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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/LH15223" target="_blank" >LH15223: Molekulární patofyziologie vybraných poruch erytropoézy</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Human Mutation

ISSN

1059-7794

e-ISSN

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Svazek periodika

37

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

4

Strana od-do

1153-1156

Kód UT WoS článku

000385804100005

EID výsledku v databázi Scopus

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