[Genetics of congenital heart diseases].

PubMed

Bonnet, Damien

2017-06-01

Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analysis of the concept of informed consent concerning the use of genetic material according to the European Convention on Bioethics and in other solutionsm - Propositions for broad consent for future genetic research from the point of view of the activity of the Biobank.

PubMed

Patryn, Rafał; Sak, Jarosław

2017-09-21

The aim of the article is a critical presentation of the typology of consents included in the European Convention on Bioethics and in other formal solutions concerning the gathering of genetic material in institutions called Biobanks. Existing types of Acts of Consent are inaccurate in their scope and possess insufficient information regarding the gathering of genetic material (application, usage, processing) and their final (future and diverse) use. Lack of precise legal regulations on the broad future use of genetic material may result in various formal problems relating both to research participants as well as those commissioning the research. Ultimately, it may lead to various complications with the appropriate legal interpretation of consent and possible claims on behalf of the donors. The presented proposition of consent with a terminal premise is to be applied eventually to legal and formal aspects of the collecting of genetic material. It is a possible solution which would clarify the issue of informed consent, and may be implemented in the regulations of the Convention as well as constitute a self-contained legislative solution to this matter. For example, Polish law in its current form, without the ratification of the Bioethical Convention, allows the collecting of material for genetic testing for determination of the risk of genetic defects in common genetic material from people who are planning to have a child.

Genetics and education: the ethics of shaping human identity.

PubMed

Ravitsky, Vardit

2002-10-01

This paper suggests an analogy between education and genetic interventions as means of shaping the identity of children and future adults. It proposes to look at issues discussed in the philosophy of education as a possible source of insight for ethical guidelines regarding future genetic interventions. The paper focuses on situations of conflict between parents and state regarding the authority to determine the child s best interests. It describes the current formulation of the conflict in the literature as lacking the crucial element of the child s right to a cultural identity. It argues that this element is a necessary component in an ethical analysis of the child s best interests in a multicultural, liberal society which respects diversity. The paper therefore proposes a better model for the moral evaluation of identity-shaping decisions and offers some implications of this model for genetics.

Genetic diversity analysis of fruit characteristics of hawthorn germplasm.

PubMed

Su, K; Guo, Y S; Wang, G; Zhao, Y H; Dong, W X

2015-12-07

One hundred and six accessions of hawthorn intraspecific resources, from the National Germplasm Repository at Shenyang, were subjected to genetic diversity and principal component analysis based on evaluation data of 15 fruit traits. Results showed that the genetic diversity of hawthorn fruit traits varied. Among the 15 traits, the fruit shape variable coefficient had the most obvious evaluation, followed by fruit surface state, dot color, taste, weight of single fruit, sepal posture, peduncle form, and metula traits. These are the primary traits by which hawthorn could be classified in the future. The principal component demonstrated that these traits are the most influential factors of hawthorn fruit characteristics.

Preliminary Design of a Manned Nuclear Electric Propulsion Vehicle Using Genetic Algorithms

NASA Technical Reports Server (NTRS)

Irwin, Ryan W.; Tinker, Michael L.

2005-01-01

Nuclear electric propulsion (NEP) vehicles will be needed for future manned missions to Mars and beyond. Candidate designs must be identified for further detailed design from a large array of possibilities. Genetic algorithms have proven their utility in conceptual design studies by effectively searching a large design space to pinpoint unique optimal designs. This research combined analysis codes for NEP subsystems with a genetic algorithm. The use of penalty functions with scaling ratios was investigated to increase computational efficiency. Also, the selection of design variables for optimization was considered to reduce computation time without losing beneficial design search space. Finally, trend analysis of a reference mission to the asteroids yielded a group of candidate designs for further analysis.

[Progress in genetic research of human height].

PubMed

Chen, Kaixu; Wang, Weilan; Zhang, Fuchun; Zheng, Xiufen

2015-08-01

It is well known that both environmental and genetic factors contribute to adult height variation in general population. However, heritability studies have shown that the variation in height is more affected by genetic factors. Height is a typical polygenic trait which has been studied by traditional linkage analysis and association analysis to identify common DNA sequence variation associated with height, but progress has been slow. More recently, with the development of genotyping and DNA sequencing technologies, tremendous achievements have been made in genetic research of human height. Hundreds of single nucleotide polymorphisms (SNPs) associated with human height have been identified and validated with the application of genome-wide association studies (GWAS) methodology, which deepens our understanding of the genetics of human growth and development and also provides theoretic basis and reference for studying other complex human traits. In this review, we summarize recent progress in genetic research of human height and discuss problems and prospects in this research area which may provide some insights into future genetic studies of human height.

Comparison of Genetic Diversity between Chinese and American Soybean (Glycine max (L.)) Accessions Revealed by High-Density SNPs

PubMed Central

Liu, Zhangxiong; Li, Huihui; Wen, Zixiang; Fan, Xuhong; Li, Yinghui; Guan, Rongxia; Guo, Yong; Wang, Shuming; Wang, Dechun; Qiu, Lijuan

2017-01-01

Soybean is one of the most important economic crops for both China and the United States (US). The exchange of germplasm between these two countries has long been active. In order to investigate genetic relationships between Chinese and US soybean germplasm, 277 Chinese soybean accessions and 300 US soybean accessions from geographically diverse regions were analyzed using 5,361 SNP markers. The genetic diversity and the polymorphism information content (PIC) of the Chinese accessions was higher than that of the US accessions. Population structure analysis, principal component analysis, and cluster analysis all showed that the genetic basis of Chinese soybeans is distinct from that of the USA. The groupings observed in clustering analysis reflected the geographical origins of the accessions; this conclusion was validated with both genetic distance analysis and relative kinship analysis. FST-based and EigenGWAS statistical analysis revealed high genetic variation between the two subpopulations. Analysis of the 10 loci with the strongest selection signals showed that many loci were located in chromosome regions that have previously been identified as quantitative trait loci (QTL) associated with environmental-adaptation-related and yield-related traits. The pattern of diversity among the American and Chinese accessions should help breeders to select appropriate parental accessions to enhance the performance of future soybean cultivars. PMID:29250088

Genome-wide genetic diversity, population structure and admixture analysis in African and Asian cattle breeds.

PubMed

Edea, Z; Bhuiyan, M S A; Dessie, T; Rothschild, M F; Dadi, H; Kim, K S

2015-02-01

Knowledge about genetic diversity and population structure is useful for designing effective strategies to improve the production, management and conservation of farm animal genetic resources. Here, we present a comprehensive genome-wide analysis of genetic diversity, population structure and admixture based on 244 animals sampled from 10 cattle populations in Asia and Africa and genotyped for 69,903 autosomal single-nucleotide polymorphisms (SNPs) mainly derived from the indicine breed. Principal component analysis, STRUCTURE and distance analysis from high-density SNP data clearly revealed that the largest genetic difference occurred between the two domestic lineages (taurine and indicine), whereas Ethiopian cattle populations represent a mosaic of the humped zebu and taurine. Estimation of the genetic influence of zebu and taurine revealed that Ethiopian cattle were characterized by considerable levels of introgression from South Asian zebu, whereas Bangladeshi populations shared very low taurine ancestry. The relationships among Ethiopian cattle populations reflect their history of origin and admixture rather than phenotype-based distinctions. The high within-individual genetic variability observed in Ethiopian cattle represents an untapped opportunity for adaptation to changing environments and for implementation of within-breed genetic improvement schemes. Our results provide a basis for future applications of genome-wide SNP data to exploit the unique genetic makeup of indigenous cattle breeds and to facilitate their improvement and conservation.

Microfluidics for Single-Cell Genetic Analysis

PubMed Central

Thompson, A. M.; Paguirigan, A. L.; Kreutz, J. E.; Radich, J. P.; Chiu, D. T.

2014-01-01

The ability to correlate single-cell genetic information to cellular phenotypes will provide the kind of detailed insight into human physiology and disease pathways that is not possible to infer from bulk cell analysis. Microfluidic technologies are attractive for single-cell manipulation due to precise handling and low risk of contamination. Additionally, microfluidic single-cell techniques can allow for high-throughput and detailed genetic analyses that increase accuracy and decreases reagent cost compared to bulk techniques. Incorporating these microfluidic platforms into research and clinical laboratory workflows can fill an unmet need in biology, delivering the highly accurate, highly informative data necessary to develop new therapies and monitor patient outcomes. In this perspective, we describe the current and potential future uses of microfluidics at all stages of single-cell genetic analysis, including cell enrichment and capture, single-cell compartmentalization and manipulation, and detection and analyses. PMID:24789374

The impact of genetics on future drug discovery in schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Walton, Noah M; Yamada, Hiroshi; Kondo, Yuji; Marek, Gerard J; Tajinda, Katsunori

2017-07-01

Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways.

Genetic diversity based on SSR analysis of the cultured snakehead fish, Channa argus, (Channidae) in China.

PubMed

Zhu, S-R; Li, J-L; Xie, N; Zhu, L-M; Wang, Q; Yue, G-H

2014-02-13

The snakehead fish Channa argus is an important food fish in China. We identified six microsatellite loci for C. argus. These six microsatellite loci and four other microsatellite markers were used to analyze genetic diversity in four cultured populations of C. argus (SD, JX, HN, and ZJ) and determine their relationships. A total of 154 alleles were detected at the 10 microsatellite loci. The average expected and observed heterozygosities varied from 0.70-0.84 and 0.69-0.83, respectively, and polymorphism information content ranged between 0.66 and 0.82 in the four populations, indicating high genetic diversity. Population JX deviated from mutation-drift equilibrium and may have experienced a recent bottleneck. Analysis of pairwise genetic differentiation revealed FST values that ranged from 0.028 to 0.100, which indicates a moderate level of genetic differentiation. The largest distances were observed between populations HN and SD, whereas the smallest distances were obtained between populations HN and JX. Genetic clustering analysis demonstrated that the ZJ and HN populations probably share the same origin. This information about the genetic diversity within each of the four populations, and their genetic relationships will be useful for future genetic improvement of C. argus through selective breeding.

[Genetic information and future medicine].

PubMed

Sakurai, Akihiro

2012-11-01

Rapid technological advances in genetic analysis have revealed the genetic background of various diseases. Elucidation of the genes responsible for a disease enables better clinical management of the disease and helps to develop targeted drugs. Also, early diagnosis and management of at-risk family members can be made by identification of a genetic disease in the proband. On the other hand, genetic issues often cause psychological distress to the family. To perform genetic testing appropriately and to protect patients and family members from any harm, guidelines for genetic testing were released from the alliance of Japanese genetics-related academic societies in 2003. As genetic testing is becoming incorporated into clinical practice more broadly, the guideline was revised and released by the Japanese Society of Medical Sciences in 2011. All medical professionals in Japan are expected to follow this guideline.

AFLP-Based Analysis of Genetic Diversity, Population Structure, and Relationships with Agronomic Traits in Rice Germplasm from North Region of Iran and World Core Germplasm Set.

PubMed

Sorkheh, Karim; Masaeli, Mohammad; Chaleshtori, Maryam Hosseini; Adugna, Asfaw; Ercisli, Sezai

2016-04-01

Analysis of the genetic diversity and population structure of crops is very important for use in breeding programs and for genetic resources conservation. We analyzed the genetic diversity and population structure of 47 rice genotypes from diverse origins using amplified fragment length polymorphism (AFLP) markers and morphological characters. The 47 genotypes, which were composed of four populations: Iranian native varieties, Iranian improved varieties, International Rice Research Institute (IRRI) rice varieties, and world rice collections, were analyzed using ten primer combinations. A total of 221 scorable bands were produced with an average of 22.1 alleles per pair of primers, of which 120 (54.30%) were polymorphic. The polymorphism information content (PIC) values varied from 0.32 to 0.41 with an average of 0.35. The high percentage of polymorphic bands (%PB) was found to be 64.71 and the resolving power (R p) collections were 63.36. UPGMA clustering based on numerical data from AFLP patterns clustered all 47 genotypes into three large groups. The genetic similarity between individuals ranged from 0.54 to 0.94 with an average of 0.74. Population genetic tree showed that Iranian native cultivars formed far distant cluster from the other populations, which may indicate that these varieties had minimal genetic change over time. Analysis of molecular variance (AMOVA) revealed that the largest proportion of the variation (84%) to be within populations showing the inbreeding nature of rice. Therefore, Iranian native varieties (landraces) may have unique genes, which can be used for future breeding programs and there is a need to conserve this unique diversity. Furthermore, crossing of Iranian genotypes with the genetically distant genotypes in the other three populations may result in useful combinations, which can be used as varieties and/or lines for future rice breeding programs.

Understanding the impact of genetic testing for inherited retinal dystrophy

PubMed Central

Combs, Ryan; McAllister, Marion; Payne, Katherine; Lowndes, Jo; Devery, Sophie; Webster, Andrew R; Downes, Susan M; Moore, Anthony T; Ramsden, Simon; Black, Graeme; Hall, Georgina

2013-01-01

The capability of genetic technologies is expanding rapidly in the field of inherited eye disease. New genetic testing approaches will deliver a step change in the ability to diagnose and extend the possibility of targeted treatments. However, evidence is lacking about the benefits of genetic testing to support service planning. Here, we report qualitative data about retinal dystrophy families' experiences of genetic testing in United Kingdom. The data were part of a wider study examining genetic eye service provision. Twenty interviewees from families in which a causative mutation had been identified by a genetic eye clinic were recruited to the study. Fourteen interviewees had chosen to have a genetic test and five had not; one was uncertain. In-depth telephone interviews were conducted allowing a thorough exploration of interviewees' views and experiences of the benefits of genetic counselling and testing. Transcripts were analysed using thematic analysis. Both affected and unaffected interviewees expressed mainly positive views about genetic testing, highlighting benefits such as diagnostic confirmation, risk information, and better preparation for the future. Negative consequences included the burden of knowledge, moral dilemmas around reproduction, and potential impact on insurance. The offer of genetic testing was often taken up, but was felt unnecessary in some cases. Interviewees in the study reported many benefits, suggesting genetic testing should be available to this patient group. The benefits and risks identified will inform future evaluation of models of service delivery. This research was part of a wider study exploring experiences of families with retinal dystrophy. PMID:23403902

Understanding the impact of genetic testing for inherited retinal dystrophy.

PubMed

Combs, Ryan; McAllister, Marion; Payne, Katherine; Lowndes, Jo; Devery, Sophie; Webster, Andrew R; Downes, Susan M; Moore, Anthony T; Ramsden, Simon; Black, Graeme; Hall, Georgina

2013-11-01

The capability of genetic technologies is expanding rapidly in the field of inherited eye disease. New genetic testing approaches will deliver a step change in the ability to diagnose and extend the possibility of targeted treatments. However, evidence is lacking about the benefits of genetic testing to support service planning. Here, we report qualitative data about retinal dystrophy families' experiences of genetic testing in United Kingdom. The data were part of a wider study examining genetic eye service provision. Twenty interviewees from families in which a causative mutation had been identified by a genetic eye clinic were recruited to the study. Fourteen interviewees had chosen to have a genetic test and five had not; one was uncertain. In-depth telephone interviews were conducted allowing a thorough exploration of interviewees' views and experiences of the benefits of genetic counselling and testing. Transcripts were analysed using thematic analysis. Both affected and unaffected interviewees expressed mainly positive views about genetic testing, highlighting benefits such as diagnostic confirmation, risk information, and better preparation for the future. Negative consequences included the burden of knowledge, moral dilemmas around reproduction, and potential impact on insurance. The offer of genetic testing was often taken up, but was felt unnecessary in some cases. Interviewees in the study reported many benefits, suggesting genetic testing should be available to this patient group. The benefits and risks identified will inform future evaluation of models of service delivery. This research was part of a wider study exploring experiences of families with retinal dystrophy.

Going forward with genetics: recent technological advances and forward genetics in mice.

PubMed

Moresco, Eva Marie Y; Li, Xiaohong; Beutler, Bruce

2013-05-01

Forward genetic analysis is an unbiased approach for identifying genes essential to defined biological phenomena. When applied to mice, it is one of the most powerful methods to facilitate understanding of the genetic basis of human biology and disease. The speed at which disease-causing mutations can be identified in mutagenized mice has been markedly increased by recent advances in DNA sequencing technology. Creating and analyzing mutant phenotypes may therefore become rate-limiting in forward genetic experimentation. We review the forward genetic approach and its future in the context of recent technological advances, in particular massively parallel DNA sequencing, induced pluripotent stem cells, and haploid embryonic stem cells. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Association of genetic and phenotypic variability with geography and climate in three southern California oaks.

PubMed

Riordan, Erin C; Gugger, Paul F; Ortego, Joaquín; Smith, Carrie; Gaddis, Keith; Thompson, Pam; Sork, Victoria L

2016-01-01

Geography and climate shape the distribution of organisms, their genotypes, and their phenotypes. To understand historical and future evolutionary and ecological responses to climate, we compared the association of geography and climate of three oak species (Quercus engelmannii, Quercus berberidifolia, and Quercus cornelius-mulleri) in an environmentally heterogeneous region of southern California at three organizational levels: regional species distributions, genetic variation, and phenotypic variation. We identified climatic variables influencing regional distribution patterns using species distribution models (SDMs), and then tested whether those individual variables are important in shaping genetic (microsatellite) and phenotypic (leaf morphology) variation. We estimated the relative contributions of geography and climate using multivariate redundancy analyses (RDA) with variance partitioning. The modeled distribution of each species was influenced by climate differently. Our analysis of genetic variation using RDA identified small but significant associations between genetic variation with climate and geography in Q. engelmannii and Q. cornelius-mulleri, but not in Q. berberidifolia, and climate explained more of the variation. Our analysis of phenotypic variation in Q. engelmannii indicated that climate had more impact than geography, but not in Q. berberidifolia. Throughout our analyses, we did not find a consistent pattern in effects of individual climatic variables. Our comparative analysis illustrates that climate influences tree response at all organizational levels, but the important climate factors vary depending on the level and on the species. Because of these species-specific and level-specific responses, today's sympatric species are unlikely to have similar distributions in the future. © 2016 Botanical Society of America.

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing. PMID:23226057

Integrative Approaches to Understanding the Pathogenic Role of Genetic Variation in Rheumatic Diseases.

PubMed

Laufer, Vincent A; Chen, Jake Y; Langefeld, Carl D; Bridges, S Louis

2017-08-01

The use of high-throughput omics may help to understand the contribution of genetic variants to the pathogenesis of rheumatic diseases. We discuss the concept of missing heritability: that genetic variants do not explain the heritability of rheumatoid arthritis and related rheumatologic conditions. In addition to an overview of how integrative data analysis can lead to novel insights into mechanisms of rheumatic diseases, we describe statistical approaches to prioritizing genetic variants for future functional analyses. We illustrate how analyses of large datasets provide hope for improved approaches to the diagnosis, treatment, and prevention of rheumatic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative maps of genetic interactions in yeast - comparative evaluation and integrative analysis.

PubMed

Lindén, Rolf O; Eronen, Ville-Pekka; Aittokallio, Tero

2011-03-24

High-throughput genetic screening approaches have enabled systematic means to study how interactions among gene mutations contribute to quantitative fitness phenotypes, with the aim of providing insights into the functional wiring diagrams of genetic interaction networks on a global scale. However, it is poorly known how well these quantitative interaction measurements agree across the screening approaches, which hinders their integrated use toward improving the coverage and quality of the genetic interaction maps in yeast and other organisms. Using large-scale data matrices from epistatic miniarray profiling (E-MAP), genetic interaction mapping (GIM), and synthetic genetic array (SGA) approaches, we carried out here a systematic comparative evaluation among these quantitative maps of genetic interactions in yeast. The relatively low association between the original interaction measurements or their customized scores could be improved using a matrix-based modelling framework, which enables the use of single- and double-mutant fitness estimates and measurements, respectively, when scoring genetic interactions. Toward an integrative analysis, we show how the detections from the different screening approaches can be combined to suggest novel positive and negative interactions which are complementary to those obtained using any single screening approach alone. The matrix approximation procedure has been made available to support the design and analysis of the future screening studies. We have shown here that even if the correlation between the currently available quantitative genetic interaction maps in yeast is relatively low, their comparability can be improved by means of our computational matrix approximation procedure, which will enable integrative analysis and detection of a wider spectrum of genetic interactions using data from the complementary screening approaches.

A set of autosomal multiple InDel markers for forensic application and population genetic analysis in the Chinese Xinjiang Hui group.

PubMed

Xie, Tong; Guo, Yuxin; Chen, Ling; Fang, Yating; Tai, Yunchun; Zhou, Yongsong; Qiu, Pingming; Zhu, Bofeng

2018-07-01

In recent years, insertion/deletion (InDel) markers have become a promising and useful supporting tool in forensic identification cases and biogeographic research field. In this study, 30 InDel loci were explored to reveal the genetic diversities and genetic relationships between Chinese Xinjiang Hui group and the 25 previously reported populations using various biostatistics methods such as forensic statistical parameter analysis, phylogenetic reconstruction, multi-dimensional scaling, principal component analysis, and STRUCTURE analysis. No deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in the Chinese Xinjiang Hui group. The observed heterozygosity and expected heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD92), 0.2222 (HLD118) to 0.5000 (HLD6), respectively. The cumulative probability of exclusion and combined power of discrimination were 0.988849 and 0.99999999999378, respectively, which indicated that these 30 loci could be qualified for personal identification and used as complementary genetic markers for paternity tests in forensic cases. The results of present research based on the different methods of population genetic analysis revealed that the Chinese Xinjiang Hui group had close relationships with most Chinese groups, especially Han populations. In spite of this, for a better understanding of genetic background of the Chinese Xinjiang Hui group, more molecular genetic markers such as ancestry informative markers, single nucleotide polymorphisms (SNPs), and copy number variations will be conducted in future studies. Copyright © 2018 Elsevier B.V. All rights reserved.

The Human Microbiome: Our Second Genome*

PubMed Central

Grice, Elizabeth A.; Segre, Julia A.

2012-01-01

The human genome has been referred to as the blueprint of human biology. In this review we consider an essential but largely ignored overlay to that blueprint, the human microbiome, which is composed of those microbes that live in and on our bodies. The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions. Characterization and analysis of the human microbiome have been greatly catalyzed by advances in genomic technologies. We discuss how these technologies have shaped this emerging field of study and advanced our understanding of the human microbiome. We also identify future challenges, many of which are common to human genetic studies, and predict that in the future, analyzing genetic variation and risk of human disease will sometimes necessitate the integration of human and microbial genomic data sets. PMID:22703178

Genetic variation and forensic efficiency of autosomal insertion/deletion polymorphisms in Chinese Bai ethnic group: phylogenetic analysis to other populations

PubMed Central

Yang, Chun-Hua; Yin, Cai-Yong; Shen, Chun-Mei; Guo, Yu-Xin; Dong, Qian; Yan, Jiang-Wei; Wang, Hong-Dan; Zhang, Yu-Dang; Meng, Hao-Tian; Jin, Rui

2017-01-01

Thirty insertion/deletion loci were utilized to study the genetic diversities of 125 bloodstain samples collected from Bai group in Yunnan Dali region, China. The observed heterozygosity and expected heterozygosity of the 30 loci ranged from 0.1520 to 0.5680, and 0.1927 to 0.4997, respectively. No deviations from Hardy-Weinberg equilibrium tests after Bonferroni correction were found at all 30 loci in Bai group. The cumulative probability of exclusion and combined discrimination power were 0.9859 and 0.9999999999887, respectively, which indicated the 30 loci could be used as complementary genetic markers for paternity testing and were qualified for personal identification in forensic cases. We found the studied Bai group had close relationships with Tibetan, Yi and Han groups from China by the population structure, principal component analysis, population differentiations, and phylogenetic reconstruction studies. Even so, for a better understanding of Bai ethnicity's genetic milieu, DNA genotyping at various genetic markers is necessary in future studies. PMID:28465476

Genetic diversity of Trichomonas vaginalis clinical isolates from Henan province in central China.

PubMed

Mao, Meng; Liu, Hui Li

2015-07-01

Trichomonas vaginalis is a flagellated protozoan parasite that infects the human urogenital tract, causing the most common non-viral, sexually transmitted disease worldwide. In this study, genetic variants of T. vaginalis were identified in Henan Province, China. Fragments of the small subunit of nuclear ribosomal RNA (18S rRNA) were amplified from 32 T. vaginalis isolates obtained from seven regions of Henan Province. Overall, 18 haplotypes were determined from the 18S rRNA sequences. Each sampled population and the total population displayed high haplotype diversity (Hd), accompanied by very low nucleotide diversity (Pi). In these molecular genetic variants, 91.58% genetic variation was derived from intra-regions. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. Demographic analysis supported population expansion of T. vaginalis isolates from central China. Our findings showing moderate-to-high genetic variations in the 32 isolates of T. vaginalis provide useful knowledge for monitoring changes in parasite populations for the development of future control strategies.

Genetic variation and forensic efficiency of autosomal insertion/deletion polymorphisms in Chinese Bai ethnic group: phylogenetic analysis to other populations.

PubMed

Yang, Chun-Hua; Yin, Cai-Yong; Shen, Chun-Mei; Guo, Yu-Xin; Dong, Qian; Yan, Jiang-Wei; Wang, Hong-Dan; Zhang, Yu-Dang; Meng, Hao-Tian; Jin, Rui; Chen, Feng; Zhu, Bo-Feng

2017-06-13

Thirty insertion/deletion loci were utilized to study the genetic diversities of 125 bloodstain samples collected from Bai group in Yunnan Dali region, China. The observed heterozygosity and expected heterozygosity of the 30 loci ranged from 0.1520 to 0.5680, and 0.1927 to 0.4997, respectively. No deviations from Hardy-Weinberg equilibrium tests after Bonferroni correction were found at all 30 loci in Bai group. The cumulative probability of exclusion and combined discrimination power were 0.9859 and 0.9999999999887, respectively, which indicated the 30 loci could be used as complementary genetic markers for paternity testing and were qualified for personal identification in forensic cases. We found the studied Bai group had close relationships with Tibetan, Yi and Han groups from China by the population structure, principal component analysis, population differentiations, and phylogenetic reconstruction studies. Even so, for a better understanding of Bai ethnicity's genetic milieu, DNA genotyping at various genetic markers is necessary in future studies.

Evolutionary Meta-Analysis of Association Studies Reveals Ancient Constraints Affecting Disease Marker Discovery

PubMed Central

Dudley, Joel T.; Chen, Rong; Sanderford, Maxwell; Butte, Atul J.; Kumar, Sudhir

2012-01-01

Genome-wide disease association studies contrast genetic variation between disease cohorts and healthy populations to discover single nucleotide polymorphisms (SNPs) and other genetic markers revealing underlying genetic architectures of human diseases. Despite scores of efforts over the past decade, many reproducible genetic variants that explain substantial proportions of the heritable risk of common human diseases remain undiscovered. We have conducted a multispecies genomic analysis of 5,831 putative human risk variants for more than 230 disease phenotypes reported in 2,021 studies. We find that the current approaches show a propensity for discovering disease-associated SNPs (dSNPs) at conserved genomic positions because the effect size (odds ratio) and allelic P value of genetic association of an SNP relates strongly to the evolutionary conservation of their genomic position. We propose a new measure for ranking SNPs that integrates evolutionary conservation scores and the P value (E-rank). Using published data from a large case-control study, we demonstrate that E-rank method prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic disease associations, many of which may explain greater proportions of genetic variance. Therefore, long-term evolutionary histories of genomic positions offer key practical utility in reassessing data from existing disease association studies, and in the design and analysis of future studies aimed at revealing the genetic basis of common human diseases. PMID:22389448

Policy analysis for prenatal genetic diagnosis.

PubMed

Thompson, M; Milunsky, A

1979-01-01

Consideration of the analytic difficulties faced in estimating the benefits and costs of prenatal genetic diagnosis, coupled with a brief review of existing benefit-cost studies, leads to the conclusion that public subsidy of prenatal testing can yield benefits substantially in excess of costs. The practical obstacles to such programs include the attitudes of prospective parents, a lack of knowledge, monetary barriers, inadequately organized medical resources, and the political issue of abortion. Policy analysis can now nevertheless formulate principles and guide immediate actions to improve present utilization of prenatal testing and to facilitate possible future expansion of these diagnostic techniques.

Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

NASA Astrophysics Data System (ADS)

Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

2017-04-01

Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main coniferous species for a sustainable forest management in the context of climate change), financed by the Executive Agency for Higher Education, Research, Development and Innovation Funding, grant number PN-II-PC-PCCA-2013-4-0695.

Identifying future research needs in landscape genetics: Where to from here?

Treesearch

Niko Balkenhol; Felix Gugerli; Sam A. Cushman; Lisette P. Waits; Aurelie Coulon; J. W. Arntzen; Rolf Holderegger; Helene H. Wagner

2009-01-01

Landscape genetics is an emerging interdisciplinary field that combines methods and concepts from population genetics, landscape ecology, and spatial statistics. The interest in landscape genetics is steadily increasing, and the field is evolving rapidly. We here outline four major challenges for future landscape genetic research that were identified during an...

Evidence of a genetic link between endometriosis and ovarian cancer.

PubMed

Lee, Alice W; Templeman, Claire; Stram, Douglas A; Beesley, Jonathan; Tyrer, Jonathan; Berchuck, Andrew; Pharoah, Paul P; Chenevix-Trench, Georgia; Pearce, Celeste Leigh

2016-01-01

To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Pooled genetic analysis. University hospital. Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. None. Endometriosis-associated genetic variation and ovarian cancer. There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions. Copyright © 2016. Published by Elsevier Inc.

Genomic evidence for the population genetic differentiation of Misgurnus anguillicaudatus in the Yangtze River basin of China.

PubMed

Yi, Shaokui; Wang, Weimin; Zhou, Xiaoyun

2018-02-21

Misgurnus anguillicaudatus, an important aquatic species, is mainly distributed in the Yangtze River basin. To reveal the population genetic structure of M. anguillicaudatus distributed in the Yangtze River basin, genotyping by sequencing (GBS) technique was employed to detect the genome wide genetic variations of M. anguillicaudatus. A total of 30.03 Gb raw data were yielded from 70 samples collected from 15 geographic sites located in the Yangtze River basin. Subsequently, 2092 high quality SNPs were genotyped across these samples and used for a series of genetic analysis. The results of genetic analysis showed that high levels of genetic diversity were observed and the populations from upper reaches (UR) were significantly differentiated from the middle and lower reaches (MLR) of Yangtze River basin. Meanwhile, no significant isolation by distance was detected among the populations. Ecological factors (e.g. complicated topography and climatic environment) and anthropogenic factors (e.g. aquaculture and agriculture cultivation) might account for the genetic disconnectivity between UR and MLR populations. This study provided valuable genetic data for the future breeding program and also for the conversation and scientific utilization of those abundant genetic resources stored in the Yangtze River basin. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis of the Multi Strategy Goal Programming for Micro-Grid Based on Dynamic ant Genetic Algorithm

NASA Astrophysics Data System (ADS)

Qiu, J. P.; Niu, D. X.

Micro-grid is one of the key technologies of the future energy supplies. Take economic planning. reliability, and environmental protection of micro grid as a basis for the analysis of multi-strategy objective programming problems for micro grid which contains wind power, solar power, and battery and micro gas turbine. Establish the mathematical model of each power generation characteristics and energy dissipation. and change micro grid planning multi-objective function under different operating strategies to a single objective model based on AHP method. Example analysis shows that in combination with dynamic ant mixed genetic algorithm can get the optimal power output of this model.

Genetic approaches of the Fe-S cluster biogenesis process in bacteria: Historical account, methodological aspects and future challenges.

PubMed

Py, Béatrice; Barras, Frédéric

2015-06-01

Since their discovery in the 50's, Fe-S cluster proteins have attracted much attention from chemists, biophysicists and biochemists. However, in the 80's they were joined by geneticists who helped to realize that in vivo maturation of Fe-S cluster bound proteins required assistance of a large number of factors defining complex multi-step pathways. The question of how clusters are formed and distributed in vivo has since been the focus of much effort. Here we review how genetics in discovering genes and investigating processes as they unfold in vivo has provoked seminal advances toward our understanding of Fe-S cluster biogenesis. The power and limitations of genetic approaches are discussed. As a final comment, we argue how the marriage of classic strategies and new high-throughput technologies should allow genetics of Fe-S cluster biology to be even more insightful in the future. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic testing in combination with preventive donepezil treatment for patients with amnestic mild cognitive impairment: an exploratory economic evaluation of personalized medicine.

PubMed

Djalalov, Sandjar; Yong, Jean; Beca, Jaclyn; Black, Sandra; Saposnik, Gustavo; Musa, Zahra; Siminovitch, Katherine; Moretti, Myla; Hoch, Jeffrey S

2012-12-01

To evaluate the cost effectiveness of genetic screening for the apolipoprotein (APOE) ε4 allele in combination with preventive donepezil treatment in comparison with the standard of care for amnestic mild cognitive impairment (AMCI) patients in Canada. We performed a cost-effectiveness analysis using a Markov model with a societal perspective and a time horizon of 30 years. For each strategy, we calculated quality-adjusted life-years (QALYs), using utilities from the literature. Costs were also based on the literature and, when appropriate, Ontario sources. One-way and probabilistic sensitivity analyses were performed. Expected value of perfect information (EVPI) analysis was conducted to explore the value of future research. The base case results in our exploratory study suggest that the combination of genetic testing and preventive donepezil treatment resulted in a gain of 0.027 QALYs and an incremental cost of $1,015 (in 2009 Canadian dollars [Can$]), compared with the standard of care. The incremental cost-effectiveness ratio (ICER) for the base case was Can$38,016 per QALY. The ICER was sensitive to the effectiveness of donepezil in slowing the rate of progression to Alzheimer's disease (AD), utility in AMCI patients, and AD and donepezil treatment costs. EVPI analysis showed that additional information on these parameters would be of value. Using presently available clinical evidence, this exploratory study illustrates that genetic testing combined with preventive donepezil treatment for AMCI patients may be economically attractive. Since our results were based on a secondary post hoc analysis, our study alone is insufficient to warrant recommending APOE genotyping in AMCI patients. Future research on the effectiveness of preventive donepezil as a targeted therapy is recommended.

Molecular genetic analysis of patients with sporadic and X-linked infantile nystagmus

PubMed Central

Zhao, Hui; Huang, Xiu-Feng; Zheng, Zhi-Li; Deng, Wen-Li; Lei, Xin-Lan; Xing, Dong-Jun; Ye, Liang; Xu, Su-Zhong; Chen, Jie; Zhang, Fang; Yu, Xin-Ping; Jin, Zi-Bing

2016-01-01

Objectives Infantile nystagmus (IN) is a genetically heterogeneous condition characterised by involuntary rhythmic oscillations of the eyes accompanied by different degrees of vision impairment. Two genes have been identified as mainly causing IN: FRMD7 and GPR143. The aim of our study was to identify the genetic basis of both sporadic IN and X-linked IN. Design Prospective analysis. Patients Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. Mutational analysis and co-segregation confirmation were then performed. Setting All clinical examinations and genetic experiments were performed in the Eye Hospital of Wenzhou Medical University. Results Two mutations in the FRMD7 gene, including one novel nonsense mutation (c.1090C>T, p.Q364X) and one reported missense mutation (c.781C>G, p.R261G), were identified in two of the five (40%) X-linked IN families. However, none of putative mutations were identified in FRMD7 or GPR143 in any of the sporadic cases. Conclusions The results suggest that mutations in FRMD7 appeared to be the major genetic cause of X-linked IN, but not of sporadic IN. Our findings provide further insights into FRMD7 mutations, which could be helpful for future genetic diagnosis and genetic counselling of Chinese patients with nystagmus. PMID:27036142

Genetic Psychophysiology: advances, problems, and future directions

PubMed Central

Anokhin, Andrey P.

2014-01-01

This paper presents an overview of historical advances and the current state of genetic psychophysiology, a rapidly developing interdisciplinary research linking genetics, brain, and human behavior, discusses methodological problems, and outlines future directions of research. The main goals of genetic psychophysiology are to elucidate the neural pathways and mechanisms mediating genetic influences on cognition and emotion, identify intermediate brain-based phenotypes for psychopathology, and provide a functional characterization of genes being discovered by large association studies of behavioral phenotypes. Since the initiation of this neurogenetic approach to human individual differences in the 1970s, numerous twin and family studies have provided strong evidence for heritability of diverse aspects of brain function including resting-state brain oscillations, functional connectivity, and event-related neural activity in a variety of cognitive and emotion processing tasks, as well as peripheral psychophysiological responses. These data indicate large differences in the presence and strength of genetic influences across measures and domains, permitting the selection of heritable characteristics for gene finding studies. More recently, candidate gene association studies began to implicate specific genetic variants in different aspects of neurocognition. However, great caution is needed in pursuing this line of research due to its demonstrated proneness to generate false-positive findings. Recent developments in methods for physiological signal analysis, hemodynamic imaging, and genomic technologies offer new exciting opportunities for the investigation of the interplay between genetic and environmental factors in the development of individual differences in behavior, both normal and abnormal. PMID:24739435

Genetic parameters and path analysis in cowpea genotypes grown in the Cerrado/Pantanal ecotone.

PubMed

Lopes, K V; Teodoro, P E; Silva, F A; Silva, M T; Fernandes, R L; Rodrigues, T C; Faria, T C; Corrêa, A M

2017-05-18

Estimating genetic parameters in plant breeding allows us to know the population potential for selecting and designing strategies that can maximize the achievement of superior genotypes. The objective of this study was to evaluate the genetic potential of a population of 20 cowpea genotypes by estimating genetic parameters and path analysis among the traits to guide the selection strategies. The trial was conducted in randomized block design with four replications. Its morphophysiological components, components of green grain production and dry grain yield were estimated from genetic use and correlations between the traits. Phenotypic correlations were deployed through path analysis into direct and indirect effects of morphophysiological traits and yield components on dry grain yield. There were significant differences (P < 0.01) between the genotypes for most the traits, indicating the presence of genetic variability in the population and the possibility of practicing selection. The population presents the potential for future genetic breeding studies and is highly promising for the selection of traits dry grain yield, the number of grains per pod, and hundred grains mass. A number of grains per green pod is the main determinant trait of dry grain yield that is also influenced by the cultivar cycle and that the selection for the dry grain yield can be made indirectly by selecting the green pod mass and green pod length.

Genetic diversity and association mapping in the Colombian Central Collection of Solanum tuberosum L. Andigenum group using SNPs markers.

PubMed

Berdugo-Cely, Jhon; Valbuena, Raúl Iván; Sánchez-Betancourt, Erika; Barrero, Luz Stella; Yockteng, Roxana

2017-01-01

The potato (Solanum tuberosum L.) is the fourth most important crop food in the world and Colombia has one of the most important collections of potato germplasm in the world (the Colombian Central Collection-CCC). Little is known about its potential as a source of genetic diversity for molecular breeding programs. In this study, we analyzed 809 Andigenum group accessions from the CCC using 5968 SNPs to determine: 1) the genetic diversity and population structure of the Andigenum germplasm and 2) the usefulness of this collection to map qualitative traits across the potato genome. The genetic structure analysis based on principal components, cluster analyses, and Bayesian inference revealed that the CCC can be subdivided into two main groups associated with their ploidy level: Phureja (diploid) and Andigena (tetraploid). The Andigena population was more genetically diverse but less genetically substructured than the Phureja population (three vs. five subpopulations, respectively). The association mapping analysis of qualitative morphological data using 4666 SNPs showed 23 markers significantly associated with nine morphological traits. The present study showed that the CCC is a highly diverse germplasm collection genetically and phenotypically, useful to implement association mapping in order to identify genes related to traits of interest and to assist future potato genetic breeding programs.

