👤 Ferran Casals

A stroke's functional outcome presents vast variability among patients, which is influenced by age, sex, characteristics of the lesion, and genetic factors. However, there is little knowledge about stroke recovery genetics. Recently, some GWAS (Genome-Wide Association Studies) have highlighted the involvement of common or low-frequency variants near or within We performed a pilot study analyzing 90 exomes of extreme good and bad recovery (modified Rankin Scale score at 3 months, 0-1 versus 4-5) to select target genes involved in stroke recovery. To expand this study, 702 additional samples were sequenced by targeted next-generation sequencing capturing loci selected from the pilot study, GWASs, and literature input. Here, we performed continuous (modified Rankin Scale score, 0-6) and dichotomous (modified Rankin Scale score, 0-1 versus 3-6) analyses, yielding 1 candidate gene. All samples were selected by a retrospective cohort study from incidental stroke cases collected at Spanish Hospitals between 2000 and 2018. The identified VNN2 variants were assessed for protein structure and stability analysis, and an analysis of their effect on basal inflammation levels was performed using UK Biobank data. Our work identified rare coding variants in We propose that Show less

Cardiovascular disease (CVD) is the main cause of mortality among long-term renal transplant recipients (RTR). On the other hand, allograft chronic nephropathy is the primary cause of graft loss among long-term RTR. Hyperlipidemia is a predisposing factor for both conditions. Polymorphisms of the apolipoproteins modulate lipid metabolism. The aim of the study was to evaluate the effect of apo A-I, apo A-IV and apo C-III genotypes on the long-term results of renal transplantation. Clinical assessment (renal allograft and patient survival) and genotyping for apo A-I (+83C/T), apo C-III (Sst I), and apo A-IV (Thr347Ser and Gln360His) polymorphisms were evaluated in 516 kidney transplant patients and correlated with the clinical evolution over 12 months. The distribution of the apo A-I (+83C/T) polymorphisms was: CC 91.9%, CT 7.9%, and TT 0.2%. The apo C-III genotype showed: S1S1 84.4%, S1S2 15.2%, and S2S2 0.4%. The apo A-IV (Pvu II) polymorphism was: GG 82%, GT 18%, and 0% TT. Finally, the frequency of apo A-IV (Hinf I) polymorphism was: AA 69%, AT 27%, and TT 4%. The frequency of polymorphisms was similar between men and women. In conclusion, there was no significant influence of apolipoprotein polymorphisms on renal and patient survival. Show less

Inactivation of HAL3 in the absence of SIT4 function leads to cell cycle arrest at the G(1)-S transition. To identify genes potentially involved in the control of this phase of the cell cycle, a screening for multicopy suppressors of a conditional sit4 hal3 mutant (strain JC002) has been developed. The screening yielded several genes known to perform key roles in cell cycle events, such as CLN3, BCK2 or SWI4, thus proving its usefulness as a tool for this type of studies. In addition, this approach allowed the identification of additional genes, most of them not previously related to the regulation of G(1)-S transition or even without known function (named here as VHS1-3, for viable in a hal3 sit4 background). Several of these gene products are involved in phospho-dephosphorylation processes, including members of the protein phosphatase 2A and protein phosphatases 2C families, as well as components of the Hal5 protein kinase family. The ability of different genes to suppress sit4 phenotypes (such as temperature sensitivity and growth on non-fermentable carbon sources) or to mimic the functions of Hal3 was evaluated. The possible relationship between the known functions of these suppressor genes and the progress through the G(1)-S transition is discussed. Show less