RESUMO
An association analysis using the Illumina porcine SNP60 beadchip was performed to identify SNPs significantly associated with porcine maternal infanticide. We previously hypothesised that this was a good animal model for human puerperal psychosis, an extreme form of postnatal mood disorder. Animals were selected from carefully phenotyped unrelated infanticide and control groups (representing extremes of the phenotypic spectrum), from four different lines. Permutation and sliding window analyses and an analysis to see which haplotypes were in linkage disequilibrium (LD) were compared to identify concordant regions. Across all analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes associated with psychiatric or neurological disorders and were significant in multiple lines. The strongest (near GWS) consistent candidate region across all analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb, syntenic to a candidate region for bipolar disorder and another at 31.9 Mb, syntenic to a candidate region for human puerperal psychosis (16p13). From the haplotype/LD analysis, two regions reached genome wide significance (GWS): the first on SSC4 (KHDRBS3 to FAM135B), which was significant (-logP 5.57) in one Duroc based breed and is syntenic to a region in humans associated with cognition and neurotism; the second on SSC15, which was significant (-log10P 5.68) in two breeds and contained PAX3, which is expressed in the brain.
Assuntos
Comportamento Animal , Modelos Animais de Doenças , Comportamento Materno , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Transtornos Puerperais/genética , Animais , Transtorno Bipolar/genética , Mapeamento Cromossômico , Proteínas de Ligação a DNA/genética , Depressão Pós-Parto/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Recém-Nascido , Desequilíbrio de Ligação , Locos de Características Quantitativas/genética , Proteínas de Ligação a RNA/genética , SuínosRESUMO
BACKGROUND: Urotensin II (UII) and its receptor UT are involved in control of the cardiovascular system and are implicated in heart failure. We measured UT expression by quantitative PCR (Q-PCR) in atrial and aortic tissue, and plasma UII while simultaneously assessing cardiac function in 40 patients undergoing coronary artery bypass surgery. METHODS: RNA extracted from atrial and aortic samples was probed with specific Q-PCR UT and housekeeper (glyceraldehyde-3-phosphate dehydrogenase, GAPDH) TaqMan primers. Plasma UII was measured using radioimmunoassay. Left ventricular ejection fraction (LVEF) was measured using preoperative trans-thoracic echocardiography and ventriculography, and intraoperatively using transoesophageal echocardiography. Q-PCR data are expressed as difference in cycle threshold (DeltaC(t)=C(tUT)-C(tGAPDH): high number indicates low expression). RESULTS: There was no difference in DeltaC(t) in either atrium or aorta between patients with normal (LVEF >50%) or those with impaired (LVEF <50%) preoperative systolic function. There was a weak negative correlation (r(2)=0.245, P=0.031) between intraoperative LVEF and DeltaC(t) in 19 patients possibly indicating down-regulation of UT with worsening LVEF. Atria expressed significantly more UT than aorta (P=0.011). In the absence of non-diseased controls, plasma UII was higher than a historical control group. CONCLUSIONS: This is the first study to simultaneously measure UT (mRNA), UII, and cardiovascular function. Collectively, these pilot data may suggest a down-regulation of UT within the right atrium of patients with heart failure.