CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration

In developed countries, age-related macular degeneration is a common cause of blindness in the elderly. A common polymorphism, encoding the sequence variation Y402H in complement factor H (CFH), has been strongly associated with disease susceptibility. Here, we examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than the Y402H variant. Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of four common haplotypes (of which two were associated with disease susceptibility and two seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). Our results suggest that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility

Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2.

PURPOSE: To report a novel mouse model of achromatopsia with a cpfl3 mutation found in the ALS/LtJ strain. METHODS: The effects of a cpfl3 mutation were documented using fundus photography, electroretinography (ERG), and histopathology. Genetic analysis was performed using linkage studies and PCR gene identification. RESULTS: Homozygous cpfl3 mice had poor cone-mediated responses on ERG at 3 weeks that became undetectable by 9 months. Rod-mediated waveforms were initially normal, but declined with age. Microscopy of the retinas revealed progressive vacuolization of the photoreceptor outer segments. Immunocytochemistry with cone-specific markers showed progressive loss of labeling for alpha-transducin, but the cone outer segments in the oldest mice examined remained intact and positive with peanut agglutinin (PNA). The cpfl3 mapped to mouse chromosome 3 at the same location as human GNAT2, known to cause achromatopsia. Sequence analysis revealed a missense mutation due to a single base pair substitution in exon 6 in cpfl3. CONCLUSIONS: The Gnat2(cpfl3) mutation leads to cone dysfunction and the progressive loss of cone alpha-transducin immunolabeling. Despite a poor cone ERG signal and loss of cone alpha-transducin label, the cones survive at 14 weeks as demonstrated by PNA staining. This mouse model of achromatopsia will be useful in the study of the development, pathophysiology, and treatment of achromatopsia and other cone degenerations. The gene symbol for the cpfl3 mutation has been changed to Gnat2(cpfl3)

Turkish nationwide survEy of glycemic and other Metabolic parameters of patients with Diabetes mellitus (TEMD study)

AIMS: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus. METHODS: A nationwide, multicenter survey consecutively enrolled patients who were under follow up for at least a year. Optimal control was defined as HbA1c < 7%, home arterial blood pressure (ABP) < 135/85 mmHg, or LDL-C < 100 mg/dL. Achieving all parameters indicated triple metabolic control. RESULTS: HbA1c levels of patients (n = 5211) were 8.6 ± 1.9% (71 ± 22 mmol/mol) and 7.7 ± 1.7% (61 ± 19 mmol/mol), in Type 1 and Type 2 diabetes, respectively. Glycemic control was achieved in 15.3% and 40.2%, and triple metabolic control was achieved in 5.5% and 10.1%, respectively. Only 1.5% of patients met all the criteria of being non-obese, non-smoker, exercising, and under triple metabolic control. Low education level was a significant predictor of poor glycemic control in both groups. CONCLUSIONS: Few patients with Type 2, and even fewer with Type 1 diabetes have optimal metabolic control in Turkey. TEMD study will provide evidence-based information to policy makers to focus more on the quality and sustainability of diabetes care in order to reduce the national burden of the disease

Ancient DNA from Mesopotamia suggests distinct Pre-Pottery and Pottery Neolithic migrations into Anatolia

We present the first ancient DNA data from the Pre-Pottery Neolithic of Mesopotamia (Southeastern Turkey and Northern Iraq), Cyprus, and the Northwestern Zagros, along with the first data from Neolithic Armenia. We show that these and neighboring populations were formed through admixture of pre-Neolithic sources related to Anatolian, Caucasus, and Levantine hunter-gatherers, forming a Neolithic continuum of ancestry mirroring the geography of West Asia. By analyzing Pre-Pottery and Pottery Neolithic populations of Anatolia, we show that the former were derived from admixture between Mesopotamian-related and local Epipaleolithic-related sources, but the latter experienced additional Levantine-related gene flow, thus documenting at least two pulses of migration from the Fertile Crescent heartland to the early farmers of Anatolia