👤 J E Pryce

Dairy cattle, particularly in Australia where dairy farming is predominantly pasture based, are experiencing an increased incidence of heat stress through rising global temperatures, causing a detrimental impact on productivity and welfare. Improving the thermotolerance of dairy cows through genetic selection is a potential proactive solution for mitigating the impact of heat stress for the dairy industry. Although heat tolerance breeding values for milk yield traits have been available to Australian dairy producers since 2017, considerable potential remains to develop genetic evaluation for heat tolerance of fertility and understanding of the underlying genetic architecture for heat tolerance. The objective of this study was to investigate the effect of heat stress measured as temperature and humidity index (THI) on fertility traits and to identify genomic regions associated with heat tolerance in 2 specific fertility traits: first service non-return rate (FNRR) and successful calving rate to first service (SCRFS). In this study, we assembled more than 892k phenotypic records of Holstein cows with THI and fertility traits and identified specific periods with respect to service day. The effect of heat stress on fertility was assessed using random regression (RR) sire model for estimating the change in genetic variance of fertility across various THI and obtaining heat tolerance solution (slope) for sires. Also, whole genome sequence genome-wide association studies (GWAS) were undertaken based on heat tolerance phenotypes of 5k Holstein bulls with at least 10 daughters with fertility data. The assessment of the different THI definitions based on different numbers of days before and after artificial service days on the fertility traits showed that the most prominent effect of THI on fertility outcomes was observed for THI 7 d preceding service (including the service day) and 6 d after service day. Heat tolerance (HT) traits with respect to FNRR and SCRFS are lowly heritable and ranged from 0.01 to 0.04 under moderate THI conditions ranging between 60 and 70. However, as the THI exceeded 70, the heritability increased to up to 0.08, indicating increased genetic variance as THI increased. Genetic correlations between extreme THI ranges were as low as 0.13, while correlations between consecutive THI ranges reached up to 0.98. This finding suggests the presence of genotype by environment interactions due to heat stress. Notable variation in heat stress sensitivity among sires was also observed for HT fertility. In total, 553 sequence variants were significantly associated HT fertility, and 52 of them were identified as independent QTL. Some of QTL regions were located near or within the genes that are involved in oxidative stress, inflammation, and fertility (e.g., TRPC5, CDK5RAP2, MGAT1, COMMD10, PRR7, GRK6, CUGBP1, MAFG, HERC2, NAPRT, HSD17B12, THRB, and EEF1D). The findings in this study will further aid in understanding genetic architecture and provide valuable information for improving the accuracy of genomic prediction of heat tolerance in dairy cattle. Show less

Decreased cerebrospinal fluid (CSF) levels of synaptic proteins, possibly reflecting impaired synaptic function, have been observed in major depressive disorder (MDD). To investigate the diagnostic utility of the soluble N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) complex protein, synaptosomal-associated protein of 25 kDa (SNAP-25), for MDD. Overall, 208 participants with one of MDD, schizophrenia (SCZ) or bipolar disorder (BD), and healthy controls (HCs) were retrospectively enrolled. CSF levels of SNAP-25 were assessed relative to MDD characteristics and the diagnostic potential was analysed. In subgroups of patients, CSF levels of presynaptic neurexin 3 (NRXN3), postsynaptic neurogranin (NRGN) and Alzheimer's disease biomarkers were measured for comparison. SNAP-25 levels, but not the levels of the other synaptic markers, were significantly decreased in MDD compared with HCs, allowing for discrimination with 68% sensitivity and 67% specificity. SNAP-25 was not associated with MDD severity or antidepressant medication. Compared with HCs, SCZ also displayed decreased SNAP-25 enabling discrimination with 64% sensitivity and 77% specificity. There were strong correlations between levels of synaptic proteins and established Alzheimer pathology markers, with subtle differences in the association pattern between disorders. Our data suggest that SNAP-25, NRXN3 and NRGN versus beta-amyloid and phosphorylated tau protein 181 (ptau) are regulated differentially across psychiatric disorders and that SNAP-25 has a moderate diagnostic potential for MDD and SCZ. We propose that CSF SNAP-25 level might represent an integrated readout of reduced synaptic function, rather than of synaptic degeneration, in MDD. Further studies are needed to analyse whether this potential can be increased by using multimarker measurements and whether it will be possible to subtype psychiatric disorders according to synaptic involvement in pathophysiology. SNAP-25 and other synaptic proteins in CSF might aid diagnosis and subtyping of MDD and SCZ. The current development of sensitive methods to also determine synaptic proteins in blood samples from patients will advance the validation of the biomarker potential and contribute to understanding of synaptic involvement in the pathophysiology of MDD and SCZ. Show less