable elements.},
volume = {82},
year = {2008}
}
TY - JOUR
ID - 772608
AU - van Zelm, Menno. C - Geertsema, Corinne - Nieuwenhuis, Nicole - de Ridder, Dick - Conley, Mary Ellen - Schiff, Claudie - Tezcan, Ilhan - Bernatowska, Ewa - Hartwig, Nico G. - Sanders, Elisabeth A.M. - Litzman, jiří - Kondratenko, Irina - van Dongen, Jacques J.M. - van der Burg, Mirjam
PY - 2008
TI - Gross deletions involving IGHM, BTK, or Artemis: a model for genomic lesions mediated by transposable elements.
JF - Genetická a funkční charakterizace rozsáhlých delecí gentů IGHM, BTK a Artemis u pacientů s vrozenou agamaglobulinenmií.
VL - 82
IS - 2
SP - 320-332
EP - 320-332
SN - 00029297
KW - BTK
KW - Artemis IGHM
KW - gross deletion
KW - immunodefeicncy
N2 - Most genetic disruptions underlying human disease are microlesions, whereas gross lesions are rare with gross deletions being most frequently found (6%). Similar observations have been made in primary immunodeficiency genes, such as BTK, but for unknown reasons the IGHM and DCLRE1C (Artemis) gene defects frequently represent gross deletions ( approximately 60%). We characterized the gross deletion breakpoints in IGHM-, BTK-, and Artemis-deficient patients. The IGHM deletion breakpoints did not show involvement of recombination signal sequences or immunoglobulin switch regions. Instead, five IGHM, eight BTK, and five unique Artemis breakpoints were located in or near sequences derived from transposable elements (TE). The breakpoints of four out of five disrupted Artemis alleles were located in highly homologous regions, similar to Ig subclass deficiencies and Vh deletion polymorphisms. Nevertheless, these observations suggest a role for TEs in mediating gross deletions. The identified gross deletion breakpoints were mostly located in TE subclasses that were specifically overrepresented in the involved gene as compared to the average in the human genome. This concerned both long (LINE1) and short (Alu, MIR) interspersed elements, as well as LTR retrotransposons (ERV). Furthermore, a high total TE content (>40%) was associated with an increased frequency of gross deletions. Both findings were further investigated and confirmed in a total set of 20 genes disrupted in human disease. Thus, to our knowledge for the first time, we provide evidence that a high TE content, irrespective of the type of element, results in the increased incidence of gross deletions as gene disruption underlying human disease.
ER -
VAN ZELM, Menno. C, Corinne GEERTSEMA, Nicole NIEUWENHUIS, Dick DE RIDDER, Mary Ellen CONLEY, Claudie SCHIFF, Ilhan TEZCAN, Ewa BERNATOWSKA, Nico G. HARTWIG, Elisabeth A.M. SANDERS, jiří LITZMAN, Irina KONDRATENKO, Jacques J.M. VAN DONGEN a Mirjam VAN DER BURG. Gross deletions involving IGHM, BTK, or Artemis: a model for genomic lesions mediated by transposable elements. \textit{Genetická a funkční charakterizace rozsáhlých delecí gentů IGHM, BTK a Artemis u pacientů s vrozenou agamaglobulinenmií.}. University of Chicago Press, 2008, roč.~82, č.~2, s.~320-332. ISSN~0002-9297.
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