dbGaPapplication/xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/manifest/Study_Report.phs001212.Globin_SickleCelliPSC.v1.p1.MULTI.pdfftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/release_notes/Release_Notes.phs001212.GlobinSickleCelliPSC.v1.p1.MULTI.pdfftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/manifest/manifest_phs001212.Globin_SickleCelliPSC.v1.p1.c1.GRU.pdfftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/GapExchange_phs001212.v1.p1.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006562.v1.Globin_Sickle_Cell_iPSC_Subject.data_dict.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006563.v1.Globin_Sickle_Cell_iPSC_Sample.data_dict.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006562.v1.p1.Globin_Sickle_Cell_iPSC_Subject.var_report.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006564.v1.p1.Globin_Sickle_Cell_iPSC_Subject_Phenotypes.var_report.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006563.v1.p1.Globin_Sickle_Cell_iPSC_Sample.var_report.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006565.v1.Globin_Sickle_Cell_iPSC_Sample_Attributes.data_dict.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006564.v1.Globin_Sickle_Cell_iPSC_Subject_Phenotypes.data_dict.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/phs001212.v1.pht006565.v1.p1.Globin_Sickle_Cell_iPSC_Sample_Attributes.var_report.xmlftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/dbGaPEx2.1.5.xsdftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/datadict_v2.xslftp://ftp.ncbi.nlm.nih.gov/dbgap/studies/phs001212/phs001212.v1.p1/pheno_variable_summaries/varreports_v3.xslprimaryOK200GenomicCase Sethttp://www.bu.edu/sicklecell/INO1, ichthyosis-prematurity syndrome, ichthyosis prematurity syndrome, Gene Expressions, IPS, ino1-B, Gene, isyna1, ichthyosis congenita IV, meniscocyte, IPS-1, Expressions, oxygen-carrying, Genotypes, Genogroups, FATP4, Genogroup, INOS, idiopathic pneumonia syndrome, ips, ichthyosis congenita 4, ACSVL4, Globin, Cell., globin, Expression, ino1-a, ino1, hemerythrin, hemocyanin, IPS 1, inos, drepanocyte, congenital ichthyosis type 4<p>Inclusion criteria: genotype-based diagnosis of sickle cell anemia</p>https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001212<p>The study was one of a group of NHLBI-supported studies (NextGen) focused on deriving iPSCs from individuals with heart, lung and blood diseases.</p>Co-Principal Investigators - George J. Murphy - Boston University School of Medicine, Boston, MA, USACo-Principal Investigators - David H.K. Chui - Boston University School of Medicine, Boston, MA, USAPrincipal Investigator - Martin H. Steinberg - Boston University School of Medicine, Boston, MA, USAFunding Source - U01 HL107443 - National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USACo-Principal Investigators - Gustavo Mostoslavsky - Boston University School of Medicine, Boston, MA, USAdbGaPbig, Base Editing, other disease, Materials, single-organism developmental process, IPS, HB-SS DIS NEC W CRISIS, Sickle cell anemia NOS (disorder), sickle cell disease, developmental stage, Sickle cell anaemia NOS, Mbp1, ino1-B, Gene, Sickle-cell disease, Trait Loci, Quantitative, body system, froggy, Gyltl1a, sickle cell anemia, Hbat1, Mutations, large, unspecified, definitive RBC differentiation, diseases, fetal haemoglobin measurement, ips, Hemoglobin S disease, disease or disorder, Other sickle-cell disease with crisis, system, diseases and disorders, Sickle cell anemia of unspecified type, IPS 1, iPS cell, hemerythrin, myd, drepanocytosis, study, human disease, anatomical systems, ichthyosis prematurity syndrome, Genetic, Gene Expressions, Erythropoieses, MDDGB6, hemoglobin SC disease, Mbp-1, messenger RNA, isyna1, Trait Locus, elevated, Sickle Cell Disease, Expressions, free, Hemoglobin SS Disease, Hb-SS disease without