Genetic diversity and association mapping in the Colombian Central Collection of Solanum tuberosum L. Andigenum group using SNPs markers

PubMed Central

Berdugo-Cely, Jhon; Valbuena, Raúl Iván; Sánchez-Betancourt, Erika; Barrero, Luz Stella

2017-01-01

The potato (Solanum tuberosum L.) is the fourth most important crop food in the world and Colombia has one of the most important collections of potato germplasm in the world (the Colombian Central Collection-CCC). Little is known about its potential as a source of genetic diversity for molecular breeding programs. In this study, we analyzed 809 Andigenum group accessions from the CCC using 5968 SNPs to determine: 1) the genetic diversity and population structure of the Andigenum germplasm and 2) the usefulness of this collection to map qualitative traits across the potato genome. The genetic structure analysis based on principal components, cluster analyses, and Bayesian inference revealed that the CCC can be subdivided into two main groups associated with their ploidy level: Phureja (diploid) and Andigena (tetraploid). The Andigena population was more genetically diverse but less genetically substructured than the Phureja population (three vs. five subpopulations, respectively). The association mapping analysis of qualitative morphological data using 4666 SNPs showed 23 markers significantly associated with nine morphological traits. The present study showed that the CCC is a highly diverse germplasm collection genetically and phenotypically, useful to implement association mapping in order to identify genes related to traits of interest and to assist future potato genetic breeding programs. PMID:28257509

The shaping of genetic variation in edge-of-range populations under past and future climate change

PubMed Central

Razgour, Orly; Juste, Javier; Ibáñez, Carlos; Kiefer, Andreas; Rebelo, Hugo; Puechmaille, Sébastien J; Arlettaz, Raphael; Burke, Terry; Dawson, Deborah A; Beaumont, Mark; Jones, Gareth; Wiens, John

2013-01-01

With rates of climate change exceeding the rate at which many species are able to shift their range or adapt, it is important to understand how future changes are likely to affect biodiversity at all levels of organisation. Understanding past responses and extent of niche conservatism in climatic tolerance can help predict future consequences. We use an integrated approach to determine the genetic consequences of past and future climate changes on a bat species, Plecotus austriacus. Glacial refugia predicted by palaeo-modelling match those identified from analyses of extant genetic diversity and model-based inference of demographic history. Former refugial populations currently contain disproportionately high genetic diversity, but niche conservatism, shifts in suitable areas and barriers to migration mean that these hotspots of genetic diversity are under threat from future climate change. Evidence of population decline despite recent northward migration highlights the need to conserve leading-edge populations for spearheading future range shifts. PMID:23890483

Use of genotyping-by-sequencing to determine the genetic structure in the medicinal plant chamomile, and to identify flowering time and alpha-bisabolol associated SNP-loci by genome-wide association mapping.

PubMed

Otto, Lars-Gernot; Mondal, Prodyut; Brassac, Jonathan; Preiss, Susanne; Degenhardt, Jörg; He, Sang; Reif, Jochen Christoph; Sharbel, Timothy Francis

2017-08-10

Chamomile (Matricaria recutita L.) has a long history of use in herbal medicine with various applications, and the flower heads contain numerous secondary metabolites which are medicinally active. In the major crop plants, next generation sequencing (NGS) approaches are intensely applied to exploit genetic resources, to develop genomic resources and to enhance breeding. Here, genotyping-by-sequencing (GBS) has been used in the non-model medicinal plant chamomile to evaluate the genetic structure of the cultivated varieties/populations, and to perform genome wide association study (GWAS) focusing on genes with large effect on flowering time and the medicinally important alpha-bisabolol content. GBS analysis allowed the identification of 6495 high-quality SNP-markers in our panel of 91 M. recutita plants from 33 origins (2-4 genotypes each) and 4 M. discoidea plants as outgroup, grown in the greenhouse in Gatersleben, Germany. M. recutita proved to be clearly distinct from the outgroup, as was demonstrated by different cluster and principal coordinate analyses using the SNP-markers. Chamomile genotypes from the same origin were mostly genetically similar. Model-based cluster analysis revealed one large group of tetraploid genotypes with low genetic differentiation including 39 plants from 14 origins. Tetraploids tended to display lower genetic diversity than diploids, probably reflecting their origin by artificial polyploidisation from only a limited set of genetic backgrounds. Analyses of flowering time demonstrated that diploids generally flowered earlier than tetraploids, and the analysis of alpha-bisabolol identified several tetraploid genotypes with a high content. GWAS identified highly significant (P < 0.01) SNPs for flowering time (9) and alpha-bisabolol (71). One sequence harbouring SNPs associated with flowering time was described to play a role in self-pollination in Arabidopsis thaliana, whereas four sequences harbouring SNPs associated with alpha-bisabolol were identified to be involved in plant biotic and abiotic stress response in various plants species. The first genomic resource for future applications to enhance breeding in chamomile was created, andanalyses of diversity will facilitate the exploitation of these genetic resources. The GWAS data pave the way for future research towards the genetics underlying important traits in chamomile, the identification of marker-trait associations, and development of reliable markers for practical breeding.

Genetic therapy in gliomas: historical analysis and future perspectives.

PubMed

Mattei, Tobias Alécio; Ramina, Ricardo; Miura, Flavio Key; Aguiar, Paulo Henrique; Valiengo, Leandro da Costa

2005-03-01

High-grade gliomas are relatively frequent in adults, and consist of the most malignant kind of primary brain tumor. Being resistant to standard treatment modalities such as surgery, radiation, and chemotherapy, it is fatal within 1 to 2 years of onset of symptoms. Although several gene therapy systems proved to be efficient in controlling or eradicating these tumors in animal models, the clinical studies performed so far were not equally successful. Most clinical studies showed that methodologies that increase tumor infection/transduction and, consequently confer more permanent activity against the tumor, will lead to enhanced therapeutic results. Due to the promising practical clinical benefits that can be expected for the near future, an exposition to the practicing neurosurgeon about the basic issues in genetic therapy of gliomas seems convenient. Among the main topics, we shall discuss anti-tumoral mechanisms of various genes that can be transfected, the advantages and drawbacks of the different vectors utilized, the possibilities of tumor targeting by modifications in the native tropism of virus vectors, as well as the different physical methods for vector delivery to the tumors. Along with the exposition we will also review of the history of the genetic therapy for gliomas, with special focus on the main problems found during the advancement of scientific discoveries in this area. A general analysis is also made of the present state of this promising therapeutic modality, with reference to the problems that still must be solved and the new paradigms for future research in this area.

Expectation and futurity: The remarkable success of genetic determinism.

PubMed

Esposito, Maurizio

2017-04-01

Genetic determinism is nowadays largely questioned and widely criticized. However, if we look at the history of biology in the last one hundred years, we realize that genetic determinism has always been controversial. Why, then, did it acquire such relevance in the past despite facing longstanding criticism? Through the analysis of some of the ambitious expectations of future scientific applications, this article explores the possibility that part of the historical success of genetic determinism lies in the powerful rhetorical strategies that have connected the germinal matter with alluring bio-technological visions. Indeed, in drawing on the recent perspectives of "expectation studies" in science and technology, it will be shown that there has been an interesting historical relationship between reductionist notions of the gene as a hereditary unit, coded information or functional DNA segment, and startling prophecies of what controlling such an entity might achieve. It will also be suggested that the well-known promissory nature of genomics is far older than the emergence of biotechnology in the 1970s. At least from the time of the bio-utopias predicted by J.B.S. Haldane and J. S. Huxley, the gene has often been surrounded by what I call the "rhetoric of futurity": a promissory rhetoric that, despite momentous changes in the life sciences throughout the 20th century, has remained relatively consistent over time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Innovations in human genetics education. Incorporation of genetics into a problem-based medical school curriculum.

PubMed Central

Swinford, A E; McKeag, D B

1990-01-01

There has been recent interest in the development of problem-based human genetics curricula in U.S. medical schools. The College of Human Medicine at Michigan State University has had a problem-based curriculum since 1974. The vertical integration of genetics within the problem-based curriculum, called "Track II," has recently been revised. On first inspection, the curriculum appeared to lack a significant genetics component; however, on further analysis it was found that many genetics concepts were covered in the biochemistry, microbiology, pathology, and clinical science components. Both basic science concepts and clinical applications of genetics are covered in the curriculum by providing appropriate references for basic concepts and including inherited conditions within the differential diagnosis in the cases studied. Evaluations consist of a multiple-choice content exam and a modified essay exam based on a clinical case, allowing evaluation of both basic concepts and problem-solving ability. This curriculum prepares students to use genetics in a clinical context in their future careers. PMID:2220816

Genetic overlap between type 2 diabetes and major depressive disorder identified by bioinformatics analysis.

PubMed

Ji, Hong-Fang; Zhuang, Qi-Shuai; Shen, Liang

2016-04-05

Our study investigated the shared genetic etiology underlying type 2 diabetes (T2D) and major depressive disorder (MDD) by analyzing large-scale genome wide association studies statistics. A total of 496 shared SNPs associated with both T2D and MDD were identified at p-value ≤ 1.0E-07. Functional enrichment analysis showed that the enriched pathways pertained to immune responses (Fc gamma R-mediated phagocytosis, T cell and B cell receptors signaling), cell signaling (MAPK, Wnt signaling), lipid metabolism, and cancer associated pathways. The findings will have potential implications for future interventional studies of the two diseases.

A role for molecular genetics in biological conservation.

PubMed Central

O'Brien, S J

1994-01-01

The recognition of recent accelerated depletion of species as a consequence of human industrial development has spawned a wide interest in identifying threats to endangered species. In addition to ecological and demographic perils, it has become clear that small populations that narrowly survive demographic contraction may undergo close inbreeding, genetic drift, and loss of overall genomic variation due to allelic loss or reduction to homozygosity. I review here the consequences of such genetic depletion revealed by applying molecular population genetic analysis to four endangered mammals: African cheetah, lion, Florida panther, and humpback whale. The accumulated genetic results, combined with physiological, ecological, and ethological data, provide a multifaceted perspective of the process of species diminution. An emerging role of population genetics, phylogenetics, and phylogeography as indicators of a population's natural history and its future prognosis provides valuable data of use in the development of conservation management plans for endangered species. PMID:7912434

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

PubMed

Beauchaine, Theodore P; Constantino, John N

2017-09-11

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.

Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV).

PubMed

Snow, M; Bain, N; Black, J; Taupin, V; Cunningham, C O; King, J A; Skall, H F; Raynard, R S

2004-10-21

The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups of isolates associated with rainbow trout aquaculture (Genotype Ia) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also confirmed. Genotype III included marine isolates from around the British Isles in addition to those associated with turbot mariculture, highlighting a continued risk to the development of this industry. Genotype IV consisted of isolates from the marine environment in North America. Taken together, these findings suggest a marine origin of VHSV in rainbow trout aquaculture. The implications of these findings with respect to the future control of VHSV are discussed. The capacity for molecular phylogenetic analysis to resolve complex epidemiological problems is also demonstrated and its likely future importance to disease management issues highlighted.

[Progress in studies on the genetic risk factors for nonsyndromic cleft lip or palate in China].

PubMed

Huang, Y Q

2017-04-09

Cleft lip and palate is the most common congenital defects of oral and maxillofacial region in human beings. The etiology of this malformation is complex, with both genetic and environmental causal factors are involved. To provide a better understanding in the genetic etiology of cleft lip or palate, the author summarized recent years studies based on Chinese population. Those researches included validation of some candidate genes for cleft lip or palate, using genome wide association analysis which included six independent cohorts from China to elucidate the genetic architecture of non-syndromic cleft lip with or without cleft palate in Chinese population and finally found a new susceptibility locus. This locus was on the 16p13.3 (rs8049367) between CREBBP and ADCY9. It has been mentioned common methods of genetic analysis involved in the researches on cleft lip or palate in this paper. Furthermore, we try to discuss new methods to illustrate the etiology of cleft lip and palate that could provide more inspiration on future researches.

Predicting the genetic consequences of future climate change: The power of coupling spatial demography, the coalescent, and historical landscape changes.

PubMed

Brown, Jason L; Weber, Jennifer J; Alvarado-Serrano, Diego F; Hickerson, Michael J; Franks, Steven J; Carnaval, Ana C

2016-01-01

Climate change is a widely accepted threat to biodiversity. Species distribution models (SDMs) are used to forecast whether and how species distributions may track these changes. Yet, SDMs generally fail to account for genetic and demographic processes, limiting population-level inferences. We still do not understand how predicted environmental shifts will impact the spatial distribution of genetic diversity within taxa. We propose a novel method that predicts spatially explicit genetic and demographic landscapes of populations under future climatic conditions. We use carefully parameterized SDMs as estimates of the spatial distribution of suitable habitats and landscape dispersal permeability under present-day, past, and future conditions. We use empirical genetic data and approximate Bayesian computation to estimate unknown demographic parameters. Finally, we employ these parameters to simulate realistic and complex models of responses to future environmental shifts. We contrast parameterized models under current and future landscapes to quantify the expected magnitude of change. We implement this framework on neutral genetic data available from Penstemon deustus. Our results predict that future climate change will result in geographically widespread declines in genetic diversity in this species. The extent of reduction will heavily depend on the continuity of population networks and deme sizes. To our knowledge, this is the first study to provide spatially explicit predictions of within-species genetic diversity using climatic, demographic, and genetic data. Our approach accounts for climatic, geographic, and biological complexity. This framework is promising for understanding evolutionary consequences of climate change, and guiding conservation planning. © 2016 Botanical Society of America.

Genetic diversity and population structure of the endangered marsupial Sarcophilus harrisii (Tasmanian devil)

PubMed Central

Miller, Webb; Hayes, Vanessa M.; Ratan, Aakrosh; Petersen, Desiree C.; Wittekindt, Nicola E.; Miller, Jason; Walenz, Brian; Knight, James; Qi, Ji; Zhao, Fangqing; Wang, Qingyu; Bedoya-Reina, Oscar C.; Katiyar, Neerja; Tomsho, Lynn P.; Kasson, Lindsay McClellan; Hardie, Rae-Anne; Woodbridge, Paula; Tindall, Elizabeth A.; Bertelsen, Mads Frost; Dixon, Dale; Pyecroft, Stephen; Helgen, Kristofer M.; Lesk, Arthur M.; Pringle, Thomas H.; Patterson, Nick; Zhang, Yu; Kreiss, Alexandre; Woods, Gregory M.; Jones, Menna E.; Schuster, Stephan C.

2011-01-01

The Tasmanian devil (Sarcophilus harrisii) is threatened with extinction because of a contagious cancer known as Devil Facial Tumor Disease. The inability to mount an immune response and to reject these tumors might be caused by a lack of genetic diversity within a dwindling population. Here we report a whole-genome analysis of two animals originating from extreme northwest and southeast Tasmania, the maximal geographic spread, together with the genome from a tumor taken from one of them. A 3.3-Gb de novo assembly of the sequence data from two complementary next-generation sequencing platforms was used to identify 1 million polymorphic genomic positions, roughly one-quarter of the number observed between two genetically distant human genomes. Analysis of 14 complete mitochondrial genomes from current and museum specimens, as well as mitochondrial and nuclear SNP markers in 175 animals, suggests that the observed low genetic diversity in today's population preceded the Devil Facial Tumor Disease disease outbreak by at least 100 y. Using a genetically characterized breeding stock based on the genome sequence will enable preservation of the extant genetic diversity in future Tasmanian devil populations. PMID:21709235

Population structure in Japanese rice population

PubMed Central

Yamasaki, Masanori; Ideta, Osamu

2013-01-01

It is essential to elucidate genetic diversity and relationships among even related individuals and populations for plant breeding and genetic analysis. Since Japanese rice breeding has improved agronomic traits such as yield and eating quality, modern Japanese rice cultivars originated from narrow genetic resource and closely related. To resolve the population structure and genetic diversity in Japanese rice population, we used a total of 706 alleles detected by 134 simple sequence repeat markers in a total of 114 cultivars composed of 94 improved varieties and 20 landraces, which are representative and important for Japanese rice breeding. The landraces exhibit greater gene diversity than improved lines, suggesting that landraces can provide additional genetic diversity for future breeding. Model-based Bayesian clustering analysis revealed six subgroups and admixture situation in the cultivars, showing good agreement with pedigree information. This method could be superior to phylogenetic method in classifying a related population. The leading Japanese rice cultivar, Koshihikari is unique due to the specific genome constitution. We defined Japanese rice diverse sets that capture the maximum number of alleles for given sample sizes. These sets are useful for a variety of genetic application in Japanese rice cultivars. PMID:23641181

Genetic association studies in osteoarthritis: is it fairytale?

PubMed

Warner, Sophie C; Valdes, Ana M

2017-01-01

Osteoarthritis is a common complex disorder with a strong genetic component. Other identified risk factors such as increasing age and overweight do not fully explain the risk of osteoarthritis. Here, we highlight the main findings from genetic association studies on osteoarthritis to date. Currently, genetic association studies have identified 21 independent susceptibility loci for osteoarthritis. Studies have focused on hip, knee and hand osteoarthritis, as well as posttotal joint replacement and minimum joint space width, a proxy for cartilage thickness. Four distinct loci have recently been identified in a genome-wide association scan on minimum joint space width. The role of mitochondrial DNA variants has been the focus of a recent meta-analysis. Findings have previously been mixed, however, this study suggests a plausible involvement of mitochondrial DNA in the progression of radiographic knee osteoarthritis. Identifying genetic locations of interest provides a framework upon which to base future studies, for example replication analysis and functional work. Genetic association studies have shaped and will continue to shape research in this field. Improving the understanding of osteoarthritis could improve the diagnosis and treatment of the disease and improve quality of life for many individuals.

Next Generation Analytic Tools for Large Scale Genetic Epidemiology Studies of Complex Diseases

PubMed Central

Mechanic, Leah E.; Chen, Huann-Sheng; Amos, Christopher I.; Chatterjee, Nilanjan; Cox, Nancy J.; Divi, Rao L.; Fan, Ruzong; Harris, Emily L.; Jacobs, Kevin; Kraft, Peter; Leal, Suzanne M.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Province, Michael A.; Ramos, Erin M.; Ritchie, Marylyn D.; Roeder, Kathryn; Schaid, Daniel J.; Stephens, Matthew; Thomas, Duncan C.; Weinberg, Clarice R.; Witte, John S.; Zhang, Shunpu; Zöllner, Sebastian; Feuer, Eric J.; Gillanders, Elizabeth M.

2012-01-01

Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled “Next Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases” on September 15–16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large-scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene-gene and gene-environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized. PMID:22147673

Genetic and environmental contributions to children's prosocial behavior: brief review and new evidence from a reanalysis of experimental twin data.

PubMed

Knafo-Noam, Ariel; Vertsberger, Dana; Israel, Salomon

2018-04-01

Children's prosocial behaviors show considerable variability. Here we discuss the genetic and environmental contributions to individual differences in children's prosocial behavior. Twin research systematically shows, at least from the age of 3 years, a genetic contribution to individual differences in prosocial behavior, both questionnaire-based and observed. This finding is demonstrated across a wide variety of cultures. We discuss the possibility that different prosocial behaviors have different genetic etiologies. A re-analysis of past twin data shows that sharing and comforting are affected by overlapping genetic factors at age 3.5 years. In contrast, the association between helping and comforting is attributed to environmental factors. The few molecular genetic studies of children's prosocial behavior are reviewed, and we point out genome-wide and polygenic methods as a key future direction. Finally, we discuss the interplay of genetic and environmental factors, focusing on both gene×environment interactions and gene-environment correlations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic variation of Taenia pisiformis collected from Sichuan, China, based on the mitochondrial cytochrome B gene.

PubMed

Yang, Deying; Ren, Yongjun; Fu, Yan; Xie, Yue; Nie, Huaming; Nong, Xiang; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

2013-08-01

Taenia pisiformis is one of the most important parasites of canines and rabbits. T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit breeding, which results in huge economic losses. In this study, the genetic variation of T. pisiformis was determined in Sichuan Province, China. Fragments of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53 isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic variation derived from intra-region. FST and Nm values suggested that 53 isolates were not genetically differentiated and had low levels of genetic diversity. Neutrality indices of the cytb sequences showed the evolution of T. pisiformis followed a neutral mode. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. These findings indicate that 53 isolates of T. pisiformis keep a low genetic variation, which provide useful knowledge for monitoring changes in parasite populations for future control strategies.

How do clinical genetics consent forms address the familial approach to confidentiality and incidental findings? A mixed-methods study.

PubMed

Dheensa, Sandi; Crawford, Gillian; Salter, Claire; Parker, Michael; Fenwick, Angela; Lucassen, Anneke

2018-01-01

Genetic test results can be relevant to patients and their relatives. Questions thus arise around whether clinicians regard genetic information as confidential to individuals or to families, and about how they broach this and other issues, including the potential for incidental findings, in consent (forms) for genetic testing. We conducted a content analysis of UK-wide genetic testing consent forms and interviewed 128 clinicians/laboratory scientists. We found that almost all genetic services offered patients multiple, sometimes unworkable, choices on forms, including an option to veto the use of familial genetic information to benefit relatives. Participants worried that documented choices were overriding professional judgement and cautioned against any future forms dictating practice around incidental findings. We conclude that 'tick-box' forms, which do little to enhance autonomy, are masking valid consent processes in clinical practice. As genome-wide testing becomes commonplace, we must re-consider consent processes, so that they protects patients'-and relatives'-interests.

"Set in Stone" or "Ray of Hope": Parents' Beliefs About Cause and Prognosis After Genomic Testing of Children Diagnosed with ASD.

PubMed

Reiff, Marian; Bugos, Eva; Giarelli, Ellen; Bernhardt, Barbara A; Spinner, Nancy B; Sankar, Pamela L; Mulchandani, Surabhi

2017-05-01

Despite increasing utilization of chromosomal microarray analysis (CMA) for autism spectrum disorders (ASD), limited information exists about how results influence parents' beliefs about etiology and prognosis. We conducted in-depth interviews and surveys with 57 parents of children with ASD who received CMA results categorized as pathogenic, negative or variant of uncertain significance. Parents tended to incorporate their child's CMA results within their existing beliefs about the etiology of ASD, regardless of CMA result. However, parents' expectations for the future tended to differ depending on results; those who received genetic confirmation for their children's ASD expressed a sense of concreteness, acceptance and permanence of the condition. Some parents expressed hope for future biomedical treatments as a result of genetic research.

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

PubMed Central

Wild, Philipp S.; Felix, Janine F.; Schillert, Arne; Chen, Ming-Huei; Leening, Maarten J.G.; Völker, Uwe; Großmann, Vera; Brody, Jennifer A.; Irvin, Marguerite R.; Shah, Sanjiv J.; Pramana, Setia; Lieb, Wolfgang; Schmidt, Reinhold; Stanton, Alice V.; Malzahn, Dörthe; Lyytikäinen, Leo-Pekka; Tiller, Daniel; Smith, J. Gustav; Di Tullio, Marco R.; Musani, Solomon K.; Morrison, Alanna C.; Pers, Tune H.; Morley, Michael; Kleber, Marcus E.; Aragam, Jayashri; Bis, Joshua C.; Bisping, Egbert; Broeckel, Ulrich; Cheng, Susan; Deckers, Jaap W.; Del Greco M, Fabiola; Edelmann, Frank; Fornage, Myriam; Franke, Lude; Friedrich, Nele; Harris, Tamara B.; Hofer, Edith; Hofman, Albert; Huang, Jie; Hughes, Alun D.; Kähönen, Mika; investigators, KNHI; Kruppa, Jochen; Lackner, Karl J.; Lannfelt, Lars; Laskowski, Rafael; Launer, Lenore J.; Lindgren, Cecilia M.; Loley, Christina; Mayet, Jamil; Medenwald, Daniel; Morris, Andrew P.; Müller, Christian; Müller-Nurasyid, Martina; Nappo, Stefania; Nilsson, Peter M.; Nuding, Sebastian; Nutile, Teresa; Peters, Annette; Pfeufer, Arne; Pietzner, Diana; Pramstaller, Peter P.; Raitakari, Olli T.; Rice, Kenneth M.; Rotter, Jerome I.; Ruohonen, Saku T.; Sacco, Ralph L.; Samdarshi, Tandaw E.; Sharp, Andrew S.P.; Shields, Denis C.; Sorice, Rossella; Sotoodehnia, Nona; Stricker, Bruno H.; Surendran, Praveen; Töglhofer, Anna M.; Uitterlinden, André G.; Völzke, Henry; Ziegler, Andreas; Münzel, Thomas; März, Winfried; Cappola, Thomas P.; Hirschhorn, Joel N.; Mitchell, Gary F.; Smith, Nicholas L.; Fox, Ervin R.; Dueker, Nicole D.; Jaddoe, Vincent W.V.; Melander, Olle; Lehtimäki, Terho; Ciullo, Marina; Hicks, Andrew A.; Lind, Lars; Gudnason, Vilmundur; Pieske, Burkert; Barron, Anthony J.; Zweiker, Robert; Schunkert, Heribert; Ingelsson, Erik; Liu, Kiang; Arnett, Donna K.; Psaty, Bruce M.; Blankenberg, Stefan; Larson, Martin G.; Felix, Stephan B.; Franco, Oscar H.; Zeller, Tanja; Vasan, Ramachandran S.; Dörr, Marcus

2017-01-01

BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING. For detailed information per study, see Acknowledgments. PMID:28394258

Can Man Control His Biological Evolution? A Symposium on Genetic Engineering. Man's Responsibility to His Future

ERIC Educational Resources Information Center

Hoagland, Hudson

1972-01-01

Biological evolution can be carried out in the laboratory. With new knowledge available in genetics, possibilities are raised that genetic characters can be transferred in the future to embryos according to a predetermined plan. (PS)

The Population Genetics of Cultivation: Domestication of a Traditional Chinese Medicine, Scrophularia ningpoensis Hemsl. (Scrophulariaceae)

PubMed Central

Chen, Chuan; Li, Pan; Wang, Rui-Hong; Schaal, Barbara A.; Fu, Cheng-Xin

2014-01-01

Background Domestic cultivation of medicinal plants is an important strategy for protecting these species from over harvesting. Some species of medicinal plants have been brought into cultivation for more than hundreds years. Concerns about severe loss of genetic diversity and sustainable cultivation can potentially limit future use of these valuable plants. Genetic studies with comprehensive sampling of multiple medicinal species by molecular markers will allow for assessment and management of these species. Here we examine the population genetic consequences of cultivation and domestication in Scrophularia ningpoensis Hemsl. We used chloroplast DNA and genomic AFLP markers to clarify not only the effects of domestication on genetic diversity, but also determine the geographic origins of cultivars and their genetic divergence from native populations. These results will allow both better management of cultivated populations, but also provide insights for crop improvement. Results Twenty-one cpDNA haplotypes of S. ningpoensis were identified. Wild populations contain all haplotypes, whereas only three haplotypes were found in cultivated populations with wild populations having twice the haplotype diversity of cultivated populations. Genetic differentiation between cultivated populations and wild populations was significant. Genomic AFLP markers revealed similar genetic diversity patterns. Furthermore, Structure analysis grouped all wild populations into two gene pools; two of which shared the same gene pool with cultivated S. ningpoensis. The result of Neighbor-Joining analysis was consistent with the structure analysis. In principal coordinate analysis, three cultivated populations from Zhejiang Province grouped together and were separated from other cultivated populations. Conclusions These results suggest that cultivated S. ningpoensis has experienced dramatic loss of genetic diversity under anthropogenic influence. We postulate that strong artificial selection for medicinal quality has resulted in genetic differentiation between cultivated and wild populations. Furthermore, it appears that wild populations in Jiangxi-Hunan area were involved in the origin of cultivated S. ningpoensis. PMID:25157628

Genetic structure in contemporary south Tyrolean isolated populations revealed by analysis of Y-chromosome, mtDNA, and Alu polymorphisms.

PubMed

Pichler, Irene; Mueller, Jakob C; Stefanov, Stefan A; De Grandi, Alessandro; Volpato, Claudia Beu; Pinggera, Gerd K; Mayr, Agnes; Ogriseg, Martin; Ploner, Franz; Meitinger, Thomas; Pramstaller, Peter P

2006-08-01

Most of the inhabitants of South Tyrol in the eastern Italian Alps can be considered isolated populations because of their physical separation by mountain barriers and their sociocultural heritage. We analyzed the genetic structure of South Tyrolean populations using three types of genetic markers: Y-chromosome, mitochondrial DNA (mtDNA), and autosomal Alu markers. Using random samples taken from the populations of Val Venosta, Val Pusteria, Val Isarco, Val Badia, and Val Gardena, we calculated genetic diversity within and among the populations. Microsatellite diversity and unique event polymorphism diversity (on the Y chromosome) were substantially lower in the Ladin-speaking population of Val Badia compared to the neighboring German-speaking populations. In contrast, the genetic diversity of mtDNA haplotypes was lowest for the upper Val Venosta and Val Pusteria. These data suggest a low effective population size, or little admixture, for the gene pool of the Ladin-speaking population from Val Badia. Interestingly, this is more pronounced for Ladin males than for Ladin females. For the pattern of genetic Alu variation, both Ladin samples (Val Gardena and Val Badia) are among the samples with the lowest diversity. An admixture analysis of one German-speaking valley (Val Venosta) indicates a relatively high genetic contribution of Ladin origin. The reduced genetic diversity and a high genetic differentiation in the Rhaetoroman- and German-speaking South Tyrolean populations may constitute an important basis for future medical genetic research and gene mapping studies in South Tyrol.

Model-based conservation planning of the genetic diversity of Phellodendron amurense Rupr due to climate change

PubMed Central

Wan, Jizhong; Wang, Chunjing; Yu, Jinghua; Nie, Siming; Han, Shijie; Zu, Yuangang; Chen, Changmei; Yuan, Shusheng; Wang, Qinggui

2014-01-01

Climate change affects both habitat suitability and the genetic diversity of wild plants. Therefore, predicting and establishing the most effective and coherent conservation areas is essential for the conservation of genetic diversity in response to climate change. This is because genetic variance is a product not only of habitat suitability in conservation areas but also of efficient protection and management. Phellodendron amurense Rupr. is a tree species (family Rutaceae) that is endangered due to excessive and illegal harvesting for use in Chinese medicine. Here, we test a general computational method for the prediction of priority conservation areas (PCAs) by measuring the genetic diversity of P. amurense across the entirety of northeast China using a single strand repeat analysis of twenty microsatellite markers. Using computational modeling, we evaluated the geographical distribution of the species, both now and in different future climate change scenarios. Different populations were analyzed according to genetic diversity, and PCAs were identified using a spatial conservation prioritization framework. These conservation areas were optimized to account for the geographical distribution of P. amurense both now and in the future, to effectively promote gene flow, and to have a long period of validity. In situ and ex situ conservation, strategies for vulnerable populations were proposed. Three populations with low genetic diversity are predicted to be negatively affected by climate change, making conservation of genetic diversity challenging due to decreasing habitat suitability. Habitat suitability was important for the assessment of genetic variability in existing nature reserves, which were found to be much smaller than the proposed PCAs. Finally, a simple set of conservation measures was established through modeling. This combined molecular and computational ecology approach provides a framework for planning the protection of species endangered by climate change. PMID:25165526

The Novel Application of Non-Lethal Citizen Science Tissue Sampling in Recreational Fisheries.

PubMed

Williams, Samuel M; Holmes, Bonnie J; Pepperell, Julian G

2015-01-01

Increasing fishing pressure and uncertainty surrounding recreational fishing catch and effort data promoted the development of alternative methods for conducting fisheries research. A pilot investigation was undertaken to engage the Australian game fishing community and promote the non-lethal collection of tissue samples from the black marlin Istiompax indica, a valuable recreational-only species in Australian waters, for the purpose of future genetic research. Recruitment of recreational anglers was achieved by publicizing the project in magazines, local newspapers, social media, blogs, websites and direct communication workshops at game fishing tournaments. The Game Fishing Association of Australia and the Queensland Game Fishing Association were also engaged to advertise the project and recruit participants with a focus on those anglers already involved in the tag-and-release of marlin. Participants of the program took small tissue samples using non-lethal methods which were stored for future genetic analysis. The program resulted in 165 samples from 49 participants across the known distribution of I. indica within Australian waters which was a sufficient number to facilitate a downstream population genetic analysis. The project demonstrated the potential for the development of citizen science sampling programs to collect tissue samples using non-lethal methods in order to achieve targeted research objects in recreationally caught species.

Establishing paternity in Whooping Cranes (Grus americana) by DNA analysis

USGS Publications Warehouse

Longmire, Jonathan L.; Gee, George F.; Hardekopf, C.L.; Mark, G.A.

1992-01-01

DNA fingerprinting was used to study paternity and genetic variability within a captive flock of Whooping Cranes (Grus americana). Fingerprint patterns for 42 individuals were obtained by digesting genomic crane DNAs with HaeIII followed by electrophoresis, blotting, and hybridization to the M13 minisatellite probe. Despite finding reduced levels of genetic variation in the Whooping Crane due to a population "bottleneck," these polymorphisms were successfully used to determine paternity in six of seven cases of captive propagation where the maternal-offspring relationship was known, but where the sire was unknown. These determinations of paternity are required for effective genetic management of the crane flock. These results also revealed a number of heterozygous minisatellite loci that will be valuable in future assessments of genetic variability in this endangered species.

Mothers' explanations of communicating past health and future risks to survivors of childhood cancer.

PubMed

Clarke, Sally-Ann; Sheppard, Linda; Eiser, Christine

2008-01-01

Mothers of survivors of Retinoblastoma (Rb) experience unique challenges communicating with their child about the condition. Children are mostly diagnosed within their first year but the consequences continue into young adult life. Here 39 mothers of Rb survivors (23 males, mean age = 10.26 years) were interviewed about their experiences. Mothers were asked about communication with their children about Rb, and future health risks. Interviews were analysed using thematic analysis. Mothers reported that they had informed children about past diagnosis and treatment but had spoken less about genetic risk or risk of secondary cancer. The child's age and information-seeking behaviour were associated with mothers' disclosure, along with mothers' perceptions that information would facilitate child coping. Findings suggest that mothers may need more guidance during follow-up care in communicating about the disease and its consequences for future health. Medical staff should also take extra care to ensure that mothers are aware of genetic counselling services and how to access them before the child is discharged from specialist care.

The Evolution of Human Genetic Studies of Cleft Lip and Cleft Palate

PubMed Central

Marazita, Mary L.

2013-01-01

Orofacial clefts (OFCs)—primarily cleft lip and cleft palate—are among the most common birth defects in all populations worldwide, and have notable population, ethnicity, and gender differences in birth prevalence. Interest in these birth defects goes back centuries, as does formal scientific interest; scientists often used OFCs as examples or evidence during paradigm shifts in human genetics, and have also used virtually every new method of human genetic analysis to deepen our understanding of OFC. This review traces the evolution of human genetic investigations of OFC, highlights the specific insights gained about OFC through the years, and culminates in a review of recent key OFC genetic findings resulting from the powerful tools of the genomics era. Notably, OFC represents a major success for genome-wide approaches, and the field is poised for further breakthroughs in the near future. PMID:22703175

The genetics of human obesity.

PubMed

Xia, Qianghua; Grant, Struan F A

2013-04-01

It has long been known that there is a genetic component to obesity, and that characterizing this underlying factor would likely offer the possibility of better intervention in the future. Monogenic obesity has proved to be relatively straightforward, with a combination of linkage analysis and mouse models facilitating the identification of multiple genes. In contrast, genome-wide association studies have successfully revealed a variety of genetic loci associated with the more common form of obesity, allowing for very strong consensus on the underlying genetic architecture of the phenotype for the first time. Although a number of significant findings have been made, it appears that very little of the apparent heritability of body mass index has actually been explained to date. New approaches for data analyses and advances in technology will be required to uncover the elusive missing heritability, and to aid in the identification of the key causative genetic underpinnings of obesity. © 2013 New York Academy of Sciences.

Proton Nuclear Magnetic Resonance-Spectroscopic Discrimination of Wines Reflects Genetic Homology of Several Different Grape (V. vinifera L.) Cultivars.

PubMed

Hu, Boran; Yue, Yaqing; Zhu, Yong; Wen, Wen; Zhang, Fengmin; Hardie, Jim W

2015-01-01

Proton nuclear magnetic resonance spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) is an important tool for the discrimination of wine products. Although 1H NMR has been shown to discriminate wines of different cultivars, a grape genetic component of the discrimination has been inferred only from discrimination of cultivars of undefined genetic homology and in the presence of many confounding environmental factors. We aimed to confirm the influence of grape genotypes in the absence of those factors. We applied 1H NMR-PCA/PLS-DA and hierarchical cluster analysis (HCA) to wines from five, variously genetically-related grapevine (V. vinifera) cultivars; all grown similarly on the same site and vinified similarly. We also compared the semi-quantitative profiles of the discriminant metabolites of each cultivar with previously reported chemical analyses. The cultivars were clearly distinguishable and there was a general correlation between their grouping and their genetic homology as revealed by recent genomic studies. Between cultivars, the relative amounts of several of the cultivar-related discriminant metabolites conformed closely with reported chemical analyses. Differences in grape-derived metabolites associated with genetic differences alone are a major source of 1H NMR-based discrimination of wines and 1H NMR has the capacity to discriminate between very closely related cultivars. The study confirms that genetic variation among grape cultivars alone can account for the discrimination of wine by 1H NMR-PCA/PLS and indicates that 1H NMR spectra of wine of single grape cultivars may in future be used in tandem with hierarchical cluster analysis to elucidate genetic lineages and metabolomic relations of grapevine cultivars. In the absence of genetic information, for example, where predecessor varieties are no longer extant, this may be a particularly useful approach.

Evolution in Australia's mesic biome under past and future climates: Insights from a phylogenetic study of the Australian Rock Orchids (Dendrobium speciosum complex, Orchidaceae).

PubMed

Simpson, Lalita; Clements, Mark A; Crayn, Darren M; Nargar, Katharina

2018-01-01

The Australian mesic biome spans c. 33° of latitude along Australia's east coast and ranges and is dissected by historical and contemporary biogeographical barriers. To investigate the impact of these barriers on evolutionary diversification and to predict the impact of future climate change on the distribution of species and genetic diversity within this biome, we inferred phylogenetic relationships within the Dendrobium speciosum complex (Orchidaceae) across its distribution and undertook environmental niche modelling (ENM) under past, contemporary and projected future climates. Neighbor Joining tree inference, NeighborNet and Structure analyses of Amplified Fragment Length Polymorphism (AFLP) profiles for D. speciosum sampled from across its distribution showed that the complex consists of two highly supported main groups that are geographically separated by the St. Lawrence gap, an area of dry sclerophyll forest and woodland. The presence of several highly admixed individuals identified by the Structure analysis provided evidence of genetic exchange between the two groups across this gap. Whereas previous treatments have recognised between one to eleven species, the molecular results support the taxonomic treatment of the complex as a single species with two subspecies. The ENM analysis supported the hypothesis that lineage divergence within the complex was driven by past climatic changes. The St. Lawrence gap represented a stronger biogeographic barrier for the D. speciosum complex during the cool and dry glacial climatic conditions of the Pleistocene than under today's interglacial conditions. Shallow genetic divergence was found within the two lineages, which mainly corresponded to three other biogeographic barriers: the Black Mountain Corridor, Glass House Mountains and the Hunter Valley. Our ENM analyses provide further support for the hypothesis that biogeographic barriers along Australia's east coast were somewhat permeable to genetic exchange due to past episodic range expansions and contractions caused by climatic change resulting in recurrent contact between previously isolated populations. An overall southward shift in the distribution of the complex under future climate scenarios was predicted, with the strongest effects on the northern lineage. This study contributes to our understanding of the factors shaping biodiversity patterns in Australia's mesic biome. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of STS and CAPS markers for variety identification and genetic diversity analysis of tea germplasm in Taiwan.

