Description: The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100 000 individuals aged 35–70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106 527participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at ( rahmanj@ppukm.ukm.edu.my ).

Description: Anna Kuta, Yaopan Mao, Tina Martin, Catia Ferreira de Sousa, Danielle Whiting, Sana Zakaria, Ivan Crespo-Enriquez, Philippa Evans, Bartosz Balczerski, Baljinder Mankoo, Kenneth D. Irvine, and Philippa H. Francis-West The protocadherins Fat4 and Dchs1 act as a receptor-ligand pair to regulate many developmental processes in mice and humans, including development of the vertebrae. Based on conservation of function between Drosophila and mammals, Fat4-Dchs1 signalling has been proposed to regulate planar cell polarity (PCP) and activity of the Hippo effectors Yap and Taz, which regulate cell proliferation, survival and differentiation. There is strong evidence for Fat regulation of PCP in mammals but the link with the Hippo pathway is unclear. In Fat4 –/– and Dchs1 –/– mice, many vertebrae are split along the midline and fused across the anterior-posterior axis, suggesting that these defects might arise due to altered cell polarity and/or changes in cell proliferation/differentiation. We show that the somite and sclerotome are specified appropriately, the transcriptional network that drives early chondrogenesis is intact, and that cell polarity within the sclerotome is unperturbed. We find that the key defect in Fat4 and Dchs1 mutant mice is decreased proliferation in the early sclerotome. This results in fewer chondrogenic cells within the developing vertebral body, which fail to condense appropriately along the midline. Analysis of Fat4;Yap and Fat4;Taz double mutants, and expression of their transcriptional target Ctgf, indicates that Fat4-Dchs1 regulates vertebral development independently of Yap and Taz. Thus, we have identified a new pathway crucial for the development of the vertebrae and our data indicate that novel mechanisms of Fat4-Dchs1 signalling have evolved to control cell proliferation within the developing vertebrae.