{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:00:23Z","timestamp":1791428423241,"version":"4.3.3"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Congenital heart defects (CHDs) are present in about 40\u201360% of newborns with Down syndrome (DS). Patients with DS can also develop acquired cardiac disorders. Mouse models suggest that a critical 3.7 Mb region located on human chromosome 21 (HSA21) could explain the association with CHDs. This region includes a cluster of genes (IFNAR1, IFNAR2, IFNGR2, IL10RB) encoding for interferon receptors (IFN-Rs). Other genes located on different chromosomes, such as the vascular endothelial growth factor A (VEGFA), have been shown to be involved in cardiac defects. So, we investigated the association between single nucleotide polymorphisms (SNPs) in IFNAR2, IFNGR2, IL10RB and VEGFA genes, and the presence of CHDs or acquired cardiac defects in patients with DS. Methods: Individuals (n = 102) with DS, and age- and gender-matched controls (n = 96), were genotyped for four SNPs (rs2229207, rs2834213, rs2834167 and rs3025039) using KASPar assays. Results: We found that the IFNGR2 rs2834213 G homozygous genotype and IL10RB rs2834167G-positive genotypes were more common in patients with DSand significantly associated with heart disorders, while VEGFA rs3025039T-positive genotypes (T\/*) were less prevalent in patients with CHDs. Conclusions: We identified some candidate risk SNPs for CHDs and acquired heart defects in DS. Our data suggest that a complex architecture of risk alleles with interplay effects may contribute to the high variability of DS phenotypes.<\/jats:p>","DOI":"10.3390\/genes11121428","type":"journal-article","created":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T03:51:16Z","timestamp":1606535476000},"page":"1428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5393-1007","authenticated-orcid":false,"given":"Carmela Rita","family":"Balistreri","sequence":"first","affiliation":[{"name":"Clinical Pathology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Leonarda","family":"Ammoscato","sequence":"additional","affiliation":[{"name":"Regional Reference Center for the Control and Treatment of Down Syndrome and Other Chromosomal and Genetic Diseases, Medical Genetics University of Palermo, Villa Sofia\/Cervello-United Hospitals, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letizia","family":"Scola","sequence":"additional","affiliation":[{"name":"Clinical Pathology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Fragapane","sequence":"additional","affiliation":[{"name":"Department of Neonatology, University Hospital Galway, h91 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Giarratana","sequence":"additional","affiliation":[{"name":"Clinical Pathology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-1389","authenticated-orcid":false,"given":"Domenico","family":"Lio","sequence":"additional","affiliation":[{"name":"Clinical Pathology, Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Piccione","sequence":"additional","affiliation":[{"name":"Regional Reference Center for the Control and Treatment of Down Syndrome and Other Chromosomal and Genetic Diseases, Medical Genetics University of Palermo, Villa Sofia\/Cervello-United Hospitals, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s00281-020-00804-1","article-title":"Down syndrome, accelerated aging and immunosenescence","volume":"42","author":"Gensous","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.jacc.2011.08.025","article-title":"Birth prevalence of congenital heart disease worldwide: A systematic review and meta-analysis","volume":"58","author":"Konings","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1093\/oxfordjournals.aje.a116466","article-title":"Improved ascertainment of cardiovascular malformations in infants with Down\u2019s syndrome, Atlanta, 1968 through 1989. Implications for the interpretationof increasing rates of cardiovascular malformationsin surveillance systems","volume":"136","author":"Khoury","year":"1992","journal-title":"Am. J. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1136\/adc.2010.210534","article-title":"Cardiovascular abnormalities in Down\u2019s syndrome: Spectrum, management and survival over 22 years","volume":"97","author":"Irving","year":"2012","journal-title":"Arch. Dis. Child."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.ejmg.2018.05.013","article-title":"Sex differences for major congenital heart defects in Down Syndrome: A population based study","volume":"61","author":"Santoro","year":"2018","journal-title":"Eur. J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0022-3476(89)80605-5","article-title":"Congenital cardiovascular rmalformations associated with chromosome abnormalities: An epidemiologic study","volume":"114","author":"Ferencz","year":"1989","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/S0022-5223(19)41445-1","article-title":"Valve replacement in children and adolescents","volume":"73","author":"Mathews","year":"1977","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"160098","DOI":"10.1183\/16000617.0098-2016","article-title":"What people with Down Syndrome can teach us about cardiopulmonary disease","volume":"26","author":"Colvin","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrg.2016.154","article-title":"Down syndrome and the complexity of genome dosage imbalance","volume":"18","author":"Antonarakis","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.5409\/wjcp.v2.i4.36","article-title":"Echocardiography in children with Down syndrome","volume":"2","year":"2013","journal-title":"World J. Clin. