PMID- 23935956
OWN - NLM
STAT- MEDLINE
DCOM- 20140421
LR  - 20231106
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - Genome wide association analysis of a founder population identified TAF3 as a 
      gene for MCHC in humans.
PG  - e69206
LID - 10.1371/journal.pone.0069206 [doi]
LID - e69206
AB  - The red blood cell related traits are highly heritable but their genetics are 
      poorly defined. Only 5-10% of the total observed variance is explained by the 
      genetic loci found to date, suggesting that additional loci should be searched 
      using approaches alternative to large meta analysis. GWAS (Genome Wide 
      Association Study) for red blood cell traits in a founder population cohort from 
      Northern Italy identified a new locus for mean corpuscular hemoglobin 
      concentration (MCHC) in the TAF3 gene. The association was replicated in two 
      cohorts (rs1887582, P = 4.25E-09). TAF3 encodes a transcription cofactor that 
      participates in core promoter recognition complex, and is involved in zebrafish 
      and mouse erythropoiesis. We show here that TAF3 is required for transcription of 
      the SPTA1 gene, encoding alpha spectrin, one of the proteins that link the plasma 
      membrane to the actin cytoskeleton. Mutations in SPTA1 are responsible for 
      hereditary spherocytosis, a monogenic disorder of MCHC, as well as for the normal 
      MCHC level. Based on our results, we propose that TAF3 is required for normal 
      erythropoiesis in human and that it might have a role in controlling the ratio 
      between hemoglobin (Hb) and cell volume and in the dynamics of RBC maturation in 
      healthy individuals. Finally, TAF3 represents a potential candidate or a modifier 
      gene for disorders of red cell membrane.
FAU - Pistis, Giorgio
AU  - Pistis G
AD  - Division of Genetics and Cell Biology, San Raffaele Research Institute and Vita 
      Salute University, Milano, Italy.
FAU - Okonkwo, Shawntel U
AU  - Okonkwo SU
FAU - Traglia, Michela
AU  - Traglia M
FAU - Sala, Cinzia
AU  - Sala C
FAU - Shin, So-Youn
AU  - Shin SY
FAU - Masciullo, Corrado
AU  - Masciullo C
FAU - Buetti, Iwan
AU  - Buetti I
FAU - Massacane, Roberto
AU  - Massacane R
FAU - Mangino, Massimo
AU  - Mangino M
FAU - Thein, Swee-Lay
AU  - Thein SL
FAU - Spector, Timothy D
AU  - Spector TD
FAU - Ganesh, Santhi
AU  - Ganesh S
CN  - CHARGE Consortium Hematology Working
FAU - Pirastu, Nicola
AU  - Pirastu N
FAU - Gasparini, Paolo
AU  - Gasparini P
FAU - Soranzo, Nicole
AU  - Soranzo N
FAU - Camaschella, Clara
AU  - Camaschella C
FAU - Hart, Daniel
AU  - Hart D
FAU - Green, Michael R
AU  - Green MR
FAU - Toniolo, Daniela
AU  - Toniolo D
LA  - eng
GR  - T34 GM008574/GM/NIGMS NIH HHS/United States
GR  - N01.AG. 821336/AG/NIA NIH HHS/United States
GR  - R01 MD009164/MD/NIMHD NIH HHS/United States
GR  - 263 MD 821336/MD/NIMHD NIH HHS/United States
GR  - 263 MD 9164 13/MD/NIMHD NIH HHS/United States
GR  - G0000111/MRC_/Medical Research Council/United Kingdom
GR  - N01.AG.916413/AG/NIA NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - R01 GM033977/GM/NIGMS NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
GR  - R01GM033977/GM/NIGMS NIH HHS/United States
GR  - BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
GR  - N01.AG. 12100/AG/NIA NIH HHS/United States
GR  - R01 HL105756/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130731
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hemoglobins)
RN  - 0 (TAF3 protein, human)
RN  - 0 (TATA-Binding Protein Associated Factors)
RN  - 0 (Transcription Factor TFIID)
RN  - 12634-43-4 (Spectrin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - Cohort Studies
MH  - Erythrocyte Indices/*genetics
MH  - Erythrocytes/cytology/metabolism
MH  - Erythropoiesis/genetics
MH  - *Founder Effect
MH  - Gene Expression Regulation
MH  - Genome-Wide Association Study/*methods
MH  - Hemoglobins/metabolism
MH  - Humans
MH  - Italy
MH  - K562 Cells
MH  - Polymorphism, Single Nucleotide
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spectrin/genetics
MH  - TATA-Binding Protein Associated Factors
MH  - Transcription Factor TFIID/*genetics/metabolism
PMC - PMC3729833
COIS- Competing Interests: The authors have declared that no competing interests exist.