PubMed

Hu, Chih-Yi; Tsai, You-Zen; Lin, Shun-Fu

2014-12-01

Tea (Camellia sinensis) is an important economic crop in Taiwan. Particularly, two major commercial types of tea (Paochong tea and Oolong tea) which are produced in Taiwan are famous around the world, and they must be manufactured with specific cultivars. Nevertheless, many elite cultivars have been illegally introduced to foreign countries. Because of the lower cost, large amount of "Taiwan-type tea" are produced and imported to Taiwan, causing a dramatic damage in the tea industry. It is very urgent to develop the stable, fast and reliable DNA markers for fingerprinting tea cultivars in Taiwan and protecting intellectual property rights for breeders. Furthermore, genetic diversity and phylogenetic relationship evaluations of tea germplasm in Taiwan are imperative for parental selection in the cross-breeding program and avoidance of genetic vulnerability. Two STS and 37 CAPS markers derived from cytoplasmic genome and ESTs of tea have been developed in this study providing a useful tool for distinguishing all investigated germplasm. For identifying 12 prevailing tea cultivars in Taiwan, five core markers, including each one of mitochondria and chloroplast, and three nuclear markers, were developed. Based on principal coordinate analysis and cluster analysis, 55 tea germplasm in Taiwan were divided into three groups: sinensis type (C. sinensis var. sinensis), assamica type (C. sinensis var. assamica) and Taiwan wild species (C. formosensis). The result of genetic diversity analysis revealed that both sinensis (0.44) and assamica (0.41) types had higher genetic diversity than wild species (0.25). The close genetic distance between the first (Chin-Shin-Oolong) and the third (Shy-Jih-Chuen) prevailing cultivars was found, and many recently released varieties are the descents of Chin-Shin-Oolong. This implies the potential risk of genetic vulnerability for tea cultivation in Taiwan. We have successfully developed a tool for tea germplasm discrimination and genetic diversity analysis, as well as a set of core markers for effective identification of prevailing cultivars in Taiwan. According to the results of phylogenetic analysis on prevailing tea cultivars, it is necessary to broaden genetic diversity from wild species or plant introduction in future breeding programs.

Uncovering trends in gene naming

PubMed Central

Seringhaus, Michael R; Cayting, Philip D; Gerstein, Mark B

2008-01-01

We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov’s dogs). We hope this analysis provides clues to better steer gene naming in the future. PMID:18254929

Latent Class Subtyping of Attention-Deficit/Hyperactivity Disorder and Comorbid Conditions

ERIC Educational Resources Information Center

Acosta, Maria T.; Castellanos, F. Xavier; Bolton, Kelly L.; Balog, Joan Z.; Eagen, Patricia; Nee, Linda; Jones, Janet; Palacio, Luis; Sarampote, Christopher; Russell, Heather F.; Berg, Kate; Arcos-Burgos, Mauricio; Muenke, Maximilian

2008-01-01

The study attempts to carry out latent class analysis (LCA) in a sample of 1010 individuals, some with Attention-Deficit/Hyperactivity disorder (ADHD) and others normal. Results indicate that LCA can feasibly allow the combination of externalizing and internalizing symptoms for future tests regarding specific genetic risk factors.

Applications of genetic programming in cancer research.

PubMed

Worzel, William P; Yu, Jianjun; Almal, Arpit A; Chinnaiyan, Arul M

2009-02-01

The theory of Darwinian evolution is the fundamental keystones of modern biology. Late in the last century, computer scientists began adapting its principles, in particular natural selection, to complex computational challenges, leading to the emergence of evolutionary algorithms. The conceptual model of selective pressure and recombination in evolutionary algorithms allow scientists to efficiently search high dimensional space for solutions to complex problems. In the last decade, genetic programming has been developed and extensively applied for analysis of molecular data to classify cancer subtypes and characterize the mechanisms of cancer pathogenesis and development. This article reviews current successes using genetic programming and discusses its potential impact in cancer research and treatment in the near future.

Genetic counseling in the era of molecular diagnostics.

PubMed

Traas, Anne M; Casal, Margret; Haskins, Mark; Henthorn, Paula

2006-08-01

Veterinarians with an interest in theriogenology will often be asked by small animal clients for advice concerning hereditary diseases in their breeds. Many new DNA-based tests for analysis of genetic diseases and traits (e.g. coat color) are now available for use by both breeders and veterinarians. With appropriate interpretation, these tests can be invaluable tools in a breeding program. For example, they can be used to produce animals free of specific diseases, to quickly eliminate a disease from an entire breed, or to select for specific traits in breeding stock. Selection strategies that do not take into account maintaining genetic diversity of the breed may be detrimental and reduce the potential for future improvement.

High-density genetic map construction and comparative genome analysis in asparagus bean.

PubMed

Huang, Haitao; Tan, Huaqiang; Xu, Dongmei; Tang, Yi; Niu, Yisong; Lai, Yunsong; Tie, Manman; Li, Huanxiu

2018-03-19

Genetic maps are a prerequisite for quantitative trait locus (QTL) analysis, marker-assisted selection (MAS), fine gene mapping, and assembly of genome sequences. So far, several asparagus bean linkage maps have been established using various kinds of molecular markers. However, these maps were all constructed by gel- or array-based markers. No maps based on sequencing method have been reported. In this study, an NGS-based strategy, SLAF-seq, was applied to create a high-density genetic map for asparagus bean. Through SLAF library construction and Illumina sequencing of two parents and 100 F2 individuals, a total of 55,437 polymorphic SLAF markers were developed and mined for SNP markers. The map consisted of 5,225 SNP markers in 11 LGs, spanning a total distance of 1,850.81 cM, with an average distance between markers of 0.35 cM. Comparative genome analysis with four other legume species, soybean, common bean, mung bean and adzuki bean showed that asparagus bean is genetically more related to adzuki bean. The results will provide a foundation for future genomic research, such as QTL fine mapping, comparative mapping in pulses, and offer support for assembling asparagus bean genome sequence.

PICALM gene rs3851179 polymorphism contributes to Alzheimer's disease in an Asian population.

PubMed

Liu, Guiyou; Zhang, Shuyan; Cai, Zhiyou; Ma, Guoda; Zhang, Liangcai; Jiang, Yongshuai; Feng, Rennan; Liao, Mingzhi; Chen, Zugen; Zhao, Bin; Li, Keshen

2013-06-01

PICALM gene rs3851179 polymorphism was reported to an Alzheimer's disease (AD) susceptibility locus in a Caucasian population. However, recent studies reported consistent and inconsistent results in an Asian population. Four studies indicated no association between rs3851179 and AD in a Chinese population and one study reported weak association in a Japanese population. We consider that the failure to replicate the significant association between rs3851179 and AD may be caused by at least two reasons. The first reason may be the genetic heterogeneity in AD among different populations, and the second may be the relatively small sample size compared with large-scale GWAS in Caucasian ancestry. In order to confirm this view, in this research, we first evaluated the genetic heterogeneity of rs3851179 polymorphism in Caucasian and Asian populations. We then investigated rs3851179 polymorphism in an Asian population by a pooled analysis method and a meta-analysis method. We did not observe significant genetic heterogeneity of rs3851179 in the Caucasian and Asian populations. Our results indicate that rs3851179 polymorphism is significantly associated with AD in the Asian population by both pooled analysis and meta-analysis methods. We believe that our findings will be very useful for future genetic studies in AD.

Neutral Theory is the Foundation of Conservation Genetics.

PubMed

Yoder, Anne D; Poelstra, Jelmer; Tiley, George P; Williams, Rachel

2018-04-16

Kimura's neutral theory of molecular evolution has been essential to virtually every advance in evolutionary genetics, and by extension, is foundational to the field of conservation genetics. Conservation genetics utilizes the key concepts of neutral theory to identify species and populations at risk of losing evolutionary potential by detecting patterns of inbreeding depression and low effective population size. In turn, this information can inform the management of organisms and their habitat providing hope for the long-term preservation of both. We expand upon Avise's "inventorial" and "functional" categories of conservation genetics by proposing a third category that is linked to the coalescent and that we refer to as "process-driven." It is here that connections between Kimura's theory and conservation genetics are strongest. Process-driven conservation genetics can be especially applied to large genomic datasets to identify patterns of historical risk, such as population bottlenecks, and accordingly, yield informed intuitions for future outcomes. By examining inventorial, functional, and process-driven conservation genetics in sequence, we assess the progression from theory, to data collection and analysis, and ultimately, to the production of hypotheses that can inform conservation policies.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

PubMed Central

Jahanshad, Neda; Kochunov, Peter; Sprooten, Emma; Mandl, René C.; Nichols, Thomas E.; Almassy, Laura; Blangero, John; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Duggirala, Ravi; Fox, Peter T.; Hong, L. Elliot; Landman, Bennett A.; Martin, Nicholas G.; McMahon, Katie L.; Medland, Sarah E.; Mitchell, Braxton D.; Olvera, Rene L.; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Hulshoff Pol, Hilleke E.; Bastin, Mark E.; McIntosh, Andrew M.; Deary, Ian J.; Thompson, Paul M.; Glahn, David C.

2013-01-01

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/). PMID:23629049

Translational Research on the Way to Effective Therapy for Alzheimer Disease

PubMed Central

Rosenberg, Roger N.

2006-01-01

Context Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. Objective A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. Conclusions A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope. PMID:16275806

Translational research on the way to effective therapy for Alzheimer disease.

PubMed

Rosenberg, Roger N

2005-11-01

Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data. including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope.

Genetic Candidate Variants in Two Multigenerational Families with Childhood Apraxia of Speech

PubMed Central

Wijsman, Ellen M.; Nato, Alejandro Q.; Matsushita, Mark M.; Chapman, Kathy L.; Stanaway, Ian B.; Wolff, John; Oda, Kaori; Gabo, Virginia B.; Raskind, Wendy H.

2016-01-01

Childhood apraxia of speech (CAS) is a severe and socially debilitating form of speech sound disorder with suspected genetic involvement, but the genetic etiology is not yet well understood. Very few known or putative causal genes have been identified to date, e.g., FOXP2 and BCL11A. Building a knowledge base of the genetic etiology of CAS will make it possible to identify infants at genetic risk and motivate the development of effective very early intervention programs. We investigated the genetic etiology of CAS in two large multigenerational families with familial CAS. Complementary genomic methods included Markov chain Monte Carlo linkage analysis, copy-number analysis, identity-by-descent sharing, and exome sequencing with variant filtering. No overlaps in regions with positive evidence of linkage between the two families were found. In one family, linkage analysis detected two chromosomal regions of interest, 5p15.1-p14.1, and 17p13.1-q11.1, inherited separately from the two founders. Single-point linkage analysis of selected variants identified CDH18 as a primary gene of interest and additionally, MYO10, NIPBL, GLP2R, NCOR1, FLCN, SMCR8, NEK8, and ANKRD12, possibly with additive effects. Linkage analysis in the second family detected five regions with LOD scores approaching the highest values possible in the family. A gene of interest was C4orf21 (ZGRF1) on 4q25-q28.2. Evidence for previously described causal copy-number variations and validated or suspected genes was not found. Results are consistent with a heterogeneous CAS etiology, as is expected in many neurogenic disorders. Future studies will investigate genome variants in these and other families with CAS. PMID:27120335

Perceptions of family history and genetic testing and feasibility of pedigree development among African Americans with hypertension

PubMed Central

Pettey, Christina M; McSweeney, Jean C; Stewart, Katharine E; Price, Elvin T; Cleves, Mario A; Heo, Seongkum; Souder, Elaine

2016-01-01

Background Pedigree development, family history, and genetic testing are thought to be useful in improving outcomes of chronic illnesses such as hypertension (HTN). However, the clinical utility of pedigree development is still unknown. Further, little is known about African Americans’ (AAs’) perceptions of family history and genetic testing. Aims This study examined the feasibility of developing pedigrees for AAs with HTN and explored perceptions of family history and genetic research among AAs with HTN. Methods The US Surgeon General’s My Family Health Portrait was administered, and 30–60 minute in-person individual interviews were conducted. Descriptive statistics were used to analyze pedigree data. Interview transcripts were analyzed with content analysis and constant comparison. Results Twenty-nine AAs with HTN were recruited from one free clinic (15 women, 14 men; mean age 49 years, SD 9.6). Twenty-six (90%) reported their family history in sufficient detail to develop a pedigree. Perceptions of family history included knowledge of HTN in the family, culturally influenced family teaching about HTN, and response to family history of HTN. Most participants agreed to future genetic testing and DNA collection because they wanted to help others; some said they needed more information and others expressed a concern for privacy. Conclusion The majority of AAs in this sample possessed extensive knowledge of HTN within their family and were able to develop a three generation pedigree with assistance. The majority were willing to participate in future genetic research. PMID:25322748

Perceptions of family history and genetic testing and feasibility of pedigree development among African Americans with hypertension.

PubMed

Pettey, Christina M; McSweeney, Jean C; Stewart, Katharine E; Price, Elvin T; Cleves, Mario A; Heo, Seongkum; Souder, Elaine

2015-02-01

Pedigree development, family history, and genetic testing are thought to be useful in improving outcomes of chronic illnesses such as hypertension (HTN). However, the clinical utility of pedigree development is still unknown. Further, little is known about the perceptions of African Americans (AAs) of family history and genetic testing. This study examined the feasibility of developing pedigrees for AAs with HTN and explored perceptions of family history and genetic research among AAs with HTN. The US Surgeon General's My Family Health Portrait was administered, and 30-60 min in-person individual interviews were conducted. Descriptive statistics were used to analyze pedigree data. Interview transcripts were analyzed with content analysis and constant comparison. Twenty-nine AAs with HTN were recruited from one free clinic (15 women, 14 men; mean age 49 years, standard deviation (SD) 9.6). Twenty-six (90%) reported their family history in sufficient detail to develop a pedigree. Perceptions of family history included knowledge of HTN in the family, culturally influenced family teaching about HTN, and response to family history of HTN. Most participants agreed to future genetic testing and DNA collection because they wanted to help others; some said they needed more information and others expressed a concern for privacy. The majority of AAs in this sample possessed extensive knowledge of HTN within their family and were able to develop a three-generation pedigree with assistance. The majority were willing to participate in future genetic research. © The European Society of Cardiology 2014.

AFLP analysis of genetic diversity and phylogenetic relationships of Brassica oleracea in Ireland.

PubMed

El-Esawi, Mohamed A; Germaine, Kieran; Bourke, Paula; Malone, Renee

2016-01-01

Brassica oleracea L. is one of the most economically important vegetable crop species of the genus Brassica L. This species is threatened in Ireland, without any prior reported genetic studies. The use of this species is being very limited due to its imprecise phylogeny and uncompleted genetic characterisation. The main objective of this study was to assess the genetic diversity and phylogenetic relationships of a set of 25 Irish B. oleracea accessions using the powerful amplified fragment length polymorphism (AFLP) technique. A total of 471 fragments were scored across all the 11 AFLP primer sets used, out of which 423 (89.8%) were polymorphic and could differentiate the accessions analysed. The dendrogram showed that cauliflowers were more closely related to cabbages than kales were, and accessions of some cabbage types were distributed among different clusters within cabbage subgroups. Approximately 33.7% of the total genetic variation was found among accessions, and 66.3% of the variation resided within accessions. The total genetic diversity (HT) and the intra-accessional genetic diversity (HS) were 0.251 and 0.156, respectively. This high level of variation demonstrates that the Irish B. oleracea accessions studied should be managed and conserved for future utilisation and exploitation in food and agriculture. In conclusion, this study addressed important phylogenetic questions within this species, and provided a new insight into the inclusion of four accessions of cabbages and kales in future breeding programs for improving varieties. AFLP markers were efficient for assessing genetic diversity and phylogenetic relationships in Irish B. oleracea species. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Genome engineering in ornamental plants: Current status and future prospects.

PubMed

Kishi-Kaboshi, Mitsuko; Aida, Ryutaro; Sasaki, Katsutomo

2018-03-13

Ornamental plants, like roses, carnations, and chrysanthemums, are economically important and are sold all over the world. In addition, numerous cut and garden flowers add colors to homes and gardens. Various strategies of plant breeding have been employed to improve traits of many ornamental plants. These approaches span from conventional techniques, such as crossbreeding and mutation breeding, to genetically modified plants. Recently, genome editing has become available as an efficient means for modifying traits in plant species. Genome editing technology is useful for genetic analysis and is poised to become a common breeding method for ornamental plants. In this review, we summarize the benefits and limitations of conventional breeding techniques and genome editing methods and discuss their future potential to accelerate the rate breeding programs in ornamental plants. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Genetic diversity among Korean bermudagrass (Cynodon spp.) ecotypes characterized by morphological, cytological and molecular approaches.

PubMed

Kang, Si-Yong; Lee, Geung-Joo; Lim, Ki Byung; Lee, Hye Jung; Park, In Sook; Chung, Sung Jin; Kim, Jin-Baek; Kim, Dong Sub; Rhee, Hye Kyung

2008-04-30

The genus Cynodon comprises ten species. The objective of this study was to evaluate the genetic diversity of Korean bermudagrasses at the morphological, cytological and molecular levels. Morphological parameters, the nuclear DNA content and ploidy levels were observed in 43 bermudagrass ecotypes. AFLP markers were evaluated to define the genetic diversity, and chromosome counts were made to confirm the inferred cytotypes. Nuclear DNA contents were in the ranges 1.42-1.56, 1.94-2.19, 2.54, and 2.77-2.85 pg/2C for the triploid, tetraploid, pentaploid, and hexaploid accessions, respectively. The inferred cytotypes were triploid (2n = 3x = 27), tetraploid (2n = 4x = 36), pentaploid (2n = 5x = 45), and hexaploid (2n = 6x = 54), but the majority of the collections were tetraploid (81%). Mitotic chromosome counts verified the corresponding ploidy levels. The fast growing fine-textured ecotypes had lower ploidy levels, while the pentaploids and hexaploids were coarse types. The genetic similarity ranged from 0.42 to 0.94 with an average of 0.64. UPGMA cluster analysis and principle coordinate analysis separated the ecotypes into 6 distinct groups. The genetic similarity suggests natural hybridization between the different cytotypes, which could be useful resources for future breeding and genetic studies.

Genetic diversity analysis among collected purslane (Portulaca oleracea L.) accessions using ISSR markers.

PubMed

Alam, M Amirul; Juraimi, Abdul Shukor; Rafii, Mohd Yusop; Hamid, Azizah Abdul; Arolu, Ibrahim Wasiu; Abdul Latif, M

2015-01-01

Genetic diversity and relationships among 45 collected purslane accessions were evaluated using ISSR markers. The 28 primers gave a total of 167 bands, among which 163 were polymorphic (97.6%). The genetic diversity as estimated by Shannon's information index was 0.513, revealing a quite high level of genetic diversity in the germplasm. The average number of observed allele, effective allele, expected heterozygosity, polymorphic information content (PIC) and Nei's index were 5.96, 1.59, 0.43, 0.35 and 0.35, respectively. The UPGMA dendrogram based on Nei's genetic distance grouped the whole germplasm into 7 distinct clusters. The analysis of molecular variance (AMOVA) revealed that 89% of total variation occurred within population, while 11% were found among populations. Based on the constructed dendrogram using ISSR markers those accessions that are far from each other by virtue of genetic origin and diversity index (like Ac1 and Ac42; Ac19 and Ac45; Ac9 and Ac23; Ac18 and A25; Ac24 and Ac18) are strongly recommended to select as parent for future breeding program to develop high yielding and stress tolerant purslane variety in contribution to global food security. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Genetic diversity of transmission-blocking vaccine candidate Pvs48/45 in Plasmodium vivax populations in China.

PubMed

Feng, Hui; Gupta, Bhavna; Wang, Meilian; Zheng, Wenqi; Zheng, Li; Zhu, Xiaotong; Yang, Yimei; Fang, Qiang; Luo, Enjie; Fan, Qi; Tsuboi, Takafumi; Cao, Yaming; Cui, Liwang

2015-12-01

The male gamete fertilization factor P48/45 in malaria parasites is a prime transmission-blocking vaccine (TBV) candidate. Efforts to develop antimalarial vaccines are often thwarted by genetic diversity of the target antigens. Here we evaluated the genetic diversity of Pvs48/45 gene in global Plasmodium vivax populations. We determined 200 Pvs48/45 sequences collected from temperate and subtropical parasite populations in China. Population genetic and evolutionary analyses were performed to determine the levels of genetic diversity, potential signature of selection, and population differentiation. Analysis of the Pvs48/45 sequences from 200 P. vivax parasites collected in a temperate and a tropical region revealed a low level of genetic diversity (π = 0.0012) with 14 single nucleotide polymorphisms, of which 11 were nonsynonymous. Analysis of 344 Pvs48/45 sequences from nine worldwide P. vivax populations detected a total of 38 haplotypes, of which 13 haplotypes were present only once. Multiple tests for selection confirmed a signature of positive selection on Pvs48/45 with selection skewed to the second cysteine domain. Haplotype network analysis and Wright's fixation index showed large geographical differentiation with the presence of continent-or region-specific mutations in this gene. Pvs48/45 displays low levels of genetic diversity with the presence of region-specific mutations. Some of the mutations may be potential epitope targets based on their positions in the predicted structure, highlighting the need for future evaluation of these mutations in designing Pvs48/45-based TBV.

Analysis of a genetically structured variance heterogeneity model using the Box-Cox transformation.

PubMed

Yang, Ye; Christensen, Ole F; Sorensen, Daniel

2011-02-01

Over recent years, statistical support for the presence of genetic factors operating at the level of the environmental variance has come from fitting a genetically structured heterogeneous variance model to field or experimental data in various species. Misleading results may arise due to skewness of the marginal distribution of the data. To investigate how the scale of measurement affects inferences, the genetically structured heterogeneous variance model is extended to accommodate the family of Box-Cox transformations. Litter size data in rabbits and pigs that had previously been analysed in the untransformed scale were reanalysed in a scale equal to the mode of the marginal posterior distribution of the Box-Cox parameter. In the rabbit data, the statistical evidence for a genetic component at the level of the environmental variance is considerably weaker than that resulting from an analysis in the original metric. In the pig data, the statistical evidence is stronger, but the coefficient of correlation between additive genetic effects affecting mean and variance changes sign, compared to the results in the untransformed scale. The study confirms that inferences on variances can be strongly affected by the presence of asymmetry in the distribution of data. We recommend that to avoid one important source of spurious inferences, future work seeking support for a genetic component acting on environmental variation using a parametric approach based on normality assumptions confirms that these are met.

A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure Is Defined as Progression to >45 Degrees.

PubMed

Bohl, Daniel D; Telles, Connor J; Ruiz, Ferrin K; Badrinath, Raghav; DeLuca, Peter A; Grauer, Jonathan N

2016-04-01

Retrospective cohort. To determine whether a genetic test is associated with successful Providence bracing for adolescent idiopathic scoliosis (AIS). Genetic factors have been defined that predict the risk of progression of AIS in a polygenic fashion. From these data, a commercially available genetic test, ScoliScore, was developed. It is now used in clinical practice for counseling and to guide clinical management. Bracing is a mainstay of treatment for AIS. Large efforts have been made recently to reduce potential confounding across studies of different braces; however, none of these have considered genetics as a potential confounder. In particular, ScoliScore has not been evaluated in a population undergoing bracing. We conducted a retrospective cohort study in which we identified a population of AIS patients who were initiated with Providence bracing and followed over time. Although these patients did not necessarily fit the commercial indications for ScoliScore, we contacted the patients and obtained a saliva sample from each for genetic analysis. We then tested whether ScoliScore correlated with the outcome of their bracing therapy. We were able to contact and invite 25 eligible subjects, of whom 16 (64.0%) returned samples for laboratory analysis. Patients were followed for an average of 2.3 years (range, 1.1-4 y) after initiation of the Providence brace. Eight patients (50.0%) progressed to >45 degrees, whereas the other 8 patients (50.0%) did not. The mean ScoliScore among those who progressed to >45 degrees was higher than that among those who did not (176 vs. 112, P=0.030). We demonstrate that a genetic test correlates with bracing outcome. It may be appropriate for future bracing studies to include analysis of genetic predisposition to limit potential confounding.

A Whole Genome DArTseq and SNP Analysis for Genetic Diversity Assessment in Durum Wheat from Central Fertile Crescent

PubMed Central

Shahid, Muhammad Qasim; Çiftçi, Vahdettin; E. Sáenz de Miera, Luis; Aasim, Muhammad; Nadeem, Muhammad Azhar; Aktaş, Husnu; Özkan, Hakan; Hatipoğlu, Rüştü

2017-01-01

Until now, little attention has been paid to the geographic distribution and evaluation of genetic diversity of durum wheat from the Central Fertile Crescent (modern-day Turkey and Syria). Turkey and Syria are considered as primary centers of wheat diversity, and thousands of locally adapted wheat landraces are still present in the farmers’ small fields. We planned this study to evaluate the genetic diversity of durum wheat landraces from the Central Fertile Crescent by genotyping based on DArTseq and SNP analysis. A total of 39,568 DArTseq and 20,661 SNP markers were used to characterize the genetic characteristic of 91 durum wheat land races. Clustering based on Neighbor joining analysis, principal coordinate as well as Bayesian model implemented in structure, clearly showed that the grouping pattern is not associated with the geographical distribution of the durum wheat due to the mixing of the Turkish and Syrian landraces. Significant correlation between DArTseq and SNP markers was observed in the Mantel test. However, we detected a non-significant relationship between geographical coordinates and DArTseq (r = -0.085) and SNP (r = -0.039) loci. These results showed that unconscious farmer selection and lack of the commercial varieties might have resulted in the exchange of genetic material and this was apparent in the genetic structure of durum wheat in Turkey and Syria. The genomic characterization presented here is an essential step towards a future exploitation of the available durum wheat genetic resources in genomic and breeding programs. The results of this study have also depicted a clear insight about the genetic diversity of wheat accessions from the Central Fertile Crescent. PMID:28099442

From what should we protect future generations: germ-line therapy or genetic screening?

PubMed

Mallia, Pierre; ten Have, Henk

2003-01-01

This paper discusses the issue of whether we have responsibilities to future generations with respect to genetic screening, including for purposes of selective abortion or discard. Future generations have been discussed at length among scholars. The concept of 'Guardian for Future Generations' is tackled and its main criticisms discussed. Whilst germ-line cures, it is argued, can only affect family trees, genetic screening and testing can have wider implications. If asking how this may affect future generations is a legitimate question and since we indeed make retrospective moral judgements, it would be wise to consider that future generations will make the same retrospective judgements on us. Moreover such technologies affect present embryos to which we indeed can be considered to have an obligation.

Genetic toxicology in the 21st century: Reflections and future directions

EPA Science Inventory

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. A...

Genetic and functional characterization of culturable plant-beneficial actinobacteria associated with yam rhizosphere.

PubMed

Arunachalam Palaniyandi, Sasikumar; Yang, Seung Hwan; Damodharan, Karthiyaini; Suh, Joo-Won

2013-12-01

Actinobacteria were isolated from the rhizosphere of yam plants from agricultural fields from Yeoju, South Korea and analyzed for their genetic and plant-beneficial functional diversity. A total of 29 highly occurring actinobacterial isolates from the yam rhizosphere were screened for various plant-beneficial traits such as antimicrobial activity on fungi and bacteria; biocontrol traits such as production of siderophore, protease, chitinase, endo-cellulase, and β-glucanase. The isolates were also screened for plant growth-promoting (PGP) traits such as auxin production, phosphate solubilization, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and in vitro Arabidopsis growth promotion. 16S rDNA sequence-based phylogenetic analysis was carried out on the actinobacterial isolates to determine their genetic relatedness to known actinobacteria. BOX-PCR analysis revealed high genetic diversity among the isolates. Several isolates were identified to belong to the genus Streptomyces and a few to Kitasatospora. The actinobacterial strains exhibited high diversity in their functionality and were identified as novel and promising candidates for future development into biocontrol and PGP agents. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Analysis of 14 individuals who requested predictive genetic testing for hereditary neuromuscular diseases].

PubMed

Yoshida, Kunihiro; Tamai, Mariko; Kubota, Takeo; Kawame, Hiroshi; Amano, Naoji; Ikeda, Shu-ichi; Fukushima, Yoshimitsu

2002-02-01

Predictive genetic testing for hereditary neuromuscular diseases is a delicate issue for individuals at risk and their families, as well as for medical staff because these diseases are often late-onset and intractable. Therefore careful pre- and post-test genetic counseling and psychosocial support should be provided along with such genetic testing. The Division of Clinical and Molecular Genetics was established at our hospital in May 1996 to provide skilled professional genetic counseling. Since its establishment, 14 individuals have visited our clinic to request predictive genetic testing for hereditary neuromuscular diseases (4 for myotonic dystrophy, 6 for spinocerebellar ataxia, 3 for Huntington's disease, and 1 for Alzheimer's disease). The main reasons for considering testing were to remove uncertainty about the genetic status and to plan for the future. Nine of 14 individuals requested testing for making decisions about a forthcoming marriage or pregnancy (family planning). Other reasons raised by the individuals included career or financial planning, planning for their own health care, and knowing the risk for their children. At the first genetic counseling session, all of the individuals expressed hopes of not being a gene carrier and of escaping from fear of disease, and seemed not to be mentally well prepared for an increased-risk result. To date, 7 of the 14 individuals have received genetic testing and only one, who underwent predictive genetic testing for spinocerebellar ataxia, was given an increased-risk result. The seven individuals including the one with an increased-risk result, have coped well with their new knowledge about their genetic status after the testing results were disclosed. None of them has expressed regret. In pre-test genetic counseling sessions, we consider it quite important not only to determine the psychological status of the individual, but also to make the individual try to anticipate the changes in his/her life upon receiving an increased-risk or a decreased-risk result. Sufficient time should be taken to build a good relationship between the individual and his/her family and the medical staff during pre-test counseling sessions. This will help the individuals feel satisfied with their own decisions for the future, whether they receive genetic testing or not.

Can Genetics and Genomics Nursing Competencies Be Successfully Taught in a Prenursing Microbiology Course?

PubMed Central

Shuster, Michèle

2011-01-01

In recognition of the entry into the era of personalized medicine, a new set of genetics and genomics competencies for nurses was introduced in 2006. Since then, there have been a number of reports about the critical importance of these competencies for nursing practices and about the challenges of addressing these competencies in the preservice (basic science) nursing curriculum. At least one suggestion has been made to infuse genetics and genomics throughout the basic science curriculum for prenursing students. Based on this call and a review of the competencies, this study sought to assess the impact of incorporation of genetics and genomics content into a prenursing microbiology course. Broadly, two areas that address the competencies were incorporated into the course: 1) the biological basis and implications of genetic diversity and 2) the technological aspects of assessing genetic diversity in bacteria and viruses. These areas address how genetics and genomics contribute to healthcare, including diagnostics and selection of treatment. Analysis of learning gains suggests that genetics and genomics content can be learned as effectively as microbiology content in this setting. Future studies are needed to explore the most effective ways to introduce genetics and genomics technology into the prenursing curriculum. PMID:21633070

Genetic diversity in mesoamerican populations of mahogany (Swietenia macrophylla), assessed using RAPDs.

PubMed

Gillies, A C; Navarro, C; Lowe, A J; Newton, A C; Hernández, M; Wilson, J; Cornelius, J P

1999-12-01

Swietenia macrophylla King, a timber species native to tropical America, is threatened by selective logging and deforestation. To quantify genetic diversity within the species and monitor the impact of selective logging, populations were sampled across Mesoamerica, from Mexico to Panama, and analysed for RAPD DNA variation. Ten decamer primers generated 102 polymorphic RAPD bands and pairwise distances were calculated between populations according to Nei, then used to construct a radial neighbour-joining dendrogram and examine intra- and interpopulation variance coefficients, by analysis of molecular variation (AMOVA). Populations from Mexico clustered closely together in the dendrogram and were distinct from the rest of the populations. Those from Belize also clustered closely together. Populations from Panama, Guatemala, Costa Rica, Nicaragua and Honduras, however, did not cluster closely by country but were more widely scattered throughout the dendrogram. This result was also reflected by an autocorrelation analysis of genetic and geographical distance. Genetic diversity estimates indicated that 80% of detected variation was maintained within populations and regression analysis demonstrated that logging significantly decreased population diversity (P = 0.034). This study represents one of the most wide-ranging surveys of molecular variation within a tropical tree species to date. It offers practical information for the future conservation of mahogany and highlights some factors that may have influenced the partitioning of genetic diversity in this species across Mesoamerica.

Microsatellite variation and genetic structure of brook trout (Salvelinus fontinalis) populations in Labrador and neighboring Atlantic Canada: evidence for ongoing gene flow and dual routes of post-Wisconsinan colonization

PubMed Central

Pilgrim, Brettney L; Perry, Robert C; Keefe, Donald G; Perry, Elizabeth A; Dawn Marshall, H

2012-01-01

In conservation genetics and management, it is important to understand the contribution of historical and contemporary processes to geographic patterns of genetic structure in order to characterize and preserve diversity. As part of a 10-year monitoring program by the Government of Newfoundland and Labrador, Canada, we measured the population genetic structure of the world's most northern native populations of brook trout (Salvelinus fontinalis) in Labrador to gather baseline data to facilitate monitoring of future impacts of the recently opened Trans-Labrador Highway. Six-locus microsatellite profiles were obtained from 1130 fish representing 32 populations from six local regions. Genetic diversity in brook trout populations in Labrador (average HE= 0.620) is within the spectrum of variability found in other brook trout across their northeastern range, with limited ongoing gene flow occurring between populations (average pairwise FST= 0.139). Evidence for some contribution of historical processes shaping genetic structure was inferred from an isolation-by-distance analysis, while dual routes of post-Wisconsinan recolonization were indicated by STRUCTURE analysis: K= 2 was the most likely number of genetic groups, revealing a separation between northern and west-central Labrador from all remaining populations. Our results represent the first data from the nuclear genome of brook trout in Labrador and emphasize the usefulness of microsatellite data for revealing the extent to which genetic structure is shaped by both historical and contemporary processes. PMID:22837834

Global optimization of small bimetallic Pd-Co binary nanoalloy clusters: a genetic algorithm approach at the DFT level.

PubMed

Aslan, Mikail; Davis, Jack B A; Johnston, Roy L

2016-03-07

The global optimisation of small bimetallic PdCo binary nanoalloys are systematically investigated using the Birmingham Cluster Genetic Algorithm (BCGA). The effect of size and composition on the structures, stability, magnetic and electronic properties including the binding energies, second finite difference energies and mixing energies of Pd-Co binary nanoalloys are discussed. A detailed analysis of Pd-Co structural motifs and segregation effects is also presented. The maximal mixing energy corresponds to Pd atom compositions for which the number of mixed Pd-Co bonds is maximised. Global minimum clusters are distinguished from transition states by vibrational frequency analysis. HOMO-LUMO gap, electric dipole moment and vibrational frequency analyses are made to enable correlation with future experiments.

Diagnosis of Fanconi Anemia: Mutation Analysis by Multiplex Ligation-Dependent Probe Amplification and PCR-Based Sanger Sequencing

PubMed Central

Gille, Johan J. P.; Floor, Karijn; Kerkhoven, Lianne; Ameziane, Najim; Joenje, Hans; de Winter, Johan P.

2012-01-01

Fanconi anemia (FA) is a rare inherited disease characterized by developmental defects, short stature, bone marrow failure, and a high risk of malignancies. FA is heterogeneous: 15 genetic subtypes have been distinguished so far. A clinical diagnosis of FA needs to be confirmed by testing cells for sensitivity to cross-linking agents in a chromosomal breakage test. As a second step, DNA testing can be employed to elucidate the genetic subtype of the patient and to identify the familial mutations. This knowledge allows preimplantation genetic diagnosis (PGD) and enables prenatal DNA testing in future pregnancies. Although simultaneous testing of all FA genes by next generation sequencing will be possible in the near future, this technique will not be available immediately for all laboratories. In addition, in populations with strong founder mutations, a limited test using Sanger sequencing and MLPA will be a cost-effective alternative. We describe a strategy and optimized conditions for the screening of FANCA, FANCB, FANCC, FANCE, FANCF, and FANCG and present the results obtained in a cohort of 54 patients referred to our diagnostic service since 2008. In addition, the follow up with respect to genetic counseling and carrier screening in the families is discussed. PMID:22778927

A population genetic transect of Panicum hallii (Poaceae).

PubMed

Lowry, David B; Purmal, Colin T; Juenger, Thomas E

2013-03-01

Understanding the relationship between climate, adaptation, and population structure is of fundamental importance to botanists because these factors are crucial for the evolution of biodiversity and the response of species to future climate change. Panicum hallii is an emerging model system for perennial grass and bioenergy research, yet very little is known about the relationship between climate and population structure in this system. • We analyzed geographic population differentiation across 39 populations of P. hallii along a longitudinal transect from the savannas of central Texas through the deserts of Arizona and New Mexico. A combination of morphological and genetic (microsatellite) analysis was used to explore patterns of population structure. • We found strong differentiation between high elevation western desert populations and lower elevation eastern populations of P. hallii, with a pronounced break in structure occurring in western Texas. In addition, we confirmed that there are high levels of morphological and genetic structure between previous recognized varieties (var. hallii and var. filipes) within this species. • The results of this study suggest that patterns of population structure within P. hallii may be driven by climatic variation over space. Overall, this study lays the groundwork for future studies on the genetics of local adaptation and reproductive isolation in this system.

Epigenetic and genetic diagnosis of Silver-Russell syndrome.

PubMed

Eggermann, Thomas; Spengler, Sabrina; Gogiel, Magdalena; Begemann, Matthias; Elbracht, Miriam

2012-06-01

Silver-Russell syndrome (SRS) is a congenital imprinting disorder characterized by intrauterine and postnatal growth restriction and further characteristic features. SRS is genetically heterogenous: 7-10% of patients carry a maternal uniparental disomy of chromosome 7; >38% show a hypomethylation in imprinting control region 1 in 11p15; and a further class of mutations are copy number variations affecting different chromosomes, but mainly 11p15 and 7. The diagnostic work-up should thus aim to detect these three molecular subtypes. Numerous techniques are currently applied in genetic SRS testing, but none of them covers all known (epi)mutations, and they should therefore be used synergistically. However, future next-generation sequencing approaches will allow a comprehensive analysis of all types of alterations in SRS.

A Comprehensive Analysis of High School Genetics Standards: Are States Keeping Pace with Modern Genetics?

PubMed Central

Dougherty, M.J.; Pleasants, C.; Solow, L.; Wong, A.; Zhang, H.

2011-01-01

Science education in the United States will increasingly be driven by testing and accountability requirements, such as those mandated by the No Child Left Behind Act, which rely heavily on learning outcomes, or “standards,” that are currently developed on a state-by-state basis. Those standards, in turn, drive curriculum and instruction. Given the importance of standards to teaching and learning, we investigated the quality of life sciences/biology standards with respect to genetics for all 50 states and the District of Columbia, using core concepts developed by the American Society of Human Genetics as normative benchmarks. Our results indicate that the states’ genetics standards, in general, are poor, with more than 85% of the states receiving overall scores of Inadequate. In particular, the standards in virtually every state have failed to keep pace with changes in the discipline as it has become genomic in scope, omitting concepts related to genetic complexity, the importance of environment to phenotypic variation, differential gene expression, and the differences between inherited and somatic genetic disease. Clearer, more comprehensive genetics standards are likely to benefit genetics instruction and learning, help prepare future genetics researchers, and contribute to the genetic literacy of the U.S. citizenry. PMID:21885828

Current status, future opportunities, and remaining challenges in landscape genetics [Chapter 14

Treesearch

Niko Balkenhol; Samuel A. Cushman; Lisette P. Waits; Andrew Storfer

2016-01-01

Landscape genetics has advanced the field of evolutionary ecology by providing a direct focus on relationships between landscape patterns and population processes, such as gene flow, selection, and genetic drift. This chapter discusses the current and emerging challenges and opportunities, which focus and facilitate future progress in the field. It presents ten...

