Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study

Introduction  

Improvement of rheumatoid arthritis (RA) during pregnancy has been causatively associated with increased galactosylation of immunoglobulin G (IgG) N-glycans. Since previous studies were small, did not include the postpartum flare and did not study sialylation, these issues were addressed in the present study.     

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.     

Binding of zinc ions to heparin. Analysis by equilibrium dialysis suggests the occurrence of two, entropy-driven, processes.

Analysis by equilibrium dialysis of the binding of Zn2+ to heparin suggested that two interactions, one of high affinity and one of low affinity, occur. The stoichiometry of binding in both cases is about one Zn2+ ion bound per average heparin disaccharide unit. Both types of interaction appear to be entropy-driven.     

Using the realized relationship matrix to disentangle confounding factors for the estimation of genetic variance components of complex traits

Background

In the analysis of complex traits, genetic effects can be confounded with non-genetic effects, especially when using full-sib families. Dominance and epistatic effects are typically confounded with additive genetic and non-genetic effects. This confounding may cause the estimated genetic variance components to be inaccurate and biased.

Methods

In this study, we constructed genetic covariance structures from whole-genome marker data, and thus used realized relationship matrices to estimate variance components in a heterogenous population of ~ 2200 mice for which four complex traits were investigated. These mice were genotyped for more than 10,000 single nucleotide polymorphisms (SNP) and the variances due to family, cage and genetic effects were estimated by models based on pedigree information only, aggregate SNP information, and model selection for specific SNP effects.

Results and conclusions

We show that the use of genome-wide SNP information can disentangle confounding factors to estimate genetic variances by separating genetic and non-genetic effects. The estimated variance components using realized relationship were more accurate and less biased, compared to those based on pedigree information only. Models that allow the selection of individual SNP in addition to fitting a relationship matrix are more efficient for traits with a significant dominance variance.     

Clinical features and predictors for disease natural progression in adults with Pompe disease: a nationwide prospective observational study

Background

Due partly to physicians’ unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.

Methods

We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3–6 months and analyzed using repeated-measures ANOVA.

Results

Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of ?1.3% point/year for manual muscle testing and of ?2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.

Conclusions

Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.

     

Environmental and seasonal influences on red raspberry flavour volatiles and identification of quantitative trait loci (QTL) and candidate genes

Raspberry volatiles are important for perceptions of sensory quality, mould resistance and some have nutraceutical activities. Twelve raspberry character volatiles were quantified, 11 of them in fruit from two seasons, from plants from the Glen Moy × Latham mapping population growing in both open field and under cover (polytunnels). Effects of season and environment were examined for their impact on the content of α-ionone, α-ionol, β-ionone, β-damascenone, linalool, geraniol, benzyl alcohol, (Z)-3-hexenol, acetoin, acetic and hexanoic acids, whilst raspberry ketone was measured in one season. A significant variation was observed in fruit volatiles in all progeny between seasons and method of cultivation. Quantitative trait loci were determined and mapped to six of the seven linkage groups, as were candidate genes in the volatiles pathways.     

Larval development of Diploptera punctata reared alone and in groups

Larvae of the cockroach Diploptera punctata were reared in isolation, in pairs, or in groups of 8–10. Duration of larval development, age at each ecdysis, weights at birth and ecdyses, and adult head-capsule width were measured. Duration of larval development was longer and adult size was larger in isolated animals than in animals reared in pairs and groups. The effect of isolation on development was more pronounced in males. All females had 4 larval instars, whereas males had 3 or 4 instars. The proportion of males with 4 larval instars was higher among animals reared in isolation. There was no difference in the duration of larval development or adult size between pair- and group-reared animals. The sex of animals in the group did not affect adult size or the duration of larval development. Males which underwent 3 or 4 larval instars had different schedules of moulting. Rates of growth of males of both instar types reared in isolation and pairs were similar. Greater adult weight of isolated animals and 4-instar-type males was a result of their longer duration of larval development. Both a higher rate of growth and longer duration of larval development contribute to the larger adult size of females than males.