The role of cytoreductive radical prostatectomy and lymph node dissection in bone-metastatic prostate cancer: A population-based study.

BACKGROUNDS: The role of cytoreductive radical prostatectomy (cRP) for bone-metastatic prostate cancer (bmPCa) remains controversial. We aimed to figure out whether cRP and lymph node dissection (LND) can benefit bmPCa. METHODS: 11,271 PCa patients with bone metastatic burden from 2010 to 2019 were identified using SEER-Medicare. Overall survival (OS) and cancer-specific survival (CSS) rates were visualized using Kaplan-Meier plots. Multivariable Cox regression analyses were constructed to examine the effects of cRP and LND on survival, after stratifying to age, prostate specific antigen (PSA), clinical stages, Gleason score, metastatic burden, radiotherapy, and chemotherapy status. RESULTS: 317 PCa patients underwent cRP and cRP was increasingly performed for bmPCa from 2010 (2.2%) to 2019 (3.0%) (p < 0.05). In multi analyses, cRP was predisposed to a better OS or CSS in patients with age < 75, PSA < 98 ng/mL, bone-only metastatic sites or patients not receiving chemotherapy (all p < 0.05). For the patients undergoing cRP, LND especially extended LND was associated with a better OS or CSS (all p < 0.05). CONCLUSIONS: cRP might benefit OS or CSS in young patients with low PSA and bone-only metastatic sites not receiving chemotherapy. And a clear OS or CSS benefit of LND especially extended LND was observed in patients undergoing cRP.

Prediction of major adverse cardiovascular events in patients with acute coronary syndrome: Development and validation of a non-invasive nomogram model based on autonomic nervous system assessment.

Background: Disruption of the autonomic nervous system (ANS) can lead to acute coronary syndrome (ACS). We developed a nomogram model using heart rate variability (HRV) and other data to predict major adverse cardiovascular events (MACEs) following emergency coronary angiography in patients with ACS. Methods: ACS patients admitted from January 2018 to June 2020 were examined. Holter monitors were used to collect HRV data for 24 h. Coronary angiograms, clinical data, and MACEs were recorded. A nomogram was developed using the results of Cox regression analysis. Results: There were 439 patients in a development cohort and 241 in a validation cohort, and the mean follow-up time was 22.80 months. The nomogram considered low-frequency/high-frequency ratio, age, diabetes, previous myocardial infarction, and current smoking. The area-under-the-curve (AUC) values for 1-year MACE-free survival were 0.790 (95% CI: 0.702-0.877) in the development cohort and 0.894 (95% CI: 0.820-0.967) in the external validation cohort. The AUCs for 2-year MACE-free survival were 0.802 (95% CI: 0.739-0.866) in the development cohort and 0.798 (95% CI: 0.693-0.902) in the external validation cohort. Development and validation were adequately calibrated and their predictions correlated with the observed outcome. Decision curve analysis (DCA) showed the model had good discriminative ability in predicting MACEs. Conclusion: Our validated nomogram was based on non-invasive ANS assessment and traditional risk factors, and indicated reliable prediction of MACEs in patients with ACS. This approach has potential for use as a method for non-invasive monitoring of health that enables provision of individualized treatment strategies.

Hemodynamic Study of a Patient-Specific Intracranial Aneurysm: Comparative Assessment of Tomographic PIV, Stereoscopic PIV, In Vivo MRI and Computational Fluid Dynamics.

