BACKGROUND: The term "position effect" is used when the expression of a gene is deleteriously affected by an alteration in its chromosomal environment even though the integrity of the protein coding sequences is maintained. We describe a patient affected by epilepsy and severe neurodevelopment delay carrying a balanced translocation t(15;16)(p11.2;q12.1)dn that we assume caused a position effect as a result of the accidental juxtaposition of heterochromatin in the euchromatic region. RESULTS: FISH mapped the translocation breakpoints (bkps) to 15p11.2 within satellite III and the 16q12.1 euchromatic band within the ITFG1 gene. The expression of the genes located on both sides of the translocation were tested by means of real-time PCR and three, all located on der(16), were found to be variously perturbed: the euchromatic gene NETO2/BTCL2 was silenced, whereas VPS35 and SHCBP1, located within the major heterochromatic block of chromosome 16q11.2, were over-expressed. Pyrosequencing and chromatin immunoprecipitation of NETO2/BTCL2 and VPS35 confirmed the expression findings. Interphase FISH analysis showed that der(16) localised to regions occupied by the beta satellite heterochromatic blocks more frequently than der(15). CONCLUSIONS: To the best of our knowledge, this is the first report of a heterochromatic position effect in humans caused by the juxtaposition of euchromatin/heterochromatin as a result of chromosomal rearrangement. The overall results are fully in keeping with the observations in Drosophila and suggest the occurrence of a human heterochromatin position effect associated with the nuclear repositioning of the der(16) and its causative role in the patient's syndromic phenotype.
BACKGROUND: The term "position effect" is used when the expression of a gene is deleteriously affected by an alteration in its chromosomal environment even though the integrity of the protein coding sequences is maintained. We describe a patient affected by epilepsy and severe neurodevelopment delay carrying a balanced translocation t(15;16)(p11.2;q12.1)dn that we assume caused a position effect as a result of the accidental juxtaposition of heterochromatin in the euchromatic region. RESULTS: FISH mapped the translocation breakpoints (bkps) to 15p11.2 within satellite III and the 16q12.1 euchromatic band within the ITFG1 gene. The expression of the genes located on both sides of the translocation were tested by means of real-time PCR and three, all located on der(16), were found to be variously perturbed: the euchromatic gene NETO2/BTCL2 was silenced, whereas VPS35 and SHCBP1, located within the major heterochromatic block of chromosome 16q11.2, were over-expressed. Pyrosequencing and chromatin immunoprecipitation of NETO2/BTCL2 and VPS35 confirmed the expression findings. Interphase FISH analysis showed that der(16) localised to regions occupied by the beta satellite heterochromatic blocks more frequently than der(15). CONCLUSIONS: To the best of our knowledge, this is the first report of a heterochromatic position effect in humans caused by the juxtaposition of euchromatin/heterochromatin as a result of chromosomal rearrangement. The overall results are fully in keeping with the observations in Drosophila and suggest the occurrence of a human heterochromatin position effect associated with the nuclear repositioning of the der(16) and its causative role in the patient's syndromic phenotype.
Authors: Girdhar G Sharma; Sairei So; Arun Gupta; Rakesh Kumar; Christelle Cayrou; Nikita Avvakumov; Utpal Bhadra; Raj K Pandita; Matthew H Porteus; David J Chen; Jacques Cote; Tej K Pandita Journal: Mol Cell Biol Date: 2010-05-17 Impact factor: 4.272
Authors: M Göttlicher; S Minucci; P Zhu; O H Krämer; A Schimpf; S Giavara; J P Sleeman; F Lo Coco; C Nervi; P G Pelicci; T Heinzel Journal: EMBO J Date: 2001-12-17 Impact factor: 11.598
Authors: P Finelli; A I Pincelli; S Russo; M T Bonati; M P Recalcati; M Masciadri; D Giardino; F Cavagnini; L Larizza Journal: Clin Genet Date: 2007-03 Impact factor: 4.438
Authors: Evgueni A Ivakine; Brooke A Acton; Vivek Mahadevan; Jake Ormond; Man Tang; Jessica C Pressey; Michelle Y Huang; David Ng; Eric Delpire; Michael W Salter; Melanie A Woodin; Roderick R McInnes Journal: Proc Natl Acad Sci U S A Date: 2013-02-11 Impact factor: 11.205
Authors: Elena Lesma; Silvia Ancona; Silvia M Sirchia; Emanuela Orpianesi; Vera Grande; Patrizia Colapietro; Eloisa Chiaramonte; Anna Maria Di Giulio; Alfredo Gorio Journal: J Cell Mol Med Date: 2014-03-07 Impact factor: 5.310
Authors: Maria S Fedorova; Anastasiya V Snezhkina; Elena A Pudova; Ivan S Abramov; Anastasiya V Lipatova; Sergey L Kharitonov; Asiya F Sadritdinova; Kirill M Nyushko; Kseniya M Klimina; Mikhail M Belyakov; Elena N Slavnova; Nataliya V Melnikova; Maria A Chernichenko; Dmitry V Sidorov; Marina V Kiseleva; Andrey D Kaprin; Boris Y Alekseev; Alexey A Dmitriev; Anna V Kudryavtseva Journal: BMC Genet Date: 2017-12-28 Impact factor: 2.797