Positive Selection and Adaptive Introgression of Haplotypes from<i> Bos indicus</i> Improve the Modern <i>Bos taurus</i> Cattle

Complex evolutionary processes, such as positive selection and introgression can be characterized by in-depth assessment of sequence variation on a whole-genome scale. Here, we demonstrate the combined effects of positive selection and adaptive introgression on genomes, resulting in observed hotspots of runs of homozygosity (ROH) haplotypes on the modern bovine (Bos taurus) genome. We first confirm that these observed ROH hotspot haplotypes are results of positive selection. The haplotypes under selection, including genes of biological interest, such as PLAG1, KIT, CYP19A1 and TSHB, were known to be associated with productive traits in modern Bos taurus cattle breeds. Among the haplotypes under selection, we demonstrate that the CYP19A1 haplotype under selection was associated with milk yield, a trait under strong recent selection, demonstrating a likely cause of the selective sweep. We further deduce that selection on haplotypes containing KIT variants affecting coat color occurred approximately 250 generations ago. The study on the genealogies and phylogenies of these haplotypes identifies that the introgression events of the RERE and REG3G haplotypes happened from Bos indicus to Bos taurus. With the aid of sequencing data and evolutionary analyses, we here report introgression events in the formation of the current bovine genome

Enteric methane emission of dairy cows supplemented with iodoform in a dose–response study

Abstract Enteric methane (CH4) emission is one of the major greenhouse gasses originating from cattle. Iodoform has in studies been found to be a potent mitigator of rumen CH4 formation in vitro. This study aimed to quantify potential of iodoform as an anti-methanogenic feed additive for dairy cows and investigate effects on feed intake, milk production, feed digestibility, rumen microbiome, and animal health indicators. The experiment was conducted as a 4 × 4 Latin square design using four lactating rumen, duodenal, and ileal cannulated Danish Holstein dairy cows. The treatments consisted of four different doses of iodoform (1) 0 mg/day, (2) 320 mg/day, (3) 640 mg/day, and (4) 800 mg/day. Iodoform was supplemented intra-ruminally twice daily. Each period consisted of 7-days of adaptation, 3-days of digesta and blood sampling, and 4-days of gas exchange measurements using respiration chambers. Milk yield and dry matter intake (DMI) were recorded daily. Rumen samples were collected for microbial analyses and investigated for fermentation parameters. Blood was sampled and analyzed for metabolic and health status indicators. Dry matter intake and milk production decreased linearly by maximum of 48% and 33%, respectively, with increasing dose. Methane yield (g CH4/kg DMI) decreased by maximum of 66%, while up to 125-fold increases were observed in hydrogen yield (g H2/kg DMI) with increasing dose of iodoform. Total tract digestibility of DM, OM, CP, C, NDF, and starch were unaffected by treatments, but large shifts, except for NDF, were observed for ruminal to small intestinal digestion of the nutrients. Some indicators of disturbed rumen microbial activity and fermentation dynamics were observed with increasing dose, but total number of ruminal bacteria was unaffected by treatment. Serum and plasma biomarkers did not indicate negative effects of iodoform on cow health. In conclusion, iodoform was a potent mitigator of CH4 emission. However, DMI and milk production were negatively affected and associated with indications of depressed ruminal fermentation. Future studies might reveal if depression of milk yield and feed intake can be avoided if iodoform is continuously administered by mixing it into a total mixed ration

Molecular classification of tissue from a transformed non-Hogkin's lymphoma case with unexpected long-time remission

BACKGROUND: The concept of precision medicine in cancer includes individual molecular studies to predict clinical outcomes. In the present N = 1 case we retrospectively have analysed lymphoma tissue by exome sequencing and global gene expression in a patient with unexpected long-term remission following relaps. The goals were to phenotype the diagnostic and relapsed lymphoma tissue and evaluate its pattern. Furthermore, to identify mutations available for targeted therapy and expression of genes to predict specific drug effects by resistance gene signatures (REGS) for R-CHOP as described at http://www.hemaclass.org. We expected that such a study could generate therapeutic information and a frame for future individual evaluation of molecular resistance detected at clinical relapse. CASE PRESENTATION: The patient was diagnosed with a transformed high-grade non-Hodgkin lymphoma stage III and treated with conventional R-CHOP [rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O) and prednisone (P)]. Unfortunately, she suffered from severe toxicity but recovered during the following 6 months’ remission until biopsy-verified relapse. The patient refused second-line combination chemotherapy, but accepted 3 months’ palliation with R and chlorambucil. Unexpectedly, she obtained continuous complete remission and is at present >9 years after primary diagnosis. Molecular studies and data evaluation by principal component analysis, mutation screening and copy number variations of the primary and relapsed tumor, identified a pattern of branched lymphoma evolution, most likely diverging from an in situ follicular lymphoma. Accordingly, the primary diagnosed transformed lymphoma was classified as a diffuse large B cell lymphoma (DLBCL) of the GCB/centrocytic subtype by “cell of origin BAGS” assignment and R sensitive and C, H, O and P resistant by “drug specific REGS” assignment. The relapsed DLBCL was classified as NC/memory subtype and R, C, H sensitive but O and P resistant. CONCLUSIONS: Thorough analysis of the tumor DNA and RNA documented a branched evolution of the two clinical diagnosed tFL, most likely transformed from an unknown in situ lymphoma. Classification of the malignant tissue for drug-specific resistance did not explain the unexpected long-term remission and potential cure. However, it is tempting to consider the anti-CD20 immunotherapy as the curative intervention in the two independent tumors of this case. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40164-016-0063-0) contains supplementary material, which is available to authorized users