Background: Reduction in functional beta cells in pancreas is the major obstacle in diabetes. Results: Mice deficient in FXYD2 subunit of Na,K-ATPase possess a metabolic phenotype of low blood glucose along with hyperplastic pancreatic islets and hyperinsulinemia. Conclusion: The phenotype observed in Fxyd2Ϫ/Ϫ mice results from an increase in beta cell mass.
Velo-cardio-facial (VCFS; 22q11.2 deletion) syndrome is a genetic disorder that results from a hemizygous deletion of the q11.2 region on chromosome 22, and is associated with greatly increased risk for psychiatric disorders, including Autism Spectrum Disorder (ASD) and schizophrenia. There is emerging evidence for the involvement of catechol O-methyltransferase (COMT) and proline dehydrogenase (oxidase) 1 (PRODH) in the psychiatric phenotype of individuals with VCFS. Here, we tested the hypothesis that PRODH and COMT are associated with ASD in youth with VCFS. We found that individuals with VCFS and the low-activity alleles of both PRODH and COMT (rs4819756A and rs4680A) were more likely to present with ASD as compared to individuals with VCFS and the high-activity alleles of these genes (p<0.05; OR=6.0 (95% CI=1.27-28.26; N=87). Our results suggest that PRODH and COMT may interact to contribute to the ASD phenotype in individuals with VCFS.
Landscape genetics aims to quantify the effect of landscape on gene flow. Broadly, the approach involves measuring genetic variation, quantifying landscape heterogeneity, and statistically testing the link between both genetic variation and landscape heterogeneity. This approach has been widely used by conservation biologists, for example to identify barriers restricting movement in threatened populations. More recently, landscape genetics has been used to study the epidemiology of infectious diseases, such as chronic wasting disease, raccoon rabies, and malaria. This method can be useful in identifying potential hotspot areas of disease movement for targeted public health interventions and containment of disease and drug resistance. However, vector-borne disease epidemiology is particularly complex, as it is affected by the movement of both the vector and human or vertebrate host. This feature could potentially inhibit the ability to detect the effect of landscape on gene flow, since the ecology of vectors and hosts are likely different and potentially conflicting. Here, we provide a summary of the latest innovations in the field of landscape genetics with a focus on those that could help increase the power to detect landscape effects in vector-borne human disease studies. We also provide a recommended framework for studying vector-borne diseases using a landscape genetics approach. Landscape genetics has the potential to be a powerful tool for the field of vector-borne disease epidemiology but has so far been underutilized. The provided synthesis of tools and considerations for conducting a landscape genetics study of a vector-borne disease aim to bridge the gap between the two disciplines.
In kidney, FXYD proteins regulate Na,K-ATPase in a nephron segment-specific way. FXYD2 is the most abundant renal FXYD but is not expressed in most renal cell lines unless induced by hypertonicity. Expression by transfection of FXYD2a or FXYD2b splice variants in NRK-52E cells reduces the apparent Na ؉ affinity of the Na,K-ATPase and slows the cell proliferation rate. Based on RT-PCR, mRNAs for both splice variants were expressed in wild type NRK-52E cells as low abundance species. DNA sequencing of the PCR products revealed a base alteration from C to T in FXYD2b but not FXYD2a from both untreated and hypertonicity-treated NRK-52E cells. The 172C3 T sequence change exposed a cryptic KKXX endoplasmic reticulum retrieval signal via a premature stop codon. The truncation affected trafficking of FXYD2b and its association with Na,KATPase and blocked its effect on enzyme kinetics and cell growth. The data may be explained by altered splicing or selective RNA editing of FXYD2b, a supplementary process that would ensure that it was inactive even if transcribed and translated, in these cells that normally express only FXYD2a. 172C3 T mutation was also identified after mutagenesis of FXYD2b by error-prone PCR coupled with a selection for cell proliferation. Furthermore, the error-prone PCR alone introduced the mutation with high frequency, implying a structural peculiarity. The data confirm truncation of FXYD2b as a potential mechanism to regulate the amount of FXYD2 at the cell surface to control activity of Na,K-ATPase and cell growth. Na,K-ATPase is an enzyme in eukaryotic cells that provides non-equilibrium distribution of Na ϩ and K ϩ ions across the plasma membrane. Besides its obligatory ␣ and  subunits, the complex contains a so-called "FXYD" subunit (1), a short single span membrane protein involved in regulation of the kinetic properties of Na,K-ATPase. In mammals, there are seven different FXYD genes that are expressed in a tissue-and cell-specific manner. Remarkably, association of the Na,K-ATPase with each of them leads to specific changes in kinetic parameters of the pump either at the level of K 0.5 for the substrates or V max (for a review, see Ref.2).FXYD2, also called the ␥ subunit, was the first accessory FXYD protein discovered in connection with the Na,K-ATPase (3). It was identified as a proteolipid in membranes from dog kidney that was labeled with a photoaffinity derivative of the specific inhibitor of the pump, ouabain, along with the ␣ and  subunits (4). Expression of the FXYD2 protein is mostly in kidney (5), although the expressed sequence tag database suggests some other tissues as potential sources for FXYD2 (for instance, pancreas and mammary glands). There are two splice variants of FXYD2, FXYD2a and FXYD2b, which are identical in structure except for the N-terminal segment comprising the first exon (6, 7). Based on results from different heterologous expression systems (Xenopus oocytes or mammalian cell transfectants), FXYD2 reduces the activity of the pump by increasing the K 0.5 for ...
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