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

PubMed

Witt, S H; Streit, F; Jungkunz, M; Frank, J; Awasthi, S; Reinbold, C S; Treutlein, J; Degenhardt, F; Forstner, A J; Heilmann-Heimbach, S; Dietl, L; Schwarze, C E; Schendel, D; Strohmaier, J; Abdellaoui, A; Adolfsson, R; Air, T M; Akil, H; Alda, M; Alliey-Rodriguez, N; Andreassen, O A; Babadjanova, G; Bass, N J; Bauer, M; Baune, B T; Bellivier, F; Bergen, S; Bethell, A; Biernacka, J M; Blackwood, D H R; Boks, M P; Boomsma, D I; Børglum, A D; Borrmann-Hassenbach, M; Brennan, P; Budde, M; Buttenschøn, H N; Byrne, E M; Cervantes, P; Clarke, T-K; Craddock, N; Cruceanu, C; Curtis, D; Czerski, P M; Dannlowski, U; Davis, T; de Geus, E J C; Di Florio, A; Djurovic, S; Domenici, E; Edenberg, H J; Etain, B; Fischer, S B; Forty, L; Fraser, C; Frye, M A; Fullerton, J M; Gade, K; Gershon, E S; Giegling, I; Gordon, S D; Gordon-Smith, K; Grabe, H J; Green, E K; Greenwood, T A; Grigoroiu-Serbanescu, M; Guzman-Parra, J; Hall, L S; Hamshere, M; Hauser, J; Hautzinger, M; Heilbronner, U; Herms, S; Hitturlingappa, S; Hoffmann, P; Holmans, P; Hottenga, J-J; Jamain, S; Jones, I; Jones, L A; Juréus, A; Kahn, R S; Kammerer-Ciernioch, J; Kirov, G; Kittel-Schneider, S; Kloiber, S; Knott, S V; Kogevinas, M; Landén, M; Leber, M; Leboyer, M; Li, Q S; Lissowska, J; Lucae, S; Martin, N G; Mayoral-Cleries, F; McElroy, S L; McIntosh, A M; McKay, J D; McQuillin, A; Medland, S E; Middeldorp, C M; Milaneschi, Y; Mitchell, P B; Montgomery, G W; Morken, G; Mors, O; Mühleisen, T W; Müller-Myhsok, B; Myers, R M; Nievergelt, C M; Nurnberger, J I; O'Donovan, M C; Loohuis, L M O; Ophoff, R; Oruc, L; Owen, M J; Paciga, S A; Penninx, B W J H; Perry, A; Pfennig, A; Potash, J B; Preisig, M; Reif, A; Rivas, F; Rouleau, G A; Schofield, P R; Schulze, T G; Schwarz, M; Scott, L; Sinnamon, G C B; Stahl, E A; Strauss, J; Turecki, G; Van der Auwera, S; Vedder, H; Vincent, J B; Willemsen, G; Witt, C C; Wray, N R; Xi, H S; Tadic, A; Dahmen, N; Schott, B H; Cichon, S; Nöthen, M M; Ripke, S; Mobascher, A; Rujescu, D; Lieb, K; Roepke, S; Schmahl, C; Bohus, M; Rietschel, M

2017-06-20

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10 -7 ) and PKP4 (P=8.67 × 10 -7 ); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P FDR =0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r g =0.28 [P=2.99 × 10 -3 ]), SCZ (r g =0.34 [P=4.37 × 10 -5 ]) and MDD (r g =0.57 [P=1.04 × 10 -3 ]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Critical overview of applications of genetic testing in sport talent identification.

PubMed

Roth, Stephen M

2012-12-01

Talent identification for future sport performance is of paramount interest for many groups given the challenges of finding and costs of training potential elite athletes. Because genetic factors have been implicated in many performance- related traits (strength, endurance, etc.), a natural inclination is to consider the addition of genetic testing to talent identification programs. While the importance of genetic factors to sport performance is generally not disputed, whether genetic testing can positively inform talent identification is less certain. The present paper addresses the science behind the genetic tests that are now commercially available (some under patent protection) and aimed at predicting future sport performance potential. Also discussed are the challenging ethical issues that emerge from the availability of these tests. The potential negative consequences associated with genetic testing of young athletes will very likely outweigh any positive benefit for sport performance prediction at least for the next several years. The paper ends by exploring the future possibilities for genetic testing as the science of genomics in sport matures over the coming decade(s).

Knowledge, group-based medical mistrust, future expectations, and perceived disadvantages of medical genetic testing: perspectives of Black African immigrants/refugees.

PubMed

Buseh, A; Kelber, S; Millon-Underwood, S; Stevens, P; Townsend, L

2014-01-01

Reasons for low participation of ethnic minorities in genetic studies are multifactorial and often poorly understood. Based on published literature, participation in genetic testing is low among Black African immigrants/refugees although they are purported to bear disproportionate disease burden. Thus, research involving Black African immigrant/refugee populations that examine their perspectives on participating in genetic studies is needed. This report examines and describes the knowledge of medical genetics, group-based medical mistrust, and future expectations of genetic research and the influence of these measures on the perceived disadvantages of genetic testing among Black African immigrants/refugees. Using a cross-sectional survey design, a nonprobability sample (n = 212) of Black African immigrants/refugees was administered a questionnaire. Participants ranged in age from 18 to 61 years (mean = 38.91, SD = 9.78). The questionnaire consisted of 5 instruments: (a) sociodemographic characteristics, (b) Knowledge of Medical Genetics scale, (c) Group-Based Medical Mistrust Scale, (d) Future Expectations/Anticipated Consequences of Genetics Research scale, and (e) Perceived Disadvantages of Genetic Testing scale. Participants were concerned that genetic research may result in scientists 'playing God,' interfering with the natural order of life. In multivariate analyses, the perceived disadvantages of genetic testing increased as medical mistrust and anticipated negative impacts of genetic testing increased. Increase in genetic knowledge contributed to a decrease in perceived disadvantages. Our findings suggest that recruitment of Black African immigrants/refugees in genetic studies should address potential low knowledge of genetics, concerns about medical mistrust, the expectations/anticipated consequences of genetic research, and the perceived disadvantages of genetic testing.

Teaching Genetics: Past, Present, and Future

PubMed Central

Smith, Michelle K.; Wood, William B.

2016-01-01

Genetics teaching at the undergraduate level has changed in many ways over the past century. Compared to those of 100 years ago, contemporary genetics courses are broader in content and are taught increasingly differently, using instructional techniques based on educational research and constructed around the principles of active learning and backward design. Future courses can benefit from wider adoption of these approaches, more emphasis on the practice of genetics as a science, and new methods of assessing student learning. PMID:27601614

Genetic diversity of Elaeis oleifera (HBK) Cortes populations using cross species SSRs: implication's for germplasm utilization and conservation.

PubMed

Ithnin, Maizura; Teh, Chee-Keng; Ratnam, Wickneswari

2017-04-19

The Elaeis oleifera genetic materials were assembled from its center of diversity in South and Central America. These materials are currently being preserved in Malaysia as ex situ living collections. Maintaining such collections is expensive and requires sizable land. Information on the genetic diversity of these collections can help achieve efficient conservation via maintenance of core collection. For this purpose, we have applied fourteen unlinked microsatellite markers to evaluate 532 E. oleifera palms representing 19 populations distributed across Honduras, Costa Rica, Panama and Colombia. In general, the genetic diversity decreased from Costa Rica towards the north (Honduras) and south-east (Colombia). Principle coordinate analysis (PCoA) showed a single cluster indicating low divergence among palms. The phylogenetic tree and STRUCTURE analysis revealed clusters based on country of origin, indicating considerable gene flow among populations within countries. Based on the values of the genetic diversity parameters, some genetically diverse populations could be identified. Further, a total of 34 individual palms that collectively captured maximum allelic diversity with reduced redundancy were also identified. High pairwise genetic differentiation (Fst > 0.250) among populations was evident, particularly between the Colombian populations and those from Honduras, Panama and Costa Rica. Crossing selected palms from highly differentiated populations could generate off-springs that retain more genetic diversity. The results attained are useful for selecting palms and populations for core collection. The selected materials can also be included into crossing scheme to generate offsprings that capture greater genetic diversity for selection gain in the future.

A fine structure genetic analysis evaluating ecoregional adaptability of a Bos taurus breed (Hereford)

PubMed Central

Krehbiel, B.; Ericsson, S. A.; Wilson, C.; Caetano, A. R.; Paiva, S. R.

2017-01-01

Ecoregional differences contribute to genetic environmental interactions and impact animal performance. These differences may become more important under climate change scenarios. Utilizing genetic diversity within a species to address such problems has not been fully explored. In this study Hereford cattle were genotyped with 50K Bead Chip or 770K Bovine Bead Chip to test the existence of genetic structure in five U.S. ecoregions characterized by precipitation, temperature and humidity and designated: cool arid (CA), cool humid (CH), transition zone (TZ), warm arid (WA), and warm humid (WH). SNP data were analyzed in three sequential analyses. Broad genetic structure was evaluated with STRUCTURE, and ADMIXTURE software using 14,312 SNPs after passing quality control variables. The second analysis was performed using principal coordinate analysis with 66 Tag SNPs associated in the literature with various aspects of environmental stressors (e.g., heat tolerance) or production (e.g., milk production). In the third analysis TreeSelect was used with the 66 SNPs to evaluate if ecoregional allelic frequencies deviated from a central frequency and by so doing are indicative of directional selection. The three analyses suggested subpopulation structures associated with ecoregions from where animals were derived. ADMIXTURE and PCA results illustrated the importance of temperature and humidity and confirm subpopulation assignments. Comparisons of allele frequencies with TreeSelect showed ecoregion differences, in particular the divergence between arid and humid regions. Patterns of genetic variability obtained by medium and high density SNP chips can be used to acclimatize a temperately derived breed to various ecoregions. As climate change becomes an important factor in cattle production, this study should be used as a proof of concept to review future breeding and conservation schemes aimed at adaptation to climatic events. PMID:28459870

Predictors of Patterns of Alcohol-Related Blackouts Over Time in Youth From the Collaborative Study of the Genetics of Alcoholism: The Roles of Genetics and Cannabis

PubMed Central

Schuckit, Marc A.; Smith, Tom L.; Shafir, Alexandra; Clausen, Peyton; Danko, George; Gonçalves, Priscila Dib; Anthenelli, Robert M.; Chan, Grace; Kuperman, Samuel; Hesselbrock, Michie; Hesselbrock, Victor; Kramer, John; Bucholz, Kathleen K.

2017-01-01

Objective: Alcohol-related blackouts (ARBs) are anterograde amnesias related to heavy alcohol intake seen in about 50% of drinkers. Although a major determinant of ARBs relates to blood alcohol concentrations, additional contributions come from genetic vulnerabilities and possible impacts of cannabis use disorders (CUDs). We evaluated relationships of genetics and cannabis use to latent class trajectories of ARBs in 829 subjects from the Collaborative Study of the Genetics of Alcoholism (COGA). Method: The number of ARBs experienced every 2 years from subjects with average ages of 18 to 25 were entered into a latent class growth analysis in Mplus, and resulting class membership was evaluated in light of baseline characteristics, including CUDs. Correlations of number of ARBs across assessments were also compared for sibling pairs versus unrelated subjects. Results: Latent class growth analysis identified ARB-based Classes 1 (consistent low = 42.5%), 2 (moderate low = 28.3%), 3 (moderate high = 22.9%), and 4 (consistent high = 6.3%). A multinomial logistic regression analysis within latent class growth analysis revealed that baseline CUDs related most closely to Classes 3 and 4. The number of ARBs across time correlated .23 for sibling pairs and -.10 for unrelated subjects. Conclusions: Baseline CUDs related to the most severe latent ARB course over time, even when considered along with other trajectory predictors, including baseline alcohol use disorders and maximum number of drinks. Data indicated significant roles for genetic factors for alcohol use disorder patterns over time. Future research is needed to improve understanding of how cannabis adds to the ARB risk and to find genes that contribute to risks for ARBs among drinkers. PMID:27936363

Genetic Diversity and Ecological Niche Modelling of Wild Barley: Refugia, Large-Scale Post-LGM Range Expansion and Limited Mid-Future Climate Threats?

PubMed Central

Russell, Joanne; van Zonneveld, Maarten; Dawson, Ian K.; Booth, Allan; Waugh, Robbie; Steffenson, Brian

2014-01-01

Describing genetic diversity in wild barley (Hordeum vulgare ssp. spontaneum) in geographic and environmental space in the context of current, past and potential future climates is important for conservation and for breeding the domesticated crop (Hordeum vulgare ssp. vulgare). Spatial genetic diversity in wild barley was revealed by both nuclear- (2,505 SNP, 24 nSSR) and chloroplast-derived (5 cpSSR) markers in 256 widely-sampled geo-referenced accessions. Results were compared with MaxEnt-modelled geographic distributions under current, past (Last Glacial Maximum, LGM) and mid-term future (anthropogenic scenario A2, the 2080s) climates. Comparisons suggest large-scale post-LGM range expansion in Central Asia and relatively small, but statistically significant, reductions in range-wide genetic diversity under future climate. Our analyses support the utility of ecological niche modelling for locating genetic diversity hotspots and determine priority geographic areas for wild barley conservation under anthropogenic climate change. Similar research on other cereal crop progenitors could play an important role in tailoring conservation and crop improvement strategies to support future human food security. PMID:24505252

Analysis of genetic and cultural conservation value of three indigenous Croatian cattle breeds in a local and global context.

PubMed

Ramljak, J; Ivanković, A; Veit-Kensch, C E; Förster, M; Medugorac, I

2011-02-01

It is widely accepted that autochthonous cattle breeds can be important genetic resources for unforeseeable environmental conditions in the future. Apart from that, they often represent local culture and tradition and thus assist in the awareness of ethnic identity of a country. In Croatia, there are only three indigenous cattle breeds, Croatian Buša, Slavonian Syrmian Podolian and Istrian Cattle. All of them are threatened but specialized in a particular habitat and production system. We analysed 93 microsatellites in 51 animals of each breed to get thorough information about genetic diversity and population structure. We further set them within an existing frame of additional 16 breeds that have been genotyped for the same marker set and cover a geographical area from the domestication centre near Anatolia, through the Balkan and alpine regions, to the north-west of Europe. The cultural value was evaluated regarding the role in landscape, gastronomy, folklore and handicraft. The overall results recognize Croatian Buša being partly admixed but harbouring an enormous genetic diversity comparable with other traditional unselected Buša breeds in the Anatolian and Balkan areas. The Podolian cattle showed the lowest genetic diversity at the highest genetic distance to all remaining breeds but are playing an important role as part of the cultural landscape and thus contribute to the tourist industry. The genetic diversity of the Istrian cattle was found in the middle range of this study. It is already included in the tourist industry as a local food speciality. Current and future conservation strategies are discussed. © 2010 Blackwell Verlag GmbH.

Genome-wide associations for birth weight and correlations with adult disease

PubMed Central

Feenstra, Bjarke; van Zuydam, Natalie R; Gaulton, Kyle J; Grarup, Niels; Bradfield, Jonathan P; Strachan, David P; Li-Gao, Ruifang; Ahluwalia, Tarunveer S; Kreiner, Eskil; Rueedi, Rico; Lyytikäinen, Leo-Pekka; Cousminer, Diana L; Wu, Ying; Thiering, Elisabeth; Wang, Carol A; Have, Christian T; Hottenga, Jouke-Jan; Vilor-Tejedor, Natalia; Joshi, Peter K; Boh, Eileen Tai Hui; Ntalla, Ioanna; Pitkänen, Niina; Mahajan, Anubha; van Leeuwen, Elisabeth M; Joro, Raimo; Lagou, Vasiliki; Nodzenski, Michael; Diver, Louise A; Zondervan, Krina T; Bustamante, Mariona; Marques-Vidal, Pedro; Mercader, Josep M; Bennett, Amanda J; Rahmioglu, Nilufer; Nyholt, Dale R; Ma, Ronald Ching Wan; Tam, Claudia Ha Ting; Tam, Wing Hung; Ganesh, Santhi K; van Rooij, Frank JA; Jones, Samuel E; Loh, Po-Ru; Ruth, Katherine S; Tuke, Marcus A; Tyrrell, Jessica; Wood, Andrew R; Yaghootkar, Hanieh; Scholtens, Denise M; Paternoster, Lavinia; Prokopenko, Inga; Kovacs, Peter; Atalay, Mustafa; Willems, Sara M; Panoutsopoulou, Kalliope; Wang, Xu; Carstensen, Lisbeth; Geller, Frank; Schraut, Katharina E; Murcia, Mario; van Beijsterveldt, Catharina EM; Willemsen, Gonneke; Appel, Emil V R; Fonvig, Cilius E; Trier, Caecilie; Tiesler, Carla MT; Standl, Marie; Kutalik, Zoltán; Bonas-Guarch, Sílvia; Hougaard, David M; Sánchez, Friman; Torrents, David; Waage, Johannes; Hollegaard, Mads V; de Haan, Hugoline G; Rosendaal, Frits R; Medina-Gomez, Carolina; Ring, Susan M; Hemani, Gibran; McMahon, George; Robertson, Neil R; Groves, Christopher J; Langenberg, Claudia; Luan, Jian'an; Scott, Robert A; Zhao, Jing Hua; Mentch, Frank D; MacKenzie, Scott M; Reynolds, Rebecca M; Lowe, William L; Tönjes, Anke; Stumvoll, Michael; Lindi, Virpi; Lakka, Timo A; van Duijn, Cornelia M; Kiess, Wieland; Körner, Antje; Sørensen, Thorkild IA; Niinikoski, Harri; Pahkala, Katja; Raitakari, Olli T; Zeggini, Eleftheria; Dedoussis, George V; Teo, Yik-Ying; Saw, Seang-Mei; Melbye, Mads; Campbell, Harry; Wilson, James F; Vrijheid, Martine; de Geus, Eco JCN; Boomsma, Dorret I; Kadarmideen, Haja N; Holm, Jens-Christian; Hansen, Torben; Sebert, Sylvain; Hattersley, Andrew T; Beilin, Lawrence J; Newnham, John P; Pennell, Craig E; Heinrich, Joachim; Adair, Linda S; Borja, Judith B; Mohlke, Karen L; Eriksson, Johan G; Widén, Elisabeth E; Kähönen, Mika; Viikari, Jorma S; Lehtimäki, Terho; Vollenweider, Peter; Bønnelykke, Klaus; Bisgaard, Hans; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Pisinger, Charlotta; Pedersen, Oluf; Power, Christine; Hyppönen, Elina; Wareham, Nicholas J; Hakonarson, Hakon; Davies, Eleanor; Walker, Brian R; Jaddoe, Vincent WV; Jarvelin, Marjo-Riitta; Grant, Struan FA; Vaag, Allan A; Lawlor, Debbie A; Frayling, Timothy M; Davey Smith, George; Morris, Andrew P; Ong, Ken K; Felix, Janine F; Timpson, Nicholas J; Perry, John RB; Evans, David M; McCarthy, Mark I; Freathy, Rachel M

2016-01-01

Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P <5x10-8). Overall, ˜15% of variance in BW could be captured by assays of foetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (rg=-0.22, P =5.5x10-13), T2D (rg=-0.27, P =1.1x10-6) and coronary artery disease (rg=-0.30, P =6.5x10-9) and, in large cohort data sets, demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P =1.9x10-4). We have demonstrated that lifecourse associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and have highlighted some of the pathways through which these causal genetic effects are mediated. PMID:27680694

Genetic adaptation to historical pathogen burdens.

PubMed

Fedderke, Johannes W; Klitgaard, Robert E; Napolioni, Valerio

2017-10-01

Historical pathogen burdens are examined as possible triggers for genetic adaptation. Evidence of adaptation emerges for the acid phosphatase locus 1 (ACP1), interleukin-6 (IL6), interleukin-10 (IL10 ), human leukocyte antigen (HLA) polymorphisms, along with a measure of heterozygosity over 783 alleles. Results are robust to controlling for the physical and historical environment humans faced, and to endogeneity of the historical pathogen burden measure. The present study represents a proof-of-concept which may pave the way to the analysis of future aggregate measures coming from whole-genome sequencing/genotyping data. Copyright © 2017 Elsevier B.V. All rights reserved.

From forensic epigenetics to forensic epigenomics: broadening DNA investigative intelligence.

PubMed

Vidaki, Athina; Kayser, Manfred

2017-12-21

Human genetic variation is a major resource in forensics, but does not allow all forensically relevant questions to be answered. Some questions may instead be addressable via epigenomics, as the epigenome acts as an interphase between the fixed genome and the dynamic environment. We envision future forensic applications of DNA methylation analysis that will broaden DNA-based forensic intelligence. Together with genetic prediction of appearance and biogeographic ancestry, epigenomic lifestyle prediction is expected to increase the ability of police to find unknown perpetrators of crime who are not identifiable using current forensic DNA profiling.

Multi-channel acoustic recording and automated analysis of Drosophila courtship songs

PubMed Central

2013-01-01

Background Drosophila melanogaster has served as a powerful model system for genetic studies of courtship songs. To accelerate research on the genetic and neural mechanisms underlying courtship song, we have developed a sensitive recording system to simultaneously capture the acoustic signals from 32 separate pairs of courting flies as well as software for automated segmentation of songs. Results Our novel hardware design enables recording of low amplitude sounds in most laboratory environments. We demonstrate the power of this system by collecting, segmenting and analyzing over 18 hours of courtship song from 75 males from five wild-type strains of Drosophila melanogaster. Our analysis reveals previously undetected modulation of courtship song features and extensive natural genetic variation for most components of courtship song. Despite having a large dataset with sufficient power to detect subtle modulations of song, we were unable to identify previously reported periodic rhythms in the inter-pulse interval of song. We provide detailed instructions for assembling the hardware and for using our open-source segmentation software. Conclusions Analysis of a large dataset of acoustic signals from Drosophila melanogaster provides novel insight into the structure and dynamics of species-specific courtship songs. Our new system for recording and analyzing fly acoustic signals should therefore greatly accelerate future studies of the genetics, neurobiology and evolution of courtship song. PMID:23369160

Insights to the Genetics of Diabetic Nephropathy through a Genome-wide Association Study of the GoKinD Collection

PubMed Central

Pezzolesi, Marcus G.; Skupien, Jan; Krolewski, Andrzej S.

2010-01-01

The Genetics of Kidneys in Diabetes (GoKinD) study was initiated to facilitate research aimed at identifying genes involved in diabetic nephropathy (DN) in type 1 diabetes (T1D). In this review, we present on overview of this study and the various reports that have utilized its collection. At the forefront of these efforts is the recent genome-wide association (GWA) scan implemented on the GoKinD collection. We highlight the results from our analysis of these data and describe compelling evidence from animal models that further support the potential role of associated loci in the susceptibility of DN. To enhance our analysis of genetic associations in GoKinD, using genome-wide imputation (GWI), we expanded our analysis of this collection to include genotype data from more than 2.4 million common SNPs. We illustrate the added utility of this enhanced dataset through the comprehensive fine-mapping of candidate genomic regions previously linked with DN and the targeted investigation of genes involved in candidate pathway implicated in its pathogenesis. Collectively, GWA and GWI data from the GoKinD collection will serve as a springboard for future investigations into the genetic basis of DN in T1D. PMID:20347642

Genetic genealogy comes of age: perspectives on the use of deep-rooted pedigrees in human population genetics.

PubMed

Larmuseau, M H D; Van Geystelen, A; van Oven, M; Decorte, R

2013-04-01

In this article, we promote the implementation of extensive genealogical data in population genetic studies. Genealogical records can provide valuable information on the origin of DNA donors in a population genetic study, going beyond the commonly collected data such as residence, birthplace, language, and self-reported ethnicity. Recent studies demonstrated that extended genealogical data added to surname analysis can be crucial to detect signals of (past) population stratification and to interpret the population structure in a more objective manner. Moreover, when in-depth pedigree data are combined with haploid markers, it is even possible to disentangle signals of temporal differentiation within a population genetic structure during the last centuries. Obtaining genealogical data for all DNA donors in a population genetic study is a labor-intensive task but the vastly growing (genetic) genealogical databases, due to the broad interest of the public, are making this job more time-efficient if there is a guarantee for sufficient data quality. At the end, we discuss the advantages and pitfalls of using genealogy within sampling campaigns and we provide guidelines for future population genetic studies. Copyright © 2013 Wiley Periodicals, Inc.

Genetic Variants in Diseases of the Extrapyramidal System

PubMed Central

Oczkowska, Anna; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

2014-01-01

Knowledge on the genetics of movement disorders has advanced significantly in recent years. It is now recognized that disorders of the basal ganglia have genetic basis and it is suggested that molecular genetic data will provide clues to the pathophysiology of normal and abnormal motor control. Progress in molecular genetic studies, leading to the detection of genetic mutations and loci, has contributed to the understanding of mechanisms of neurodegeneration and has helped clarify the pathogenesis of some neurodegenerative diseases. Molecular studies have also found application in the diagnosis of neurodegenerative diseases, increasing the range of genetic counseling and enabling a more accurate diagno-sis. It seems that understanding pathogenic processes and the significant role of genetics has led to many experiments that may in the future will result in more effective treatment of such diseases as Parkinson’s or Huntington’s. Currently used molecular diagnostics based on DNA analysis can identify 9 neurodegenerative diseases, including spinal cerebellar ataxia inherited in an autosomal dominant manner, dentate-rubro-pallido-luysian atrophy, Friedreich’s disease, ataxia with ocu-lomotorapraxia, Huntington's disease, dystonia type 1, Wilson’s disease, and some cases of Parkinson's disease. PMID:24653660

Application of RAD Sequencing for Evaluating the Genetic Diversity of Domesticated Panax notoginseng (Araliaceae)

PubMed Central

Pan, Yuezhi; Wang, Xueqin; Sun, Guiling; Li, Fusheng; Gong, Xun

2016-01-01

Panax notoginseng, a traditional Chinese medicinal plant, has been cultivated and domesticated for approximately 400 years, mainly in Yunnan and Guangxi, two provinces in southwest China. This species was named according to cultivated rather than wild individuals, and no wild populations had been found until now. The genetic resources available on farms are important for both breeding practices and resource conservation. In the present study, the recently developed technology RADseq, which is based on next-generation sequencing, was used to analyze the genetic variation and differentiation of P. notoginseng. The nucleotide diversity and heterozygosity results indicated that P. notoginseng had low genetic diversity at both the species and population levels. Almost no genetic differentiation has been detected, and all populations were genetically similar due to strong gene flow and insufficient splitting time. Although the genetic diversity of P. notoginseng was low at both species and population levels, several traditional plantations had relatively high genetic diversity, as revealed by the He and π values and by the private allele numbers. These valuable genetic resources should be protected as soon as possible to facilitate future breeding projects. The possible geographical origin of Sanqi domestication was discussed based on the results of the genetic diversity analysis. PMID:27846268

From ecology to base pairs: nursing and genetic science.

PubMed

Williams, J K; Tripp-Reimer, T

2001-07-01

With the mapping of the human genome has come the opportunity for nursing research to explore topics of concern to the maintenance, restoration, and attainment of genetic-related health. Initially, nursing research on genetic topics originated primarily from physical anthropology and from a clinical, disease-focused perspective. Nursing research subsequently focused on psychosocial aspects of genetic conditions for individuals and their family members. As findings emerge from current human genome discovery, new programs of genetic nursing research are originating from a biobehavioral interface, ranging from the investigations of the influence of specific molecular changes on gene function to social/ethical issues of human health and disease. These initiatives reflect nursing's response to discoveries of gene mutations related to phenotypic expression in both clinical and community-based populations. Genetic research programs are needed that integrate or adapt theoretical and methodological advances in epidemiology, family systems, anthropology, and ethics with those from nursing. Research programs must address not only populations with a specific disease but also community-based genetic health care issues. As genetic health care practice evolves, so will opportunities for research by nurses who can apply genetic concepts and interventions to improve the health of the public. This article presents an analysis of the evolution of genetic nursing research and challengesfor the future.

Race, Genomics and Chronic Disease: What Patients with African Ancestry Have to Say

PubMed Central

Horowitz, Carol R.; Ferryman, Kadija; Negron, Rennie; Sabin, Tatiana; Rodriguez, Mayra; Zinberg, Randi F.; Böttinger, Erwin; Robinson, Mimsie

2017-01-01

Background Variants of the APOL1 gene increase risk for kidney failure 10- fold, and are nearly exclusively found in people with African ancestry. To translate genomic discoveries into practice, we gathered information about effects and challenges incorporating genetic risk in clinical care. Methods An academic- community- clinical team tested 26 adults with self- reported African ancestry for APOL1 variants, conducting in- depth interviews about patients' beliefs and attitudes toward genetic testing- before, immediately, and 30 days after receiving test results. We used constant comparative analysis of interview transcripts to identify themes. Results Themes included: Knowledge of genetic risk for kidney failure may motivate providers and patients to take hypertension more seriously, rather than inspiring fatalism or anxiety. Having genetic risk for a disease may counter stereotypes of Blacks as non- adherent or low- literate, rather than exacerbate stereotypes. Conclusion Populations most likely to benefit from genomic research can inform strategies for genetic testing and future research. PMID:28238999

Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

PubMed Central

Saad, Mohamed N.; Mabrouk, Mai S.; Eldeib, Ayman M.; Shaker, Olfat G.

2015-01-01

Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field. PMID:26843965

Genetics and Epigenetics of Eating Disorders

PubMed Central

Yilmaz, Zeynep; Hardaway, J. Andrew; Bulik, Cynthia M.

2015-01-01

Eating disorders (EDs) are serious psychiatric conditions influenced by biological, psychological, and sociocultural factors. A better understanding of the genetics of these complex traits and the development of more sophisticated molecular biology tools have advanced our understanding of the etiology of EDs. The aim of this review is to critically evaluate the literature on the genetic research conducted on three major EDs: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). We will first review the diagnostic criteria, clinical features, prevalence, and prognosis of AN, BN, and BED, followed by a review of family, twin, and adoption studies. We then review the history of genetic studies of EDs covering linkage analysis, candidate gene association studies, genome-wide association studies, and the study of rare variants in EDs. Our review also incorporates a translational perspective by covering animal models of ED-related phenotypes. Finally, we review the nascent field of epigenetics of EDs and a look forward to future directions for ED genetic research. PMID:27013903

Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

PubMed

Levin, M

1999-01-01

Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed.

A practical guide to environmental association analysis in landscape genomics.

PubMed

Rellstab, Christian; Gugerli, Felix; Eckert, Andrew J; Hancock, Angela M; Holderegger, Rolf

2015-09-01

Landscape genomics is an emerging research field that aims to identify the environmental factors that shape adaptive genetic variation and the gene variants that drive local adaptation. Its development has been facilitated by next-generation sequencing, which allows for screening thousands to millions of single nucleotide polymorphisms in many individuals and populations at reasonable costs. In parallel, data sets describing environmental factors have greatly improved and increasingly become publicly accessible. Accordingly, numerous analytical methods for environmental association studies have been developed. Environmental association analysis identifies genetic variants associated with particular environmental factors and has the potential to uncover adaptive patterns that are not discovered by traditional tests for the detection of outlier loci based on population genetic differentiation. We review methods for conducting environmental association analysis including categorical tests, logistic regressions, matrix correlations, general linear models and mixed effects models. We discuss the advantages and disadvantages of different approaches, provide a list of dedicated software packages and their specific properties, and stress the importance of incorporating neutral genetic structure in the analysis. We also touch on additional important aspects such as sampling design, environmental data preparation, pooled and reduced-representation sequencing, candidate-gene approaches, linearity of allele-environment associations and the combination of environmental association analyses with traditional outlier detection tests. We conclude by summarizing expected future directions in the field, such as the extension of statistical approaches, environmental association analysis for ecological gene annotation, and the need for replication and post hoc validation studies. © 2015 John Wiley & Sons Ltd.

Analysis of genetic diversity in Bolivian llama populations using microsatellites.

PubMed

Barreta, J; Gutiérrez-Gil, B; Iñiguez, V; Romero, F; Saavedra, V; Chiri, R; Rodríguez, T; Arranz, J J

2013-08-01

South American camelids (SACs) have a major role in the maintenance and potential future of rural Andean human populations. More than 60% of the 3.7 million llamas living worldwide are found in Bolivia. Due to the lack of studies focusing on genetic diversity in Bolivian llamas, this analysis investigates both the genetic diversity and structure of 12 regional groups of llamas that span the greater part of the range of distribution for this species in Bolivia. The analysis of 42 microsatellite markers in the considered regional groups showed that, in general, there were high levels of polymorphism (a total of 506 detected alleles; average PIC across per marker: 0.66), which are comparable with those reported for other populations of domestic SACs. The estimated diversity parameters indicated that there was high intrapopulational genetic variation (average number of alleles and average expected heterozygosity per marker: 12.04 and 0.68, respectively) and weak genetic differentiation among populations (FST range: 0.003-0.052). In agreement with these estimates, Bolivian llamas showed a weak genetic structure and an intense gene flow between all the studied regional groups, which is due to the exchange of reproductive males between the different flocks. Interestingly, the groups for which the largest pairwise FST estimates were observed, Sud Lípez and Nor Lípez, showed a certain level of genetic differentiation that is probably due to the pattern of geographic isolation and limited communication infrastructures of these southern localities. Overall, the population parameters reported here may serve as a reference when establishing conservation policies that address Bolivian llama populations. © 2012 Blackwell Verlag GmbH.

Genetic diversity of the captive Asian tapir population in Thailand, based on mitochondrial control region sequence data and the comparison of its nucleotide structure with Brazilian tapir.

PubMed

Muangkram, Yuttamol; Amano, Akira; Wajjwalku, Worawidh; Pinyopummintr, Tanu; Thongtip, Nikorn; Kaolim, Nongnid; Sukmak, Manakorn; Kamolnorranath, Sumate; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Maikaew, Umaporn; Thomas, Warisara; Polsrila, Kanda; Dongsaard, Kwanreaun; Sanannu, Saowaphang; Wattananorrasate, Anuwat

2017-07-01

The Asian tapir (Tapirus indicus) has been classified as Endangered on the IUCN Red List of Threatened Species (2008). Genetic diversity data provide important information for the management of captive breeding and conservation of this species. We analyzed mitochondrial control region (CR) sequences from 37 captive Asian tapirs in Thailand. Multiple alignments of the full-length CR sequences sized 1268 bp comprised three domains as described in other mammal species. Analysis of 16 parsimony-informative variable sites revealed 11 haplotypes. Furthermore, the phylogenetic analysis using median-joining network clearly showed three clades correlated with our earlier cytochrome b gene study in this endangered species. The repetitive motif is located between first and second conserved sequence blocks, similar to the Brazilian tapir. The highest polymorphic site was located in the extended termination associated sequences domain. The results could be applied for future genetic management based in captivity and wild that shows stable populations.

Genetic analysis of some agronomic and fiber traits in Gossypium hirsutum L. grown in field conditions

USDA-ARS?s Scientific Manuscript database

Cotton production is an essential component of the economy of Pakistan, and continuing to improve the yield and fiber quality of this crop will ensure the future stability of this industry. Combining ability describes the performance of genotypes when they are crossed together, and it is a common me...

Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens

PubMed Central

Zeng, Y.; Yin, T.; Brügemann, K.

2018-01-01

Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle. PMID:29608619

Genetic Differentiation in the Stingless Bee, Scaptotrigona xanthotricha Moure, 1950 (Apidae, Meliponini): a Species with Wide Geographic Distribution in the Atlantic Rainforest.

PubMed

Duarte, Olívia M P; Gaiotto, Fernanda A; Costa, Marco A

2014-01-01

Stingless bees are important pollinators that are severely threatened by anthropic interference, resulting in a strong population decline. Scaptotrigona xanthotricha has a wide distribution in the Atlantic Rainforest, ranging from the northeastern state of Bahia to Santa Catarina in southern Brazil. To understand the genetic structure of S. xanthotricha, 12 species-specific microsatellite loci were analyzed in 42 colonies sampled throughout the species range. The results indicated 5 distinct clusters throughout the sampled area with high rates of genetic diversity, and the greatest diversity was found in southern Bahia. Greater differentiation was observed between samples from the extremes of the distribution, with an F ST value of 0.189 between cluster 1 and 5. The genetic differentiation analysis for all loci had an F ST value of 0.113, a result that is consistent with the analysis of molecular variance, which revealed 7.72% of the variation occurring between groups. The Mantel correlation between a genetic differentiation matrix and a geographic distance matrix (r = 0.184, P = 0.043) indicated a tendency toward increased differentiation with increased distance. This study revealed the profile of differentiation and distribution of genetic diversity in this species and indicates parameters that should be considered in future taxonomic revisions and activities for its management and conservation. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Start Codon Targeted (SCoT) marker reveals genetic diversity of Dendrobium nobile Lindl., an endangered medicinal orchid species.

PubMed

Bhattacharyya, Paromik; Kumaria, Suman; Kumar, Shrawan; Tandon, Pramod

2013-10-15

Genetic variability in the wild genotypes of Dendrobium nobile Lindl. collected from different parts of Northeast India, was analyzed using a Start Codon Targeted (SCoT) marker system. A total of sixty individuals comprising of six natural populations were investigated for the existing natural genetic diversity. One hundred and thirty two (132) amplicons were produced by SCoT marker generating 96.21% polymorphism. The PIC value of the SCoT marker system was 0.78 and the Rp values of the primers ranged between 4.43 and 7.50. The percentage of polymorphic loci (Pp) ranging from 25% to 56.82%, Nei's gene diversity (h) from 0.08 to 0.15 with mean Nei's gene diversity of 0.28, and Shannon's information index (I) values ranging from 0.13 to 0.24 with an average value of 0.43 were recorded. The gene flow value (0.37) and the diversity among populations (0.57) demonstrated higher genetic variation among the populations. Analysis of molecular variance (AMOVA) showed 43.37% of variation within the populations, whereas 56.63% variation was recorded among the populations. Cluster analysis also reveals high genetic variation among the genotypes. Present investigation suggests the effectiveness of SCoT marker system to estimate the genetic diversity of D. nobile and that it can be seen as a preliminary point for future research on the population and evolutionary genetics of this endangered orchid species of medicinal importance. © 2013.

"I Don't Want to Be an Ostrich": Managing Mothers' Uncertainty during BRCA1/2 Genetic Counseling.

PubMed

Fisher, Carla L; Roccotagliata, Thomas; Rising, Camella J; Kissane, David W; Glogowski, Emily A; Bylund, Carma L

2017-06-01

Families who face genetic disease risk must learn how to grapple with complicated uncertainties about their health and future on a long-term basis. Women who undergo BRCA 1/2 genetic testing describe uncertainty related to personal risk as well as their loved ones', particularly daughters', risk. The genetic counseling setting is a prime opportunity for practitioners to help mothers manage uncertainty in the moment but also once they leave a session. Uncertainty Management Theory (UMT) helps to illuminate the various types of uncertainty women encounter and the important role of communication in uncertainty management. Informed by UMT, we conducted a thematic analysis of 16 genetic counseling sessions between practitioners and mothers at risk for, or carriers of, a BRCA1/2 mutation. Five themes emerged that represent communication strategies used to manage uncertainty: 1) addresses myths, misunderstandings, or misconceptions; 2) introduces uncertainty related to science; 3) encourages information seeking or sharing about family medical history; 4) reaffirms or validates previous behavior or decisions; and 5) minimizes the probability of personal risk or family members' risk. Findings illustrate the critical role of genetic counseling for families in managing emotionally challenging risk-related uncertainty. The analysis may prove beneficial to not only genetic counseling practice but generations of families at high risk for cancer who must learn strategic approaches to managing a complex web of uncertainty that can challenge them for a lifetime.

Genetic diversity of turmeric germplasm (Curcuma longa; Zingiberaceae) identified by microsatellite markers.

