{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Congenital dyserythropoietic anemia type I (CDA‐I) is now known to be caused by biallelic mutations in two genes of previously unknown function: CDAN1 and CDIN1 (formerly known as C15orf41)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n The CDIN1 gene product is predicted to be a novel nuclease belonging to the Holliday junction resolvase family, and its biochemical characteristics suggest a role in DNA or chromatin processing.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the cellular level, CDIN1 is predominantly nuclear and forms a nearly stoichiometric complex with Codanin-1—the protein encoded by CDAN1. This interaction not only stabilizes CDIN1 but also appears to regulate its subcellular localization, as overexpression of Codanin-1 can shift CDIN1 from the nucleus to the cytoplasm."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n Moreover, studies using erythroid culture systems have demonstrated that disruption of CDIN1 function delays terminal erythroid differentiation, alters chromatin accessibility, and is associated with abnormal nucleolar structure—features that underlie ineffective erythropoiesis in CDA‐I."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Interestingly, beyond its established role in erythropoiesis, recent whole‐genome sequencing studies have implicated rare variants mapping to CDIN1 in Alzheimer’s disease risk, suggesting that the protein may also participate in broader cellular pathways—potentially in RNA metabolism and synaptic function—similar to scaffold proteins such as CNOT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings indicate that CDIN1 functions as a critical regulator in erythroid cell maturation by coordinating chromatin replication and possibly RNA processing. Its interaction with Codanin-1 appears to be essential for maintaining normal nuclear architecture and effective red blood cell production; disruption of this pathway leads to the characteristic ineffective erythropoiesis observed in CDA‐I.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Caroline Scott, Damien J Downes, Jill M Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haematologica (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3324/haematol.2020.260158"}], "href": "https://doi.org/10.3324/haematol.2020.260158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33121234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33121234"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maithili Shroff, Axel Knebel, Rachel Toth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A complex comprising C15ORF41 and Codanin-1: the products of two genes mutated in congenital dyserythropoietic anaemia type I (CDA-I)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20190944"}], "href": "https://doi.org/10.1042/BCJ20190944"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32239177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32239177"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Grace Swickley, Yehoshua Bloch, Lidor Malka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in congenital dyserythropoietic anemia type I disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Mol Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12860-020-00258-1"}], "href": "https://doi.org/10.1186/s12860-020-00258-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32293259"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32293259"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Md Shakil Ahmed, Md Shahjaman, Enamul Kabir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure modeling to function prediction of Uncharacterized Human Protein C15orf41."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioinformation (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.6026/97320630014206"}], "href": "https://doi.org/10.6026/97320630014206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30108417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30108417"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dmitry Prokopenko, Sarah L Morgan, Kristina Mullin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alzheimers Dement (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/alz.12319"}], "href": "https://doi.org/10.1002/alz.12319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33797837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33797837"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dmitry Prokopenko, Sarah L Morgan, Kristina Mullin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Whole-genome sequencing reveals new Alzheimer's disease-associated rare variants in loci related to synaptic function and neuronal development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "medRxiv (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/2020.11.03.20225540"}], "href": "https://doi.org/10.1101/2020.11.03.20225540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33173892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33173892"}]}]}]}