INTRODUCTION: Wall shear stress (WSS) is associated with the growth and rupture of an intracranial aneurysm. To reveal their underlying connections, many image-based computational fluid dynamics (CFD) studies have been conducted. However, the methodological validations using both in vivo medical imaging and in vitro optical flow measurements were rarely accompanied in such studies. METHODS: In the present study, we performed a comparative assessment on the hemodynamics of a patient-specific intracranial saccular aneurysm using in vivo 4D Flow MRI, in silico CFD, in vitro stereoscopic and tomographic particle imaging velocimetry (Stereo-PIV and Tomo-PIV) techniques. PIV experiments and CFD were conducted under steady state corresponding to the peak systole of 4D Flow MRI. RESULTS: The results showed that all modalities provided similar flow features and overall surface distribution of WSS. However, a large variation in the absolute WSS values was found. 4D Flow MRI estimated a 2- to 4-fold lower peak WSS (3.99 Pa) and a 1.6- to 2-fold lower mean WSS (0.94 Pa) than Tomo-PIV, Stereo-PIV, and CFD. Bland-Altman plots of WSS showed that the differences between PIV-/CFD-based WSS and 4D Flow MRI-based WSS increase with higher WSS magnitude. Such proportional trend was absent in the Bland-Altman comparison of velocity where the resolutions of PIV and CFD datasets were matched to 4D Flow MRI. We also found that because of superior resolution in the out-of-plane direction, WSS estimation by Tomo-PIV was higher than Stereo-PIV. CONCLUSIONS: Our results indicated that the differences in spatial resolution could be the main contributor to the discrepancies between each modality. The findings of this study suggest that with current techniques, care should be taken when using absolute WSS values to perform a quantitative risk analysis of aneurysm rupture.

[Distribution, Sources, and Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) in Tributary Waters of the Lower Reaches of the Yangtze River, China].

The lower reaches of the Yangtze River are a typical gathering place of chemical industrial parks in China. Polycyclic aromatic hydrocarbons (PAHs) emitted in the production process of chemical enterprises enter the tributary water body through atmospheric deposition and surface runoff, and finally merge into the Yangtze River. In this study, the distribution characteristics, source analysis, and ecological risk assessment of PAHs in a series of typical water samples collected in the tributary waters of the Yangtze River were studied. PAH monomers in the samples were mainly low-ring. The total concentration of PAHs was in the range of 37.27 to 285.88 ng·L-1 with a mean value of 78.31 ng·L-1, while the monomer concentration of PAHs ranged from 0 to 61.35 ng·L-1. The lowest detection rate was benzo[k] fluoranthene and benzo[a] pyrene at 75%. As a toxic PAH monomer, the concentration of benzo[a] pyrene ranged from 0 to 11.08 ng·L-1. According to "Water Quality Standards for Drinking Water Sources (CJ 3020-1993)" of China, the concentration of benzo[a] pyrene in a water sample (S12) located near Wuxi City exceeded the limit of drinking water standards (10 ng·L-1). Compared with the total concentration of PAHs in rivers in some typical regions of the world, the concentration of PAHs in this study was generally at low to moderate levels. According to the source analysis results of the ratio method and principal component analysis, the concentration of PAHs in water was mainly affected by fossil combustion, automobile exhaust, and chemical emissions. To assess the potential ecosystem risk of PAHs in the investigated area, the risk quotient (RQ) was used. In addition to the DBA monomer, the relative quantities (RQs) (replication) of the remaining monomers were greater than 1, and the RQ (MPCs) values in all the monomers were less than 1, indicating that the ecological risk of water samples was at a medium level. From the perspective of long-term environmental exposure, appropriate control measures should be considered to prevent further pollution. The results can provide reference for PAH risk assessment and pollution control of chemical industrial parks in the lower reaches of the Yangtze River.

IPDN-China promotes the development of pediatric dialysis in China.