PubMed

Sigrist, M S; Pinheiro, J B; Filho, J A Azevedo; Zucchi, M I

2011-03-09

Turmeric (Curcuma longa) is a triploid, vegetatively propagated crop introduced early during the colonization of Brazil. Turmeric rhizomes are ground into a powder used as a natural dye in the food industry, although recent research suggests a greater potential for the development of drugs and cosmetics. In Brazil, little is known about the genetic variability available for crop improvement. We examined the genetic diversity among turmeric accessions from a Brazilian germplasm collection comprising 39 accessions collected from the States of Goiás, Mato Grosso do Sul, Minas Gerais, São Paulo, and Pará. For comparison, 18 additional genotypes were analyzed, including samples from India and Puerto Rico. Total DNA was extracted from lyophilized leaf tissue and genetic analysis was performed using 17 microsatellite markers (single-sequence repeats). Shannon-Weiner indexes ranged from 0.017 (Minas Gerais) to 0.316 (São Paulo). Analyses of molecular variance (AMOVA) demonstrated major differences between countries (63.4%) and that most of the genetic diversity in Brazil is found within states (75.3%). Genotypes from São Paulo State were the most divergent and potentially useful for crop improvement. Structure analysis indicated two main groups of accessions. These results can help target future collecting efforts for introduction of new materials needed to develop more productive and better adapted cultivars.

Additive genetic contribution to symptom dimensions in major depressive disorder.

PubMed

Pearson, Rahel; Palmer, Rohan H C; Brick, Leslie A; McGeary, John E; Knopik, Valerie S; Beevers, Christopher G

2016-05-01

Major depressive disorder (MDD) is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum-likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with MDD (N = 1,558) who participated in the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed 4 depression symptom components: (a) appetite, (b) core depression symptoms (e.g., depressed mood, anhedonia), (c) insomnia, and (d) anxiety. These symptom dimensions were associated with SNP-based heritability (hSNP2) estimates of 30%, 14%, 30%, and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Proton Nuclear Magnetic Resonance-Spectroscopic Discrimination of Wines Reflects Genetic Homology of Several Different Grape (V. vinifera L.) Cultivars

PubMed Central

Zhu, Yong; Wen, Wen; Zhang, Fengmin; Hardie, Jim W.

2015-01-01

Background and Aims Proton nuclear magnetic resonance spectroscopy coupled multivariate analysis (1H NMR-PCA/PLS-DA) is an important tool for the discrimination of wine products. Although 1H NMR has been shown to discriminate wines of different cultivars, a grape genetic component of the discrimination has been inferred only from discrimination of cultivars of undefined genetic homology and in the presence of many confounding environmental factors. We aimed to confirm the influence of grape genotypes in the absence of those factors. Methods and Results We applied 1H NMR-PCA/PLS-DA and hierarchical cluster analysis (HCA) to wines from five, variously genetically-related grapevine (V. vinifera) cultivars; all grown similarly on the same site and vinified similarly. We also compared the semi-quantitative profiles of the discriminant metabolites of each cultivar with previously reported chemical analyses. The cultivars were clearly distinguishable and there was a general correlation between their grouping and their genetic homology as revealed by recent genomic studies. Between cultivars, the relative amounts of several of the cultivar-related discriminant metabolites conformed closely with reported chemical analyses. Conclusions Differences in grape-derived metabolites associated with genetic differences alone are a major source of 1H NMR-based discrimination of wines and 1H NMR has the capacity to discriminate between very closely related cultivars. Significance of the Study The study confirms that genetic variation among grape cultivars alone can account for the discrimination of wine by 1H NMR-PCA/PLS and indicates that 1H NMR spectra of wine of single grape cultivars may in future be used in tandem with hierarchical cluster analysis to elucidate genetic lineages and metabolomic relations of grapevine cultivars. In the absence of genetic information, for example, where predecessor varieties are no longer extant, this may be a particularly useful approach. PMID:26658757

A Qualitative Inquiry of the Financial Concerns of Couples Opting to Use Preimplantation Genetic Diagnosis to Prevent the Transmission of Known Genetic Disorders

PubMed Central

Drazba, Kathryn T.; Kelley, Michele A.; Hershberger, Patricia E.

2013-01-01

Preimplantation genetic diagnosis (PGD) is an innovative prenatal testing option because the determination of whether a genetic disorder or chromosomal abnormality is evident occurs prior to pregnancy. However, PGD is not covered financially under the majority of private and public health insurance institutions in the United States, leaving couples to decide whether PGD is financially feasible. The aim of this qualitative study was to understand the role of finances in the decision-making process among couples who were actively considering PGD. In-depth, semi-structured interviews were completed with 18 genetic high-risk couples (36 individual partners). Grounded theory guided the analysis, whereby three themes emerged: 1) Cost is salient, 2) Emotions surrounding affordability, and 3) Financial burden and sacrifice. Ultimately, couples determined that the opportunity to avoid passing on a genetic disorder to a future child was paramount to the cost of PGD, but expressed financial concerns and recognized financial access as a major barrier to PGD utilization. PMID:23949612

Black and white and read all over: the past, present and future of giant panda genetics.

PubMed

Wei, Fuwen; Hu, Yibo; Zhu, Lifeng; Bruford, Michael W; Zhan, Xiangjiang; Zhang, Lei

2012-12-01

Few species attract much more attention from the public and scientists than the giant panda (Ailuropoda melanoleuca), a popular, enigmatic but highly endangered species. The application of molecular genetics to its biology and conservation has facilitated surprising insights into the biology of giant pandas as well as the effectiveness of conservation efforts during the past decades. Here, we review the history of genetic advances in this species, from phylogeny, demographical history, genetic variation, population structure, noninvasive population census and adaptive evolution to reveal to what extent the current status of the giant panda is a reflection of its evolutionary legacy, as opposed to the influence of anthropogenic factors that have negatively impacted this species. In addition, we summarize the conservation implications of these genetic findings applied for the management of this high-profile species. Finally, on the basis of these advances and predictable future changes in genetic technology, we discuss future research directions that seem promising for giant panda biology and conservation. © 2012 Blackwell Publishing Ltd.

Genetics of ischemic stroke: future clinical applications.

PubMed

Wang, Michael M

2006-11-01

Ischemic stroke has long been thought to have a genetic component that is independent of conventional vascular risk factors. It has been estimated that over one half of stroke risk is determined by inherited genes. However, until recently, strong evidence of genetic influence on ischemic stroke has been subject to criticism because the risk factors for stroke are also inherited and because previous studies suffered from limitations imposed by this highly heterogeneous neurological disorder. Recent advances in molecular genetics have led to the identification of specific genetic loci that impart susceptibility to ischemic stroke. We review the studies of these genes and discuss the future potential applications of genetic markers on the management of ischemic stroke patients.

Genetic variation analysis and relationships among environmental strains of Scedosporium apiospermum sensu stricto in Bangkok, Thailand.

PubMed

Wongsuk, Thanwa; Pumeesat, Potjaman; Luplertlop, Natthanej

2017-01-01

The Scedosporium apiospermum species complex is an emerging filamentous fungi that has been isolated from environment. It can cause a wide range of infections in both immunocompetent and immunocompromised individuals. We aimed to study the genetic variation and relationships between 48 strains of S. apiospermum sensu stricto isolated from soil in Bangkok, Thailand. For PCR, sequencing and phylogenetic analysis, we used the following genes: actin; calmodulin exons 3 and 4; the second largest subunit of the RNA polymerase II; ß-tubulin exon 2-4; manganese superoxide dismutase; internal transcribed spacer; transcription elongation factor 1α; and beta-tubulin exons 5 and 6. The present study is the first phylogenetic analysis of relationships among S. apiospermum sensu stricto in Thailand and South-east Asia. This result provides useful information for future epidemiological study and may be correlated to clinical manifestation.

Genetic variation analysis and relationships among environmental strains of Scedosporium apiospermum sensu stricto in Bangkok, Thailand

PubMed Central

2017-01-01

The Scedosporium apiospermum species complex is an emerging filamentous fungi that has been isolated from environment. It can cause a wide range of infections in both immunocompetent and immunocompromised individuals. We aimed to study the genetic variation and relationships between 48 strains of S. apiospermum sensu stricto isolated from soil in Bangkok, Thailand. For PCR, sequencing and phylogenetic analysis, we used the following genes: actin; calmodulin exons 3 and 4; the second largest subunit of the RNA polymerase II; ß-tubulin exon 2–4; manganese superoxide dismutase; internal transcribed spacer; transcription elongation factor 1α; and beta-tubulin exons 5 and 6. The present study is the first phylogenetic analysis of relationships among S. apiospermum sensu stricto in Thailand and South-east Asia. This result provides useful information for future epidemiological study and may be correlated to clinical manifestation. PMID:28704511

Climate-driven range shifts explain the distribution of extant gene pools and predict future loss of unique lineages in a marine brown alga.

PubMed

Assis, J; Serrão, E A; Claro, B; Perrin, C; Pearson, G A

2014-06-01

The climate-driven dynamics of species ranges is a critical research question in evolutionary ecology. We ask whether present intraspecific diversity is determined by the imprint of past climate. This is an ongoing debate requiring interdisciplinary examination of population genetic pools and persistence patterns across global ranges. Previously, contrasting inferences and predictions have resulted from distinct genomic coverage and/or geographical information. We aim to describe and explain the causes of geographical contrasts in genetic diversity and their consequences for the future baseline of the global genetic pool, by comparing present geographical distribution of genetic diversity and differentiation with predictive species distribution modelling (SDM) during past extremes, present time and future climate scenarios for a brown alga, Fucus vesiculosus. SDM showed that both atmospheric and oceanic variables shape the global distribution of intertidal species, revealing regions of persistence, extinction and expansion during glacial and postglacial periods. These explained the distribution and structure of present genetic diversity, consisting of differentiated genetic pools with maximal diversity in areas of long-term persistence. Most of the present species range comprises postglacial expansion zones and, in contrast to highly dispersive marine organisms, expansions involved only local fronts, leaving distinct genetic pools at rear edges. Besides unravelling a complex phylogeographical history and showing congruence between genetic diversity and persistent distribution zones, supporting the hypothesis of niche conservatism, range shifts and loss of unique genetic diversity at the rear edge were predicted for future climate scenarios, impoverishing the global gene pool. © 2014 John Wiley & Sons Ltd.

Molecular phylogeny, population genetics, and evolution of heterocystous cyanobacteria using nifH gene sequences.

PubMed

Singh, Prashant; Singh, Satya Shila; Elster, Josef; Mishra, Arun Kumar

2013-06-01

In order to assess phylogeny, population genetics, and approximation of future course of cyanobacterial evolution based on nifH gene sequences, 41 heterocystous cyanobacterial strains collected from all over India have been used in the present study. NifH gene sequence analysis data confirm that the heterocystous cyanobacteria are monophyletic while the stigonematales show polyphyletic origin with grave intermixing. Further, analysis of nifH gene sequence data using intricate mathematical extrapolations revealed that the nucleotide diversity and recombination frequency is much greater in Nostocales than the Stigonematales. Similarly, DNA divergence studies showed significant values of divergence with greater gene conversion tracts in the unbranched (Nostocales) than the branched (Stigonematales) strains. Our data strongly support the origin of true branching cyanobacterial strains from the unbranched strains.

Training future physicians in the era of genomic medicine: trends in undergraduate medical genetics education.

PubMed

Plunkett-Rondeau, Jevon; Hyland, Katherine; Dasgupta, Shoumita

2015-11-01

Advances in genomic technologies are transforming medical practice, necessitating the expertise of genomically-literate physicians. This study examined 2013-2014 trends in genetics curricula in US and Canadian medical schools to ascertain whether and how curricula are keeping pace with this rapid evolution. Medical genetics course directors received a 60-item electronic questionnaire covering curriculum design, assessment, remediation of failing grades, and inclusion of specific topics. The response rate was 74%. Most schools teach the majority of genetics during the first 2 years, with an increase in the number of integrated curricula. Only 26% reported formal genetics teaching during years 3 and 4, and most respondents felt the amount of time spent on genetics was insufficient preparation for clinical practice. Most participants are using the Association of Professors of Human and Medical Genetics Core Curriculum(1) as a guide. Topics recently added include personalized medicine (21%) and direct-to-consumer testing (18%), whereas eugenics (17%), linkage analysis (16%), and evolutionary genetics (15%) have been recently eliminated. Remediation strategies were heterogeneous across institutions. These findings provide an important update on how genetics and genomics is taught at US and Canadian medical schools. Continuous improvement of educational initiatives will aid in producing genomically-literate physicians.

Family Environmental and Genetic Influences on Children's Future Chemical Dependency.

ERIC Educational Resources Information Center

Kumpfer, Karol L.; DeMarsh, Joseph

1985-01-01

Discusses the following in relation to their predictability to future drug abuse in youth: (1) susceptibility of children of chemically dependent parents; (2) genetic transmutation; (3) family structure and management; (4) socialization; and (5) cognitive family characteristics. (Author/LHW)

Association of four genetic loci with uric acid levels and reduced renal function: the J-SHIPP Suita study.

PubMed

Tabara, Yasuharu; Kohara, Katsuhiko; Kawamoto, Ryuichi; Hiura, Yumiko; Nishimura, Kunihiro; Morisaki, Takayuki; Kokubo, Yoshihiro; Okamura, Tomonori; Tomoike, Hitonobu; Iwai, Naoharu; Miki, Tetsuro

2010-01-01

Recent genome-wide association studies have identified several genetic variants as susceptibility loci for serum uric acid (UA) levels. We also identified a common nonsense mutation, W258X, responsible for renal hypouricemia. Here, we investigated clinical implications of these genetic variants by cross-sectional and longitudinal genetic epidemiological analysis. The study enrolled 5,165 Japanese subjects aged 64 ± 12 years from the general population. Clinical parameters were obtained from the personal health records, evaluated at medical checkups. Serum UA levels were significantly different between the SLC22A12 rs11231825 (CC/CT/TT: 4.5 ± 1.6, 5.0 ± 1.4, 5.3 ± 1.4 mg/dl; p = 7.6 × 10(-20)), SLC2A9 rs1014290 (TT/TG/GG: 4.9 ± 1.4, 5.1 ± 1.4, 5.3 ± 1.4 mg/dl; p = 3.1 × 10(-11)) and ABCG2 rs2231142 (TT/TG/GG: 5.3 ± 1.5, 5.2 ± 1.4, 5.1 ± 1.4 mg/dl; p = 2.0 × 10(-5)) genotypes. During 9.4 years of follow-up, 87 new cases of hyperuricemia were diagnosed. Multiple logistic regression analysis identified the accumulation of risk alleles as a significant determinant of future development of hyperuricemia (OR = 7.94; 95% CI: 1.97-53.6). In contrast, subjects with nonsense mutation predominantly showed lower UA levels (XX/XW/WW: 1.3 ± 1.7, 3.6 ± 1.0, 5.2 ± 1.4 mg/dl; p = 9.3 × 10(-82)). However, these subjects showed significantly reduced renal function (β = -0.111; p < 0.001) independently of possible covariates. Accumulation of risk genotypes was an independent risk factor for future development of hyperuricemia. Genetically developed hypouricemia was an independent risk factor for decreased renal function. Copyright © 2010 S. Karger AG, Basel.

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

PubMed Central

Smoller, Jordan W

2016-01-01

Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories—posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders—for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene–environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research. PMID:26321314

Multiple capacitors for natural genetic variation in Drosophila melanogaster.

PubMed

Takahashi, Kazuo H

2013-03-01

Cryptic genetic variation (CGV) or a standing genetic variation that is not ordinarily expressed as a phenotype is released when the robustness of organisms is impaired under environmental or genetic perturbations. Evolutionary capacitors modulate the amount of genetic variation exposed to natural selection and hidden cryptically; they have a fundamental effect on the evolvability of traits on evolutionary timescales. In this study, I have demonstrated the effects of multiple genomic regions of Drosophila melanogaster on CGV in wing shape. I examined the effects of 61 genomic deficiencies on quantitative and qualitative natural genetic variation in the wing shape of D. melanogaster. I have identified 10 genomic deficiencies that do not encompass a known candidate evolutionary capacitor, Hsp90, exposing natural CGV differently depending on the location of the deficiencies in the genome. Furthermore, five genomic deficiencies uncovered qualitative CGV in wing morphology. These findings suggest that CGV in wing shape of wild-type D. melanogaster is regulated by multiple capacitors with divergent functions. Future analysis of genes encompassed by these genomic regions would help elucidate novel capacitor genes and better understand the general features of capacitors regarding natural genetic variation. © 2012 Blackwell Publishing Ltd.

Marker-based quantitative genetics in the wild?: the heritability and genetic correlation of chemical defenses in eucalyptus.

PubMed

Andrew, R L; Peakall, R; Wallis, I R; Wood, J T; Knight, E J; Foley, W J

2005-12-01

Marker-based methods for estimating heritability and genetic correlation in the wild have attracted interest because traditional methods may be impractical or introduce bias via G x E effects, mating system variation, and sampling effects. However, they have not been widely used, especially in plants. A regression-based approach, which uses a continuous measure of genetic relatedness, promises to be particularly appropriate for use in plants with mixed-mating systems and overlapping generations. Using this method, we found significant narrow-sense heritability of foliar defense chemicals in a natural population of Eucalyptus melliodora. We also demonstrated a genetic basis for the phenotypic correlation underlying an ecological example of conditioned flavor aversion involving different biosynthetic pathways. Our results revealed that heritability estimates depend on the spatial scale of the analysis in a way that offers insight into the distribution of genetic and environmental variance. This study is the first to successfully use a marker-based method to measure quantitative genetic parameters in a tree. We suggest that this method will prove to be a useful tool in other studies and offer some recommendations for future applications of the method.

Speciation genetics: current status and evolving approaches

PubMed Central

Wolf, Jochen B. W.; Lindell, Johan; Backström, Niclas

2010-01-01

The view of species as entities subjected to natural selection and amenable to change put forth by Charles Darwin and Alfred Wallace laid the conceptual foundation for understanding speciation. Initially marred by a rudimental understanding of hereditary principles, evolutionists gained appreciation of the mechanistic underpinnings of speciation following the merger of Mendelian genetic principles with Darwinian evolution. Only recently have we entered an era where deciphering the molecular basis of speciation is within reach. Much focus has been devoted to the genetic basis of intrinsic postzygotic isolation in model organisms and several hybrid incompatibility genes have been successfully identified. However, concomitant with the recent technological advancements in genome analysis and a newfound interest in the role of ecology in the differentiation process, speciation genetic research is becoming increasingly open to non-model organisms. This development will expand speciation research beyond the traditional boundaries and unveil the genetic basis of speciation from manifold perspectives and at various stages of the splitting process. This review aims at providing an extensive overview of speciation genetics. Starting from key historical developments and core concepts of speciation genetics, we focus much of our attention on evolving approaches and introduce promising methodological approaches for future research venues. PMID:20439277

Predictive genetic testing in minors for late-onset conditions: a chronological and analytical review of the ethical arguments.

PubMed

Mand, Cara; Gillam, Lynn; Delatycki, Martin B; Duncan, Rony E

2012-09-01

Predictive genetic testing is now routinely offered to asymptomatic adults at risk for genetic disease. However, testing of minors at risk for adult-onset conditions, where no treatment or preventive intervention exists, has evoked greater controversy and inspired a debate spanning two decades. This review aims to provide a detailed longitudinal analysis and concludes by examining the debate's current status and prospects for the future. Fifty-three relevant theoretical papers published between 1990 and December 2010 were identified, and interpretative content analysis was employed to catalogue discrete arguments within these papers. Novel conclusions were drawn from this review. While the debate's first voices were raised in opposition of testing and their arguments have retained currency over many years, arguments in favour of testing, which appeared sporadically at first, have gained momentum more recently. Most arguments on both sides are testable empirical claims, so far untested, rather than abstract ethical or philosophical positions. The dispute, therein, lies not so much in whether minors should be permitted to access predictive genetic testing but whether these empirical claims on the relative benefits or harms of testing should be assessed.

Mutation scanning analysis of genetic variation within and among Echinococcus species: implications and future prospects.

PubMed

Jabbar, Abdul; Gasser, Robin B

2013-07-01

Adult tapeworms of the genus Echinococcus (family Taeniidae) occur in the small intestines of carnivorous definitive hosts and are transmitted to particular intermediate mammalian hosts, in which they develop as fluid-filled larvae (cysts) in internal organs (usually lung and liver), causing the disease echinococcosis. Echinococcus species are of major medical importance and also cause losses to the meat and livestock industries, mainly due to the condemnation of infected offal. Decisions regarding the treatment and control of echinococcosis rely on the accurate identification of species and population variants (strains). Conventional, phenetic methods for specific identification have some significant limitations. Despite advances in the development of molecular tools, there has been limited application of mutation scanning methods to species of Echinococcus. Here, we briefly review key genetic markers used for the identification of Echinococcus species and techniques for the analysis of genetic variation within and among populations, and the diagnosis of echinococcosis. We also discuss the benefits of utilizing mutation scanning approaches to elucidate the population genetics and epidemiology of Echinococcus species. These benefits are likely to become more evident following the complete characterization of the genomes of E. granulosus and E. multilocularis.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Evaluation: A Qualitative Pilot Study of Novel Information Technology Infrastructure to Communicate Genetic Variant Updates.

PubMed

Klinkenberg-Ramirez, Stephanie; Neri, Pamela M; Volk, Lynn A; Samaha, Sara J; Newmark, Lisa P; Pollard, Stephanie; Varugheese, Matthew; Baxter, Samantha; Aronson, Samuel J; Rehm, Heidi L; Bates, David W

2016-01-01

Partners HealthCare Personalized Medicine developed GeneInsight Clinic (GIC), a tool designed to communicate updated variant information from laboratory geneticists to treating clinicians through automated alerts, categorized by level of variant interpretation change. The study aimed to evaluate feedback from the initial users of the GIC, including the advantages and challenges to receiving this variant information and using this technology at the point of care. Healthcare professionals from two clinics that ordered genetic testing for cardiomyopathy and related disorders were invited to participate in one-hour semi-structured interviews and/ or a one-hour focus group. Using a Grounded Theory approach, transcript concepts were coded and organized into themes. Two genetic counselors and two physicians from two treatment clinics participated in individual interviews. Focus group participants included one genetic counselor and four physicians. Analysis resulted in 8 major themes related to structuring and communicating variant knowledge, GIC's impact on the clinic, and suggestions for improvements. The interview analysis identified longitudinal patient care, family data, and growth in genetic testing content as potential challenges to optimization of the GIC infrastructure. Participants agreed that GIC implementation increased efficiency and effectiveness of the clinic through increased access to genetic variant information at the point of care. Development of information technology (IT) infrastructure to aid in the organization and management of genetic variant knowledge will be critical as the genetic field moves towards whole exome and whole genome sequencing. Findings from this study could be applied to future development of IT support for genetic variant knowledge management that would serve to improve clinicians' ability to manage and care for patients.

Managing diversity: Domestication and gene flow in Stenocereus stellatus Riccob. (Cactaceae) in Mexico

PubMed Central

Cruse-Sanders, Jennifer M; Parker, Kathleen C; Friar, Elizabeth A; Huang, Daisie I; Mashayekhi, Saeideh; Prince, Linda M; Otero-Arnaiz, Adriana; Casas, Alejandro

2013-01-01

Microsatellite markers (N = 5) were developed for analysis of genetic variation in 15 populations of the columnar cactus Stenocereus stellatus, managed under traditional agriculture practices in central Mexico. Microsatellite diversity was analyzed within and among populations, between geographic regions, and among population management types to provide detailed insight into historical gene flow rates and population dynamics associated with domestication. Our results corroborate a greater diversity in populations managed by farmers compared with wild ones (HE = 0.64 vs. 0.55), but with regional variation between populations among regions. Although farmers propagated S. stellatus vegetatively in home gardens to diversify their stock, asexual recruitment also occurred naturally in populations where more marginal conditions have limited sexual recruitment, resulting in lower genetic diversity. Therefore, a clear-cut relationship between the occurrence of asexual recruitment and genetic diversity was not evident. Two managed populations adjacent to towns were identified as major sources of gene movement in each sampled region, with significant migration to distant as well as nearby populations. Coupled with the absence of significant bottlenecks, this suggests a mechanism for promoting genetic diversity in managed populations through long distance gene exchange. Cultivation of S. stellatus in close proximity to wild populations has led to complex patterns of genetic variation across the landscape that reflects the interaction of natural and cultural processes. As molecular markers become available for nontraditional crops and novel analysis techniques allow us to detect and evaluate patterns of genetic diversity, genetic studies provide valuable insights into managing crop genetic resources into the future against a backdrop of global change. Traditional agriculture systems play an important role in maintaining genetic diversity for plant species. PMID:23762520

Whole-genome sequencing and genetic variant analysis of a Quarter Horse mare.

PubMed

Doan, Ryan; Cohen, Noah D; Sawyer, Jason; Ghaffari, Noushin; Johnson, Charlie D; Dindot, Scott V

2012-02-17

The catalog of genetic variants in the horse genome originates from a few select animals, the majority originating from the Thoroughbred mare used for the equine genome sequencing project. The purpose of this study was to identify genetic variants, including single nucleotide polymorphisms (SNPs), insertion/deletion polymorphisms (INDELs), and copy number variants (CNVs) in the genome of an individual Quarter Horse mare sequenced by next-generation sequencing. Using massively parallel paired-end sequencing, we generated 59.6 Gb of DNA sequence from a Quarter Horse mare resulting in an average of 24.7X sequence coverage. Reads were mapped to approximately 97% of the reference Thoroughbred genome. Unmapped reads were de novo assembled resulting in 19.1 Mb of new genomic sequence in the horse. Using a stringent filtering method, we identified 3.1 million SNPs, 193 thousand INDELs, and 282 CNVs. Genetic variants were annotated to determine their impact on gene structure and function. Additionally, we genotyped this Quarter Horse for mutations of known diseases and for variants associated with particular traits. Functional clustering analysis of genetic variants revealed that most of the genetic variation in the horse's genome was enriched in sensory perception, signal transduction, and immunity and defense pathways. This is the first sequencing of a horse genome by next-generation sequencing and the first genomic sequence of an individual Quarter Horse mare. We have increased the catalog of genetic variants for use in equine genomics by the addition of novel SNPs, INDELs, and CNVs. The genetic variants described here will be a useful resource for future studies of genetic variation regulating performance traits and diseases in equids.

Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

PubMed

de Moor, Marleen H M; van den Berg, Stéphanie M; Verweij, Karin J H; Krueger, Robert F; Luciano, Michelle; Arias Vasquez, Alejandro; Matteson, Lindsay K; Derringer, Jaime; Esko, Tõnu; Amin, Najaf; Gordon, Scott D; Hansell, Narelle K; Hart, Amy B; Seppälä, Ilkka; Huffman, Jennifer E; Konte, Bettina; Lahti, Jari; Lee, Minyoung; Miller, Mike; Nutile, Teresa; Tanaka, Toshiko; Teumer, Alexander; Viktorin, Alexander; Wedenoja, Juho; Abecasis, Goncalo R; Adkins, Daniel E; Agrawal, Arpana; Allik, Jüri; Appel, Katja; Bigdeli, Timothy B; Busonero, Fabio; Campbell, Harry; Costa, Paul T; Davey Smith, George; Davies, Gail; de Wit, Harriet; Ding, Jun; Engelhardt, Barbara E; Eriksson, Johan G; Fedko, Iryna O; Ferrucci, Luigi; Franke, Barbara; Giegling, Ina; Grucza, Richard; Hartmann, Annette M; Heath, Andrew C; Heinonen, Kati; Henders, Anjali K; Homuth, Georg; Hottenga, Jouke-Jan; Iacono, William G; Janzing, Joost; Jokela, Markus; Karlsson, Robert; Kemp, John P; Kirkpatrick, Matthew G; Latvala, Antti; Lehtimäki, Terho; Liewald, David C; Madden, Pamela A F; Magri, Chiara; Magnusson, Patrik K E; Marten, Jonathan; Maschio, Andrea; Medland, Sarah E; Mihailov, Evelin; Milaneschi, Yuri; Montgomery, Grant W; Nauck, Matthias; Ouwens, Klaasjan G; Palotie, Aarno; Pettersson, Erik; Polasek, Ozren; Qian, Yong; Pulkki-Råback, Laura; Raitakari, Olli T; Realo, Anu; Rose, Richard J; Ruggiero, Daniela; Schmidt, Carsten O; Slutske, Wendy S; Sorice, Rossella; Starr, John M; St Pourcain, Beate; Sutin, Angelina R; Timpson, Nicholas J; Trochet, Holly; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Wouda, Jasper; Wright, Margaret J; Zgaga, Lina; Porteous, David; Minelli, Alessandra; Palmer, Abraham A; Rujescu, Dan; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Metspalu, Andres; Kaprio, Jaakko; Deary, Ian J; Räikkönen, Katri; Wilson, James F; Keltikangas-Järvinen, Liisa; Bierut, Laura J; Hettema, John M; Grabe, Hans J; van Duijn, Cornelia M; Evans, David M; Schlessinger, David; Pedersen, Nancy L; Terracciano, Antonio; McGue, Matt; Penninx, Brenda W J H; Martin, Nicholas G; Boomsma, Dorret I

2015-07-01

Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P < .05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. This study identifies a novel locus for neuroticism. The variant is located in a known gene that has been associated with bipolar disorder and schizophrenia in previous studies. In addition, the study shows that neuroticism is influenced by many genetic variants of small effect that are either common or tagged by common variants. These genetic variants also influence MDD. Future studies should confirm the role of the MAGI1 locus for neuroticism and further investigate the association of MAGI1 and the polygenic association to a range of other psychiatric disorders that are phenotypically correlated with neuroticism.

High-Content Screening for Quantitative Cell Biology.

PubMed

Mattiazzi Usaj, Mojca; Styles, Erin B; Verster, Adrian J; Friesen, Helena; Boone, Charles; Andrews, Brenda J

2016-08-01

High-content screening (HCS), which combines automated fluorescence microscopy with quantitative image analysis, allows the acquisition of unbiased multiparametric data at the single cell level. This approach has been used to address diverse biological questions and identify a plethora of quantitative phenotypes of varying complexity in numerous different model systems. Here, we describe some recent applications of HCS, ranging from the identification of genes required for specific biological processes to the characterization of genetic interactions. We review the steps involved in the design of useful biological assays and automated image analysis, and describe major challenges associated with each. Additionally, we highlight emerging technologies and future challenges, and discuss how the field of HCS might be enhanced in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

A panel of ancestry informative markers to estimate and correct potential effects of population stratification in Han Chinese.

PubMed

Qin, Pengfei; Li, Zhiqiang; Jin, Wenfei; Lu, Dongsheng; Lou, Haiyi; Shen, Jiawei; Jin, Li; Shi, Yongyong; Xu, Shuhua

2014-02-01

Population stratification acts as a confounding factor in genetic association studies and may lead to false-positive or false-negative results. Previous studies have analyzed the genetic substructures in Han Chinese population, the largest ethnic group in the world comprising ∼20% of the global human population. In this study, we examined 5540 Han Chinese individuals with about 1 million single-nucleotide polymorphisms (SNPs) and screened a panel of ancestry informative markers (AIMs) to facilitate the discerning and controlling of population structure in future association studies on Han Chinese. Based on genome-wide data, we first confirmed our previous observation of the north-south differentiation in Han Chinese population. Second, we developed a panel of 150 validated SNP AIMs to determine the northern or southern origin of each Han Chinese individual. We further evaluated the performance of our AIMs panel in association studies in simulation analysis. Our results showed that this AIMs panel had sufficient power to discern and control population stratification in Han Chinese, which could significantly reduce false-positive rates in both genome-wide association studies (GWAS) and candidate gene association studies (CGAS). We suggest this AIMs panel be genotyped and used to control and correct population stratification in the study design or data analysis of future association studies, especially in CGAS which is the most popular approach to validate previous reports on genetic associations of diseases in post-GWAS era.

Holo-analysis.

PubMed

Rosen, G D

2006-06-01

Meta-analysis is a vague descriptor used to encompass very diverse methods of data collection analysis, ranging from simple averages to more complex statistical methods. Holo-analysis is a fully comprehensive statistical analysis of all available data and all available variables in a specified topic, with results expressed in a holistic factual empirical model. The objectives and applications of holo-analysis include software production for prediction of responses with confidence limits, translation of research conditions to praxis (field) circumstances, exposure of key missing variables, discovery of theoretically unpredictable variables and interactions, and planning future research. Holo-analyses are cited as examples of the effects on broiler feed intake and live weight gain of exogenous phytases, which account for 70% of variation in responses in terms of 20 highly significant chronological, dietary, environmental, genetic, managemental, and nutrient variables. Even better future accountancy of variation will be facilitated if and when authors of papers routinely provide key data for currently neglected variables, such as temperatures, complete feed formulations, and mortalities.

Photosynthetic Energy Conversion Efficiency: Setting a Baseline for Gauging Future Improvements in Important Food and Biofuel Crops1

PubMed Central

2015-01-01

The conversion efficiency (εc) of absorbed radiation into biomass (MJ of dry matter per MJ of absorbed photosynthetically active radiation) is a component of yield potential that has been estimated at less than half the theoretical maximum. Various strategies have been proposed to improve εc, but a statistical analysis to establish baseline εc levels across different crop functional types is lacking. Data from 164 published εc studies conducted in relatively unstressed growth conditions were used to determine the means, greatest contributors to variation, and genetic trends in εc across important food and biofuel crop species. εc was greatest in biofuel crops (0.049–0.066), followed by C4 food crops (0.046–0.049), C3 nonlegumes (0.036–0.041), and finally C3 legumes (0.028–0.035). Despite confining our analysis to relatively unstressed growth conditions, total incident solar radiation and average growing season temperature most often accounted for the largest portion of εc variability. Genetic improvements in εc, when present, were less than 0.7% per year, revealing the unrealized potential of improving εc as a promising contributing strategy to meet projected future agricultural demand. PMID:25829463

Synthetic Genome Recoding: New genetic codes for new features

PubMed Central

Kuo, James; Stirling, Finn; Lau, Yu Heng; Shulgina, Yekaterina; Way, Jeffrey C.; Silver, Pamela A.

2018-01-01

Full genome recoding, or rewriting codon meaning, through chemical synthesis of entire bacterial chromosomes has become feasible in the past several years. Recoding an organism can impart new properties including non-natural amino acid incorporation, virus resistance, and biocontainment. The estimated cost of construction that includes DNA synthesis, assembly by recombination, and troubleshooting, is now comparable to costs of early stage development of drugs or other high-tech products. Here we discuss several recently published assembly methods and provide some thoughts on the future, including how synthetic efforts might benefit from analysis of natural recoding processes and organisms that use alternative genetic codes. PMID:28983660

Genetics, the facial plastic and reconstructive surgeon, and the future.

PubMed

Seidman, M D

2001-01-01

Predicting the future is a daunting task that is typically reserved for visionaries or tarot card readers. Nonetheless, the challenge is set, and this brief essay will predict how genetics and molecular biology may affect diseases in facial plastic and reconstructive surgery.

Genetic diversity is related to climatic variation and vulnerability in threatened bull trout

USGS Publications Warehouse

Kovach, Ryan; Muhlfeld, Clint C.; Wade, Alisa A.; Hand, Brian K.; Whited, Diane C.; DeHaan, Patrick W.; Al-Chokhachy, Robert K.; Luikart, Gordon

2015-01-01

Understanding how climatic variation influences ecological and evolutionary processes is crucial for informed conservation decision-making. Nevertheless, few studies have measured how climatic variation influences genetic diversity within populations or how genetic diversity is distributed across space relative to future climatic stress. Here, we tested whether patterns of genetic diversity (allelic richness) were related to climatic variation and habitat features in 130 bull trout (Salvelinus confluentus) populations from 24 watersheds (i.e., ~4–7th order river subbasins) across the Columbia River Basin, USA. We then determined whether bull trout genetic diversity was related to climate vulnerability at the watershed scale, which we quantified on the basis of exposure to future climatic conditions (projected scenarios for the 2040s) and existing habitat complexity. We found a strong gradient in genetic diversity in bull trout populations across the Columbia River Basin, where populations located in the most upstream headwater areas had the greatest genetic diversity. After accounting for spatial patterns with linear mixed models, allelic richness in bull trout populations was positively related to habitat patch size and complexity, and negatively related to maximum summer temperature and the frequency of winter flooding. These relationships strongly suggest that climatic variation influences evolutionary processes in this threatened species and that genetic diversity will likely decrease due to future climate change. Vulnerability at a watershed scale was negatively correlated with average genetic diversity (r = −0.77;P < 0.001); watersheds containing populations with lower average genetic diversity generally had the lowest habitat complexity, warmest stream temperatures, and greatest frequency of winter flooding. Together, these findings have important conservation implications for bull trout and other imperiled species. Genetic diversity is already depressed where climatic vulnerability is highest; it will likely erode further in the very places where diversity may be most needed for future persistence.

Using population viability analysis, genomics, and habitat suitability to forecast future population patterns of Little Owl Athene noctua across Europe.

PubMed

Andersen, Line Holm; Sunde, Peter; Pellegrino, Irene; Loeschcke, Volker; Pertoldi, Cino

2017-12-01

The agricultural scene has changed over the past decades, resulting in a declining population trend in many species. It is therefore important to determine the factors that the individual species depend on in order to understand their decline. The landscape changes have also resulted in habitat fragmentation, turning once continuous populations into metapopulations. It is thus increasingly important to estimate both the number of individuals it takes to create a genetically viable population and the population trend. Here, population viability analysis and habitat suitability modeling were used to estimate population viability and future prospects across Europe of the Little Owl Athene noctua , a widespread species associated with agricultural landscapes. The results show a high risk of population declines over the coming 100 years, especially toward the north of Europe, whereas populations toward the southeastern part of Europe have a greater probability of persistence. In order to be considered genetically viable, individual populations must count 1,000-30,000 individuals. As Little Owl populations of several countries count <30,000, and many isolated populations in northern Europe count <1,000 individuals, management actions resulting in exchange of individuals between populations or even countries are probably necessary to prevent losing <1% genetic diversity over a 100-year period. At a continental scale, a habitat suitability analysis suggested Little Owl to be affected positively by increasing temperatures and urban areas, whereas an increased tree cover, an increasing annual rainfall, grassland, and sparsely vegetated areas affect the presence of the owl negatively. However, the low predictive power of the habitat suitability model suggests that habitat suitability might be better explained at a smaller scale.

Asthma pharmacogenetics and the development of genetic profiles for personalized medicine

PubMed Central

Ortega, Victor E; Meyers, Deborah A; Bleecker, Eugene R

2015-01-01

Human genetics research will be critical to the development of genetic profiles for personalized or precision medicine in asthma. Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual. Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness. This review summarizes these pharmacogenetic discoveries and the future of genetic profiles for personalized medicine in asthma. The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway. Prior pharmacogenetic discoveries, in combination with additional variants identified in future studies, will form the basis for future genetic profiles for personalized tailored approaches to maximize therapeutic benefit for an individual asthmatic while minimizing the risk for adverse events. PMID:25691813

Using population genetic tools to develop a control strategy for feral cats (Felis catus) in Hawai'i

USGS Publications Warehouse

Hansen, H.; Hess, S.C.; Cole, D.; Banko, P.C.

2007-01-01

Population genetics can provide information about the demographics and dynamics of invasive species that is beneficial for developing effective control strategies. We studied the population genetics of feral cats on Hawai'i Island by microsatellite analysis to evaluate genetic diversity and population structure, assess gene flow and connectivity among three populations, identify potential source populations, characterise population dynamics, and evaluate sex-biased dispersal. High genetic diversity, low structure, and high number of migrants per generation supported high gene flow that was not limited spatially. Migration rates revealed that most migration occurred out of West Mauna Kea. Effective population size estimates indicated increasing cat populations despite control efforts. Despite high gene flow, relatedness estimates declined significantly with increased geographic distance and Bayesian assignment tests revealed the presence of three population clusters. Genetic structure and relatedness estimates indicated male-biased dispersal, primarily from Mauna Kea, suggesting that this population should be targeted for control. However, recolonisation seems likely, given the great dispersal ability that may not be inhibited by barriers such as lava flows. Genetic monitoring will be necessary to assess the effectiveness of future control efforts. Management of other invasive species may benefit by employing these population genetic tools. ?? CSIRO 2007.

