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Selective DNA pooling (SDP) is a cost-effective means for an initial scan for linkage between marker and quantitative trait loci (QTL) in suitable populations. The method is based on scoring marker allele frequencies in DNA pools from the tails of the population trait distribution. Various analytical approaches have been proposed for QTL detection using data on multiple families with SDP analysis. This article presents a new experimental procedure, fractioned-pool design (FPD), aimed to increase the reliability of SDP mapping results, by 'fractioning' the tails of the population distribution into independent subpools. FPD is a conceptual and structural modification of SDP that allows for the first time the use of permutation tests for QTL detection rather than relying on presumed asymptotic distributions of the test statistics. For situations of family and cross mapping design we propose a spectrum of new tools for QTL mapping in FPD that were previously possible only with individual genotyping. These include: joint analysis of multiple families and multiple markers across a chromosome, even when the marker loci are only partly shared among families; detection of families segregating (heterozygous) for the QTL; estimation of confidence intervals for the QTL position; and analysis of multiple-linked QTL. These new advantages are of special importance for pooling analysis with SNP chips. Combining SNP microarray analysis with DNA pooling can dramatically reduce the cost of screening large numbers of SNPs on large samples, making chip technology readily applicable for genomewide association mapping in humans and farm animals. This extension, however, will require additional, nontrivial, development of FPD analytical tools.

The bovine Growth Hormone gene (bGH) is an attractive candidate gene for milk production in cattle. Single-strand conformation polymorphisms at bGH were identified and used to define haplotype configurations at this gene in the Israeli Holstein dairy cattle population (Bos taurus) and in the parent animals of the International Bovine Reference Family Panel (a collection of B. taurus and B. indicus crosses). B. taurus and B. indicus haplotypes at the bGH gene differed qualitatively, confirming the previously proposed long evolutionary separation of these cattle subraces. Only a small number of bGH haplotypes were present in the Israel Holstein population. One of the haplotypes, apparently of B. indicus origin, was found to have a highly significant positive effect on milk protein percentage. This illustrates the utility of the haplotype approach for uncovering candidate gene involvement in quantitative genetic variation in agricultural populations. The strong effect of an indicine haplotype in a murine background raises the possibility that indicine alleles at other candidate genes may comprise a genetic resource for improvement of taurine populations. It is proposed that haplotype analysis may be a useful adjunct to measures of genetic distance for evaluating rare breeds with respect to gene conservation.

A selective DNA pooling approach was applied to identify QTL for conjugated linoleic acid ( CLA), vaccenic acid ( VA) and Δ9-desaturase (D9D) milk content in Italian Brown Swiss dairy cattle. Milk samples from 60 animals with higher values (after correction for environmental factors) and 60 animals with lower values for each of these traits from each of five half-sib families were pooled separately. The pools were genotyped using the Illumina Bovine SNP50 BeadChip. Sire allele frequencies were compared between high and low tails at the sire and marker level for SNPs for which the sires were heterozygous. An r procedure was implemented to perform data analysis in a selective DNA pooling design. A correction for multiple tests was applied using the proportion of false positives among all test results. BTA 19 showed the largest number of markers in association with CLA. Associations between SNPs and the VA and Δ9-desaturase traits were found on several chromosomes. A bioinformatics survey identified genes with an important role in pathways for milk fat and fatty acids metabolism within 1 Mb of SNP markers associated with fatty acids contents. [ABSTRACT FROM AUTHOR]

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r =-0.29, -0.30, and -0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS. [ABSTRACT FROM AUTHOR]

Bone gamma-carboxyglutamic acid containing protein (BGP) has been utilized effectively as a serum marker of bone turnover in healthy normals and in individuals with a variety of metabolic bone disorders including postmenopausal osteoporosis and Paget's disease. The utility of this serum marker in other bone disorders, including that associated with the maintenance of patients on long-term parenteral nutrition, still requires definition. Because of our interest in this clinical syndrome and the availability of serum and of bone formation rates (BFR) measured directly from double tetracycline labeling in 11 long-term parenteral nutrition patients, we measured BGP levels in these patients and attempted to correlate this measure with BFR. Serum vitamin D metabolites, immunoreactive parathyroid hormone (PTH), and alkaline phosphatase (alk phos) were also measured. Serum BGP was only weakly and not significantly correlated (r = 0.24, p = NS) with bone formation rate for the group as a whole. However, in a subgroup of 10 patients without hyperparathyroidism, there was strong and significant correlation (r = 0.81, P less than 0.01) between BGP and BFR. There was also a strong correlation between bone formation rate and serum 1,25 dihydroxyvitamin D [1,25(OH)2D] levels (r = 0.89, P less than 0.01, n = 11). The mechanism of this association could not be established. A correlation of borderline significance was observed between bone formation rate and serum alk phos (r = 0.60, P = 0.05, n = 11). The current data suggest that additional studies may help to more fully define the utility of serum measurements in quantifying bone dynamics in parenteral nutrition patients, and that measures of vitamin D metabolites, BGP, and alk phos may prove useful. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between obesity measures and albuminuria in adults with type 2 diabetes.Research Design and Methods: In the Look AHEAD (Action for Health in Diabetes) Study, BMI and waist circumference were measured among 4,985 participants while total percent body fat was measured by whole-body DEXA scans among 1,351 participants. Odds of albuminuria by quartiles of BMI, waist circumference, and percent total body fat were calculated using logistic regression analysis while adjusting for covariates.Results: The highest quartile of BMI (odds ratio [OR] 1.72 [95% CI 1.40-2.11]) and waist circumference (OR 1.75 [95% CI 1.42-2.15]) was significantly associated with albuminuria compared with the lowest quartile after adjustment for covariates. No associations were noted between quartiles of percent total body fat and albuminuria in any model.Conclusions: Increased BMI and abdominal obesity are associated with albuminuria in overweight and obese adults with type 2 diabetes. [ABSTRACT FROM AUTHOR]

An abstract of the article "Optical coherence tomography in optic neuritis and MS," by M. Pulicken, E. Gordon-Lipkin, L. J. Balcer, G. R. Cutter and P. Calabresi is presented.

Marek's Disease (MD), which can result in neurological damage and tumour formation, has large effects on the economy and animal welfare of the poultry industry worldwide. Previously, we mapped autosomal MD QTL regions (QTLRs) by individual genotyping of an F 6 population from a full-sib advanced intercross line. We further mapped MD QTLRs on the chicken Z chromosome (GGZ) using the same F 6 population, and by selective DNA pooling (SDP) of 8 elite egg production lines. Here we used SDP of the same pools used on GGZ to map autosomal MD QTLRs. Thirty-seven QTLRs were found. Seven of the QTLRs were tested by all sires from the same 8 lines, individually genotyped for QTLR markers. Five of the tested QTLRs were confirmed. Linkage disequilibrium (LD) was calculated for all QTLR markers on the same chromosome, and complex LD blocks were found. Distribution of P and LD values were used to assess the QTLR causative elements. Allele substitution effects were calculated based on both pooled SNP microarray genotypes, and individual genotypes of QTLRs markers. Substantial allele effect and contribution to the phenotypic and genotypic variation were obtained. The results explain part of the MD response, and provide targets for mitigating MD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: Institutional Review Board Statement: The animal study protocol was approved by Hy-Line International Institutional Animal Care and Use Committee guidelines. Hy-Line do not have specific project identification codes. All of these samples had been collected in the past and stored frozen until use. At the termination of the study animals were humanely euthanized under the approval of the Hy-Line IACUC and supervision of licensed veterinarians., (© 2024. The Author(s).)

Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men., Purpose: Intentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known., Methods: Data from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6-16.3 years after randomization (year 12-16)., Results: At year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck (p = 0.0122) but this finding was not observed at the year 12-16 visit. In analyses stratified by gender, bone density loss (%) was greater at the total hip for men in the ILI group than the DSE group at both the year 8 and year 12-16 visits (year 8 p = 0.0263 and year 12-16 p = 0.0062). This finding was not observed among women., Conclusion: Long term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted., Trial Registration: Clinicaltrials.gov Identifier: NCT00017953. June 21, 2001., (© 2023. The Author(s).)