FIR - Ganesh, Santhi K
IR  - Ganesh SK
FIR - Zakai, Neil A
IR  - Zakai NA
FIR - van Rooij, Frank J A
IR  - van Rooij FJ
FIR - Smith, Albert V
IR  - Smith AV
FIR - Chen, Ming-Huei
IR  - Chen MH
FIR - Nalls, Michael
IR  - Nalls M
FIR - Kottgen, Anna
IR  - Kottgen A
FIR - Glazer, Nicole L
IR  - Glazer NL
FIR - Dehghan, Abbas
IR  - Dehghan A
FIR - Aspelund, Thor
IR  - Aspelund T
FIR - Yang, Qiong
IR  - Yang Q
FIR - Tanaka, Toshiko
IR  - Tanaka T
FIR - Jaffe, Andrew
IR  - Jaffe A
FIR - Bis, Joshua C M
IR  - Bis JC
FIR - Verwoert, Germaine
IR  - Verwoert G
FIR - Fox, Caroline S
IR  - Fox CS
FIR - Guralnik, Jack M
IR  - Guralnik JM
FIR - Ehret, Georg
IR  - Ehret G
FIR - Rice, Kenneth
IR  - Rice K
FIR - Oostra, Ben A
IR  - Oostra BA
FIR - Eiriksdottir, Gudny
IR  - Eiriksdottir G
FIR - Levy, Daniel
IR  - Levy D
FIR - Patel, Kushang V
IR  - Patel KV
FIR - Boerwinkle, Eric
IR  - Boerwinkle E
FIR - Rotter, Jerome I
IR  - Rotter JI
FIR - Hofman, Albert
IR  - Hofman A
FIR - Hernandez, Dena
IR  - Hernandez D
FIR - Zheng, Gang
IR  - Zheng G
FIR - Singleton, Andrew B
IR  - Singleton AB
FIR - Coresh, Josef
IR  - Coresh J
FIR - Lumley, Thomas
IR  - Lumley T
FIR - Uitterlinden, Andre G
IR  - Uitterlinden AG
FIR - Launer, Lenore J
IR  - Launer LJ
FIR - Cupples, L Adrienne
IR  - Cupples L
FIR - van Duijn, Cornelia M
IR  - van Duijn CM
FIR - Gudnason, Vilmundur
IR  - Gudnason V
FIR - Psaty, Bruce M
IR  - Psaty BM
FIR - Ferrucci, Luigi
IR  - Ferrucci L
FIR - Chakravarti, Aravinda
IR  - Chakravarti A
FIR - O' Donnell, Christopher J
IR  - O' Donnell CJ
FIR - Witteman, Jacqueline C M
IR  - Witteman JC
FIR - Furth, Susan
IR  - Furth S
FIR - Cushman, Mary
IR  - Cushman M
FIR - Harris, Tamara B
IR  - Harris TB
FIR - Lin, JingPing
IR  - Lin J
EDAT- 2013/08/13 06:00
MHDA- 2014/04/22 06:00
PMCR- 2013/07/31
CRDT- 2013/08/13 06:00
PHST- 2013/02/21 00:00 [received]
PHST- 2013/06/06 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/04/22 06:00 [medline]
PHST- 2013/07/31 00:00 [pmc-release]
AID - PONE-D-13-08317 [pii]
AID - 10.1371/journal.pone.0069206 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 31;8(7):e69206. doi: 10.1371/journal.pone.0069206. Print 2013.