BACKGROUND: In mainland China, dialysis for children with end-stage renal disease (ESRD) was not introduced until the 1980s. To describe the development of pediatric dialysis in different regions of China, a national pediatric dialysis network, namely, International Pediatric Dialysis Network-China (IPDN-China) ( www.pedpd.org.cn ), was launched in 2012. METHODS: Original and updated information from the renal centers registered with the IPDN-China was collected between 2012 and 2016 from two sources, namely, the registry and the survey, and demographic features were analyzed. RESULTS: Due to promotion by the IPDN-China, the number of registered renal centers increased from 12 to 39 between 2012 and 2016, with a significant increase in the coverage of the Chinese administrative divisions (from 26.5 to 67.6%) (p < 0.01); and the coverage of the pediatric (0~14 years old) population increased to nearly 90% in 2016. The distribution of renal centers indicated that East China had the highest average number of registered centers per million population (pmp) 0~14-year-old age group. Seventeen relatively large dialysis centers were distributed across 14 divisions. Various modalities of renal replacement therapy (RRT) were available in most centers. The IPDN-China has promoted collaborations between dieticians, psychologists, and social workers on dialysis teams to provide better service to children with ESRD and their families. The proportion of centers with all three types of paramedic support (i.e., dieticians, psychologists, and social workers) as well as the proportion of centers with a partial paramedic team significantly increased between 2012 (25.0%) and 2016 (69.2%) (p < 0.05). In terms of the point prevalent cases of patients (aged < 18 years), data from the survey of 39 registered centers revealed that the number of children with ESRD who were on RRT was 578 (49% received a kidney transplant) at the end of 2016, which was more than that reported in previous surveys. Data from the registry showed that 349 dialysis patients had been enrolled as of the end of 2016. The median age at RRT start was 9.5 years, and the leading cause of ESRD was congenital abnormalities of the kidney and urinary tract (CAKUT). CONCLUSIONS: The IPDN-China has helped to promote the development of pediatric dialysis for ESRD in China by improving the organization of care for dialysis patients and increasing the availability and the quality of RRT for patients who need it. To improve knowledge about the epidemiology and outcomes of pediatric RRT around the country, a sustained effort needs to be made by the IPDN-China to increase the enrollment of dialysis patients and increase the number of registered centers in the future.

Are Bus Company Regulations Associated with Crash Risk? Findings from a Retrospective Survey in Four Chinese Cities.

Bus crashes are common in urban China, and bus company regulations are hypothesized to be related to bus crash risk. We conducted a retrospective survey to examine the association in four large Chinese cities (Changsha, Shenzhen, Fuzhou, and Wuhan). Four types of bus crashes were considered: (a) passengers injured while riding the bus; (b) bus colliding with or scraping other motor vehicles; (c) bus colliding with non-motorized vehicles or pedestrians; and (d) bus damaging public facilities. Based on regulations governing the drivers' work, complete round trips per day, and their paid salary, three categories of companies were studied: type A: ≥14 h worked/day, ≥6 round trips/day, and >70% of salary based on performance; type B: 8-13 h/day, 4 or 5 round trips/day, and 36-70% of salary; and type C: <36% of salary and no other specified requirements. Of the 926 respondents, 20.7% reported one or more crashes or related risk events in the past month. Drivers from the three types of companies reported crash incidence rates of 31.9%, 8.8%, and 6.0%, respectively, in the past month. Type A crash rates were significantly higher than type C after controlling for relevant covariates (adjusted odds ratio (OR) = 7.1, 95% confidence interval (CI): 3.74-13.47). We conclude that more stringent bus company regulations, which mandate drivers to work long hours and obtain salary based on job performance in meeting demanding metrics, are associated with elevated bus-related crash risks. Local governments in China should regulate bus companies to ensure drivers work reasonable hours and are paid based on the quality of their work (e.g., safety).

Fast genomic prediction of breeding values using parallel Markov chain Monte Carlo with convergence diagnosis.