Marek's Disease (MD) has a significant impact on both the global poultry economy and animal welfare. The disease pathology can include neurological damage and tumour formation. Sexual dimorphism in immunity and known higher susceptibility of females to MD makes the chicken Z chromosome (GGZ) a particularly attractive target to study the chicken MD response. Previously, we used a Hy-Line F 6 population from a full-sib advanced intercross line to map MD QTL regions (QTLRs) on all chicken autosomes. Here, we mapped MD QTLRs on GGZ in the previously utilized F 6 population with individual genotypes and phenotypes, and in eight elite commercial egg production lines with daughter-tested sires and selective DNA pooling (SDP). Four MD QTLRs were found from each analysis. Some of these QTLRs overlap regions from previous reports. All QTLRs were tested by individuals from the same eight lines used in the SDP and genotyped with markers located within and around the QTLRs. All QTLRs were confirmed. The results exemplify the complexity of MD resistance in chickens and the complex distribution of p -values and Linkage Disequilibrium (LD) pattern and their effect on localization of the causative elements. Considering the fragments and interdigitated LD blocks while using LD to aid localization of causative elements, one must look beyond the non-significant markers, for possible distant markers and blocks in high LD with the significant block. The QTLRs found here may explain at least part of the gender differences in MD tolerance, and provide targets for mitigating the effects of MD.

Background: Children with developmental disabilities are vulnerable to morbidity associated with COVID-19., Aims: To understand attitudes toward routine childhood vaccinations versus the COVID-19 vaccine in a population of families affected by mitochondrial disease (MtD), a form of developmental disability., Methods and Procedures: An online survey was administered via several advocacy groups for children with MtD., Outcomes and Result: Eighty-six percent of families reported being up to date with the childhood vaccine schedule and seventy percent reported that their affected child receives the annual flu shot. However, only fifty percent reported that the benefits of the COVID-19 vaccine outweighed the risk for their affected child. One quarter of families expressed concern that their child may become sick or deteriorate after the COVID-19 vaccine. In comparison to other routine childhood vaccines, families expressed less confidence in the COVID-19 vaccine., Conclusions and Implications: Families affected by this population of developmental disabilities are more comfortable with the vaccines included in the routine childhood immunization schedule than with the newly introduced COVID-19 vaccine, even despite this group's vulnerability., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (Published by Elsevier Ltd.)

Background: Pediatric patients undergoing intestinal rehabilitation (IR) using parenteral nutrition (PN) are at higher risk for intestinal failure-associated liver disease (IFALD). Nutrition support, growth, and liver enzymes must be closely monitored while incorporating hepatoprotective lipid injectable emulsions for optimal patient outcomes., Objective: Describe trends of liver profile and nutrition outcomes for pediatric patients undergoing IR using SMOFlipid[SO,MCT,OO,FO-ILE])., Methods: After IRB approval, patients undergoing IR using SO,MCT,OO,FO-ILE were observed prospectively from January 1, 2017, through December 1, 2019. The following values were documented monthly: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), triene/tetraene ratio (TTR), micronutrient and trace element levels, z-scores for growth, and nutrition support regimen. Values were compared., Results: The group involved 16 pediatric patients for an average of 16.4 months on SO,MCT,OO,FO-ILE. By the end of the study, mean PN hours per day decreased by 34.7%, P < 0.0001. Mean PN calories per kilogram decreased from 60.4 to 48.3, P = 0.004. SO,MCT,OO,FO-ILE calories met the recommended dietary intake goal of 30% at the average 1.6 g/kg. Growth z-scores increased in those <2 YOA , although the body mass index decreased in our >2 YOA cohort. Total nutrition received from PN decreased to 62%: a 32% change, P = 0.001. There were no statistically significant changes in AST or ALT. TB decreased by 67.08%, P <0.05. No essential fatty acid deficiency was reported (TTR < 0.02). There were no changes in micronutrient and trace element deficiencies. There was zero new incidences of IFALD., Conclusions: SO,MCT,OO,FO-ILE may be used long term in pediatric patients while promoting growth and development., (© 2021 American Society for Parenteral and Enteral Nutrition.)