Functional analysis of regulatory single-nucleotide polymorphisms.

PubMed

Pampín, Sandra; Rodríguez-Rey, José C

2007-04-01

The identification of regulatory polymorphisms has become a key problem in human genetics. In the past few years there has been a conceptual change in the way in which regulatory single-nucleotide polymorphisms are studied. We revise the new approaches and discuss how gene expression studies can contribute to a better knowledge of the genetics of common diseases. New techniques for the association of single-nucleotide polymorphisms with changes in gene expression have been recently developed. This, together with a more comprehensive use of the old in-vitro methods, has produced a great amount of genetic information. When added to current databases, it will help to design better tools for the detection of regulatory single-nucleotide polymorphisms. The identification of functional regulatory single-nucleotide polymorphisms cannot be done by the simple inspection of DNA sequence. In-vivo techniques, based on primer-extension, and the more recently developed 'haploChIP' allow the association of gene variants to changes in gene expression. Gene expression analysis by conventional in-vitro techniques is the only way to identify the functional consequences of regulatory single-nucleotide polymorphisms. The amount of information produced in the last few years will help to refine the tools for the future analysis of regulatory gene variants.

Genetic and Biochemical Diversity among Valeriana jatamansi Populations from Himachal Pradesh

PubMed Central

Singh, Sunil Kumar; Katoch, Rajan; Kapila, Rakesh Kumar

2015-01-01

Valeriana jatamansi Jones is an important medicinal plant that grows wild in Himachal Pradesh, India. Molecular and biochemical diversity among 13 natural populations from Himachal Pradesh was assessed using RAPD and GC-MS to know the extent of existing variation. A total of seven genetically diverse groups have been identified based on RAPD analysis which corroborated well with the analysis based on chemical constituents. The essential oil yield ranged from 0.6% to 1.66% (v/w). A negative correlation between patchouli alcohol and viridiflorol, the two major valued constituents, limits the scope of their simultaneous improvement. However, other few populations like Chamba-II and Kandi-I were found promising for viridiflorol and patchouli alcohol, respectively. The analysis of chemical constitution of oil of the populations from a specific region revealed predominance of specific constituents indicating possibility of their collection/selection for specific end uses like phytomedicines. The prevalence of genetically diverse groups along with sufficient chemical diversity in a defined region clearly indicates the role of ecology in the maintenance of evolution of this species. Sufficient molecular and biochemical diversity detected among natural populations of this species will form basis for the future improvement. PMID:25741533

Genetic variation and population structure of maize inbred lines adapted to the mid-altitude sub-humid maize agro-ecology of Ethiopia using single nucleotide polymorphic (SNP) markers.

PubMed

Ertiro, Berhanu Tadesse; Semagn, Kassa; Das, Biswanath; Olsen, Michael; Labuschagne, Maryke; Worku, Mosisa; Wegary, Dagne; Azmach, Girum; Ogugo, Veronica; Keno, Tolera; Abebe, Beyene; Chibsa, Temesgen; Menkir, Abebe

2017-10-12

Molecular characterization is important for efficient utilization of germplasm and development of improved varieties. In the present study, we investigated the genetic purity, relatedness and population structure of 265 maize inbred lines from the Ethiopian Institute of Agricultural Research (EIAR), the International Maize and Wheat Improvement Centre (CIMMYT) and the International Institute of Tropical Agriculture (IITA) using 220,878 single nucleotide polymorphic (SNP) markers obtained using genotyping by sequencing (GBS). Only 22% of the inbred lines were considered pure with <5% heterogeneity, while the remaining 78% of the inbred lines had a heterogeneity ranging from 5.1 to 31.5%. Pairwise genetic distances among the 265 inbred lines varied from 0.011 to 0.345, with 89% of the pairs falling between 0.301 and 0.345. Only <1% of the pairs had a genetic distance lower than 0.200, which included 14 pairs of sister lines that were nearly identical. Relative kinship analysis showed that the kinship coefficients for 59% of the pairs of lines was close to zero, which agrees with the genetic distance estimates. Principal coordinate analysis, discriminant analysis of principal components (DAPC) and the model-based population structure analysis consistently suggested the presence of three groups, which generally agreed with pedigree information (genetic background). Although not distinct enough, the SNP markers showed some level of separation between the two CIMMYT heterotic groups A and B established based on pedigree and combining ability information. The high level of heterogeneity detected in most of the inbred lines suggested the requirement for purification or further inbreeding except those deliberately maintained at early inbreeding level. The genetic distance and relative kinship analysis clearly indicated the uniqueness of most of the inbred lines in the maize germplasm available for breeders in the mid-altitude maize breeding program of Ethiopia. Results from the present study facilitate the maize breeding work in Ethiopia and germplasm exchange among breeding programs in Africa. We suggest the incorporation of high density molecular marker information in future heterotic group assignments.

A DNA fingerprinting procedure for ultra high-throughput genetic analysis of insects.

PubMed

Schlipalius, D I; Waldron, J; Carroll, B J; Collins, P J; Ebert, P R

2001-12-01

Existing procedures for the generation of polymorphic DNA markers are not optimal for insect studies in which the organisms are often tiny and background molecular information is often non-existent. We have used a new high throughput DNA marker generation protocol called randomly amplified DNA fingerprints (RAF) to analyse the genetic variability in three separate strains of the stored grain pest, Rhyzopertha dominica. This protocol is quick, robust and reliable even though it requires minimal sample preparation, minute amounts of DNA and no prior molecular analysis of the organism. Arbitrarily selected oligonucleotide primers routinely produced approximately 50 scoreable polymorphic DNA markers, between individuals of three independent field isolates of R. dominica. Multivariate cluster analysis using forty-nine arbitrarily selected polymorphisms generated from a single primer reliably separated individuals into three clades corresponding to their geographical origin. The resulting clades were quite distinct, with an average genetic difference of 37.5 +/- 6.0% between clades and of 21.0 +/- 7.1% between individuals within clades. As a prelude to future gene mapping efforts, we have also assessed the performance of RAF under conditions commonly used in gene mapping. In this analysis, fingerprints from pooled DNA samples accurately and reproducibly reflected RAF profiles obtained from individual DNA samples that had been combined to create the bulked samples.

The influence of genetic selection and feed system on the reproductive performance of spring-calving dairy cows within future pasture-based production systems.

PubMed

Coleman, J; Pierce, K M; Berry, D P; Brennan, A; Horan, B

2009-10-01

Three genetic groups of Holstein-Friesian dairy cows were established from within the Moorepark (Teagasc, Ireland) dairy research herd: LowNA, indicative of the Irish national average-genetic-merit North American Holstein-Friesian; HighNA, high-genetic-merit North American Holstein-Friesian; HighNZ, high-genetic-merit New Zealand Holstein-Friesian. Genetic merit in this study was based on the Irish total merit index, the Economic Breeding Index. Animals from within each genetic group were randomly allocated to 1 of 2 possible post-European Union-milk-quota pasture-based feeding systems (FS): 1) The Moorepark (MP) pasture system (2.64 cows/ha and 500 kg of concentrate supplement per cow per lactation) and 2) a high output per hectare (HC) pasture system (2.85 cows/ha and 1,200 kg of concentrate supplement per cow per lactation). A total of 126, 128, and 140 spring-calving dairy cows were used during the years 2006, 2007, and 2008, respectively. Each group had an individual farmlet of 17 paddocks, and all groups were managed similarly throughout the study. The effects of genetic group, FS, and the interaction between genetic group and FS on reproductive performance, body weight, body condition score, and blood metabolite concentrations were studied using mixed models with factorial arrangements of genetic groups and FS. Odds ratios were used in the analysis of binary fertility traits, and survival analysis was used in the analysis of survival after first calving. When treatment means were compared, the HighNA and HighNZ genotypes (with greater genetic merit for fertility performance) had greater first-service pregnancy rates and had a greater proportion of cows pregnant after 42 d of the breeding season than the LowNA group. Both HighNA and HighNZ genotypes were submitted for artificial insemination earlier in the breeding season and had greater survival than the LowNA genotype. There was no significant FS or genotype by FS interactions for any of the reproductive, blood metabolite, body weight, or body condition score measures. The results demonstrate that increased genetic merit for fertility traits resulted in improved reproductive performance and that the poor reproductive capacity of inferior-genetic-merit animals for fertility was not improved through concentrate supplementation at pasture.

Applying landscape genomic tools to forest management and restoration of Hawaiian koa (Acacia koa) in a changing environment.

PubMed

Gugger, Paul F; Liang, Christina T; Sork, Victoria L; Hodgskiss, Paul; Wright, Jessica W

2018-02-01

Identifying and quantifying the importance of environmental variables in structuring population genetic variation can help inform management decisions for conservation, restoration, or reforestation purposes, in both current and future environmental conditions. Landscape genomics offers a powerful approach for understanding the environmental factors that currently associate with genetic variation, and given those associations, where populations may be most vulnerable under future environmental change. Here, we applied genotyping by sequencing to generate over 11,000 single nucleotide polymorphisms from 311 trees and then used nonlinear, multivariate environmental association methods to examine spatial genetic structure and its association with environmental variation in an ecologically and economically important tree species endemic to Hawaii, Acacia koa . Admixture and principal components analyses showed that trees from different islands are genetically distinct in general, with the exception of some genotypes that match other islands, likely as the result of recent translocations. Gradient forest and generalized dissimilarity models both revealed a strong association between genetic structure and mean annual rainfall. Utilizing a model for projected future climate on the island of Hawaii, we show that predicted changes in rainfall patterns may result in genetic offset, such that trees no longer may be genetically matched to their environment. These findings indicate that knowledge of current and future rainfall gradients can provide valuable information for the conservation of existing populations and also help refine seed transfer guidelines for reforestation or replanting of koa throughout the state.

Development of novel SSR markers for evaluation of genetic diversity and population structure in Tribulus terrestris L. (Zygophyllaceae).

PubMed

Kaur, Kuljit; Sharma, Vikas; Singh, Vijay; Wani, Mohammad Saleem; Gupta, Raghbir Chand

2016-12-01

Tribulus terrestris L., commonly called puncture vine and gokhru, is an important member of Zygophyllaceae. The species is highly important in context to therapeutic uses and provides important active principles responsible for treatment of various diseases and also used as tonic. It is widely distributed in tropical regions of India and the world. However, status of its genetic diversity remained concealed due to lack of research work in this species. In present study, genetic diversity and structure of different populations of T. terrestris from north India was examined at molecular level using newly developed Simple Sequence Repeat (SSR) markers. In total, 20 primers produced 48 alleles in a size range of 100-500 bp with maximum (4) fragments amplified by TTMS-1, TTMS-25 and TTMS-33. Mean Polymorphism Information Content (PIC) and Marker Index (MI) were 0.368 and 1.01, respectively. Dendrogram showed three groups, one of which was purely containing accessions from Rajasthan while other two groups corresponded to Punjab and Haryana regions with intermixing of few other accessions. Analysis of molecular variance partitioned 76 % genetic variance within populations and 24 % among populations. Bayesian model based STRUCTURE analysis detected two genetic stocks for analyzed germplasm and also detected some admixed individuals. Different geographical populations of this species showed high level of genetic diversity. Results of present study can be useful in identifying diverse accessions and management of this plant resource. Moreover, the novel SSR markers developed can be utilized for various genetic analyses in this species in future.

CRISPR–Cas9 Genetic Analysis of Virus–Host Interactions

PubMed Central

Gebre, Makda; Nomburg, Jason L.; Gewurz, Benjamin E.

2018-01-01

Clustered regularly interspaced short palindromic repeats (CRISPR) has greatly expanded the ability to genetically probe virus–host interactions. CRISPR systems enable focused or systematic, genomewide studies of nearly all aspects of a virus lifecycle. Combined with its relative ease of use and high reproducibility, CRISPR is becoming an essential tool in studies of the host factors important for viral pathogenesis. Here, we review the use of CRISPR–Cas9 for the loss-of-function analysis of host dependency factors. We focus on the use of CRISPR-pooled screens for the systematic identification of host dependency factors, particularly in Epstein–Barr virus-transformed B cells. We also discuss the use of CRISPR interference (CRISPRi) and gain-of-function CRISPR activation (CRISPRa) approaches to probe virus–host interactions. Finally, we comment on the future directions enabled by combinatorial CRISPR screens. PMID:29385696

Infectious diseases: Surveillance, genetic modification and simulation

USGS Publications Warehouse

Koh, H. L.; Teh, S.Y.; De Angelis, D. L.; Jiang, J.

2011-01-01

Infectious diseases such as influenza and dengue have the potential of becoming a worldwide pandemic that may exert immense pressures on existing medical infrastructures. Careful surveillance of these diseases, supported by consistent model simulations, provides a means for tracking the disease evolution. The integrated surveillance and simulation program is essential in devising effective early warning systems and in implementing efficient emergency preparedness and control measures. This paper presents a summary of simulation analysis on influenza A (H1N1) 2009 in Malaysia. This simulation analysis provides insightful lessons regarding how disease surveillance and simulation should be performed in the future. This paper briefly discusses the controversy over the experimental field release of genetically modified (GM) Aedes aegypti mosquito in Malaysia. Model simulations indicate that the proposed release of GM mosquitoes is neither a viable nor a sustainable control strategy. ?? 2011 WIT Press.

CRISPR-Cas9 Genetic Analysis of Virus-Host Interactions.

PubMed

Gebre, Makda; Nomburg, Jason L; Gewurz, Benjamin E

2018-01-30

Clustered regularly interspaced short palindromic repeats (CRISPR) has greatly expanded the ability to genetically probe virus-host interactions. CRISPR systems enable focused or systematic, genomewide studies of nearly all aspects of a virus lifecycle. Combined with its relative ease of use and high reproducibility, CRISPR is becoming an essential tool in studies of the host factors important for viral pathogenesis. Here, we review the use of CRISPR-Cas9 for the loss-of-function analysis of host dependency factors. We focus on the use of CRISPR-pooled screens for the systematic identification of host dependency factors, particularly in Epstein-Barr virus-transformed B cells. We also discuss the use of CRISPR interference (CRISPRi) and gain-of-function CRISPR activation (CRISPRa) approaches to probe virus-host interactions. Finally, we comment on the future directions enabled by combinatorial CRISPR screens.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

PubMed

Warren, Helen R; Evangelou, Evangelos; Cabrera, Claudia P; Gao, He; Ren, Meixia; Mifsud, Borbala; Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Lepe, Marcelo P Segura; O'Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

2017-03-01

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

PubMed Central

Ntalla, Ioanna; Surendran, Praveen; Liu, Chunyu; Cook, James P; Kraja, Aldi T; Drenos, Fotios; Loh, Marie; Verweij, Niek; Marten, Jonathan; Karaman, Ibrahim; Segura Lepe, Marcelo P; O’Reilly, Paul F; Knight, Joanne; Snieder, Harold; Kato, Norihiro; He, Jiang; Tai, E Shyong; Said, M Abdullah; Porteous, David; Alver, Maris; Poulter, Neil; Farrall, Martin; Gansevoort, Ron T; Padmanabhan, Sandosh; Mägi, Reedik; Stanton, Alice; Connell, John; Bakker, Stephan J L; Metspalu, Andres; Shields, Denis C; Thom, Simon; Brown, Morris; Sever, Peter; Esko, Tõnu; Hayward, Caroline; van der Harst, Pim; Saleheen, Danish; Chowdhury, Rajiv; Chambers, John C; Chasman, Daniel I; Chakravarti, Aravinda; Newton-Cheh, Christopher; Lindgren, Cecilia M; Levy, Daniel; Kooner, Jaspal S; Keavney, Bernard; Tomaszewski, Maciej; Samani, Nilesh J; Howson, Joanna M M; Tobin, Martin D; Munroe, Patricia B; Ehret, Georg B; Wain, Louise V

2017-01-01

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. Combined with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure raising genetic variants on future cardiovascular disease risk. PMID:28135244

Recombination Promoted by DNA Viruses: Phage λ to Herpes Simplex Virus

PubMed Central

Weller, Sandra K.; Sawitzke, James A.

2015-01-01

The purpose of this review is to explore recombination strategies in DNA viruses. Homologous recombination is a universal genetic process that plays multiple roles in the biology of all organisms, including viruses. Recombination and DNA replication are interconnected, with recombination being essential for repairing DNA damage and supporting replication of the viral genome. Recombination also creates genetic diversity, and viral recombination mechanisms have important implications for understanding viral origins as well as the dynamic nature of viral-host interactions. Both bacteriophage λ and herpes simplex virus (HSV) display high rates of recombination, both utilizing their own proteins and commandeering cellular proteins to promote recombination reactions. We focus primarily on λ and HSV, as they have proven amenable to both genetic and biochemical analysis and have recently been shown to exhibit some surprising similarities that will guide future studies. PMID:25002096

Genetic disruption of voltage-gated calcium channels in psychiatric and neurological disorders

PubMed Central

Heyes, Samuel; Pratt, Wendy S.; Rees, Elliott; Dahimene, Shehrazade; Ferron, Laurent; Owen, Michael J.; Dolphin, Annette C.

2015-01-01

This review summarises genetic studies in which calcium channel genes have been connected to the spectrum of neuropsychiatric syndromes, from bipolar disorder and schizophrenia to autism spectrum disorders and intellectual impairment. Among many other genes, striking numbers of the calcium channel gene superfamily have been implicated in the aetiology of these diseases by various DNA analysis techniques. We will discuss how these relate to the known monogenic disorders associated with point mutations in calcium channels. We will then examine the functional evidence for a causative link between these mutations or single nucleotide polymorphisms and the disease processes. A major challenge for the future will be to translate the expanding psychiatric genetic findings into altered physiological function, involvement in the wider pathology of the diseases, and what potential that provides for personalised and stratified treatment options for patients. PMID:26386135

Genetics of Attention Deficit Hyperactivity Disorder: A Current Review and Future Prospects

ERIC Educational Resources Information Center

Levy, Florence; Hay, David A.; Bennett, Kellie S.

2006-01-01

While there have been significant advances in both the behaviour genetics and molecular genetics of Attention Deficit Hyperactivity Disorder (ADHD), researchers are now beginning to develop hypotheses about relationships between phenotypes and genetic mechanisms. Twin studies are able to model genetic, shared environmental and non-shared…

STOCKING THE GENETIC SUPERMARKET: REPRODUCTIVE GENETIC TECHNOLOGIES AND COLLECTIVE ACTION PROBLEMS

PubMed Central

Gyngell, Chris; Douglas, Thomas

2015-01-01

Reproductive genetic technologies (RGTs) allow parents to decide whether their future children will have or lack certain genetic predispositions. A popular model that has been proposed for regulating access to RGTs is the ‘genetic supermarket’. In the genetic supermarket, parents are free to make decisions about which genes to select for their children with little state interference. One possible consequence of the genetic supermarket is that collective action problems will arise: if rational individuals use the genetic supermarket in isolation from one another, this may have a negative effect on society as a whole, including future generations. In this article we argue that RGTs targeting height, innate immunity, and certain cognitive traits could lead to collective action problems. We then discuss whether this risk could in principle justify state intervention in the genetic supermarket. We argue that there is a plausible prima facie case for the view that such state intervention would be justified and respond to a number of arguments that might be adduced against that view. PMID:24720568

Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics

NASA Astrophysics Data System (ADS)

Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

2015-12-01

Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics.

PubMed

Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

2015-12-22

Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

Human genetic susceptibility and infection with Leishmania peruviana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaw, M.A.; Davis, C.R.; Collins, A.

1995-11-01

Racial differences, familial clustering, and murine studies are suggestive of host genetic control of Leishmania infections. Complex segregation analysis has been carried out by use of the programs POINTER and COMDS and data from a total population survey, comprising 636 nuclear families, from an L. perurviana endemic area. The data support genetic components controlling susceptibility to clinical leishmaniasis, influencing severity of disease and resistance to disease among healthy individuals. A multifactorial model is favored over a sporadic model. Two-locus models provided the best fit to the data, the optimal model being a recessive gene (frequency .57) plus a modifier locus.more » Individuals infected at an early age and with recurrent lesions are genetically more susceptible than those infected with a single episode of disease at a later age. Among people with no lesions, those with a positive skin-test response are genetically less susceptible than those with a negative response. The possibility of the involvement of more than one gene together with environmental effects has implications for the design of future linkage studies. 31 refs., 7 tabs.« less

Two closely related species differ in their regional genetic differentiation despite admixing

PubMed Central

Fischer, Markus; Oja, Tatjana

2018-01-01

Abstract Regional genetic differentiation within species is often addressed in evolutionary ecology and conservation biology. Here, we address regional differentiation in two closely related hybridizing taxa, the perennial sedges Carex flava and C. viridula and their hybrid C. × subviridula in 37 populations in the north and centre of their distribution range in Europe (Estonia, Lowland (<1000 m a.s.l.) and Highland Switzerland) using 10 putative microsatellite loci. We ask whether regional differentiation was larger in the less common taxon C. viridula or whether, possibly due to hybridization, it was similar between taxa. Our results showed similar, low to moderate genetic diversity for the three studied taxa. In total, we found 12 regional species-specific alleles. Analysis of molecular variance (AMOVA), STRUCTURE and multidimensional scaling analysis showed regional structure in genetic variation, where intraspecific differentiation between regions was lower for C. flava (AMOVA: 6.84 %) than for C. viridula (20.77 %) or C. × subviridula (18.27 %) populations. Hybrids differed from the parental taxa in the two regions where they occurred, i.e. in Estonia and Lowland Switzerland. We conclude that C. flava and C. viridula clearly differ from each other genetically, that there is pronounced regional differentiation and that, despite hybridization, this regional differentiation is more pronounced in the less common taxon, C. viridula. We encourage future studies on hybridizing taxa to work with plant populations from more than one region. PMID:29479408

Genetic features of Mycobacterium tuberculosis modern Beijing sublineage

PubMed Central

Liu, Qingyun; Luo, Tao; Dong, Xinran; Sun, Gang; Liu, Zhu; Gan, Mingyun; Wu, Jie; Shen, Xin; Gao, Qian

2016-01-01

Mycobacterium tuberculosis (MTB) Beijing strains have caused a great concern because of their rapid emergence and increasing prevalence in worldwide regions. Great efforts have been made to investigate the pathogenic characteristics of Beijing strains such as hypervirulence, drug resistance and favoring transmission. Phylogenetically, MTB Beijing family was divided into modern and ancient sublineages. Modern Beijing strains displayed enhanced virulence and higher prevalence when compared with ancient Beijing strains, but the genetic basis for this difference remains unclear. In this study, by analyzing previously published sequencing data of 1082 MTB Beijing isolates, we determined the genetic changes that were commonly present in modern Beijing strains but absent in ancient Beijing strains. These changes include 44 single-nucleotide polymorphisms (SNPs) and two short genomic deletions. Through bioinformatics analysis, we demonstrated that these genetic changes had high probability of functional effects. For example, 4 genes were frameshifted due to premature stop mutation or genomic deletions, 19 nonsynonymous SNPs located in conservative codons, and there is a significant enrichment in regulatory network for all nonsynonymous mutations. Besides, three SNPs located in promoter regions were verified to alter downstream gene expressions. Our study precisely defined the genetic features of modern Beijing strains and provided interesting clues for future researches to elucidate the mechanisms that underlie this sublineage's successful expansion. These findings from the analysis of the modern Beijing sublineage could provide us a model to understand the dynamics of pathogenicity of MTB. PMID:26905026

Lost in Translation? A Comparison of Cancer-Genetics Reporting in the Press Release and its Subsequent Coverage in Lay Press1

PubMed Central

Brechman, Jean M.; Lee, Chul-joo; Cappella, Joseph N.

2014-01-01

Understanding how genetic science is communicated to the lay public is of great import, given that media coverage of genetics is increasing exponentially and that the ways in which discoveries are presented in the news can have significant effects on a variety of health outcomes. To address this issue, this study examines the presentation of genetic research relating to cancer outcomes and behaviors (i.e., prostate cancer, breast cancer, colon cancer, smoking and obesity) in both the press release (N = 23) and its subsequent news coverage (N = 71) by using both quantitative content analysis and qualitative textual analysis. In contrast to earlier studies reporting that news stories often misrepresent genetics by presenting biologically deterministic and simplified portrayals (e.g., Mountcastle-Shah et al., 2003; Ten Eych & Williment, 2003), our data shows no clear trends in the direction of distortion toward deterministic claims in news articles. Also, other errors commonly attributed to science journalism, such as lack of qualifying details and use of oversimplified language (e.g., “fat gene”) are observed in press releases. These findings suggest that the intermediary press release rather than news coverage may serve as a source of distortion in the dissemination of science to the lay public. The implications of this study for future research in this area are discussed. PMID:25568611

Genetic susceptibility to bone and soft tissue sarcomas: a field synopsis and meta-analysis.

PubMed

Benna, Clara; Simioni, Andrea; Pasquali, Sandro; De Boni, Davide; Rajendran, Senthilkumar; Spiro, Giovanna; Colombo, Chiara; Virgone, Calogero; DuBois, Steven G; Gronchi, Alessandro; Rossi, Carlo Riccardo; Mocellin, Simone

2018-04-06

The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases. To evaluate result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Integrative analysis of genetic and eQTL (expression quantitative trait locus) data was coupled with network and pathway analysis to explore the hypothesis that specific cell functions are involved in sarcoma predisposition. We retrieved 90 eligible studies comprising 47,796 subjects (cases: 14,358, 30%) and investigating 1,126 polymorphisms involving 320 distinct genes. Meta-analysis identified 55 single nucleotide polymorphisms (SNPs) significantly associated with disease risk with a high (N=9), moderate (N=38) and low (N=8) level of evidence, findings being classified as noteworthy basically only when the level of evidence was high. The estimated joint population attributable risk for three independent SNPs (rs11599754 of ZNF365/EGR2 , rs231775 of CTLA4 , and rs454006 of PRKCG ) was 37.2%. We also identified 53 SNPs significantly associated with sarcoma risk based on single studies.Pathway analysis enabled us to propose that sarcoma predisposition might be linked especially to germline variation of genes whose products are involved in the function of the DNA repair machinery. We built the first knowledgebase on the evidence linking DNA variation to sarcomas susceptibility, which can be used to generate mechanistic hypotheses and inform future studies in this field of oncology.

Genetic variation in the USDA Chamaecrista fasciculata collection

USDA-ARS?s Scientific Manuscript database

Germplasm collections serve as critical repositories of genetic variation. Characterizing genetic diversity in existing collections is necessary to maximize their utility and to guide future collecting efforts. We have used AFLP markers to characterize genetic variation in the USDA germplasm collect...

ASSESSMENT OF ALLERGENIC POTENTIAL OF GENETICALLY MODIFIED FOODS: AN AGENDA FOR FUTURE RESEARCH

EPA Science Inventory

Abstract
Speakers and participants in the Workshop Assessment of the Allergenic Potential of Genetically Modified Foods met in breakout groups to discuss a number of issues including needs for future research. There was agreement that research should move forward quickly in t...

Approaches in Characterizing Genetic Structure and Mapping in a Rice Multiparental Population.

PubMed

Raghavan, Chitra; Mauleon, Ramil; Lacorte, Vanica; Jubay, Monalisa; Zaw, Hein; Bonifacio, Justine; Singh, Rakesh Kumar; Huang, B Emma; Leung, Hei

2017-06-07

Multi-parent Advanced Generation Intercross (MAGIC) populations are fast becoming mainstream tools for research and breeding, along with the technology and tools for analysis. This paper demonstrates the analysis of a rice MAGIC population from data filtering to imputation and processing of genetic data to characterizing genomic structure, and finally quantitative trait loci (QTL) mapping. In this study, 1316 S6:8 indica MAGIC (MI) lines and the eight founders were sequenced using Genotyping by Sequencing (GBS). As the GBS approach often includes missing data, the first step was to impute the missing SNPs. The observable number of recombinations in the population was then explored. Based on this case study, a general outline of procedures for a MAGIC analysis workflow is provided, as well as for QTL mapping of agronomic traits and biotic and abiotic stress, using the results from both association and interval mapping approaches. QTL for agronomic traits (yield, flowering time, and plant height), physical (grain length and grain width) and cooking properties (amylose content) of the rice grain, abiotic stress (submergence tolerance), and biotic stress (brown spot disease) were mapped. Through presenting this extensive analysis in the MI population in rice, we highlight important considerations when choosing analytical approaches. The methods and results reported in this paper will provide a guide to future genetic analysis methods applied to multi-parent populations. Copyright © 2017 Raghavan et al.

Fine-scale genetic response to landscape change in a gliding mammal.

PubMed

Goldingay, Ross L; Harrisson, Katherine A; Taylor, Andrea C; Ball, Tina M; Sharpe, David J; Taylor, Brendan D

2013-01-01

Understanding how populations respond to habitat loss is central to conserving biodiversity. Population genetic approaches enable the identification of the symptoms of population disruption in advance of population collapse. However, the spatio-temporal scales at which population disruption occurs are still too poorly known to effectively conserve biodiversity in the face of human-induced landscape change. We employed microsatellite analysis to examine genetic structure and diversity over small spatial (mostly 1-50 km) and temporal scales (20-50 years) in the squirrel glider (Petaurus norfolcensis), a gliding mammal that is commonly subjected to a loss of habitat connectivity. We identified genetically differentiated local populations over distances as little as 3 km and within 30 years of landscape change. Genetically isolated local populations experienced the loss of genetic diversity, and significantly increased mean relatedness, which suggests increased inbreeding. Where tree cover remained, genetic differentiation was less evident. This pattern was repeated in two landscapes located 750 km apart. These results lend support to other recent studies that suggest the loss of habitat connectivity can produce fine-scale population genetic change in a range of taxa. This gives rise to the prediction that many other vertebrates will experience similar genetic changes. Our results suggest the future collapse of local populations of this gliding mammal is likely unless habitat connectivity is maintained or restored. Landscape management must occur on a fine-scale to avert the erosion of biodiversity.

A Report on Ten Asia Pacific Countries on Current Status and Future Directions of the Genetic Counseling Profession: The Establishment of the Professional Society of Genetic Counselors in Asia.

PubMed

Laurino, Mercy Y; Leppig, Kathleen A; Abad, Peter James; Cham, Breana; Chu, Yoyo Wing Yiu; Kejriwal, Saahil; Lee, Juliana M H; Sternen, Darci L; Thompson, Jennifer K; Burgess, Matthew J; Chien, Shu; Elackatt, Niby; Lim, Jiin Ying; Sura, Thanyachai; Faradz, Sultana; Padilla, Carmencita; Paz, Eva Cutiongco de-la; Nauphar, Donny; Nguyen, Khanh Ngoc; Zayts, Olya; Vu, Dung Chi; Thong, Meow-Keong

2018-02-01

The Professional Society of Genetic Counselors in Asia (PSGCA) was recently established as a special interest group of the Asia Pacific Society of Human Genetics. Fostering partnerships across the globe, the PSGCA's vision is to be the lead organization that advances and mainstreams the genetic counseling profession in Asia and ensures individuals have access to genetic counseling services. Its mission is to promote quality genetic counseling services in the region by enhancing practice and curricular standards, research and continuing education. The PSGCA was formally launched during the Genetic Counseling Pre-Conference Workshop held at the 11th Asia-Pacific Conference on Human Genetics in Hanoi, Viet Nam, September 16, 2015. The pre-conference workshop provided an opportunity for medical geneticists and genetic counselors from across 10 Asia Pacific countries to learn about the varied genetic counseling practices and strategies for genetic counseling training. This paper provides an overview of the current status and challenges in these countries, and proposed course of unified actions for the future of the genetic counseling profession.

Spread of the Tiger: Global Risk of Invasion by the Mosquito Aedes albopictus

PubMed Central

BENEDICT, MARK Q.; LEVINE, REBECCA S.; HAWLEY, WILLIAM A.; LOUNIBOS, L. PHILIP

2008-01-01

Aedes albopictus, commonly known as the Asian tiger mosquito, is currently the most invasive mosquito in the world. It is of medical importance due to its aggressive daytime human-biting behavior and ability to vector many viruses, including dengue, LaCrosse, and West Nile. Invasions into new areas of its potential range are often initiated through the transportation of eggs via the international trade in used tires. We use a genetic algorithm, Genetic Algorithm for Rule Set Production (GARP), to determine the ecological niche of Ae. albopictus and predict a global ecological risk map for the continued spread of the species. We combine this analysis with risk due to importation of tires from infested countries and their proximity to countries that have already been invaded to develop a list of countries most at risk for future introductions and establishments. Methods used here have potential for predicting risks of future invasions of vectors or pathogens. PMID:17417960

Current and future developments in patents for quantitative trait loci in dairy cattle.

PubMed

Weller, Joel I

2007-01-01

Many studies have proposed that rates of genetic gain in dairy cattle can be increased by direct selection on the individual quantitative loci responsible for the genetic variation in these traits, or selection on linked genetic markers. The development of DNA-level genetic markers has made detection of QTL nearly routine in all major livestock species. The studies that attempted to detect genes affecting quantitative traits can be divided into two categories: analysis of candidate genes, and genome scans based on within-family genetic linkage. To date, 12 patent cooperative treaty (PCT) and US patents have been registered for DNA sequences claimed to be associated with effects on economic traits in dairy cattle. All claim effects on milk production, but other traits are also included in some of the claims. Most of the sequences found by the candidate gene approach are of dubious validity, and have been repeated in only very few independent studies. The two missense mutations on chromosomes 6 and 14 affecting milk concentration derived from genome scans are more solidly based, but the claims are also disputed. A few PCT in dairy cattle are commercialized as genetic tests where commercial dairy farmers are the target market.

Who should know about our genetic makeup and why?

PubMed Central

Takala, T.; Gylling, H. A.

2000-01-01

Recent developments in biology have made it possible to acquire more and more precise information concerning our genetic makeup. Although the most far-reaching effects of these developments will probably be felt only after the Human Genome Project has been completed in a few years' time, scientists can even today identify a number of genetic disorders which may cause illness and disease in their carriers. The improved knowledge regarding the human genome will, it is predicted, in the near future make diagnoses more accurate and treatments more effective, and thereby considerably reduce and prevent unnecessary suffering. On the other hand, however, the knowledge can also be, depending on the case, futile, distressing or plainly harmful. This is why we propose to answer in this paper the dual question: who should know about our genetic makeup and why? Through an analysis of prudential, moral and legal grounds for acquiring the information, we conclude that, at least on the levels of law and social policy, practically nobody is either duty-bound to receive or entitled to have that knowledge. Key Words: Genetic testing • genetic screening • law • ethics • duties PMID:10860207

Translating Discovery in Zebrafish Pancreatic Development to Human Pancreatic Cancer: Biomarkers, Targets, Pathogenesis, and Therapeutics

PubMed Central

Kazi, Abid A.; Yee, Rosemary K.

2013-01-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer. PMID:23682805

Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

PubMed

Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

2013-06-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

Genetic variability affecting Exserohilum turcicum resistance in popcorn lines grown under high and low phosphorus conditions.

PubMed

Amaral, A T; Ribeiro, R M; Santos, P H D; Poltronieri, T P S; Vivas, J M S; Gerhardt, I F S; Carvalho, B M; Freitas, C S; Miranda, S B

2016-12-19

Northern leaf blight (NLB), caused by Exserohilum turcicum, is one of the main foliar diseases that affect popcorn culture. Farmers use many control measures to minimize damage caused by this disease, among which, the use of cultivars with genetic resistance is the most effective and economical. The aim of this study was to investigate genetic variability influencing resistance to NLB in 25 popcorn maize lines grown under high and low phosphorus conditions in relation to foliar fungal disease caused by E. turcicum. We evaluated the disease incidence and severity, by analysis of variance and cluster test (Scott-Knott). There was sufficient genetic variability between strains for resistance traits. Genotypic variance was higher than environmental variance, and had more discriminatory power. We conclude that new progenies could be selected for the establishment of future populations. P-7, P-9, L-59, L-71, and L-76 progenies possess promising characteristics that simultaneously reduce the severity and the incidence of NLB in popcorn plants.

Informed Choice in Direct-to-Consumer Genetic Testing for Alzheimer and Other Diseases: Lessons from Two Cases

PubMed Central

Messner, Donna A.

2011-01-01

Health-related direct-to-consumer (DTC) genetic testing has been a controversial practice. Especially problematic is predictive testing for Alzheimer disease (AD), since the disease is incurable, prevention is inconclusive, and testing does not definitively predict an individual’s future disease status. In this paper, I examine two contrasting cases of subjects who learn through genetic testing that they have an elevated risk of developing AD later in life. In these cases, the subject’s emotional response to the result is related to how well prepared she was for the real-life personal implications of possible test results. Analysis leads to the conclusion that when groups of health-related genetic tests are offered as packages by DTC companies, informed consumer choice is rendered impossible. Moreover, I argue, this marketing approach contravenes U.S. Federal Trade Commission policies for non-deceptive commercial communications. I conclude by suggesting ways to improve the prospects for informed consumer choice in DTC testing. PMID:21603253

Genetic Alterations in Glioma

PubMed Central

Bralten, Linda B. C.; French, Pim J.

2011-01-01

Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes. PMID:24212656

Comparative genetic diversity in a sample of pony breeds from the U.K. and North America: a case study in the conservation of global genetic resources.

PubMed

Winton, Clare L; Plante, Yves; Hind, Pamela; McMahon, Robert; Hegarty, Matthew J; McEwan, Neil R; Davies-Morel, Mina C G; Morgan, Charly M; Powell, Wayne; Nash, Deborah M

2015-08-01

Most species exist as subdivided ex situ daughter population(s) derived from a single original group of individuals. Such subdivision occurs for many reasons both natural and manmade. Traditional British and Irish pony breeds were introduced to North America (U.S.A. and Canada) within the last 150 years, and subsequently equivalent breed societies were established. We have analyzed selected U.K. and North American equivalent pony populations as a case study for understanding the relationship between putative source and derived subpopulations. Diversity was measured using mitochondrial DNA and a panel of microsatellite markers. Genetic signatures differed between the North American subpopulations according to historical management processes. Founder effect and stochastic drift was apparent, particularly pronounced in some breeds, with evidence of admixture of imported mares of different North American breeds. This demonstrates the importance of analysis of subpopulations to facilitate understanding the genetic effects of past management practices and to lead to informed future conservation strategies.

Genetic diversity and structure of Brazilian ginger germplasm (Zingiber officinale) revealed by AFLP markers.

PubMed

Blanco, Eleonora Zambrano; Bajay, Miklos Maximiliano; Siqueira, Marcos Vinícius Bohrer Monteiro; Zucchi, Maria Imaculada; Pinheiro, José Baldin

2016-12-01

Ginger is a vegetable with medicinal and culinary properties widely cultivated in the Southern and Southeastern Brazil. The knowledge of ginger species' genetic variability is essential to direct correctly future studies of conservation and genetic improvement, but in Brazil, little is known about this species' genetic variability. In this study, we analyzed the genetic diversity and structure of 55 Brazilian accessions and 6 Colombian accessions of ginger, using AFLP (Amplified Fragment Length Polymorphism) molecular markers. The molecular characterization was based on 13 primers combinations, which generated an average of 113.5 polymorphic loci. The genetic diversity estimates of Nei (Hj), Shannon-Weiner index (I) and an effective number of alleles (n e ) were greater in the Colombian accessions in relation to the Brazilian accessions. The analysis of molecular variance showed that most of the genetic variation occurred between the two countries while in the Brazilian populations there is no genetic structure and probably each region harbors 100 % of genetic variation found in the samples. The bayesian model-based clustering and the dendrogram using the dissimilarity's coefficient of Jaccard were congruent with each other and showed that the Brazilian accessions are highly similar between themselves, regardless of the geographic region of origin. We suggested that the exploration of the interspecific variability and the introduction of new varieties of Z.officinale are viable alternatives for generating diversity in breeding programs in Brazil. The introduction of new genetic materials will certainly contribute to a higher genetic basis of such crop.

