SwePub
Sök i LIBRIS databas

  Utökad sökning

onr:"swepub:oai:DiVA.org:uu-440426"
 

Sökning: onr:"swepub:oai:DiVA.org:uu-440426" > Genetic and functio...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00007734naa a2200721 4500
001oai:DiVA.org:uu-440426
003SwePub
008210421s2021 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4404262 URI
0247 a https://doi.org/10.1136/jmedgenet-2020-1068802 DOI
040 a (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Olijnik, Aude-Anaisu Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
2451 0a Genetic and functional insights into CDA-I prevalence and pathogenesis
264 c 2020-06-09
264 1b BMJ Publishing Group Ltd,c 2021
338 a print2 rdacarrier
520 a Background Congenital dyserythropoietic anaemia type I (CDA-I) is a hereditary anaemia caused by biallelic mutations in the widely expressed genes CDAN1 and C15orf41. Little is understood about either protein and it is unclear in which cellular pathways they participate. Methods Genetic analysis of a cohort of patients with CDA-I identifies novel pathogenic variants in both known causative genes. We analyse the mutation distribution and the predicted structural positioning of amino acids affected in Codanin-1, the protein encoded by CDAN1. Using western blotting, immunoprecipitation and immunofluorescence, we determine the effect of particular mutations on both proteins and interrogate protein interaction, stability and subcellular localisation. Results We identify six novel CDAN1 mutations and one novel mutation in C15orf41 and uncover evidence of further genetic heterogeneity in CDA-I. Additionally, population genetics suggests that CDA-I is more common than currently predicted. Mutations are enriched in six clusters in Codanin-1 and tend to affect buried residues. Many missense and in-frame mutations do not destabilise the entire protein. Rather C15orf41 relies on Codanin-1 for stability and both proteins, which are enriched in the nucleolus, interact to form an obligate complex in cells. Conclusion Stability and interaction data suggest that C15orf41 may be the key determinant of CDA-I and offer insight into the mechanism underlying this disease. Both proteins share a common pathway likely to be present in a wide variety of cell types; however, nucleolar enrichment may provide a clue as to the erythroid specific nature of CDA-I. The surprisingly high predicted incidence of CDA-I suggests that better ascertainment would lead to improved patient care.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Hematologi0 (SwePub)302022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Hematology0 (SwePub)302022 hsv//eng
653 a molecular genetics
653 a cell biology
653 a clinical genetics
653 a haematology (incl Blood transfusion)
7001 a Roy, Noemi B. A.u Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.;Oxford Univ Hosp NHS Fdn Trust, Dept Haematol, Oxford, England.;John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Oxford, England.;John Radcliffe Hosp, BRC NHS Translat Mol Diagnost Ctr, Oxford, England.4 aut
7001 a Scott, Carolineu Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Marsh, Joseph A.u Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.4 aut
7001 a Brown, Jillu Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Lauschke, Karinu Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark.;Tech Univ Denmark, Natl Food Inst, Lyngby, Denmark.4 aut
7001 a Ask, Katrineu Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark.;Eli Lilly Danmark, Herlev, Denmark.4 aut
7001 a Roberts, Nigelu Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Downes, Damien J.u Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Brolih, Sanjau Univ Oxford, MRC Weatherall Inst Mol Med, Dept Oncol, Oxford, England.4 aut
7001 a Johnson, Errinu Univ Oxford, Sir William Dunn Sch Pathol, Oxford, England.4 aut
7001 a Xella, Barbarau Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Proven, Melanieu Oxford Univ Hosp NHS Fdn Trust, Mol Haematol Lab, Oxford, England.4 aut
7001 a Hipkiss, Riau Oxford Univ Hosp NHS Fdn Trust, Mol Haematol Lab, Oxford, England.4 aut
7001 a Ryan, Kateu Manchester Univ NHS Fdn Trust, Haematol Dept, Manchester, Lancs, England.4 aut
7001 a Frisk, Per,d 1966-u Uppsala universitet,Barnneurologi/Barnonkologi,Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.;Uppsala Univ, Childrens Hosp, Uppsala, Sweden.4 aut0 (Swepub:uu)pefri226
7001 a Mäkk, Johanu Uppsala universitet,Centrum för klinisk forskning, Västerås4 aut
7001 a Stattin, Evalenau Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)evast375
7001 a Sadasivam, Nandiniu Manchester Univ NHS Fdn Trust, Haematol Dept, Manchester, Lancs, England.4 aut
7001 a McIlwaine, Louisau NHS Trust Greater Glasgow & Clyde, Dept Haematol, Glasgow, Lanark, Scotland.4 aut
7001 a Hill, Quentin A.u St James Univ Hosp, Dept Haematol, Leeds, W Yorkshire, England.4 aut
7001 a Renella, Raffaeleu Lausanne Univ Hosp, Pediat Hematol Oncol Lab, Lausanne, VD, Switzerland.;Univ Lausanne, Lausanne, VD, Switzerland.4 aut
7001 a Hughes, Jim R.u Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Gibbons, Richard J.u Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Groth, Anjau Univ Copenhagen, Fac Hlth Sci, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Ctr Prot Res CPR, Copenhagen, Denmark.4 aut
7001 a McHugh, Peter J.u Univ Oxford, MRC Weatherall Inst Mol Med, Dept Oncol, Oxford, England.4 aut
7001 a Higgs, Douglas R.u Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Buckle, Veronica J.u Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7001 a Babbs, Christianu Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.4 aut
7102 a Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.b Univ Oxford, MRC Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford, England.;Oxford Univ Hosp NHS Fdn Trust, Dept Haematol, Oxford, England.;John Radcliffe Hosp, NIHR Oxford Biomed Res Ctr, Oxford, England.;John Radcliffe Hosp, BRC NHS Translat Mol Diagnost Ctr, Oxford, England.4 org
7730 t Journal of Medical Geneticsd : BMJ Publishing Group Ltdg 58:3, s. 185-195q 58:3<185-195x 0022-2593x 1468-6244
8564 u https://doi.org/10.1136/jmedgenet-2020-106880y Fulltext
8564 u https://backend.orbit.dtu.dk/ws/files/216098681/jmedgenet_2020_106880.full.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-440426
8564 8u https://doi.org/10.1136/jmedgenet-2020-106880

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy