Comparing genomic prediction accuracy from purebred,crossbred and combined purebred and crossbred reference populations in sheep

Background

The accuracy of genomic prediction depends largely on the number of animals with phenotypes and genotypes. In some industries, such as sheep and beef cattle, data are often available from a mixture of breeds, multiple strains within a breed or from crossbred animals. The objective of this study was to compare the accuracy of genomic prediction for several economically important traits in sheep when using data from purebreds, crossbreds or a combination of those in a reference population.

Methods

The reference populations were purebred Merinos, crossbreds of Border Leicester (BL), Poll Dorset (PD) or White Suffolk (WS) with Merinos and combinations of purebred and crossbred animals. Genomic breeding values (GBV) were calculated based on genomic best linear unbiased prediction (GBLUP), using a genomic relationship matrix calculated based on 48 599 Ovine SNP (single nucleotide polymorphisms) genotypes. The accuracy of GBV was assessed in a group of purebred industry sires based on the correlation coefficient between GBV and accurate estimated breeding values based on progeny records.

Results

The accuracy of GBV for Merino sires increased with a larger purebred Merino reference population, but decreased when a large purebred Merino reference population was augmented with records from crossbred animals. The GBV accuracy for BL, PD and WS breeds based on crossbred data was the same or tended to decrease when more purebred Merinos were added to the crossbred reference population. The prediction accuracy for a particular breed was close to zero when the reference population did not contain any haplotypes of the target breed, except for some low accuracies that were obtained when predicting PD from WS and vice versa.

Conclusions

This study demonstrates that crossbred animals can be used for genomic prediction of purebred animals using 50 k SNP marker density and GBLUP, but crossbred data provided lower accuracy than purebred data. Including data from distant breeds in a reference population had a neutral to slightly negative effect on the accuracy of genomic prediction. Accounting for differences in marker allele frequencies between breeds had only a small effect on the accuracy of genomic prediction from crossbred or combined crossbred and purebred reference populations.     

Toward functional glycomics by localization of tissue lectins: immunohistochemical galectin fingerprinting during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster

The current study focused on galectins (-1, -3, -4, -7, and –8) and deliberately performed immunohistochemical fingerprinting to explore their complexity in a context of experimental renal carcinogenesis. The diethylstilbestrol (DES)-induced renal tumors in male Syrian hamster kidney (SHKT) represent a unique animal model for the study of estrogen-dependent renal malignancies. Kidney sections of DES-treated hamsters (3 days to 11 months of DES exposure) were analyzed by immunohistochemistry using a panel of non-crossreactive antibodies raised against galectins-1, -3, -4, -7, and -8. Levels of expression were quantitatively determined by using computer-assisted microscopy on immunostained tissue sections. Except for galectin-4, all above mentioned galectins were expressed in kidney tumors. Small clusters of galectin-1-positive, most likely preneoplastic cells at the corticomedullary junction were already evident 1 week after DES administration. Galectin-1 and -3 expression was apparently associated with the first steps of the neoplastic transformation, because small tumorous buds were found to be positive after 1 month of treatment. In contrast, galectins-7 and -8 were detected in large tumors and medium-sized tumors, respectively, thereby indicating an involvement in later stages of DES-induced SHKT. Galectins-1, -3, -7, and -8 were also detected by immunofluorescence staining in the HKT-1097 cell line established from SHKT, thus illustrating the stability of galectin expression in tumor cells. Our data document the presence and differential regulation of galectins in the course of renal tumorigenesis in the model of DES-induced SHKT.     

Sertoli cell expression of galectin-1 and -3 and accessible binding sites in normal human testis and Sertoli cell only-syndrome.

Galectins are vertebrate lectins interacting with beta-galactosides and derivates thereof such as blood group A, B and H determinants. The expression of gelectin-1 and -3 and galectin-specific binding sites by human Sertoli cells was analyzed in normal human testis and Sertoli cell only-syndrome (SCOS). Staining intensity was scored semiquantitatively on a 4-grade scale. Sertoli cells in normal testes displayed a moderate cytoplasmic and weak nuclear staining for galectin-1-specific binding sites. Galectin-3-specific binding sites were expressed in Sertoli cells less intensely than accessible ligands for galectin-1 (mean score 2.25 for galectin-1 and 1.50 for galectin-3). Germ cells were only weakly reactive. Tubular walls were negative for both classes of galectin-specific binding sites. In SCOS, galectin-1 binding was moderate to strong and more pronounced than galectin-3 binding by Sertoli cells (mean scores 4.00 and 2.25). Tubular walls were negative for galectin-staining. The ratio for galectin-1-/galectin-3-specific binding (staining score ratio) was 1.50 form normal testis and 1.78 for SCOS disclosing a relative increase of galectin-3 binding sites in the latter. Staining with galectin-1- and -3-specific antisera showed a strong cytoplasmic galectin-1 immunoreactivity in Sertoli cells of normal and SCOS testis (score 4.00 for both). Anti-galectin-3 did not stain Sertoli cells or germ cells in normal testis. Only Leydig cells were labeled (score 3.00). In SCOS a weak to moderate nuclear staining of Sertoli cells was noted (score 2.00). Galectin-3 expression and galectin-1-specific binding sites were found to be increased in Sertoli cells of SCOS. This modulation of reactivity can have implications for Sertoli cell interactions with galectin-reactive extracellular matrix components like laminin and for anti-apoptotic effects.     

Binding of T-antigen-bearing neoglycoprotein and peanut agglutinin to cultured tumor cells and breast carcinomas

Chemical conjugation of appropriate carbohydrate ligands to an inert labeled carrier renders probes available to screen for the presence of respective binding sites. A set with a certain plant lectin and a suitable neoglycoprotein can thus determine complementary parts of a potentially relevant glycobiological interaction system. Owing to the interest in the peanut agglutinin-reactive T-antigen, we performed chemical synthesis of the respective disaccharide structure to serve as glycohistochemical ligand and established refinements of the synthetic patway. Coupling of the derivatized monomers had to be performed in the presence of sodium sulfate for optimal results. Complete removal of the protective groups from the p-nitrophenyl derivative of the N-acetylgalactosamine moiety was achieved under mild conditions with 2,3-dichloro-5,6-dicyanobenzoquinone without affecting any other functional groups. Specific binding sites for the synthetic neoglycoprotein as well as for the plant lectin were demonstrated in cell lines of human breast carcinoma colon adenocarcinoma, and erythroleukemia. ABC reagents in conjunction with DAB as peroxidase substrate were used to visualize specific binding sites. Binding complied with the accepted criteria for specificity. Moreover, carbohydrate-specific binding sites were detected in sections of nine out of 14 cases with malignant breast lesions. The percentage of positive tumor cells with both neoglycoprotein and lectin was similar in each of the individual sections, regardless of quantitative variations between cases, lectin staining intensity often being more pronounced. The reactivity pattern in sections of primary and metastatic lesions was not significantly correlated with the lymph node status. This study emphasized that custom synthesis of saccharides and histochemical application of the resulting neoglycoprotein has a remarkable potential for complementary assessment of endogenous binding sites for carbohydrate structures, localized by external tools such as plant lectins, as a step to elucidate the importance of a putative proteincarbohydrate interaction.     

Comparative Histochemical and Biochemical Analysis of Endogenous Receptors for Glycoproteins in Human and Pig Peripheral Nerve

Endogenous sugar-binding proteins were localized in sections of human and pig peripheral nerves by the application of two types of labelled ligands: neoglycoproteins (chemically glycosylated carrier proteins that had proven to be histochemically inert) and desialylated, naturally occurring glycoproteins. These proteins allowed evaluation of the presence and distribution of endogenous receptors for carbohydrates, commonly present in cellular glycoconjugates. (Neo)glycoprotein binding was similar, but not identical, for the two types of mammalian peripheral nerves. The pig nerve differed from the human nerve in more pronounced staining when using different types of beta-galactoside-terminated (neo)glycoproteins and charge-carrying neoglycoproteins, such as bovine serum albumin, bearing galactose-6-phosphate residues, glucuronic acid residues, and sialic acid residues. Comparative biochemical analysis of certain classes of sugar receptors by affinity chromatography and gel electrophoresis revealed the presence of sugar receptors that can contribute to the histochemical staining in a pattern with certain significant differences among rather similar expression for the two species. The assessment of sugar receptor distribution by application of (neo)glycoprotein binding among morphologically defined regions in nerves may hold promise in detecting developmental regulation and changes during nerve degeneration and subsequent regeneration after trauma or pathological states. Correlation of these results to changes in the structure and abundance of glycoconjugates, which are the potential physiological ligands of endogenous sugar receptors commonly detected by plant lectins, may help to infer functional relationships.     

The small-subunit ribosomal RNA gene sequences from the hypotrichous ciliates Oxytricha nova and Stylonychia pustulata

We have determined the complete nucleotide sequence of the small- subunit ribosomal RNA genes for the ciliate protozoans Stylonychia pustulata and Oxytricha nova. The sequences are homologous and sufficiently similar that these organisms must be closely related. In a phylogeny inferred from comparisons of several eukaryotic small-subunit ribosomal RNAs, the divergence of the ciliates from the eukaryotic line of descent is seen to coincide with the radiation of the plants, the animals, and the fungi. This radiation is preceded by the divergence of the slime mold, Dictyostelium discoideum.      

Generation of H2O2 by Human Neutrophils and Changes of Cytosolic Ca2+ and pH of Rat Thymocytes in Response to Galactoside-Binding Proteins (Lectins or Immunoglobulins)

In contrast to plant agglutinins, biological activities of animal/human lectins are not well defined yet. Testing a panel of seven mammalian carbohydrate-binding proteins we have found that the dimeric lectin from chicken liver (CL-16) was a stimulator of H₂O₂ release from human neutrophils as well as effector for induction of cytosolic Ca²⁺ and pH increase in rat thymocytes. Activity of this lectin was comparable to potent galactoside-specific plant lectins such as Viscum album L. agglutinin. The activities of the tested plant lectins depended significantly on their nominal carbohydrate specificity as well as on the source. The results indicate that endogenous lectins may be involved in the regulation of neutrophil and lymphocyte functions by elicitation of selective biosignaling reactions.