BACKGROUND: Running multiple-chain Markov Chain Monte Carlo (MCMC) provides an efficient parallel computing method for complex Bayesian models, although the efficiency of the approach critically depends on the length of the non-parallelizable burn-in period, for which all simulated data are discarded. In practice, this burn-in period is set arbitrarily and often leads to the performance of far more iterations than required. In addition, the accuracy of genomic predictions does not improve after the MCMC reaches equilibrium. RESULTS: Automatic tuning of the burn-in length for running multiple-chain MCMC was proposed in the context of genomic predictions using BayesA and BayesCπ models. The performance of parallel computing versus sequential computing and tunable burn-in MCMC versus fixed burn-in MCMC was assessed using simulation data sets as well by applying these methods to genomic predictions of a Chinese Simmental beef cattle population. The results showed that tunable burn-in parallel MCMC had greater speedups than fixed burn-in parallel MCMC, and both had greater speedups relative to sequential (single-chain) MCMC. Nevertheless, genomic estimated breeding values (GEBVs) and genomic prediction accuracies were highly comparable between the various computing approaches. When applied to the genomic predictions of four quantitative traits in a Chinese Simmental population of 1217 beef cattle genotyped by an Illumina Bovine 770 K SNP BeadChip, tunable burn-in multiple-chain BayesCπ (TBM-BayesCπ) outperformed tunable burn-in multiple-chain BayesCπ (TBM-BayesA) and Genomic Best Linear Unbiased Prediction (GBLUP) in terms of the prediction accuracy, although the differences were not necessarily caused by computational factors and could have been intrinsic to the statistical models per se. CONCLUSIONS: Automatically tunable burn-in multiple-chain MCMC provides an accurate and cost-effective tool for high-performance computing of Bayesian genomic prediction models, and this algorithm is generally applicable to high-performance computing of any complex Bayesian statistical model.

Diffusion-weighted 7.0T Magnetic Resonance Imaging in Assessment of Intervertebral Disc Degeneration in Rats.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major cause of disc protrusion, likely to be associated with decrease of water content. This research aimed to evaluate IDD by diffusion-weighted imaging (DWI) with a 7.0 Tesla (T) magnetic resonance imaging (MRI) machine. METHODS: A total of 24 healthy Sprague-Dawley rats were randomly selected and divided into four groups (A, B, C, and D), each consisting of 3 male and 3 female rats (28, 42, 56, and 70 days old, respectively). All the rats were imaged with a 7.0T MRI, producing T2WI, T1WI, and functional DWI sequences. Data were collected and apparent diffusion coefficient (ADC) charts were constructed. Nucleus pulposus and annulus fibrosus regions were identified, several regions of interest were chosen, and their ADC values were obtained. After imaging, rats were sacrificed and their intervertebral discs (L1-L6) were dissected, yielding a total of 144 discs. Protein was extracted for the purpose of Western blotting. Comparison among multiple samples used one-way analysis of variance and least significant difference methods. RESULTS: 7.0T MRI revealed evident decrease in signal intensity within intervertebral discs of Sprague-Dawley rats with age. Intervertebral disc ADC values significantly decreased from Group A (0.00154 ± 0.00008) to Group D (0.00107 ± 0.00007; P < 0.01); nucleus pulposus ADC values significantly decreased from Group A (0.00164 ± 0.00005) to Group D (0.00140 ± 0.00007; P < 0.01) and annulus fibrosus ADC values significantly decreased from Group A (0.00129 ± 0.00014) to Group D (0.00082 ± 0.00012; P < 0.01). Meanwhile, it also revealed evident decrease from high spinal level to low spinal level: nucleus pulposus ADC values in Group A significantly decreased from L1/L2 (0.00163 ± 0.00006) to L6/S1 (0.00139 ± 0.00004; P < 0.01). While annulus fibrosus ADC values did not differ significantly between levels in Group A (P > 0.05). Western blotting showed that aggrecan content of intervertebral discs decreased from Group A (1.88 ± 0.16) to Group D (0.17 ± 0.04) with age (P < 0.01); Type II collagen content of intervertebral discs decreased from Group A (2.22 ± 0.04) to Group D (0.20 ± 0.01) with age (P < 0.01). No significant differences in aggrecan and Type II collagen content of L1-L6 intervertebral discs in Group A were noted (P > 0.05). Mean ADC values of different intervertebral regions were positively correlated with aggrecan and Type II collagen content (aggrecan: r = 0.631, P < 0.01; Type II collagen: r = 0.680, P < 0.01). CONCLUSION: 7.0T MRI-DWI could be applied to effectively diagnose and research early IDD in tiny variations.

Construction and assessment of bio-engineered intervertebral discs.

