Silent Phase of Johne’s Disease in Experimentally Infected Goats – A Study on New and Established Diagnostic Approaches Using Specific and Non-Specific Parameters

The current gold standard diagnostic test for Johne’s disease (JD) is detecting Mycobacterium avium subsp. paratuberculosis (MAP) from fecal samples via culture and/or PCR. Other commercially available JD diagnostic tests focus on the detection of specific antibodies within the serum or milk of infected ruminants. These tests have a high specificity but low their sensitivity and usually fail to diagnose the disease until later stages of the disease. The ideal diagnostic test should detect infected animals already during the silent phase. Here, we evaluate the use of new and established approaches to define the silent phase of JD in experimentally infected goats. None of the established diagnostic tests or new approaches for the detection of humoral and cellular immune responses were positive during the first year of infection. Only the characterization of various subsets of peripheral blood leukocytes and the weight development gave some indication for the presence of a chronic, but silent, infection. Weight differences were present throughout the first year. In addition, some of the subsets of leukocytes (WC1+ T cells, MHC class II+ leukocytes, CD1+ leukocytes, CD14+ granulocytes, and CD14+/MHC class II+ granulocytes) demonstrated significant differences, but only at certain time points

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe

Early weight development of goats experimentally infected with Mycobacterium avium subsp. paratuberculosis.

Johne's disease is an infectious chronic inflammatory bowel disease in ruminants. The key factor for the management of this disease is an early positive diagnosis. Unfortunately, most diagnostics detect animals with Johne's disease in the clinical stage with positive serology and/or positive fecal cultures. However, for effective management of the disease within herds, it is important to detect infected animals as early as possible. This might only be possible with the help of parameters not specific for Johne's disease but that give an early indication for chronic infections such as weight development. Here we report our findings on the development of total body weight and weight gain during the first six months of goats experimentally infected to induce Johne's disease. Twenty dairy goat kids age 2 to 5 days were included in this study. Goats were divided into two groups: a negative control group and a positive infected group. The weight was obtained weekly throughout the study. Goats of the positive group were infected at the age of seven weeks. We detected significant changes in weight gain and total body weight as early as one week after infection. Differences are significant throughout the six month time period. Weight as a non-specific parameter should be used to monitor infection especially in studies on Johne's disease using the goat model. Our study suggests that goats with Johne's disease have a reduced weight gain and reduced weight when compared with healthy goats of the same age

Comparison of average weight gain for four-week intervals of infected goats (red columns) versus uninfected goats (blue columns).

<p>There are one interval prior infection, one interval around infection, and six intervals after infection. Above each column pair is the p-value corresponding to the comparison. The infection occurred during the second time interval. Error bars represent the standard error for each time point.</p

Range of weight development of infected goats.

<p>Average weight development of infected goats together with the highest and lowest weight per measuring point. The arrow marks the time point of infection. Week numbers reflect the time compared to the time point of infection with negative numbers representing weeks prior to infection and positive numbers representing weeks after infection.</p

Range of weight development of uninfected goats.

<p>Average weight development of uninfected goats together with the highest and lowest weight per measuring point. The arrow marks the time point of infection. Week numbers reflect the time compared to the time point of infection with negative numbers representing weeks prior to infection and positive numbers representing weeks after infection.</p

Average weight development of infected and uninfected goats.

<p>Development of the average total body weight of goats experimentally infected with <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (red squares/lines) in comparison with the average total body weight development of uninfected goats (blue squares/lines). The arrow marks the time point of infection. Week numbers reflect the time compared to the time point of infection with negative numbers representing weeks prior to infection and positive numbers representing weeks after infection.</p

Comparison of the average of total body weight of infected goats (red columns) and uninfected goats (blue columns) of selected weeks.

<p>Above each column pair is the p-value corresponding to the comparison. The time point of infection is marked with an arrow. Error bars represent the standard error for each time point.</p