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.pedhc.2006.02.006","article-title":"Part II: Clinical practice guidelines for adolescents and young adults with down syndrome: 12 to 21 Years","volume":"20","author":"Cannon","year":"2006","journal-title":"J. Pediatr. Health Care"},{"key":"ref_12","first-page":"293","article-title":"The \u201cgene dosage effect\u201d hypothesis versus the \u201camplified developmental instability\u201d hypothesis in Down syndrome","volume":"57","author":"Pritchard","year":"1999","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1006\/bbrc.1998.9743","article-title":"Evidence against the current hypothesis of \u201cgene dosage effects\u201d of trisomy 21: Ets-2, encoded on chromosome 21\u201d is not overexpressed in hearts of patients with Down Syndrome","volume":"254","author":"Wollenek","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ling, K.H., Hewitt, C.A., Tan, K.L., Cheah, P.S., Vidyadaran, S., Lai, M.I., Lee, H.C., Simpson, K., Hyde, L., and Pritchard, M.A. (2014). Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-624"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00439-011-0980-2","article-title":"Genetic analysis of Down syndrome-associated heart defects in mice","volume":"130","author":"Liu","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s00439-013-1407-z","article-title":"Engineered chromosome-based genetic mapping establishes a 3.7 Mb critical genomic region for Down syndrome-associated heart defects in mice","volume":"133","author":"Liu","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nrd2422","article-title":"Interferons at age 50: Past, current and future impact on biomedicine","volume":"6","author":"Borden","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s10875-020-00803-9","article-title":"Three copies of four interferon receptor genes underlie a mild type interferonopathy in Down syndrome","volume":"40","author":"Kong","year":"2020","journal-title":"J. Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.cyto.2012.08.020","article-title":"Expression of interferon-\u03b3, interferon-\u03b1 and related genes in individuals with Down syndrome and periodontitis","volume":"60","author":"Tanaka","year":"2012","journal-title":"Cytokine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1242\/dev.127.18.3941","article-title":"Embryonic development disrupted by modest increases in vascular endothelial growth factor gene expression","volume":"127","author":"Miquerol","year":"2000","journal-title":"Development"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/dvdy.20559","article-title":"Vascular endothelial growth factor receptor signaling is required for cardiac valve formation in zebrafish","volume":"235","author":"Lee","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18051","DOI":"10.1038\/s41598-020-74650-4","article-title":"Identifying genetic factors that contribute to the increased risk of congenital heart defects in infants with Down syndrome","volume":"10","author":"Trevino","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1080\/08977194.2018.1513505","article-title":"The roles of vascular endothelial growth factor gene polymorphisms in congenital heart diseases: A meta-analysis","volume":"36","author":"Wang","year":"2018","journal-title":"Growth Factors"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.ajhg.2012.08.017","article-title":"An excess of deleterious variants in VEGFA pathway genes in Down-syndrome-associated atrioventricular septal defects","volume":"91","author":"Ackerman","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100706","DOI":"10.1016\/j.mgene.2020.100706","article-title":"Genotyping strategy of SMAD-3 rs3825977 gene variant for a differential management of ascending aorta aneurysm in women people: Gender oriented diagnostic tools","volume":"25","author":"Scola","year":"2020","journal-title":"Meta Gene"},{"key":"ref_26","first-page":"e653","article-title":"Genetic basis for congenital heart disease: Revisited: A scientific statement from the American heart association","volume":"20","author":"Pierpont","year":"2018","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/hep.22877","article-title":"Variants in interferon-\u03b1 pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial","volume":"49","author":"Welzel","year":"2009","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00439-011-1112-8","article-title":"Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese","volume":"131","author":"Hijikata","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.archoralbio.2009.07.009","article-title":"Influences of interferon-\u03b3 on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts","volume":"54","author":"Iwamoto","year":"2009","journal-title":"Arch. Oral Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/267165a0","article-title":"Effect of human interferon preparations on lymphoblastogenesis in Down\u2019s syndrome","volume":"267","author":"Cupples","year":"1977","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1086\/519248","article-title":"Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance","volume":"81","author":"Prandini","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e16220","DOI":"10.7554\/eLife.16220","article-title":"Trisomy 21 consistently activates the interferon response","volume":"5","author":"Sullivan","year":"2016","journal-title":"Elife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s13287-019-1489-1","article-title":"Immunomodulatory effects of interferon-\u03b3 on human fetal cardiac mesenchymal stromal cells","volume":"10","author":"Grinnemo","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1001\/jama.292.1.75","article-title":"Transfer of fetal cells with multilineage potential to maternal tissue","volume":"292","author":"Khosrotehrani","year":"2004","journal-title":"JAMA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/S0140-6736(03)14795-2","article-title":"Myocardial tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block","volume":"362","author":"Stevens","year":"2003","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/leu.2010.310","article-title":"Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase","volume":"25","author":"Meisel","year":"2011","journal-title":"Leukemia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/PGP.0000000000000305","article-title":"PD-L1 