The present study assessed the value of bone marrow-mesenchymal stem cells (BM-MSCs) transformed by nucleus pulposus cells (NPs) for engineering of intervertebral discs. BM-MSCs and fetal NPs were cultured, planted onto polylactic acid-polyglycolic acid co-polymer (PLGA) and observed under inverted and scanning electron microscopes. PLGA scaffolds with adherent or suspended BM-MSCs and NPs were implanted into intervertebral discs of New Zealand white rabbits. Intervertebral signal intensity was evaluated by Thompson grading after 12 weeks. Proteoglycan and type II collagen were measured spectrophotometrically and immunohistochemically, respectively. Spindle or multi-angular BM-MSCs developed fibro-like phenotypesin co-culture with NPs and grew with a normal morphology when attached to PLGA scaffolds. A significant difference was observed in intervertebral proteoglycan expression and collagen II expression in the PLGA scaffold group vs. that in the control group implanted with BM-MSCs and NPs without a scaffold (3.93±0.31 vs. 3.52±0.26 mg/100 mg, 12.70±2.83 vs. 9.50±2.06, respectively). Thus, BM-MSCs can be co-cultured with NPs to enhance their differentiation into NPs for disc regeneration. In conclusion, PLGA scaffolds offer viable growing conditions and allow for the maintenance of mechanical properties and spatial structures of the engineered tissue, which meets the requirements of tissue-engineered discs that do not degenerate.

Parallel Markov chain Monte Carlo - bridging the gap to high-performance Bayesian computation in animal breeding and genetics.

BACKGROUND: Most Bayesian models for the analysis of complex traits are not analytically tractable and inferences are based on computationally intensive techniques. This is true of Bayesian models for genome-enabled selection, which uses whole-genome molecular data to predict the genetic merit of candidate animals for breeding purposes. In this regard, parallel computing can overcome the bottlenecks that can arise from series computing. Hence, a major goal of the present study is to bridge the gap to high-performance Bayesian computation in the context of animal breeding and genetics. RESULTS: Parallel Monte Carlo Markov chain algorithms and strategies are described in the context of animal breeding and genetics. Parallel Monte Carlo algorithms are introduced as a starting point including their applications to computing single-parameter and certain multiple-parameter models. Then, two basic approaches for parallel Markov chain Monte Carlo are described: one aims at parallelization within a single chain; the other is based on running multiple chains, yet some variants are discussed as well. Features and strategies of the parallel Markov chain Monte Carlo are illustrated using real data, including a large beef cattle dataset with 50K SNP genotypes. CONCLUSIONS: Parallel Markov chain Monte Carlo algorithms are useful for computing complex Bayesian models, which does not only lead to a dramatic speedup in computing but can also be used to optimize model parameters in complex Bayesian models. Hence, we anticipate that use of parallel Markov chain Monte Carlo will have a profound impact on revolutionizing the computational tools for genomic selection programs.

Bayesian model averaging for evaluation of candidate gene effects.

Statistical assessment of candidate gene effects can be viewed as a problem of variable selection and model comparison. Given a certain number of genes to be considered, many possible models may fit to the data well, each including a specific set of gene effects and possibly their interactions. The question arises as to which of these models is most plausible. Inference about candidate gene effects based on a specific model ignores uncertainty about model choice. Here, a Bayesian model averaging approach is proposed for evaluation of candidate gene effects. The method is implemented through simultaneous sampling of multiple models. By averaging over a set of competing models, the Bayesian model averaging approach incorporates model uncertainty into inferences about candidate gene effects. Features of the method are demonstrated using a simulated data set with ten candidate genes under consideration.

Bayesian structural equation models for inferring relationships between phenotypes: a review of methodology, identifiability, and applications.

Structural equation models provide a general statistical modelling technique for estimating and testing relationships among variables. Such relationships are often not revealed by standard linear models, but are of importance for understanding mechanisms underlying e.g., production-related diseases, such as mastitis. This paper gives a review of Bayesian structural equation models concerning methodology and identifiability, focused on animal breeding and genetics modelling. Applications of this type of methods in animal breeding are also reviewed critically, with discussion on advantages and disadvantages of these approaches.