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

PubMed Central

Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

2016-01-01

Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

PubMed

Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

2017-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x environmental interactions affecting brain functioning in health and disease.

INTEGRATIVE ANALYSIS OF GENETIC, GENOMIC AND PHENOTYPIC DATA FOR ETHANOL BEHAVIORS: A NETWORK-BASED PIPELINE FOR IDENTIFYING MECHANISMS AND POTENTIAL DRUG TARGETS

PubMed Central

Bogenpohl, James W.; Mignogna, Kristin M.; Smith, Maren L.; Miles, Michael F.

2016-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce non-biased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x environmental interactions affecting brain functioning in health and disease. PMID:27933543

Genome-Wide SNP Discovery and Analysis of Genetic Diversity in Farmed Sika Deer (Cervus nippon) in Northeast China Using Double-Digest Restriction Site-Associated DNA Sequencing.

PubMed

Ba, Hengxing; Jia, Boyin; Wang, Guiwu; Yang, Yifeng; Kedem, Gilead; Li, Chunyi

2017-09-07

Sika deer are an economically valuable species owing to their use in traditional Chinese medicine, particularly their velvet antlers. Sika deer in northeast China are mostly farmed in enclosure. Therefore, genetic management of farmed sika deer would benefit from detailed knowledge of their genetic diversity. In this study, we generated over 1.45 billion high-quality paired-end reads (288 Gbp) across 42 unrelated individuals using double-digest restriction site-associated DNA sequencing (ddRAD-seq). A total of 96,188 (29.63%) putative biallelic SNP loci were identified with an average sequencing depth of 23×. Based on the analysis, we found that the majority of the loci had a deficit of heterozygotes (F IS >0) and low values of H obs , which could be due to inbreeding and Wahlund effects. We also developed a collection of high-quality SNP probes that will likely be useful in a variety of applications in genotyping for cervid species in the future. Copyright © 2017 Ba et al.

Genome-Wide SNP Discovery and Analysis of Genetic Diversity in Farmed Sika Deer (Cervus nippon) in Northeast China Using Double-Digest Restriction Site-Associated DNA Sequencing

PubMed Central

Ba, Hengxing; Jia, Boyin; Wang, Guiwu; Yang, Yifeng; Kedem, Gilead; Li, Chunyi

2017-01-01

Sika deer are an economically valuable species owing to their use in traditional Chinese medicine, particularly their velvet antlers. Sika deer in northeast China are mostly farmed in enclosure. Therefore, genetic management of farmed sika deer would benefit from detailed knowledge of their genetic diversity. In this study, we generated over 1.45 billion high-quality paired-end reads (288 Gbp) across 42 unrelated individuals using double-digest restriction site-associated DNA sequencing (ddRAD-seq). A total of 96,188 (29.63%) putative biallelic SNP loci were identified with an average sequencing depth of 23×. Based on the analysis, we found that the majority of the loci had a deficit of heterozygotes (FIS >0) and low values of Hobs, which could be due to inbreeding and Wahlund effects. We also developed a collection of high-quality SNP probes that will likely be useful in a variety of applications in genotyping for cervid species in the future. PMID:28751500

New approaches in GMO detection.

PubMed

Querci, Maddalena; Van den Bulcke, Marc; Zel, Jana; Van den Eede, Guy; Broll, Hermann

2010-03-01

The steady rate of development and diffusion of genetically modified plants and their increasing diversification of characteristics, genes and genetic control elements poses a challenge in analysis of genetically modified organisms (GMOs). It is expected that in the near future the picture will be even more complex. Traditional approaches, mostly based on the sequential detection of one target at a time, or on a limited multiplexing, allowing only a few targets to be analysed at once, no longer meet the testing requirements. Along with new analytical technologies, new approaches for the detection of GMOs authorized for commercial purposes in various countries have been developed that rely on (1) a smart and accurate strategy for target selection, (2) the use of high-throughput systems or platforms for the detection of multiple targets and (3) algorithms that allow the conversion of analytical results into an indication of the presence of individual GMOs potentially present in an unknown sample. This paper reviews the latest progress made in GMO analysis, taking examples from the most recently developed strategies and tools, and addresses some of the critical aspects related to these approaches.

Molecular genetic markers for thyroid FNAB. Established assays and future perspective.

PubMed

Musholt, Thomas J; Musholt, P B

2015-01-01

Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18-65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Global trends on fears and concerns of genetic discrimination: a systematic literature review.

PubMed

Wauters, Annet; Van Hoyweghen, Ine

2016-04-01

Since the 1990s, developments in the field of genetics have led to many questions on the use and possible misuse of genetic information. 'Genetic discrimination' has been defined as the differential treatment of asymptomatic individuals or their relatives on the basis of their real or assumed genetic characteristics. Despite the public policy attention around genetic discrimination, there is currently still much confusion surrounding this phenomenon. On the one hand, there is little evidence of the occurrence of genetic discrimination. On the other hand, it appears that people remain concerned about this theme, and this fear influences their health and life choices. This article makes use of a systematic literature review to investigate what is already known about the nature, extent and background of these fears and concerns. The 42 included studies have found considerable levels of concerns about genetic discrimination. Concerns dominate in insurance contexts and within personal interactions. The extent of concerns appears to vary depending on the type of genetic illness. Furthermore, installed laws prohibiting genetic discrimination do not seem to alleviate existing fears. This raises important questions as to the origins of these fears. Based on the findings, recommendations for future research are made. First, research on the background of fears is needed. Second, future research needs to assess more fully all different forms (for example, direct and indirect) of genetic discrimination. Thirdly, it has to be studied whether genetic discrimination is a form of discrimination that is distinguishable from discrimination based on an illness or disability. Finally, a last element that should be addressed in future research is the most recent developments in research on genomics, such as next-generation sequencing or genome-wide association studies.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

PubMed

Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017. Published by Elsevier Inc.

The behavioral genetics of nonhuman primates: Status and prospects.

PubMed

Rogers, Jeffrey

2018-01-01

The complexity and diversity of primate behavior have long attracted the attention of ethologists, psychologists, behavioral ecologists, and neuroscientists. Recent studies have advanced our understanding of the nature of genetic influences on differences in behavior among individuals within species. A number of analyses have focused on the genetic analysis of behavioral reactions to specific experimental tests, providing estimates of the degree of genetic control over reactivity, and beginning to identify the genes involved. Substantial progress is also being made in identifying genetic factors that influence the structure and function of the primate brain. Most of the published studies on these topics have examined either cercopithecines or chimpanzees, though a few studies have addressed these questions in other primate species. One potentially important line of research is beginning to identify the epigenetic processes that influence primate behavior, thus revealing specific cellular and molecular mechanisms by which environmental experiences can influence gene expression or gene function relevant to behavior. This review summarizes many of these studies of non-human primate behavioral genetics. The primary focus is on analyses that address the nature of the genes and genetic processes that affect differences in behavior among individuals within non-human primate species. Analyses of between species differences and potential avenues for future research are also discussed. © 2018 American Association of Physical Anthropologists.

Genetic factors in exercise adoption, adherence and obesity.

PubMed

Herring, M P; Sailors, M H; Bray, M S

2014-01-01

Physical activity and exercise play critical roles in energy balance. While many interventions targeted at increasing physical activity have demonstrated efficacy in promoting weight loss or maintenance in the short term, long term adherence to such programmes is not frequently observed. Numerous factors have been examined for their ability to predict and/or influence physical activity and exercise adherence. Although physical activity has been demonstrated to have a strong genetic component in both animals and humans, few studies have examined the association between genetic variation and exercise adherence. In this review, we provide a detailed overview of the non-genetic and genetic predictors of physical activity and adherence to exercise. In addition, we report the results of analysis of 26 single nucleotide polymorphisms in six candidate genes examined for association to exercise adherence, duration, intensity and total exercise dose in young adults from the Training Interventions and Genetics of Exercise Response (TIGER) Study. Based on both animal and human research, neural signalling and pleasure/reward systems in the brain may drive in large part the propensity to be physically active and to adhere to an exercise programme. Adherence/compliance research in other fields may inform future investigation of the genetics of exercise adherence. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

Birds in space and time: genetic changes accompanying anthropogenic habitat fragmentation in the endangered black-capped vireo (Vireo atricapilla)

PubMed Central

Athrey, Giridhar; Barr, Kelly R; Lance, Richard F; Leberg, Paul L

2012-01-01

Anthropogenic alterations in the natural environment can be a potent evolutionary force. For species that have specific habitat requirements, habitat loss can result in substantial genetic effects, potentially impeding future adaptability and evolution. The endangered black-capped vireo (Vireo atricapilla) suffered a substantial contraction of breeding habitat and population size during much of the 20th century. In a previous study, we reported significant differentiation between remnant populations, but failed to recover a strong genetic signal of bottlenecks. In this study, we used a combination of historical and contemporary sampling from Oklahoma and Texas to (i) determine whether population structure and genetic diversity have changed over time and (ii) evaluate alternate demographic hypotheses using approximate Bayesian computation (ABC). We found lower genetic diversity and increased differentiation in contemporary samples compared to historical samples, indicating nontrivial impacts of fragmentation. ABC analysis suggests a bottleneck having occurred in the early part of the 20th century, resulting in a magnitude decline in effective population size. Genetic monitoring with temporally spaced samples, such as used in this study, can be highly informative for assessing the genetic impacts of anthropogenic fragmentation on threatened or endangered species, as well as revealing the dynamics of small populations over time. PMID:23028396

Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

PubMed Central

Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

2016-01-01

Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

PubMed Central

2014-01-01

Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10−8. Findings We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10−10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10−9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10−9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the ultimate aim of assisting in disease classification and prognosis. The data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype. Future genetic analyses might benefit from both lumping (ie, grouping of epilepsy types together) or splitting (ie, analysis of specific clinical subtypes). Funding International League Against Epilepsy and multiple governmental and philanthropic agencies. PMID:25087078

An intra-specific consensus genetic map of pigeonpea [Cajanus cajan (L.) Millspaugh] derived from six mapping populations.

PubMed

Bohra, Abhishek; Saxena, Rachit K; Gnanesh, B N; Saxena, Kulbhushan; Byregowda, M; Rathore, Abhishek; Kavikishor, P B; Cook, Douglas R; Varshney, Rajeev K

2012-10-01

Pigeonpea (Cajanus cajan L.) is an important food legume crop of rainfed agriculture. Owing to exposure of the crop to a number of biotic and abiotic stresses, the crop productivity has remained stagnant for almost last five decades at ca. 750 kg/ha. The availability of a cytoplasmic male sterility (CMS) system has facilitated the development and release of hybrids which are expected to enhance the productivity of pigeonpea. Recent advances in genomics and molecular breeding such as marker-assisted selection (MAS) offer the possibility to accelerate hybrid breeding. Molecular markers and genetic maps are pre-requisites for deploying MAS in breeding. However, in the case of pigeonpea, only one inter- and two intra-specific genetic maps are available so far. Here, four new intra-specific genetic maps comprising 59-140 simple sequence repeat (SSR) loci with map lengths ranging from 586.9 to 881.6 cM have been constructed. Using these four genetic maps together with two recently published intra-specific genetic maps, a consensus map was constructed, comprising of 339 SSR loci spanning a distance of 1,059 cM. Furthermore, quantitative trait loci (QTL) analysis for fertility restoration (Rf) conducted in three mapping populations identified four major QTLs explaining phenotypic variances up to 24 %. To the best of our knowledge, this is the first report on construction of a consensus genetic map in pigeonpea and on the identification of QTLs for fertility restoration. The developed consensus genetic map should serve as a reference for developing new genetic maps as well as correlating with the physical map in pigeonpea to be developed in near future. The availability of more informative markers in the bins harbouring QTLs for sterility mosaic disease (SMD) and Rf will facilitate the selection of the most suitable markers for genetic analysis and molecular breeding applications in pigeonpea.

Ethylene Production Via Sunlight Opens Door to Future | News | NREL

Science.gov Websites

genetically engineered strains to promote ethylene production. Photo by Dennis Schroeder Here's the future of (storage) compounds in cyanobacteria at the molecular biology lab at NREL. Photo by Dennis Schroeder Jianping Yu to cultivate genetic strains of cyanobacteria to increase ethylene production. Photo by Dennis

Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

PubMed Central

Diaz-Cano, Salvador J.

2012-01-01

Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

Selkirk Rex: Morphological and Genetic Characterization of a New Cat Breed

PubMed Central

2012-01-01

Rexoid, curly hair mutations have been selected to develop new domestic cat breeds. The Selkirk Rex is the most recently established curly-coated cat breed originating from a spontaneous mutation that was discovered in the United States in 1987. Unlike the earlier and well-established Cornish and Devon Rex breeds with curly-coat mutations, the Selkirk Rex mutation is suggested as autosomal dominant and has a different curl phenotype. This study provides a genetic analysis of the Selkirk Rex breed. An informal segregation analysis of genetically proven matings supported an autosomal, incomplete dominant expression of the curly trait in the Selkirk Rex. Homozygous curl cats can be distinguished from heterozygous cats by head and body type, as well as the presentation of the hair curl. Bayesian clustering of short tandem repeat (STR) genotypes from 31 cats that represent the future breeding stock supported the close relationship of the Selkirk Rex to the British Shorthair, Scottish Fold, Persian, and Exotic Shorthair, suggesting the Selkirk as part of the Persian breed family. The high heterozygosity of 0.630 and the low mean inbreeding coefficient of 0.057 suggest that Selkirk Rex has a diverse genetic foundation. A new locus for Selkirk autosomal dominant Rex, SADRE, is suggested for the curly trait. PMID:22837475

Genetic Testing of Maturity-Onset Diabetes of the Young Current Status and Future Perspectives

PubMed Central

Firdous, Parveena; Nissar, Kamran; Ali, Sajad; Ganai, Bashir Ahmad; Shabir, Uzma; Hassan, Toyeeba; Masoodi, Shariq Rashid

2018-01-01

Diabetes is a global epidemic problem growing exponentially in Asian countries posing a serious threat. Among diabetes, maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders that occurs due to β cell dysfunction. Genetic defects in the pancreatic β-cells result in the decrease of insulin production required for glucose utilization thereby lead to early-onset diabetes (often <25 years). It is generally considered as non-insulin dependent form of diabetes and comprises of 1–5% of total diabetes. Till date, 14 genes have been identified and mutation in them may lead to MODY. Different genetic testing methodologies like linkage analysis, restriction fragment length polymorphism, and DNA sequencing are used for the accurate and correct investigation of gene mutations associated with MODY. The next-generation sequencing has emerged as one of the most promising and effective tools to identify novel mutated genes related to MODY. Diagnosis of MODY is mainly relying on the sequential screening of the three marker genes like hepatocyte nuclear factor 1 alpha (HNF1α), hepatocyte nuclear factor 4 alpha (HNF4α), and glucokinase (GCK). Interestingly, MODY patients can be managed by diet alone for many years and may also require minimal doses of sulfonylureas. The primary objective of this article is to provide a review on current status of MODY, its prevalence, genetic testing/diagnosis, possible treatment, and future perspective. PMID:29867778

Advances in Engineering the Fly Genome with the CRISPR-Cas System

PubMed Central

Bier, Ethan; Harrison, Melissa M.; O’Connor-Giles, Kate M.; Wildonger, Jill

2018-01-01

Drosophila has long been a premier model for the development and application of cutting-edge genetic approaches. The CRISPR-Cas system now adds the ability to manipulate the genome with ease and precision, providing a rich toolbox to interrogate relationships between genotype and phenotype, to delineate and visualize how the genome is organized, to illuminate and manipulate RNA, and to pioneer new gene drive technologies. Myriad transformative approaches have already originated from the CRISPR-Cas system, which will likely continue to spark the creation of tools with diverse applications. Here, we provide an overview of how CRISPR-Cas gene editing has revolutionized genetic analysis in Drosophila and highlight key areas for future advances. PMID:29301946

Genetic divergence through joint analysis of morphoagronomic and molecular characters in accessions of Jatropha curcas.

PubMed

Pestana-Caldas, C N; Silva, S A; Machado, E L; de Souza, D R; Cerqueira-Pereira, E C; Silva, M S

2016-10-05

The aim of this study was to investigate the genetic divergence between accessions of Jatropha curcas through joint analysis of morphoagronomic and molecular characters. To this end, we investigated 11 morphoagronomic characters and performed molecular genotyping, using 23 inter-simple sequence repeat (ISSR) primers in 46 accessions of J. curcas. We calculated the contribution of each character on divergence using analysis of variance. The grouping among accessions was performed using the Ward-MLM (modified location model) method, using morphoagronomic and molecular data, whereas the cophenetic correlation was obtained based on Gower's algorithm. There were significant differences in all growth-related characteristics: number of primary and secondary branches per plant, plant height, and stem diameter. For characters related to grain production, differences were found for number of fruit clusters per plant and number of inflorescence clusters per plant and average number of seeds per fruit. The greatest phenotypic variation was found in plant height (59.67- 222.33 cm), whereas the smallest variation was found in average number of seeds per fruit (0-2.90), followed by the number of fruit clusters per plant (0-8.67). In total, 94 polymorphic ISSR fragments were obtained. The genotypic grouping identified six groups, indicating that there is genetic divergence among the accessions. The most promising crossings for future hybridization were identified among accessions UFRB60 and UFVJC45, and UFRB61 and UFVJC18. In conclusion, the joint analysis of morphoagronomic characters and ISSR markers is an efficient method to assess the genetic divergence in J. curcas.

Experience with environmental issues in GM crop production and the likely future scenarios.

PubMed

Gaugitsch, Helmut

2002-02-28

In the Cartagena Protocol on Biosafety, standards for risk assessment of genetically modified organisms (GMOs) have been set. The criteria and information basis for the risk assessment of GMOs have been modified by the EU Directive 2001/18/EC. Various approaches to further improve the criteria for environmental risk assessment of GMOs are described in this study. Reports on the ecological impacts of the cultivation of certain non-transgenic crop plants with novel or improved traits as analogy models to transgenic plants showed that the effects of agricultural practice can be at least equally important as the effects of gene transfer and invasiveness, although the latter currently play a major role in risk assessment of transgenic crops. Based on these results the applicability of the methodology of 'Life Cycle Analysis (LCA)' for genetically modified plants in comparison with conventionally bred and organically grown crop plants was evaluated. The methodology was regarded as applicable with some necessary future improvements. In current projects, the assessment of toxicology and allergenicity of GM crops are analysed, and suggestions for standardization are developed. Based on results and recommendations from these efforts there are still the challenges of how to operationalize the precautionary principle and how to take into account ecologically sensitive ecosystems, including centres of origin and centres of genetic diversity.

Probing the Xenopus laevis inner ear transcriptome for biological function

PubMed Central

2012-01-01

Background The senses of hearing and balance depend upon mechanoreception, a process that originates in the inner ear and shares features across species. Amphibians have been widely used for physiological studies of mechanotransduction by sensory hair cells. In contrast, much less is known of the genetic basis of auditory and vestibular function in this class of animals. Among amphibians, the genus Xenopus is a well-characterized genetic and developmental model that offers unique opportunities for inner ear research because of the amphibian capacity for tissue and organ regeneration. For these reasons, we implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis. Results Microarray analysis uncovered genes within the X. laevis inner ear transcriptome associated with inner ear function and impairment in other organisms, thereby supporting the inclusion of Xenopus in cross-species genetic studies of the inner ear. The use of gene categories (inner ear tissue; deafness; ion channels; ion transporters; transcription factors) facilitated the assignment of functional significance to probe set identifiers. We enhanced the biological relevance of our microarray data by using a variety of curation approaches to increase the annotation of the Affymetrix GeneChip® Xenopus laevis Genome array. In addition, annotation analysis revealed the prevalence of inner ear transcripts represented by probe set identifiers that lack functional characterization. Conclusions We identified an abundance of targets for genetic analysis of auditory and vestibular function. The orthologues to human genes with known inner ear function and the highly expressed transcripts that lack annotation are particularly interesting candidates for future analyses. We used informatics approaches to impart biologically relevant information to the Xenopus inner ear transcriptome, thereby addressing the impediment imposed by insufficient gene annotation. These findings heighten the relevance of Xenopus as a model organism for genetic investigations of inner ear organogenesis, morphogenesis, and regeneration. PMID:22676585

The genetic consequences of selection in natural populations.

PubMed

Thurman, Timothy J; Barrett, Rowan D H

2016-04-01

The selection coefficient, s, quantifies the strength of selection acting on a genetic variant. Despite this parameter's central importance to population genetic models, until recently we have known relatively little about the value of s in natural populations. With the development of molecular genetic techniques in the late 20th century and the sequencing technologies that followed, biologists are now able to identify genetic variants and directly relate them to organismal fitness. We reviewed the literature for published estimates of natural selection acting at the genetic level and found over 3000 estimates of selection coefficients from 79 studies. Selection coefficients were roughly exponentially distributed, suggesting that the impact of selection at the genetic level is generally weak but can occasionally be quite strong. We used both nonparametric statistics and formal random-effects meta-analysis to determine how selection varies across biological and methodological categories. Selection was stronger when measured over shorter timescales, with the mean magnitude of s greatest for studies that measured selection within a single generation. Our analyses found conflicting trends when considering how selection varies with the genetic scale (e.g., SNPs or haplotypes) at which it is measured, suggesting a need for further research. Besides these quantitative conclusions, we highlight key issues in the calculation, interpretation, and reporting of selection coefficients and provide recommendations for future research. © 2016 John Wiley & Sons Ltd.

Genetic assessment of captive red panda (Ailurus fulgens) population.

PubMed

Kumar, Arun; Rai, Upashna; Roka, Bhupen; Jha, Alankar K; Reddy, P Anuradha

2016-01-01

Red panda (Ailurus fulgens) is threatened across its range by detrimental human activities and rapid habitat changes necessitating captive breeding programs in various zoos globally to save this flagship species from extinction. One of the ultimate aims of ex situ conservation is reintroduction of endangered animals into their natural habitats while maintaining 90 % of the founder genetic diversity. Advances in molecular genetics and microsatellite genotyping techniques make it possible to accurately estimate genetic diversity of captive animals of unknown ancestry. Here we assess genetic diversity of the red panda population in Padmaja Naidu Himalayan Zoological Park, Darjeeling, which plays a pivotal role in ex situ conservation of red panda in India. We generated microsatellite genotypes of fifteen red pandas with a set of fourteen loci. This population is genetically diverse with 68 % observed heterozygosity (H O ) and mean inbreeding (F IS ) coefficient of 0.05. However population viability analysis reveals that this population has a very low survival probability (<2 %) and will rapidly loose its genetic diversity to 37 % mainly due to small population size and skewed male-biased sex ratio. Regular supplementation with a pair of adult individuals every five years will increase survival probability and genetic diversity to 99 and 61 % respectively and will also support future harvesting of individuals for reintroduction into the wild and exchange with other zoos.

Genetic parameters for different growth scales in GIFT strain of Nile tilapia (Oreochromis niloticus).

PubMed

He, J; Gao, H; Xu, P; Yang, R

2015-12-01

Body weight, length, width and depth at two growth stages were observed for a total of 5015 individuals of GIFT strain, along with a pedigree including 5588 individuals from 104 sires and 162 dams was collected. Multivariate animal models and a random regression model were used to genetically analyse absolute and relative growth scales of these growth traits. In absolute growth scale, the observed growth traits had moderate heritabilities ranging from 0.321 to 0.576, while pairwise ratios between body length, width and depth were lowly inherited and maximum heritability was only 0.146 for length/depth. All genetic correlations were above 0.5 between pairwise growth traits and genetic correlation between length/width and length/depth varied between both growth stages. Based on those estimates, selection index of multiple traits of interest can be formulated in future breeding program to improve genetically body weight and morphology of the GIFT strain. In relative growth scale, heritabilities in relative growths of body length, width and depth to body weight were 0.257, 0.412 and 0.066, respectively, while genetic correlations among these allometry scalings were above 0.8. Genetic analysis for joint allometries of body weight to body length, width and depth will contribute to genetically regulate the growth rate between body shape and body weight. © 2015 Blackwell Verlag GmbH.

The first genetic map of a synthesized allohexaploid Brassica with A, B and C genomes based on simple sequence repeat markers.

PubMed

Yang, S; Chen, S; Geng, X X; Yan, G; Li, Z Y; Meng, J L; Cowling, W A; Zhou, W J

2016-04-01

We present the first genetic map of an allohexaploid Brassica species, based on segregating microsatellite markers in a doubled haploid mapping population generated from a hybrid between two hexaploid parents. This study reports the first genetic map of trigenomic Brassica. A doubled haploid mapping population consisting of 189 lines was obtained via microspore culture from a hybrid H16-1 derived from a cross between two allohexaploid Brassica lines (7H170-1 and Y54-2). Simple sequence repeat primer pairs specific to the A genome (107), B genome (44) and C genome (109) were used to construct a genetic linkage map of the population. Twenty-seven linkage groups were resolved from 274 polymorphic loci on the A genome (109), B genome (49) and C genome (116) covering a total genetic distance of 3178.8 cM with an average distance between markers of 11.60 cM. This is the first genetic framework map for the artificially synthesized Brassica allohexaploids. The linkage groups represent the expected complement of chromosomes in the A, B and C genomes from the original diploid and tetraploid parents. This framework linkage map will be valuable for QTL analysis and future genetic improvement of a new allohexaploid Brassica species, and in improving our understanding of the genetic control of meiosis in new polyploids.

Scientists' and science writers' experiences reporting genetic discoveries: toward an ethic of trust in science journalism.

PubMed

Geller, Gail; Bernhardt, Barbara A; Gardner, Mary; Rodgers, Joann; Holtzman, Neil A

2005-03-01

To describe the relationship between scientists and science writers and their experiences with media reporting of genetic discoveries. This study included individual interviews with 15 scientists who specialize in genetics and 22 science writers who have covered their stories and a qualitative analysis of the data. Scientists and science writers place an equally high priority on accuracy of media reports. They agree on what makes genetics stories newsworthy and the particular challenges in reporting genetic discoveries (i.e., poor public understanding of genetics, the association of genetics with eugenics, and the lack of immediately apparent applications of genetic discoveries to human health). The relationship between scientists and bona fide science writers is largely positive. Scientists tend to trust, respect, and be receptive to science writers. Both scientists and science writers acknowledge that trust is an essential component of a good interview. Science writers report a fair degree of autonomy with respect to the relationship they have with their editors. To the degree that trust facilitates the access that science writers have to scientists, as well as higher quality interviews between scientists and science writers, trust might also contribute to higher quality media reporting. Therefore, scientists and science writers have an ethical obligation to foster trusting relationships with each other. Future research should systematically explore ways to cultivate such relationships and assess their impact on the quality of science journalism.

Predicted extinction of unique genetic diversity in marine forests of Cystoseira spp.

PubMed

Buonomo, Roberto; Chefaoui, Rosa M; Lacida, Ricardo Bermejo; Engelen, Aschwin H; Serrão, Ester A; Airoldi, Laura

2018-07-01

Climate change is inducing shifts in species ranges across the globe. These can affect the genetic pools of species, including loss of genetic variability and evolutionary potential. In particular, geographically enclosed ecosystems, like the Mediterranean Sea, have a higher risk of suffering species loss and genetic erosion due to barriers to further range shifts and to dispersal. In this study, we address these questions for three habitat-forming seaweed species, Cystoseira tamariscifolia, C. amentacea and C. compressa, throughout their entire ranges in the Atlantic and Mediterranean regions. We aim to 1) describe their population genetic structure and diversity, 2) model the present and predict the future distribution and 3) assess the consequences of predicted future range shifts for their population genetic structure, according to two contrasting future climate change scenarios. A net loss of suitable areas was predicted in both climatic scenarios across the range of distribution of the three species. This loss was particularly severe for C. amentacea in the Mediterranean Sea (less 90% in the most extreme climatic scenario), suggesting that the species could become potentially at extinction risk. For all species, genetic data showed very differentiated populations, indicating low inter-population connectivity, and high and distinct genetic diversity in areas that were predicted to become lost, causing erosion of unique evolutionary lineages. Our results indicated that the Mediterranean Sea is the most threatened region, where future suitable Cystoseira habitats will become more limited. This is likely to have wider ecosystem impacts as there is a lack of species with the same ecological niche and functional role in the Mediterranean. The projected accelerated loss of already fragmented and disturbed populations and the long-term genetic effects highlight the urge for local scale management strategies that sustain the capacity of these habitat-forming species to persist despite climatic impacts while waiting for global emission reductions. Copyright © 2018 Elsevier Ltd. All rights reserved.

The molecular genetics of eyelid tumors: recent advances and future directions.

PubMed

Milman, Tatyana; McCormick, Steven A

2013-02-01

Unprecedented recent advances in the molecular genetics of cutaneous malignancies have markedly improved our ability to diagnose, treat, and counsel patients with skin tumors. This review provides an update on molecular genetics of periocular cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma, Merkel cell carcinoma, and malignant melanoma and describes how the knowledge of molecular genetics is translated into clinical practice. A literature search of peer-reviewed and indexed publications from 1965 to 2012 using the PubMed search engine was performed. Key terms included: molecular genetics, eyelid, basal cell carcinoma, squamous cell carcinoma, sebaceous adenoma, sebaceous epithelioma, sebaceoma, sebaceous carcinoma, Merkel cell carcinoma, and melanoma. Seminal articles prior to 1965 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. We reviewed the literature regarding the advances in molecular genetics of cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous neoplasia, Merkel cell carcinoma, and malignant melanoma, and possible future directions towards diagnosing and treating cutaneous tumors at the genetic level. Cell culture experiments, animal models, and molecular genetic studies on the patients' tumor tissues helped to elucidate genetic aberrations in these lesions. Cell culture experiments, animal studies and, ultimately, clinical trials provided means to test and develop novel therapeutic strategies, namely targeted therapy directed at specific molecular genetic defects. While remarkable progress has been made in this process, the complexity of the molecular genetics of skin tumors makes complete elucidation of the genetic mechanisms and the search for ideal therapies challenging. The recent studies focusing on molecular genetics of cutaneous malignancies show promising results, thereby improving our ability to diagnose, treat and counsel patients with these lesions. Future studies will hopefully help unravel further molecular mechanisms involved in cutaneous neoplasia and provide insights into novel preventative and therapeutic modalities.

Sparse models for correlative and integrative analysis of imaging and genetic data

PubMed Central

Lin, Dongdong; Cao, Hongbao; Calhoun, Vince D.

2014-01-01

The development of advanced medical imaging technologies and high-throughput genomic measurements has enhanced our ability to understand their interplay as well as their relationship with human behavior by integrating these two types of datasets. However, the high dimensionality and heterogeneity of these datasets presents a challenge to conventional statistical methods; there is a high demand for the development of both correlative and integrative analysis approaches. Here, we review our recent work on developing sparse representation based approaches to address this challenge. We show how sparse models are applied to the correlation and integration of imaging and genetic data for biomarker identification. We present examples on how these approaches are used for the detection of risk genes and classification of complex diseases such as schizophrenia. Finally, we discuss future directions on the integration of multiple imaging and genomic datasets including their interactions such as epistasis. PMID:25218561

Genetic and Quantitative Trait Locus Analysis for Bio-Oil Compounds after Fast Pyrolysis in Maize Cobs.

PubMed

Jeffrey, Brandon; Kuzhiyil, Najeeb; de Leon, Natalia; Lübberstedt, Thomas

2016-01-01

Fast pyrolysis has been identified as one of the biorenewable conversion platforms that could be a part of an alternative energy future, but it has not yet received the same attention as cellulosic ethanol in the analysis of genetic inheritance within potential feedstocks such as maize. Ten bio-oil compounds were measured via pyrolysis/gas chromatography-mass spectrometry (Py/GC-MS) in maize cobs. 184 recombinant inbred lines (RILs) of the intermated B73 x Mo17 (IBM) Syn4 population were analyzed in two environments, using 1339 markers, for quantitative trait locus (QTL) mapping. QTL mapping was performed using composite interval mapping with significance thresholds established by 1000 permutations at α = 0.05. 50 QTL were found in total across those ten traits with R2 values ranging from 1.7 to 5.8%, indicating a complex quantitative inheritance of these traits.

Common variants in ZMIZ1 and near NGF confer risk for primary dysmenorrhoea

PubMed Central

Li, Zhiqiang; Chen, Jianhua; Zhao, Ying; Wang, Yujiong; Xu, Jinrui; Ji, Jue; Shen, Jingyi; Zhang, Weiping; Chen, Zuosong; Sun, Qilin; Mao, Lijuan; Cheng, Shulin; Yang, Bo; Zhang, Dongtao; Xu, Yufeng; Zhao, Yingying; Liu, Danping; Shen, Yinhuan; Zhang, Weijie; Li, Changgui; Shen, Jiawei; Shi, Yongyong

2017-01-01

Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10−8) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has previously been associated with several autoimmune diseases, and NGF plays a key role in the generation of pain and hyperalgesia and has been associated with migraine. These findings provide future directions for research on susceptibility mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture analysis provides molecular support for the heritability and polygenic nature of this condition. PMID:28447608

Complex polarimetric and spectral techniques in diagnostics of blood plasma of patients with ovarian cancer as a preliminary stage molecular genetic screening

NASA Astrophysics Data System (ADS)

Grzegorzewski, B.; Peresunko, O. P.; Yermolenko, S. B.

2018-01-01

This work is devoted to the substantiation and selection of patients with ovarian cancer (OC) for the purpose of conducting expensive molecular genetic studies on genotyping. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5 - 25 microns) dry residue of plasma polarization and laser diagnostic technique of thin histological sections of biological tissues. Obtained results showed that the use of spectrophotometry in the range of 1000-3000 cm-1 allowed to establish quantitative parameters of the plasma absorption rate of blood of patients in the third group in different ranges, which would allow in the future to conduct an express analysis of the patient's condition (procedure screening) for further molecular-genetic typing on BRCA I and II.

Stocking the genetic supermarket: reproductive genetic technologies and collective action problems.

PubMed

Gyngell, Chris; Douglas, Thomas

2015-05-01

Reproductive genetic technologies (RGTs) allow parents to decide whether their future children will have or lack certain genetic predispositions. A popular model that has been proposed for regulating access to RGTs is the 'genetic supermarket'. In the genetic supermarket, parents are free to make decisions about which genes to select for their children with little state interference. One possible consequence of the genetic supermarket is that collective action problems will arise: if rational individuals use the genetic supermarket in isolation from one another, this may have a negative effect on society as a whole, including future generations. In this article we argue that RGTs targeting height, innate immunity, and certain cognitive traits could lead to collective action problems. We then discuss whether this risk could in principle justify state intervention in the genetic supermarket. We argue that there is a plausible prima facie case for the view that such state intervention would be justified and respond to a number of arguments that might be adduced against that view. © 2014 The Authors. Bioethics published by John Wiley & Sons Ltd.

VTE Risk assessment - a prognostic Model: BATER Cohort Study of young women.

PubMed

Heinemann, Lothar Aj; Dominh, Thai; Assmann, Anita; Schramm, Wolfgang; Schürmann, Rolf; Hilpert, Jan; Spannagl, Michael

2005-04-18

BACKGROUND: Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE). There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. MATERIALS AND METHODS: A 10-year observation period of the Bavarian Thromboembolic Risk (BATER) study, a cohort study of 4337 women (18-55 years), was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993). The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. RESULTS: Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs). A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI) and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation). Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%), moderate risk (21.1%), high risk (6.0%), very high risk of future VTE (0.9%). In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 104 WYs for no, moderate, high, and very high risk, respectively. CONCLUSION: Our prognostic tool - containing clinical information (and if available also genetic data) - seems to be worthwhile testing in medical practice in order to confirm or refute the positive findings of this study. Our cohort study will be continued to include more VTE cases and to increase predictive value of the model.

Genetic diversity analysis in Malaysian giant prawns using expressed sequence tag microsatellite markers for stock improvement program.

PubMed

Atin, K H; Christianus, A; Fatin, N; Lutas, A C; Shabanimofrad, M; Subha, B

2017-08-17

The Malaysian giant prawn is among the most commonly cultured species of the genus Macrobrachium. Stocks of giant prawns from four rivers in Peninsular Malaysia have been used for aquaculture over the past 25 years, which has led to repeated harvesting, restocking, and transplantation between rivers. Consequently, a stock improvement program is now important to avoid the depletion of wild stocks and the loss of genetic diversity. However, the success of such an improvement program depends on our knowledge of the genetic variation of these base populations. The aim of the current study was to estimate genetic variation and differentiation of these riverine sources using novel expressed sequence tag-microsatellite (EST-SSR) markers, which not only are informative on genetic diversity but also provide information on immune and metabolic traits. Our findings indicated that the tested stocks have inbreeding depression due to a significant deficiency in heterozygotes, and F IS was estimated as 0.15538 to 0.31938. An F-statistics analysis suggested that the stocks are composed of one large panmictic population. Among the four locations, stocks from Johor, in the southern region of the peninsular, showed higher allelic and genetic diversity than the other stocks. To overcome inbreeding problems, the Johor population could be used as a base population in a stock improvement program by crossing to the other populations. The study demonstrated that EST-SSR markers can be incorporated in future marker assisted breeding to aid the proper management of the stocks by breeders and stakeholders in Malaysia.

Familial mesial temporal lobe epilepsy (FMTLE) : a clinical and genetic study of 15 Italian families.

PubMed

Striano, Pasquale; Gambardella, Antonio; Coppola, Antonietta; Di Bonaventura, Carlo; Bovo, Giorgia; Diani, Erica; Boaretto, Francesca; Egeo, Gabriella; Ciampa, Clotilde; Labate, Angelo; Testoni, Stefania; Passarelli, Daniela; Manna, Ida; Sferro, Caterina; Aguglia, Umberto; Caranci, Ferdinando; Giallonardo, Anna Teresa; Striano, Salvatore; Nobile, Carlo; Michelucci, Roberto

2008-01-01

Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.

Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: a systematic review.

PubMed

Hoofwijk, D M N; van Reij, R R I; Rutten, B P; Kenis, G; Buhre, W F; Joosten, E A

2016-12-01

Although several patient characteristic, clinical, and psychological risk factors for chronic postsurgical pain (CPSP) have been identified, genetic variants including single nucleotide polymorphisms have also become of interest as potential risk factors for the development of CPSP. The aim of this review is to summarize the current evidence on genetic polymorphisms associated with the prevalence and severity of CPSP in adult patients. A systematic review of the literature was performed, and additional literature was obtained by reference tracking. The primary outcome was CPSP, defined as pain at least 2 months after the surgery. Studies performed exclusively in animals were excluded. Out of the 1001 identified studies, 14 studies were selected for inclusion. These studies described 5269 participants in 17 cohorts. A meta-analysis was not possible because of heterogeneity of data and data analysis. Associations with the prevalence or severity of CPSP were reported for genetic variants in the COMT gene, OPRM1, potassium channel genes, GCH1, CACNG, CHRNA6, P2X7R, cytokine-associated genes, human leucocyte antigens, DRD2, and ATXN1 CONCLUSIONS: Research on the topic of genetic variants associated with CPSP is still in its initial phase. Hypothesis-free, genome-wide association studies on large cohorts are needed in this field. In addition, future studies may also integrate genetic risk factors and patient characteristic, clinical, and psychological predictors for CPSP. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Genetic architecture and temporal patterns of biomass accumulation in spring barley revealed by image analysis.

