Morphological and molecular genetic diversity of Syrian indigenous goat populations

Domestic goats in Syria may provide an interesting source of genetic variability due to its proximity to the centers of domestication. This study aimed to assess the morphological variation, genetic diversity and population substructure of the Syrian goat populations. Commonly, three goat genotypes are distinguished in Syria, namely Jabali or mountain goat, Baladi or local goat and Shami or Damascus (a well-known dairy goat). A pre-tested semi-structured questionnaire was used in recording both qualitative (coat color, eye color, horn length, horn orientation, nose profile) and quantitative (height  at wither, chest girth, cannon length, body length, ear length and ear width) morphological data. Data  from a total of 5,730 individual goats of the three goat populations reared in ten representative  provinces of Syria were collected and analyzed using GenStat version 14 statistical packages. Results of the morphological analysis confirmed that there were clear morphological variations among the three  goat populations. The three goat populations are mainly distinguished by their straight (Baladi, 71.1%  and Jabali, 82.8%) and curved (Shami, 89.5%) nose profiles. Substantial phenotypic variability was found among and within the breeds suggesting that these goat breeds have not yet undergone an organized breeding program. The genetic variability and population substructures from 398 individual animals of the three breeds were genotyped using 12 DNA microsatellite markers from Food and Agricultural Organization (FAO) panel. All microsatellites typed were found to be polymorphic and a total of 41 distinct alleles were detected on Baladi, Jabali and Shami goat populations. The Syrian goat populations had observed and expected heterozygosity values that ranged from 0.50 to 0.62 and 0.74 to 0.85, respectively, and an average of 13.97 alleles per locus across breeds. For all loci, an average inbreeding values (FIS) of low to moderate level was obtained across the three goat breeds, which ranged from 0.29 (Shami goats) to 0.34 (Baladi goats) indicating the absence of mating between close relatives within these populations. The observed positive FIS coefficients among the studied goat breeds also suggested heterozygote deficiencies. The analyses of the molecular data using STRUCURE program indicated there were two  primary populations, which did support the results based on morphological data of the same goat populations that clustered these goat populations into two main groups and confirmed the admixture nature of the Baladi and Jabali goat populations, while the Shami goat breed was well differentiated and grouped into a separate cluster that suggests its evolutionary and genetic uniqueness. The analysis of molecular variance (AMOVA) results detected genetic variations within individuals in a population (96%). The high genetic variability within individuals in a population provides a good base for  designing genetic improvement programs under the existing goat management systems.Key words: Characterization, cluster, genetic differentiation, population structure, Syria

GoMiner: a resource for biological interpretation of genomic and proteomic data

We have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure analogous to that in the AmiGO browser and the second is a compact, dynamically interactive 'directed acyclic graph'. Genes displayed in GoMiner are linked to major public bioinformatics resources

Gene markers of cellular aging in human multipotent stromal cells in culture

INTRODUCTION: Human multipotent stromal cells (MSCs) isolated from bone marrow or other tissue sources have great potential to treat a wide range of injuries and disorders in the field of regenerative medicine and tissue engineering. In particular, MSCs have inherent characteristics to suppress the immune system and are being studied in clinical studies to prevent graft-versus-host disease. MSCs can be expanded in vitro and have potential for differentiation into multiple cell lineages. However, the impact of cell passaging on gene expression and function of the cells has not been determined. METHODS: Commercially available human MSCs derived from bone marrow from six different donors, grown under identical culture conditions and harvested at cell passages 3, 5, and 7, were analyzed with gene-expression profiling by using microarray technology. RESULTS: The phenotype of these cells did not change as reported previously; however, a statistical analysis revealed a set of 78 significant genes that were distinguishable in expression between passages 3 and 7. None of these significant genes corresponded to the markers established by the International Society for Cellular Therapy (ISCT) for MSC identification. When the significant gene lists were analyzed through pathway analysis, these genes were involved in the top-scoring networks of cellular growth and proliferation and cellular development. A meta-analysis of the literature for significant genes revealed that the MSCs seem to be undergoing differentiation into a senescent cell type when cultured extensively. Consistent with the differences in gene expression at passage 3 and 7, MSCs exhibited a significantly greater potential for cell division at passage 3 in comparison to passage 7. CONCLUSIONS: Our results identified specific gene markers that distinguish aging MSCs grown in cell culture. Confirmatory studies are needed to correlate these molecular markers with biologic attributes that may facilitate the development of assays to test the quality of MSCs before clinical use

Assessing Reproducibility of Inherited Variants Detected With Short-Read Whole Genome Sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when \u3e 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30x. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.Peer reviewe

A Nonparametric Estimation Problem From Indirect Observations

nonparametric estimation, indirect observation, efficient estimators,

Overall conceptual framework for studying the genetics of autoimmune diseases following vaccination: a regulatory perspective

The US Vaccine Adverse Event Reporting System contains case reports of autoimmune diseases (ADs) occurring following vaccinations. ADs are rare and occur in unvaccinated people, making the potential association between vaccines and ADs challenging to evaluate. Developing mechanistic pathways that link genes, immune mediators, vaccine components and ADs would be helpful for hypothesis generation, enhancing theories of biologic plausibility and grouping rare autoimmune adverse events to increase the ability to detect and evaluate safety signals. Here, we propose a conceptual framework for investigating the genetics of ADs as safety signals following vaccination, potentially contributing to the identification of relevant biomarkers. We also discuss a study design that incorporates genetic information into postmarket clinical evaluation of autoimmune adverse events following vaccination. </jats:p