Identification of common genetic variants that account for transcript isoform variation between human populations.

In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as response to stimulus and transcription were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations. Our findings provide new insights into the complexity of the human genome as well as the health disparities between the two populations.

Accurate whole human genome sequencing using reversible terminator chemistry.

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high-quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterize four million single-nucleotide polymorphisms and four hundred thousand structural variants, many of which were previously unknown. Our approach is effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.

Single nucleotide polymorphism discovery and functional assessment of variation in the UDP-glucuronosyltransferase 2B7 gene.

OBJECTIVE: UDP-glucuronosyltransferase 2B7 (UGT2B7) plays a central role in the liver-mediated biotransformation of endogenous and exogenous compounds. The genetic basis of interindividual variability in UGT2B7 function is unknown. This study aimed to discover novel gene variants of functional significance. METHODS: Caucasian human livers (n=54) were used. UGT2B7 was resequenced in 12 samples [(six highest and six lowest for the formation of morphine-3-glucuronide (M3G)]. Haplotype-tagging single nucleotide polymorphisms were genotyped in the entire sample set. Samples were phenotyped for mRNA expression. RESULTS: 10 haplotype-tagging single nucleotide polymorphisms were identified and their haplotypes were inferred. Haplotype 4 (-45597G; -6682_-6683A; 372A; IVS1+9_IVS1+10A; IVS1+829T; IVS1+985G; IVS1+999C; IVS1+1250G; 801T; IVS4+185C) (frequency of 0.12) was associated with an increase in enzyme activity and gene expression. The 1/4 and 4/6 diplotypes had higher M3G formation compared with 1/1 (P<0.05) and 2/3 (P<0.01) diplotypes. Diplotypes containing haplotype 4 resulted in a significant 45% average increase in the formation of M3G compared with diplotypes without haplotype 4 (P=0.002). There was also an association between haplotype 4 and increased mRNA expression. IVS1+985A>G, 735A>G, and 1062C>T are the putative functional variants of haplotype 4. We also identified two mRNA splicing variants (UGT2B7_v2 and UGT2B7_v3) splicing out exon 1, 4, 5, and 6 but sharing exons 2 and 3 with the involvement of additional 5' exons. UGT2B7_v2 was detected in all livers tested, but UGT2B7_v3 was present at much lower levels compared with UGT2B7_v2. The UGT2B7 reference sequence mRNA is now named UGT2B7_v1. CONCLUSION: UGT2B7 haplotype 4 is functional and its effects on the biotransformation of UGT2B7 substrates should be tested in controlled clinical trials. Biochemical studies should investigate the functional role of the newly discovered mRNA splicing variants.

Exploration of lagged relationships between mastitis and milk yield in dairy cows using a Bayesian structural equation Gaussian-threshold model.

A Gaussian-threshold model is described under the general framework of structural equation models for inferring simultaneous and recursive relationships between binary and Gaussian characters, and estimating genetic parameters. Relationships between clinical mastitis (CM) and test-day milk yield (MY) in first-lactation Norwegian Red cows were examined using a recursive Gaussian-threshold model. For comparison, the data were also analyzed using a standard Gaussian-threshold, a multivariate linear model, and a recursive multivariate linear model. The first 180 days of lactation were arbitrarily divided into three periods of equal length, in order to investigate how these relationships evolve in the course of lactation. The recursive model showed negative within-period effects from (liability to) CM to test-day MY in all three lactation periods, and positive between-period effects from test-day MY to (liability to) CM in the following period. Estimates of recursive effects and of genetic parameters were time-dependent. The results suggested unfavorable effects of production on liability to mastitis, and dynamic relationships between mastitis and test-day MY in the course of lactation. Fitting recursive effects had little influence on the estimation of genetic parameters. However, some differences were found in the estimates of heritability, genetic, and residual correlations, using different types of models (Gaussian-threshold vs. multivariate linear).

Optimal sampling of a population to determine QTL location, variance, and allelic number.

