Loss of Major DNase I Hypersensitive Sites in Duplicated -globin Gene Cluster Incompletely Silences HBB Gene Expression

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F16%3A00124600" target="_blank" >RIV/00216224:14110/16:00124600 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/16:00472091 RIV/61989592:15110/16:33162128

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1002/humu.23061" target="_blank" >https://onlinelibrary.wiley.com/doi/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 Duplicated -globin Gene Cluster Incompletely Silences HBB Gene Expression

Popis výsledku v původním jazyce

We report an infant with sickle cell disease phenotype by biochemical analysis whose -globin gene (HBB) sequencing showed sickle cell mutation (HBBS) heterozygosity. The proband has a unique head-to-tail duplication of the -globin 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 duplicated -globin 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 with -globin 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 Duplicated -globin Gene Cluster Incompletely Silences HBB Gene Expression

Popis výsledku anglicky

We report an infant with sickle cell disease phenotype by biochemical analysis whose -globin gene (HBB) sequencing showed sickle cell mutation (HBBS) heterozygosity. The proband has a unique head-to-tail duplication of the -globin 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 duplicated -globin 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 with -globin 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_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

—

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

1098-1004

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

2-s2.0-84991270771