Browsing by Author "Burn, John"

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    Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression
    (Public Library of Science, 2010) Cunnington, Michael S; Koref, Mauro Santibanez; Mayosi, Bongani M; Burn, John; Keavney, Bernard
    Author Summary Genetic variants on chromosome 9p21 have been associated with several important diseases including coronary artery disease, diabetes, and multiple cancers. Most of the risk variants in this region do not alter any protein sequence and are therefore likely to act by influencing the expression of nearby genes. We investigated whether chromosome 9p21 variants are correlated with expression of the three nearest genes ( CDKN2A , CDKN2B , and ANRIL ) which might mediate the association with disease. Using two different techniques to study effects on expression in blood from two separate populations of healthy volunteers, we show that variants associated with disease are all correlated with ANRIL expression, but associations with the other two genes are weaker and less consistent. Multiple genetic variants are independently associated with expression of all three genes. Although total expression levels of CDKN2A , CDKN2B , and ANRIL are positively correlated, individual genetic variants influence ANRIL and CDKN2B expression in opposite directions, suggesting a possible role of ANRIL in CDKN2B regulation. Our study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases.
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    Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries
    (2022-03-31) Halim-Fikri, Bin Hashim; Lederer, Carsten W; Baig, Atif Amin; Mat-Ghani, Siti Nor Assyuhada; Syed-Hassan, Sharifah-Nany Rahayu-Karmilla; Yusof, Wardah; Abdul Rashid, Diana; Azman, Nurul Fatihah; Fucharoen, Suthat; Panigoro, Ramdan; Silao, Catherine Lynn T; Viprakasit, Vip; Jalil, Norunaluwar; Mohd Yasin, Norafiza; Bahar, Rosnah; Selvaratnam, Veena; Mohamad, Norsarwany; Nik Hassan, Nik Norliza; Esa, Ezalia; Krause, Amanda; Robinson, Helen; Hasler, Julia; Stephanou, Coralea; Raja-Sabudin, Raja-Zahratul-Azma; Elion, Jacques; El-Kamah, Ghada; Coviello, Domenico; Yusoff, Narazah; Abdul Latiff, Zarina; Arnold, Chris; Burn, John; Kountouris, Petros; Kleanthous, Marina; Ramesar, Raj; Zilfalil, Bin Alwi
    The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden.