Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans.
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...
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oai:doaj.org-article:10f20b756ddf47168cadb980f6421b742021-11-18T09:01:52ZGenome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans.1932-620310.1371/journal.pone.0069206https://doaj.org/article/10f20b756ddf47168cadb980f6421b742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935956/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Giorgio PistisShawntel U OkonkwoMichela TragliaCinzia SalaSo-Youn ShinCorrado MasciulloIwan BuettiRoberto MassacaneMassimo ManginoSwee-Lay TheinTimothy D SpectorSanthi GaneshCHARGE Consortium Hematology WorkingNicola PirastuPaolo GaspariniNicole SoranzoClara CamaschellaDaniel HartMichael R GreenDaniela TonioloPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69206 (2013) |
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Medicine R Science Q Giorgio Pistis Shawntel U Okonkwo Michela Traglia Cinzia Sala So-Youn Shin Corrado Masciullo Iwan Buetti Roberto Massacane Massimo Mangino Swee-Lay Thein Timothy D Spector Santhi Ganesh CHARGE Consortium Hematology Working Nicola Pirastu Paolo Gasparini Nicole Soranzo Clara Camaschella Daniel Hart Michael R Green Daniela Toniolo Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. |
| description |
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. |
| format |
article |
| author |
Giorgio Pistis Shawntel U Okonkwo Michela Traglia Cinzia Sala So-Youn Shin Corrado Masciullo Iwan Buetti Roberto Massacane Massimo Mangino Swee-Lay Thein Timothy D Spector Santhi Ganesh CHARGE Consortium Hematology Working Nicola Pirastu Paolo Gasparini Nicole Soranzo Clara Camaschella Daniel Hart Michael R Green Daniela Toniolo |
| author_facet |
Giorgio Pistis Shawntel U Okonkwo Michela Traglia Cinzia Sala So-Youn Shin Corrado Masciullo Iwan Buetti Roberto Massacane Massimo Mangino Swee-Lay Thein Timothy D Spector Santhi Ganesh CHARGE Consortium Hematology Working Nicola Pirastu Paolo Gasparini Nicole Soranzo Clara Camaschella Daniel Hart Michael R Green Daniela Toniolo |
| author_sort |
Giorgio Pistis |
| title |
Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. |
| title_short |
Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. |
| title_full |
Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. |
| title_fullStr |
Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. |
| title_full_unstemmed |
Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans. |
| title_sort |
genome wide association analysis of a founder population identified taf3 as a gene for mchc in humans. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/10f20b756ddf47168cadb980f6421b74 |
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