GEPHE SUMMARY Print
Entry Status
Published
GepheID
GP00001603
Main curator
Prigent
PHENOTYPIC CHANGE
Trait Category
Trait State in Taxon A
Human - Estonia Biobank
Trait State in Taxon B
Human - Estonia Biobank. Basophil count-decrease
Ancestral State
Unknown
Taxonomic Status
Taxon A
Latin Name
Common Name
human
Synonyms
human; man; Homo sapiens Linnaeus, 1758; Home sapiens; Homo sampiens; Homo sapeins; Homo sapian; Homo sapians; Homo sapien; Homo sapience; Homo sapiense; Homo sapients; Homo sapines; Homo spaiens; Homo spiens; Humo sapiens
Rank
species
Lineage
Show more ... opterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini; Hominoidea; Hominidae; Homininae; Homo
NCBI Taxonomy ID
is Taxon A an Infraspecies?
Yes
Taxon A Description
Human - Estonia Biobank
Taxon B
Latin Name
Common Name
human
Synonyms
human; man; Homo sapiens Linnaeus, 1758; Home sapiens; Homo sampiens; Homo sapeins; Homo sapian; Homo sapians; Homo sapien; Homo sapience; Homo sapiense; Homo sapients; Homo sapines; Homo spaiens; Homo spiens; Humo sapiens
Rank
species
Lineage
Show more ... opterygii; Dipnotetrapodomorpha; Tetrapoda; Amniota; Mammalia; Theria; Eutheria; Boreoeutheria; Euarchontoglires; Primates; Haplorrhini; Simiiformes; Catarrhini; Hominoidea; Hominidae; Homininae; Homo
NCBI Taxonomy ID
is Taxon B an Infraspecies?
Yes
Taxon B Description
Human - Estonia Biobank. Basophil count-decrease
GENOTYPIC CHANGE
Generic Gene Name
CEBPA
Synonyms
CEBP; C/EBP-alpha
Sequence Similarities
Belongs to the bZIP family. C/EBP subfamily.
GO - Biological Process
GO:0055088 : lipid homeostasis ... show more
UniProtKB
Homo sapiens
GenebankID or UniProtKB
Presumptive Null
No
Molecular Type
Aberration Type
SNP
Molecular Details of the Mutation
C>T at the associated SNP which resides 39kb dowstream from CEBPA near a separate enhancer that influences CEBPA expression along various myeloid lineages. T allele was associated with a 28.6% reduction in enhancer activity.
Experimental Evidence
Authors
Guo MH; Nandakumar SK; Ulirsch JC; Zekavat SM; Buenrostro JD; Natarajan P; Salem RM; Chiarle R; et al. ... show more
Abstract
Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.
Additional References
EXTERNAL LINKS
COMMENTS
the enhancer specifically regulates CEBPA expression during basophil differentiation according to CRISPR/Cas9 mutagenesis
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