crisis, non-neoplastic, genetic, BPFD#36, FATP4, template RNA, Sickle cell anemia of unspecified type (disorder), undulated, Erythroid Cell, Sickle cell anaemia, idiopathic pneumonia syndrome, Clients, great, SICKLE CELL DISEASE NOS, Loci, disorder, Homo sapiens disease, stage, globin, Expression, hunchback, Quantitative Trait Loci Genes, associated, constitutitional genetic, high elevation, definitive erythropoiesis, Hemoglobin SS disease, INO1, ichthyosis-prematurity syndrome, Hba, Drepanocythemia, gyltl1b-b, HB-S DIS W/O CRISIS NEC, response to HU, Hb S disease, SKCA, disorders, familial, Sickle Cell Anemia, Haemoglobin S-S disease, medical condition, un, IPS-1, iPSC., Cistrons, erythropoiesis, sickling disorder due to Hemoglobin S, Client, Hb SC disease, Cell, Sickle cell anaemia of unspecified type, Quantitative Trait, Genome Editing, development, HGBF, haemoglobin SC disease, Hemoglobin S-S disease, Hemoglobin S disease without crisis, iPSC, Hba1, sickling disorder due to Haemoglobin S, MDDGA6, mKIAA0609, ichthyosis congenita 4, Quantitative Trait Locus, erythrocyte cell differentiation, sickle-cell/Hb-C disease without crisis, definitive red blood cell differentiation, Diseases, HbS disease, INSDC_feature:mRNA, sequence, Genetic Materials, condition, Sickle cell anemia NOS, Erythroid, Hb SS disease, fetal hemoglobin levels, ino1, connected anatomical system, Other sickle-cell disease without crisis, hbs, Hereditary hemoglobinopathy disorder homozygous for hemoglobin S (disorder), Hb-S/Hb-C disease, Genetic Material, congenital ichthyosis type 4, fg, Sickle cell anemia, Drepanocythaemia, gyltl1b, red blood cell differentiation, protein_coding_transcript, Editing, mRNA, Haemoglobin S disease without crisis, mdc1d, expanded, ichthyosis congenita IV, Haemoglobin S disease, Locus, wt, primary structure of sequence macromolecule, oxygen-carrying, Hemoglobin F, RBC differentiation, organ system, Sickle cell syndrome, Hemoglobin S disease without crisis (disorder), MDC1D, disease, HbF levels, enr, enlarged, Hereditary hemoglobinopathy disorder homozygous for hemoglobin S, Patient, Material, INOS, Cells, Base, ACSVL4, Globin, Cistron, inherited genetic, ino1-a, hemocyanin, inos, Fetal Hemoglobin, hereditary, Genome, Hemoglobin SS disease without crisis (disorder), Pax-1falseNextGen Consortium: Globin Gene Expression in Sickle Cell Genotype-Specific iPS Cells<p> <ol> <li>Implement an efficient, highly reproducible and 'scalable' system for the production of large numbers of sickle cell anemia-specific iPS cells (iPSC).</li> <li>Derive and characterize a novel, in vitro system for the production of an unlimited supply of erythroid lineage cells from the directed differentiation of 'clinical grade' transgene-free iPS cells; use this system to recapitulate erythroid-lineage ontogeny in vitro with the sequential development of primitive and definitive erythropoiesis, accompanied by the appropriate expression of stage-specific globin genes.</li> <li>Identify developmental gene expression profile differences between erythroid precursors that produce primarily HbF and those that produce primarily HbA or HbS.</li> <li>Determine the effects of the three known HbF major quantitative trait loci (QTL) on globin gene expression in disease-specific iPS cells during in vitro erythropoiesis.</li> <li>Search for novel HbF genetic modifiers associated with markedly elevated HbF levels found in sickle cell anemia patients naturally, or in response to hydroxyurea treatment, by examining gene expression profiles and mRNA sequence of their iPSC-derived erythroid cells.</li> <li>Develop and use a CRISPR-based gene editing platform to study the effect of novel HbF genetic modifiers, explore globin switching, and correct the HbS mutation in sickle iPSC lines.</li> </ol> </p>2017-12-082016-09-12phs001212Fetal Hemoglobin281112793981023723449