Expression in human placentas and gestational trophoblastic diseases","volume":"36","author":"Veras","year":"2017","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1095\/biolreprod.108.073353","article-title":"Interferon \u03b3 in successful pregnancies","volume":"80","author":"Murphy","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"30146","DOI":"10.1038\/srep30146","article-title":"Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13287-019-1311-0","article-title":"Interferon \u03b3 inhibits the differentiation of mouse adult liver and bone marrow hematopoietic stem cells by inhibiting the activation of notch signaling","volume":"10","author":"Qin","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1016\/j.bcp.2010.07.010","article-title":"Inflammation dysregulates Notch signaling in endothelial cells: Implication of Notch2 and Notch4 to endothelial dysfunction","volume":"80","author":"Quillard","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.devcel.2013.06.007","article-title":"ETS factors regulate Vegf-dependent arterial specification","volume":"26","author":"Wythe","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1161\/01.RES.0000124300.76171.C9","article-title":"Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation","volume":"94","author":"Noseda","year":"2004","journal-title":"Circ. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9148","DOI":"10.1073\/pnas.0602800103","article-title":"Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence","volume":"103","author":"Frodsham","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.mad.2011.02.002","article-title":"Transcriptomic biomarkers of the response of hospitalized geriatric patients admitted with heart failure. Comparison to hospitalized geriatric patients with infectious diseases or hip fracture","volume":"132","author":"Vo","year":"2011","journal-title":"Mech. Ageing Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s11033-012-2232-5","article-title":"Association between IL10, IL10RA, and IL10RB SNPs and ischemic stroke with hypertension in Korean population","volume":"40","author":"Park","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1902\/jop.2011.110056","article-title":"Expression of the interleukin-10 signaling pathway genes in individuals with Down syndrome and periodontitis","volume":"83","author":"Cavalcante","year":"2012","journal-title":"J. Periodontol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S1074-7613(01)00169-8","article-title":"Crystal structure of the IL-10\/IL-10R1 complex reveals a shared receptor binding site","volume":"15","author":"Josephson","year":"2001","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e2133","DOI":"10.1038\/cddis.2016.44","article-title":"IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways","volume":"7","author":"Shi","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41419-019-1752-5","article-title":"mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy","volume":"10","author":"Bordi","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nrg2774","article-title":"The primary cilium: A signalling centre during vertebrate development","volume":"11","author":"Goetz","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1172\/JCI98890","article-title":"Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis","volume":"129","author":"Burkhalter","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/dvdy.24524","article-title":"A role for primary cilia in aortic valve development and disease","volume":"246","author":"Toomer","year":"2017","journal-title":"Dev. Dyn."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/2046-2530-1-23","article-title":"Multiple essential roles for primary cilia in heart development","volume":"1","author":"Willaredt","year":"2012","journal-title":"Cilia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1172\/JCI129827","article-title":"Cilia, mitochondria, and cardiac development","volume":"129","author":"Chaudhry","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ma, W.Q., Wang, Y., Han, X.Q., Zhu, Y., and Liu, N.F. (2018). Association of genetic polymorphisms in vascular endothelial growth factor with susceptibility to coronary artery disease: A meta-analysis. BMC Med. Genet., 19.","DOI":"10.1186\/s12881-018-0628-3"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12013-013-9710-9","article-title":"DNA microarray and quantitative analysis reveal enhanced myocardial VEGF expression with stunted angiogenesis in human tetralogy of Fallot","volume":"67","author":"Peters","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2217\/14622416.8.1.49","article-title":"Vascular endothelial growth factor pharmacogenetics: A new perspective for anti-angiogenic therapy","volume":"8","author":"Pasqualetti","year":"2007","journal-title":"Pharmacogenomics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cyto.2018.03.003","article-title":"Association of VEGFA variants with altered VEGF secretion and type 2 diabetes: A case-control study","volume":"106","author":"Sellami","year":"2018","journal-title":"Cytokine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1684\/ecn.2011.0289","article-title":"Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population","volume":"22","author":"Sater","year":"2011","journal-title":"Eur. Cytokine Netw."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"44","DOI":"10.15252\/embr.201439583","article-title":"Stem and progenitor cell dysfunction in human trisomies","volume":"16","author":"Liu","year":"2015","journal-title":"EMBO Rep."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1428\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:38:44Z","timestamp":1760179124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,28]]},"references-count":61,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["genes11121428"],"URL":"https:\/\/doi.org\/10.3390\/genes11121428","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,28]]}}}