التفاصيل البيبلوغرافية
| العنوان: |
Ancestral origin of two most prevalent mutations in the PROP1 gene causing combined pituitary hormone deficiency in selected European populations |
| المؤلفون: |
Dusatkova, Petra, Pfäffle, Roland W., Obermannova, Barbora, Verkauskienė, Rasa, Akulevich, Natallia, Malikova, Jana, Pribilincova, Zuzana, Sallai, Agnes, Stipancic, Gordana, Krzisnik, Ciril, Blum, Werner, Parks, John, Cinek, Ondrej, Lebl, Jan |
| المصدر: |
9th Joint Meeting of Paediatric Endocrinology. Theme: "Predictive Medicine to Improve the Care of Children" : September 19-22, Milan, Italy : Abstract Book / Organising Committee: Franco Chiarelli, Chieti Marco Cappa [et al.] ; ESPE-PES-APEG-APPES-ASPAE-JSPE-SLEP, Milano : European Society for Paediatric Endocrinology (PSPE), 2013, p. 50, no. FC10-179 |
| سنة النشر: |
2013 |
| المجموعة: |
LSRC VL (Lithuanian Social Research Centre Virtual Library) / LSTC VB (Lietuvos socialinių tyrimų centras virtualią biblioteką) |
| مصطلحات موضوعية: |
Pituitary gland, Pathology, Pituitary hormones, Deficiency, Homeodomain proteins, Genetics, Mutation, Europe, info:eu-repo/classification/udc/616.43 |
| الوصف: |
Background: The PROP1 gene whose recessive mutations cause combined deficiency of pituitary hormones, harbours two frequent mutations: c.296delGA and c.150delA. These mutations are responsible for a proportion of cases worldwide, with especially notable clustering of cases in Central and Eastern Europe. This suggests that each of the mutations has spread from its respective common ancestor. Objective: The aim of our collaborative research project was to investigate whether this mutation clustering reflected a presence of a common ancestor. Methods: We investigated 115 patients, homozygotes or compound heterozygotes for the c.296delGA or c.150delA mutations, originating from 106 families in 11 European countries. We genotyped 22 single nucleotide polymorphism markers flanking the PROP1 gene in the distance of 9.6Mb that are not in mutual linkage disequilibrium in the general European populations (Pearson’s r2≤0.1 for all pairs from HapMap, further verified in 94 unrelated population controls) - consequently, a finding of a common haplotype would be indicative of ancestral origin of the mutation. Haplotypes were reconstructed by Phase and Haploview software, and the age of the mutations estimated using the DMLE+ program. Results: The c.296delGA mutation was carried on a haplotype spanning up to 0.7Mb around the PROP1 gene, which yielded strong evidence (p≤3x10-4) for a common origin of this mutation arising about 112 generations ago. A similar founder effect was documented also for the c.150delA mutation that was carried on a haplotype spanning about 0.9Mb (p≤0.003); the estimated mutation origin was 97 generations ago. Conclusions: Our large international multicentric study documents the existence of two common ancestors carrying c.296delGA and c.150delA mutations in the PROP1 gene. This contradicts the previous assumption of mutation hot-spots in the PROP1 gene. Supported by: Eli Lilly IIT grant (B9R-CY-O057). |
| نوع الوثيقة: |
conference object |
| اللغة: |
English |
| Relation: |
http://lsmu.lvb.lt/LSMU:ELABAPDB5658606&prefLang=en_US |
| الاتاحة: |
http://lsmu.lvb.lt/LSMU:ELABAPDB5658606&prefLang=en_US |
| رقم الانضمام: |
edsbas.891C83F |
| قاعدة البيانات: |
BASE |