In a population intended for breeding and selection, questions of interest relative to a specific segregating QTL are the variance it generates in the population, and the number and effects of its alleles. One approach to address these questions is to extract several inbreds from the population and use them to generate multiple mapping families. Given random sampling of parents, sampling strategy may be an important factor determining the power of the analysis and its accuracy in estimating QTL variance and allelic number. We describe appropriate multiple-family QTL mapping methodology and apply it to simulated data sets to determine optimal sampling strategies in terms of family number versus family size. Genomes were simulated with seven chromosomes, on which 107 markers and six QTL were distributed. The total heritability was 0.60. Two to ten alleles were segregating at each QTL. Sampling strategies ranged from sampling two inbreds and generating a single family of 600 progeny to sampling 40 inbreds and generating 40 families of 15 progeny each. Strategies involving only one to five families were subject to variation due to the sampling of inbred parents. For QTL where more than two alleles were segregating, these strategies did not sample QTL alleles representative of the original population. Conversely, strategies involving 30 or more parents were subject to variation due to sampling of QTL genotypes within the small families obtained. Given these constraints, greatest QTL detection power was obtained for strategies involving five to ten mapping families. The most accurate estimation of the variance generated by the QTL, however, was obtained with strategies involving 20 or more families. Finally, strategies with an intermediate number of families best estimated the number of QTL alleles. We conclude that no overall optimal sampling strategy exists but that the strategy adopted must depend on the objective.

[Genetic linkage between Atrn gene and microsatellite markers and the effects to some economic traits in pigs].

The genetic polymorphisms of Atrn gene, which were from 174 F0-F5 Danish resource family pigs (DRF) that has undergone five successive generations of inbreeding and 129 F9 Hunan yellow pigs (HY) that were developed by crossbreeding, were tested by PCR-RFLP method, and the effects to carcass and growth traits were also analyzed. The results showed that: (1) Three genotypes of AA, AB, BB were detected by Taq I-RFLP in the two pig breeds, and highly significant differences (P<0.01) in genotype frequencies were found between the two breeds; (2) Based on the linkage analysis of resource family pigs using CRI-MAP V2.4 software, Atrn gene loci in DRF was found to be linked with SW1031 loci on chromosome 17, the recombination frequency and LOD score for Atrn gene were 0.21 and 3.19 respectively; (3) With the least square analysis of multi-variable model, the significant differences among Atrn genotypes were found in ADSG and ABF traits in DRF and also in ADG, ABF and LMP traits in HY (P<0.05 or P<0.01), BB genotype pigs were superior to AA or AB genotype pigs. Based on the above mentioned results, B gene has favorable effects in important economic traits, and thus selection to BB genotype will get favorable effects in important economic traits. This will provide theory basis for Atrn gene being regarded as a candidate gene in pig carcass and growth traits.

Estimating allelic number and identity in state of QTLs in interconnected families.

When multiple related families derived from inbred lines are jointly analysed to detect quantitative trait loci (QTLs), the analysis should estimate allelic effects as accurately as possible and estimate the probability that different parents carry alleles that are identical in state. Analyses exist that assume that all parents carry unique alleles or that all parents but one carry the same allele. In practice, many configurations are possible that group different parents according to their identity-in-state condition at a putative QTL allele. Here, we propose a variable model Bayesian analysis that selects among possible identity-in-state configurations and jointly estimates the allelic effects of identical-in-state parents. We contrast this analysis with a fixed model analysis that estimates unique allelic effects for all parents. We analyse two simulated mating designs: an experimental design in which three inbred parents were crossed to generate two families of 150 doubled haploid lines; and a breeding design in which 20 inbred parents were crossed to generate 60 families of 20 doubled haploid lines, with each parent contributing to six families. In all cases where some parents were simulated to carry alleles of identical effect (that is, they were identical in state), the variable analysis estimated allelic effects with lower mean-squared error than the fixed analysis. The variable analysis showed that, unless each family contains many individuals (more than 100), there is insufficient information in DNA-marker and phenotypic data to determine with high probability the QTL allelic number.