PubMed

Neumann, Kerstin; Zhao, Yusheng; Chu, Jianting; Keilwagen, Jens; Reif, Jochen C; Kilian, Benjamin; Graner, Andreas

2017-08-10

Genetic mapping of phenotypic traits generally focuses on a single time point, but biomass accumulates continuously during plant development. Resolution of the temporal dynamics that affect biomass recently became feasible using non-destructive imaging. With the aim to identify key genetic factors for vegetative biomass formation from the seedling stage to flowering, we explored growth over time in a diverse collection of two-rowed spring barley accessions. High heritabilities facilitated the temporal analysis of trait relationships and identification of quantitative trait loci (QTL). Biomass QTL tended to persist only a short period during early growth. More persistent QTL were detected around the booting stage. We identified seven major biomass QTL, which together explain 55% of the genetic variance at the seedling stage, and 43% at the booting stage. Three biomass QTL co-located with genes or QTL involved in phenology. The most important locus for biomass was independent from phenology and is located on chromosome 7HL at 141 cM. This locus explained ~20% of the genetic variance, was significant over a long period of time and co-located with HvDIM, a gene involved in brassinosteroid synthesis. Biomass is a dynamic trait and is therefore orchestrated by different QTL during early and late growth stages. Marker-assisted selection for high biomass at booting stage is most effective by also including favorable alleles from seedling biomass QTL. Selection for dynamic QTL may enhance genetic gain for complex traits such as biomass or, in the future, even grain yield.

Prenatal Testing for Adult-Onset Conditions: the Position of the National Society of Genetic Counselors.

PubMed

Hercher, Laura; Uhlmann, Wendy R; Hoffman, Erin P; Gustafson, Shanna; Chen, Kelly M

2016-12-01

Advances in genetic testing and the availability of such testing in pregnancy allows prospective parents to test their future child for adult-onset conditions. This ability raises several complex ethical issues. Prospective parents have reproductive rights to obtain information about their fetus. This information may or may not alter pregnancy management. These rights can be in conflict with the rights of the future individual, who will be denied the right to elect or decline testing. This paper highlights the complexity of these issues, details discussions that went into the National Society of Genetic Counselors (NSGC) Public Policy Task Force's development of the Prenatal testing for Adult-Onset Conditions position statement adopted in November 2014, and cites relevant literature on this topic through December 2015. Issues addressed include parental rights and autonomy, rights of the future child, the right not to know, possible adverse effects on childhood and the need for genetic counseling. This paper will serve as a reference to genetic counselors and healthcare professionals when faced with this situation in clinical practice.

Photosynthetic energy conversion efficiency: setting a baseline for gauging future improvements in important food and biofuel crops.

PubMed

Slattery, Rebecca A; Ort, Donald R

2015-06-01

The conversion efficiency (ε(c)) of absorbed radiation into biomass (MJ of dry matter per MJ of absorbed photosynthetically active radiation) is a component of yield potential that has been estimated at less than half the theoretical maximum. Various strategies have been proposed to improve ε(c), but a statistical analysis to establish baseline ε(c) levels across different crop functional types is lacking. Data from 164 published ε(c) studies conducted in relatively unstressed growth conditions were used to determine the means, greatest contributors to variation, and genetic trends in ε(c )across important food and biofuel crop species. ε(c) was greatest in biofuel crops (0.049-0.066), followed by C4 food crops (0.046-0.049), C3 nonlegumes (0.036-0.041), and finally C3 legumes (0.028-0.035). Despite confining our analysis to relatively unstressed growth conditions, total incident solar radiation and average growing season temperature most often accounted for the largest portion of ε(c) variability. Genetic improvements in ε(c), when present, were less than 0.7% per year, revealing the unrealized potential of improving ε(c) as a promising contributing strategy to meet projected future agricultural demand. © 2015 American Society of Plant Biologists. All Rights Reserved.

Phylogeographic study of Chinese seabuckthorn (Hippophae rhamnoides subsp. sinensis Rousi) reveals two distinct haplotype groups and multiple microrefugia on the Qinghai-Tibet Plateau

PubMed Central

Wang, Hongfang; Liu, Han; Yang, Mingbo; Bao, Lei; Ge, Jianping

2014-01-01

Historical climate change can shape the genetic pattern of a species. Studies on this phenomenon provide great advantage in predicting the response of species to current and future global climate change. Chinese seabuckthorn (Hippophae rhamnoides subsp. sinensis) is one of the most important cultivated plants in Northwest China. However, the subspecies history and the potential genetic resources within the subspecies range remain unclear. In this study, we utilized two intergenic chloroplast regions to characterize the spatial genetic distribution of the species. We found 19 haplotypes in total, 12 of which were unique to the Chinese seabuckthorn. The populations observed on the Qinghai-Tibet Plateau (QTP) consisted of most of the haplotypes, while in the northeast of the range of the subspecies, an area not on the QTP, only four haplotypes were detected. Our study also revealed two distinct haplotype groups of the subspecies with a sharp transition region located in the south of the Zoige Basin. 89.96% of the genetic variation located between the regions. Mismatch analysis indicated old expansions of these two haplotype groups, approximately around the early stage of Pleistocene. Additional morphological proofs from existing studies and habitat differentiation supported a long independent colonization history among the two regions. Potential adaptation probably occurred but needs more genome and morphology data in future. Chinese seabuckthorn have an older population expansion compared with subspecies in Europe. The lack of large land ice sheets and the heterogeneous landscape of the QTP could have provided extensive microrefugia for Chinese seabuckthorn during the glaciation period. Multiple localities sustaining high-frequency private haplotypes support this hypothesis. Our study gives clear insight into the distribution of genetic resources and the evolutionary history of Chinese seabuckthorn. PMID:25540697

Genome-Wide Analysis of Yield in Europe: Allelic Effects Vary with Drought and Heat Scenarios1[OPEN

PubMed Central

Millet, Emilie J.; Welcker, Claude; Kruijer, Willem; Negro, Sandra; Coupel-Ledru, Aude; Laborde, Jacques; Bauland, Cyril; Praud, Sebastien; Presterl, Thomas; Usadel, Björn; Charcosset, Alain; Van Eeuwijk, Fred; Tardieu, François

2016-01-01

Assessing the genetic variability of plant performance under heat and drought scenarios can contribute to reduce the negative effects of climate change. We propose here an approach that consisted of (1) clustering time courses of environmental variables simulated by a crop model in current (35 years × 55 sites) and future conditions into six scenarios of temperature and water deficit as experienced by maize (Zea mays L.) plants; (2) performing 29 field experiments in contrasting conditions across Europe with 244 maize hybrids; (3) assigning individual experiments to scenarios based on environmental conditions as measured in each field experiment; frequencies of temperature scenarios in our experiments corresponded to future heat scenarios (+5°C); (4) analyzing the genetic variation of plant performance for each environmental scenario. Forty-eight quantitative trait loci (QTLs) of yield were identified by association genetics using a multi-environment multi-locus model. Eight and twelve QTLs were associated to tolerances to heat and drought stresses because they were specific to hot and dry scenarios, respectively, with low or even negative allelic effects in favorable scenarios. Twenty-four QTLs improved yield in favorable conditions but showed nonsignificant effects under stress; they were therefore associated with higher sensitivity. Our approach showed a pattern of QTL effects expressed as functions of environmental variables and scenarios, allowing us to suggest hypotheses for mechanisms and candidate genes underlying each QTL. It can be used for assessing the performance of genotypes and the contribution of genomic regions under current and future stress situations and to accelerate breeding for drought-prone environments. PMID:27436830

Comparative genome and methylome analysis reveals restriction/modification system diversity in the gut commensal Bifidobacterium breve

PubMed Central

Bottacini, Francesca; Morrissey, Ruth; Roberts, Richard John; James, Kieran; van Breen, Justin; Egan, Muireann; Lambert, Jolanda; van Limpt, Kees; Knol, Jan; Motherway, Mary O’Connell; van Sinderen, Douwe

2018-01-01

Abstract Bifidobacterium breve represents one of the most abundant bifidobacterial species in the gastro-intestinal tract of breast-fed infants, where their presence is believed to exert beneficial effects. In the present study whole genome sequencing, employing the PacBio Single Molecule, Real-Time (SMRT) sequencing platform, combined with comparative genome analysis allowed the most extensive genetic investigation of this taxon. Our findings demonstrate that genes encoding Restriction/Modification (R/M) systems constitute a substantial part of the B. breve variable gene content (or variome). Using the methylome data generated by SMRT sequencing, combined with targeted Illumina bisulfite sequencing (BS-seq) and comparative genome analysis, we were able to detect methylation recognition motifs and assign these to identified B. breve R/M systems, where in several cases such assignments were confirmed by restriction analysis. Furthermore, we show that R/M systems typically impose a very significant barrier to genetic accessibility of B. breve strains, and that cloning of a methyltransferase-encoding gene may overcome such a barrier, thus allowing future functional investigations of members of this species. PMID:29294107

De novo transcriptomic analysis of cowpea (Vigna unguiculata L. Walp.) for genic SSR marker development.

PubMed

Chen, Honglin; Wang, Lixia; Liu, Xiaoyan; Hu, Liangliang; Wang, Suhua; Cheng, Xuzhen

2017-07-11

Cowpea [Vigna unguiculata (L.) Walp.] is one of the most important legumes in tropical and semi-arid regions. However, there is relatively little genomic information available for genetic research on and breeding of cowpea. The objectives of this study were to analyse the cowpea transcriptome and develop genic molecular markers for future genetic studies of this genus. Approximately 54 million high-quality cDNA sequence reads were obtained from cowpea based on Illumina paired-end sequencing technology and were de novo assembled to generate 47,899 unigenes with an N50 length of 1534 bp. Sequence similarity analysis revealed 36,289 unigenes (75.8%) with significant similarity to known proteins in the non-redundant (Nr) protein database, 23,471 unigenes (49.0%) with BLAST hits in the Swiss-Prot database, and 20,654 unigenes (43.1%) with high similarity in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Further analysis identified 5560 simple sequence repeats (SSRs) as potential genic molecular markers. Validating a random set of 500 SSR markers yielded 54 polymorphic markers among 32 cowpea accessions. This transcriptomic analysis of cowpea provided a valuable set of genomic data for characterizing genes with important agronomic traits in Vigna unguiculata and a new set of genic SSR markers for further genetic studies and breeding in cowpea and related Vigna species.

The ups and downs of coral reef fishes: the genetic characteristics of a formerly severely overfished but currently recovering Nassau grouper fish spawning aggregation

NASA Astrophysics Data System (ADS)

Bernard, A. M.; Feldheim, K. A.; Nemeth, R.; Kadison, E.; Blondeau, J.; Semmens, B. X.; Shivji, M. S.

2016-03-01

The Nassau grouper ( Epinephelus striatus) has sustained large declines across its distribution, including extirpation of many of its fish spawning aggregations (FSAs). Within US Virgin Islands (USVI) waters, Nassau grouper FSAs were overfished until their disappearance in the 1970s and 1980s. In the early 2000s, however, Nassau grouper were found gathering at Grammanik Bank, USVI, a mesophotic coral reef adjacent to one of the extinct aggregation sites, and regulatory protective measures were implemented to protect this fledgling FSA. The population genetic dynamics of this rapid FSA deterioration followed by protection-facilitated, incipient recovery are unknown. We addressed two objectives: (1) we explored which factors (i.e., local vs. external recruitment) might be key in shaping the USVI FSA recovery; and (2) we examined the consequences of severe past overfishing on this FSA's current genetic status. We genotyped individuals (15 microsatellites) from the USVI FSA comprising three successive spawning years (2008-2010), as well as individuals from a much larger, presumably less impacted, Nassau grouper FSA in the Cayman Islands, to assess their comparative population dynamics. No population structure was detected between the USVI and Cayman FSAs ( F ST = -0.0004); however, a temporally waning, genetic bottleneck signal was detected in the USVI FSA. Parentage analysis failed to identify any parent-offspring matches between USVI FSA adults and nearby juveniles, and relatedness analysis showed low levels of genetic relatedness among USVI FSA individuals. Genetic diversity across USVI FSA temporal collections was relatively high, and no marked differences were found between the USVI and Cayman FSAs. These collective results suggest that external recruitment is an important driver of the USVI FSA recovery. Furthermore, despite an apparent genetic bottleneck, the genetic diversity of USVI Nassau grouper has not been severely compromised. Our findings also provide a baseline for future genetic monitoring of the nascent USVI aggregation.

Present spatial diversity patterns of Theobroma cacao L. in the neotropics reflect genetic differentiation in pleistocene refugia followed by human-influenced dispersal.

PubMed

Thomas, Evert; van Zonneveld, Maarten; Loo, Judy; Hodgkin, Toby; Galluzzi, Gea; van Etten, Jacob

2012-01-01

Cacao (Theobroma cacao L.) is indigenous to the Amazon basin, but is generally believed to have been domesticated in Mesoamerica for the production of chocolate beverage. However, cacao's distribution of genetic diversity in South America is also likely to reflect pre-Columbian human influences that were superimposed on natural processes of genetic differentiation. Here we present the results of a spatial analysis of the intra-specific diversity of cacao in Latin America, drawing on a dataset of 939 cacao trees genotypically characterized by means of 96 SSR markers. To assess continental diversity patterns we performed grid-based calculations of allelic richness, Shannon diversity and Nei gene diversity, and distinguished different spatially coherent genetic groups by means of cluster analysis. The highest levels of genetic diversity were observed in the Upper Amazon areas from southern Peru to the Ecuadorian Amazon and the border areas between Colombia, Peru and Brazil. On the assumption that the last glaciation (22,000-13,000 BP) had the greatest pre-human impact on the current distribution and diversity of cacao, we modeled the species' Pleistocene niche suitability and overlaid this with present-day diversity maps. The results suggest that cacao was already widely distributed in the Western Amazon before the onset of glaciation. During glaciations, cacao populations were likely to have been restricted to several refugia where they probably underwent genetic differentiation, resulting in a number of genetic clusters which are representative for, or closest related to, the original wild cacao populations. The analyses also suggested that genetic differentiation and geographical distribution of a number of other clusters seem to have been significantly affected by processes of human management and accompanying genetic bottlenecks. We discuss the implications of these results for future germplasm collection and in situ, on farm and ex situ conservation of cacao.

Present Spatial Diversity Patterns of Theobroma cacao L. in the Neotropics Reflect Genetic Differentiation in Pleistocene Refugia Followed by Human-Influenced Dispersal

PubMed Central

Thomas, Evert; van Zonneveld, Maarten; Loo, Judy; Hodgkin, Toby; Galluzzi, Gea; van Etten, Jacob

2012-01-01

Cacao (Theobroma cacao L.) is indigenous to the Amazon basin, but is generally believed to have been domesticated in Mesoamerica for the production of chocolate beverage. However, cacao’s distribution of genetic diversity in South America is also likely to reflect pre-Columbian human influences that were superimposed on natural processes of genetic differentiation. Here we present the results of a spatial analysis of the intra-specific diversity of cacao in Latin America, drawing on a dataset of 939 cacao trees genotypically characterized by means of 96 SSR markers. To assess continental diversity patterns we performed grid-based calculations of allelic richness, Shannon diversity and Nei gene diversity, and distinguished different spatially coherent genetic groups by means of cluster analysis. The highest levels of genetic diversity were observed in the Upper Amazon areas from southern Peru to the Ecuadorian Amazon and the border areas between Colombia, Peru and Brazil. On the assumption that the last glaciation (22,000–13,000 BP) had the greatest pre-human impact on the current distribution and diversity of cacao, we modeled the species’ Pleistocene niche suitability and overlaid this with present-day diversity maps. The results suggest that cacao was already widely distributed in the Western Amazon before the onset of glaciation. During glaciations, cacao populations were likely to have been restricted to several refugia where they probably underwent genetic differentiation, resulting in a number of genetic clusters which are representative for, or closest related to, the original wild cacao populations. The analyses also suggested that genetic differentiation and geographical distribution of a number of other clusters seem to have been significantly affected by processes of human management and accompanying genetic bottlenecks. We discuss the implications of these results for future germplasm collection and in situ, on farm and ex situ conservation of cacao. PMID:23112832

Statistical power and utility of meta-analysis methods for cross-phenotype genome-wide association studies.

PubMed

Zhu, Zhaozhong; Anttila, Verneri; Smoller, Jordan W; Lee, Phil H

2018-01-01

Advances in recent genome wide association studies (GWAS) suggest that pleiotropic effects on human complex traits are widespread. A number of classic and recent meta-analysis methods have been used to identify genetic loci with pleiotropic effects, but the overall performance of these methods is not well understood. In this work, we use extensive simulations and case studies of GWAS datasets to investigate the power and type-I error rates of ten meta-analysis methods. We specifically focus on three conditions commonly encountered in the studies of multiple traits: (1) extensive heterogeneity of genetic effects; (2) characterization of trait-specific association; and (3) inflated correlation of GWAS due to overlapping samples. Although the statistical power is highly variable under distinct study conditions, we found the superior power of several methods under diverse heterogeneity. In particular, classic fixed-effects model showed surprisingly good performance when a variant is associated with more than a half of study traits. As the number of traits with null effects increases, ASSET performed the best along with competitive specificity and sensitivity. With opposite directional effects, CPASSOC featured the first-rate power. However, caution is advised when using CPASSOC for studying genetically correlated traits with overlapping samples. We conclude with a discussion of unresolved issues and directions for future research.

Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred mice.

PubMed

Jones, Leslie C; McCarthy, Kristin A; Beard, John L; Keen, Carl L; Jones, Byron C

2006-01-01

Copper and zinc are trace nutrients essential for normal brain function, yet an excess of these elements can be toxic. It is important therefore that these metals be closely regulated. We recently conducted a quantitative trait loci (QTL) analysis to identify chromosomal regions in the mouse containing possible regulatory genes. The animals came from 15 strains of the BXD/Ty recombinant inbred (RI) strain panel and the brain regions analyzed were frontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. Several QTL were identified for copper and/or zinc, most notably on chromosomes 1, 8, 16 and 17. Genetic correlational analysis also revealed associations between these metals and dopamine, cocaine responses, saccharine preference, immune response and seizure susceptibility. Notably, the QTL on chromosome 17 is also associated with seizure susceptibility and contains the histocompatibility H2 complex. This work shows that regulation of zinc and copper is under polygenic influence and is intimately related to CNS function. Future work will reveal genes underlying the QTL and how they interact with other genes and the environment. More importantly, revelation of the genetic underpinnings of copper and zinc brain homeostasis will aid our understanding of neurological diseases that are related to copper and zinc imbalance.

A Belated Green Revolution for Cannabis: Virtual Genetic Resources to Fast-Track Cultivar Development

PubMed Central

Welling, Matthew T.; Shapter, Tim; Rose, Terry J.; Liu, Lei; Stanger, Rhia; King, Graham J.

2016-01-01

Cannabis is a predominantly diecious phenotypically diverse domesticated genus with few if any extant natural populations. International narcotics conventions and associated legislation have constrained the establishment, characterization, and use of Cannabis genetic resource collections. This has resulted in the underutilization of genepool variability in cultivar development and has limited the inclusion of secondary genepools associated with genetic improvement strategies of the Green Revolution. The structured screening of ex situ germplasm and the exploitation of locally-adapted intraspecific traits is expected to facilitate the genetic improvement of Cannabis. However, limited attempts have been made to establish the full extent of genetic resources available for pre-breeding. We present a thorough critical review of Cannabis ex situ genetic resources, and discuss recommendations for conservation, pre-breeding characterization, and genetic analysis that will underpin future cultivar development. We consider East Asian germplasm to be a priority for conservation based on the prolonged historical cultivation of Cannabis in this region over a range of latitudes, along with the apparent high levels of genetic diversity and relatively low representation in published genetic resource collections. Seed cryopreservation could improve conservation by reducing hybridization and genetic drift that may occur during Cannabis germplasm regeneration. Given the unique legal status of Cannabis, we propose the establishment of a global virtual core collection based on the collation of consistent and comprehensive provenance meta-data and the adoption of high-throughput DNA sequencing technologies. This would enable representative core collections to be used for systematic phenotyping, and so underpin breeding strategies for the genetic improvement of Cannabis. PMID:27524992

A Belated Green Revolution for Cannabis: Virtual Genetic Resources to Fast-Track Cultivar Development.

PubMed

Welling, Matthew T; Shapter, Tim; Rose, Terry J; Liu, Lei; Stanger, Rhia; King, Graham J

2016-01-01

Cannabis is a predominantly diecious phenotypically diverse domesticated genus with few if any extant natural populations. International narcotics conventions and associated legislation have constrained the establishment, characterization, and use of Cannabis genetic resource collections. This has resulted in the underutilization of genepool variability in cultivar development and has limited the inclusion of secondary genepools associated with genetic improvement strategies of the Green Revolution. The structured screening of ex situ germplasm and the exploitation of locally-adapted intraspecific traits is expected to facilitate the genetic improvement of Cannabis. However, limited attempts have been made to establish the full extent of genetic resources available for pre-breeding. We present a thorough critical review of Cannabis ex situ genetic resources, and discuss recommendations for conservation, pre-breeding characterization, and genetic analysis that will underpin future cultivar development. We consider East Asian germplasm to be a priority for conservation based on the prolonged historical cultivation of Cannabis in this region over a range of latitudes, along with the apparent high levels of genetic diversity and relatively low representation in published genetic resource collections. Seed cryopreservation could improve conservation by reducing hybridization and genetic drift that may occur during Cannabis germplasm regeneration. Given the unique legal status of Cannabis, we propose the establishment of a global virtual core collection based on the collation of consistent and comprehensive provenance meta-data and the adoption of high-throughput DNA sequencing technologies. This would enable representative core collections to be used for systematic phenotyping, and so underpin breeding strategies for the genetic improvement of Cannabis.

Filipino-American Nurses' Knowledge, Perceptions, Beliefs and Practice of Genetics and Genomics.

PubMed

Saligan, Leorey N; Rivera, Reynaldo R

2014-01-01

There is limited information on the knowledge, perceptions, beliefs, and practice, about genetics and genomics among Filipino-American nurses. The National Coalition of Ethnic Minority Organizations (NCEMNA), in which the Philippine Nurses Association of America (PNAA) is a member organization, conducted an online survey to describe the genomic knowledge, perceptions, beliefs, and practice of minority nurses. This study reports on responses from Filipino-American survey participants, which is a subset analysis of the larger NCEMNA survey. The purpose of this study was to explore the knowledge, perceptions, beliefs, practice and genomic education of Filipino-American nurses. An online survey of 112 Filipino-American nurses was conducted to describe the knowledge, perceptions, beliefs, and practice of genetics/genomics. Survey responses were analyzed using descriptive statistics. Most (94%) Filipino-American nurses wanted to learn more about genetics. Although 41% of the respondents indicated good understanding of genetics of common diseases, 60% had not attended any related continuing education courses since RN licensure, and 73% reported unavailability of genetic courses to take. The majority (83%) of PNAA respondents indicated that they would attend genetics/genomics awareness training if it was offered by their national organization during their annual conference, and 86% reported that the national organization should have a visible role in genetics/genomics initiatives in their community. Filipino-American nurses wanted to learn more about genetics and were willing to attend genetics/genomics trainings if offered by PNAA. The study findings can assist PNAA in planning future educational programs that incorporates genetics and genomics information.

Genetic diversity and genetic structure of an endemic Mexican Dusky Rattlesnake (Crotalus triseriatus) in a highly modified agricultural landscape: implications for conservation.

PubMed

Sunny, Armando; Monroy-Vilchis, Octavio; Zarco-González, Martha M; Mendoza-Martínez, Germán David; Martínez-Gómez, Daniel

2015-12-01

It is necessary to determine genetic diversity of fragmented populations in highly modified landscapes to understand how populations respond to land-use change. This information will help guide future conservation and management strategies. We conducted a population genetic study on an endemic Mexican Dusky Rattlesnake (Crotalus triseriatus) in a highly modified landscape near the Toluca metropolitan area, in order to provide crucial information for the conservation of this species. There was medium levels of genetic diversity, with a few alleles and genotypes. We identified three genetically differentiated clusters, likely as a result of different habitat cover type. We also found evidence of an ancestral genetic bottleneck and medium values of effective population size. Inbreeding coefficients were low and there was a moderate gene flow. Our results can be used as a basis for future research and C. triseriatus conservation efforts, particularly considering that the Trans-Mexican Volcanic Belt is heavily impacted by destructive land-use practices.

Genetic information: Special or not? Responses from focus groups with members of a health maintenance organization.

PubMed

Diergaarde, Brenda; Bowen, Deborah J; Ludman, Evette J; Culver, Julie O; Press, Nancy; Burke, Wylie

2007-03-15

Genetic information is used increasingly in health care. Some experts have argued that genetic information is qualitatively different from other medical information and, therefore, raises unique social issues. This view, called "genetic exceptionalism," has importantly influenced recent policy efforts. Others have argued that genetic information is like other medical information and that treating it differently may actually result in unintended disparities. Little is known about how the general public views genetic information. To identify opinions about implications of genetic and other medical information among the general population, we conducted a series of focus groups in Seattle, WA. Participants were women and men between ages 18 and 74, living within 30 miles of Seattle and members of the Group Health Cooperative. A structured discussion guide was used to ensure coverage of all predetermined topics. Sessions lasted approximately 2 hr; were audio taped and transcribed. The transcripts formed the basis of the current analysis. Key findings included the theme that genetic information was much like other medical information and that all sensitive medical information should be well protected. Personal choice (i.e., the right to choose whether to know health risk information and to control who else knows) was reported to be of crucial importance. Participants had an understanding of the tensions involved in protecting privacy versus sharing medical information to help another person. These data may guide future research and policy concerning the use and protection of medical information, including genetic information. (c) 2007 Wiley-Liss, Inc.

Fine-Scale Genetic Response to Landscape Change in a Gliding Mammal

PubMed Central

Goldingay, Ross L.; Harrisson, Katherine A.; Taylor, Andrea C.; Ball, Tina M.; Sharpe, David J.; Taylor, Brendan D.

2013-01-01

Understanding how populations respond to habitat loss is central to conserving biodiversity. Population genetic approaches enable the identification of the symptoms of population disruption in advance of population collapse. However, the spatio-temporal scales at which population disruption occurs are still too poorly known to effectively conserve biodiversity in the face of human-induced landscape change. We employed microsatellite analysis to examine genetic structure and diversity over small spatial (mostly 1-50 km) and temporal scales (20-50 years) in the squirrel glider (Petaurus norfolcensis), a gliding mammal that is commonly subjected to a loss of habitat connectivity. We identified genetically differentiated local populations over distances as little as 3 km and within 30 years of landscape change. Genetically isolated local populations experienced the loss of genetic diversity, and significantly increased mean relatedness, which suggests increased inbreeding. Where tree cover remained, genetic differentiation was less evident. This pattern was repeated in two landscapes located 750 km apart. These results lend support to other recent studies that suggest the loss of habitat connectivity can produce fine-scale population genetic change in a range of taxa. This gives rise to the prediction that many other vertebrates will experience similar genetic changes. Our results suggest the future collapse of local populations of this gliding mammal is likely unless habitat connectivity is maintained or restored. Landscape management must occur on a fine-scale to avert the erosion of biodiversity. PMID:24386079

How lay people respond to messages about genetics, health, and race.

PubMed

Condit, C; Bates, B

2005-08-01

There is a growing movement in medical genetics to develop, implement, and promote a model of race-based medicine. Although race-based medicine may become a widely disseminated standard of care, messages that advocate race-based selection for diagnosing, screening and prescribing drugs may exacerbate health disparities. These messages are present in clinical genetic counseling sessions, mass media, and everyday talk. Messages promoting linkages among genes, race, and health and messages emphasizing genetic causation may promote both general racism and genetically based racism. This mini-review examines research in three areas: studies that address the effects of these messages about genetics on levels of genetic determinism and genetic discrimination; studies that address the effects of these messages on attitudes about race; and, studies of the impacts of race-specific genetic messages on recipients. Following an integration of this research, this mini-review suggests that the current literature appears fragmented because of methodological and measurement issues and offers strategies for future research. Finally, the authors offer a path model to help organize future research examining the effects of messages about genetics on socioculturally based racism, genetically based racism, and unaccounted for racism. Research in this area is needed to understand and mitigate the negative attitudinal effects of messages that link genes, race, and health and/or emphasize genetic causation.

Population genetics studies of the walrus (Odobenus rosmarus): A summary and interpretation of results and research needs

USGS Publications Warehouse

Scribner, Kim T.; Hills, Susan; Fain, Steven R.; Cronin, Matthew A.; Dizon, Andrew E.; Chivers, Susan J.; Perrin, William F.

1997-01-01

A summary of population genetics data is presented for the walrus (Odobenus rosmarus). Current information on the ecology and behavior of the species is highlighted to aid in the interpretation of genetics results and to suggest future areas of research. Walruses are discontinuously distributed across the Arctic and are currently subdivided into six regional populations on the basis of historical distribution and morphology. Few population genetics studies have been conducted on the walrus. Only three of the six trigonal populations have been surveyed with biochemical or molecular techniques. Analysis of mitochondrial DNA (mtDNA) variation among walruses from the northern Pacific (Chukchi Sea) and western Atlantic (Greenland) regions revealed 13 haplotypes; 6 were found only in Pacific walruses while 7 were unique to the Atlantic subspecies. Estimates of sequence divergence between Atlantic and Pacific haplotypes were 1.0%-1.6%. No evidence of microgeographic structuring within the northern Pacific or western Atlantic regional populations was found on the basis of mtDNA haplotype frequency distributions or multilocus minisatellite band sharing. Minisatellite analysis of adult-juvenile and adult-adult pairs suggests that assemblages of walruses on individual ice floes are made up at least in part by groups of related individuals from more than one generation. Furthermore, high mtDNA haplotype diversities and low minisatellite band-sharing values suggest that both the northern Pacific and western Atlantic walruses have retained a high degree of genetic variability.

Rescuing valuable genomes by animal cloning: a case for natural disease resistance in cattle.

PubMed

Westhusin, M E; Shin, T; Templeton, J W; Burghardt, R C; Adams, L G

2007-01-01

Tissue banking and animal cloning represent a powerful tool for conserving and regenerating valuable animal genomes. Here we report an example involving cattle and the rescue of a genome affording natural disease resistance. During the course of a 2-decade study involving the phenotypic and genotypic analysis for the functional and genetic basis of natural disease resistance against bovine brucellosis, a foundation sire was identified and confirmed to be genetically resistant to Brucella abortus. This unique animal was utilized extensively in numerous animal breeding studies to further characterize the genetic basis for natural disease resistance. The bull died in 1996 of natural causes, and no semen was available for AI, resulting in the loss of this valuable genome. Fibroblast cell lines had been established in 1985, cryopreserved, and stored in liquid nitrogen for future genetic analysis. Therefore, we decided to utilize these cells for somatic cell nuclear transfer to attempt the production of a cloned bull and salvage this valuable genotype. Embryos were produced by somatic cell nuclear transfer and transferred to 20 recipient cows, 10 of which became pregnant as determined by ultrasound at d 40 of gestation. One calf survived to term. At present, the cloned bull is 4.5 yr old and appears completely normal as determined by physical examination and blood chemistry. Furthermore, in vitro assays performed to date indicate this bull is naturally resistant to B. abortus, Mycobacterium bovis, and Salmonella typhimurium, as was the original genetic donor.

A possible genetic association with chronic fatigue in primary Sjögren's syndrome: a candidate gene study.

PubMed

Norheim, Katrine Brække; Le Hellard, Stephanie; Nordmark, Gunnel; Harboe, Erna; Gøransson, Lasse; Brun, Johan G; Wahren-Herlenius, Marie; Jonsson, Roland; Omdal, Roald

2014-02-01

Fatigue is prevalent and disabling in primary Sjögren's syndrome (pSS). Results from studies in chronic fatigue syndrome (CFS) indicate that genetic variation may influence fatigue. The aim of this study was to investigate single nucleotide polymorphism (SNP) variations in pSS patients with high and low fatigue. A panel of 85 SNPs in 12 genes was selected based on previous studies in CFS. A total of 207 pSS patients and 376 healthy controls were genotyped. One-hundred and ninety-three patients and 70 SNPs in 11 genes were available for analysis after quality control. Patients were dichotomized based on fatigue visual analogue scale (VAS) scores, with VAS <50 denominated "low fatigue" (n = 53) and VAS ≥50 denominated "high fatigue" (n = 140). We detected signals of association with pSS for one SNP in SLC25A40 (unadjusted p = 0.007) and two SNPs in PKN1 (both p = 0.03) in our pSS case versus control analysis. The association with SLC25A40 was stronger when only pSS high fatigue patients were analysed versus controls (p = 0.002). One SNP in PKN1 displayed an association in the case-only analysis of pSS high fatigue versus pSS low fatigue (p = 0.005). This candidate gene study in pSS did reveal a trend for associations between genetic variation in candidate genes and fatigue. The results will need to be replicated. More research on genetic associations with fatigue is warranted, and future trials should include larger cohorts and multicentre collaborations with sharing of genetic material to increase the statistical power.

Recommendations for the Integration of Genomics into Clinical Practice

PubMed Central

Bowdin, Sarah; Gilbert, Adel; Bedoukian, Emma; Carew, Christopher; Adam, Margaret P; Belmont, John; Bernhardt, Barbara; Biesecker, Leslie; Bjornsson, Hans T.; Blitzer, Miriam; D’Alessandro, Lisa C. A.; Deardorff, Matthew A.; Demmer, Laurie; Elliott, Alison; Feldman, Gerald L.; Glass, Ian A.; Herman, Gail; Hindorff, Lucia; Hisama, Fuki; Hudgins, Louanne; Innes, A. Micheil; Jackson, Laird; Jarvik, Gail; Kim, Raymond; Korf, Bruce; Ledbetter, David H.; Li, Mindy; Liston, Eriskay; Marshall, Christian; Medne, Livija; Meyn, M. Stephen; Monfared, Nasim; Morton, Cynthia; Mulvihill, John J.; Plon, Sharon E.; Rehm, Heidi; Roberts, Amy; Shuman, Cheryl; Spinner, Nancy B.; Stavropoulos, D. James; Valverde, Kathleen; Waggoner, Darrel J.; Wilkens, Alisha; Cohn, Ronald D.; Krantz, Ian D.

2017-01-01

The introduction of diagnostic clinical genome and exome sequencing (CGES) is changing the scope of practice for clinical geneticists. Many large institutions are making a significant investment in infrastructure and technology, allowing clinicians to access CGES especially as health care coverage begins to extend to clinically indicated genomic sequencing-based tests. Translating and realizing the comprehensive clinical benefits of genomic medicine remains a key challenge for the current and future care of patients. With the increasing application of CGES, it is necessary for geneticists and other health care providers to understand its benefits and limitations, in order to interpret the clinical relevance of genomic variants identified in the context of health and disease. Establishing new, collaborative working relationships with specialists across diverse disciplines (e.g., clinicians, laboratorians, bioinformaticians) will undoubtedly be key attributes of the future practice of clinical genetics and may serve as an example for other specialties in medicine. These new skills and relationships will also inform the development of the future model of clinical genetics training curricula. To address the evolving role of the clinical geneticist in the rapidly changing climate of genomic medicine, two Clinical Genetics Think Tank meetings were held which brought together physicians, laboratorians, scientists, genetic counselors, trainees and patients with experience in clinical genetics, genetic diagnostics, and genetics education. This paper provides recommendations that will guide the integration of genomics into clinical practice. PMID:27171546

Genetic diversity trend in Indian rice varieties: an analysis using SSR markers.

PubMed

Singh, Nivedita; Choudhury, Debjani Roy; Tiwari, Gunjan; Singh, Amit Kumar; Kumar, Sundeep; Srinivasan, Kalyani; Tyagi, R K; Sharma, A D; Singh, N K; Singh, Rakesh

2016-09-05

The knowledge of the extent and pattern of diversity in the crop species is a prerequisite for any crop improvement as it helps breeders in deciding suitable breeding strategies for their future improvement. Rice is the main staple crop in India with the large number of varieties released every year. Studies based on the small set of rice genotypes have reported a loss in genetic diversity especially after green revolution. However, a detailed study of the trend of diversity in Indian rice varieties is lacking. SSR markers have proven to be a marker of choice for studying the genetic diversity. Therefore, the present study was undertaken with the aim to characterize and assess trends of genetic diversity in a large set of Indian rice varieties (released between 1940-2013), conserved in the National Gene Bank of India using SSR markers. A set of 729 Indian rice varieties were genotyped using 36 HvSSR markers to assess the genetic diversity and genetic relationship. A total of 112 alleles was amplified with an average of 3.11 alleles per locus with mean Polymorphic Information Content (PIC) value of 0.29. Cluster analysis grouped these varieties into two clusters whereas the model based population structure divided them into three populations. AMOVA study based on hierarchical cluster and model based approach showed 3 % and 11 % variation between the populations, respectively. Decadal analysis for gene diversity and PIC showed increasing trend from 1940 to 2005, thereafter values for both the parameters showed decreasing trend between years 2006-2013. In contrast to this, allele number demonstrated increasing trend in these varieties released and notified between1940 to 1985, it remained nearly constant during 1986 to 2005 and again showed an increasing trend. Our results demonstrated that the Indian rice varieties harbors huge amount of genetic diversity. However, the trait based improvement program in the last decades forced breeders to rely on few parents, which resulted in loss of gene diversity during 2006 to 2013. The present study indicates the need for broadening the genetic base of Indian rice varieties through the use of diverse parents in the current breeding program.

Selection for sow longevity.

PubMed

Serenius, T; Stalder, K J

2006-04-01

Sow longevity plays an important role in economically efficient piglet production because sow longevity is related to the number of piglets produced during its productive lifetime; however, selection for sow longevity is not commonly practiced in any pig breeding program. There is relatively little scientific literature concerning the genetic parameters (genetic variation and genetic correlations) or methods available for breeding value estimation for effective selection for sow longevity. This paper summarizes the current knowledge about the genetics of sow longevity and discusses the available breeding value estimation methods for sow longevity traits. The studies in the literature clearly indicate that sow longevity is a complex trait, and even the definition of sow longevity is variable depending on the researcher and research objective. In general, the measures and analyses of sow longevity can be divided into 1) continuous traits (e.g., productive lifetime) analyzed with proportional hazard models; and 2) more simple binary traits such as stayability until some predetermined fixed parity. Most studies have concluded that sufficient genetic variation exists for effective selection on sow longevity, and heritability estimates have ranged between 0.02 and 0.25. Moreover, sow longevity has shown to be genetically associated with prolificacy and leg conformation traits. Variable results from previous research have led to a lack of consensus among swine breeders concerning the valid methodology of estimating breeding values for longevity traits. One can not deny the superiority of survival analysis in the modeling approach of longevity data; however, multiple-trait analyses are not possible using currently available survival analysis software. Less sophisticated approaches have the advantage of evaluating multiple traits simultaneously, and thus, can use the genetic associations between sow longevity and other traits. Additional research is needed to identify the most efficient selection methods for sow longevity. Future research needs to concentrate on multiple trait analysis of sow longevity traits. Moreover, because longevity is a fitness trait, the nonadditive genetic effects (e.g., dominance) may play important role in the inheritance of sow longevity. Currently, not a single estimate for dominance variance of sow longevity could be identified from the scientific literature.

Phenome-Wide Association Studies as a Tool to Advance Precision Medicine

PubMed Central

Denny, Joshua C.; Bastarache, Lisa; Roden, Dan M.

2017-01-01

Beginning in the early 2000s, the accumulation of biospecimens linked to electronic health records (EHRs) made possible genome-phenome studies (i.e., comparative analyses of genetic variants and phenotypes) using only data collected as a by-product of typical health care. In addition to disease and trait genetics, EHRs proved a valuable resource for analyzing pharmacogenetic traits and developing reverse genetics approaches such as phenome-wide association studies (PheWASs). PheWASs are designed to survey which of many phenotypes may be associated with a given genetic variant. PheWAS methods have been validated through replication of hundreds of known genotype-phenotype associations, and their use has differentiated between true pleiotropy and clinical comorbidity, added context to genetic discoveries, and helped define disease subtypes, and may also help repurpose medications. PheWAS methods have also proven to be useful with research-collected data. Future efforts that integrate broad, robust collection of phenotype data (e.g., EHR data) with purpose-collected research data in combination with a greater understanding of EHR data will create a rich resource for increasingly more efficient and detailed genome-phenome analysis to usher in new discoveries in precision medicine. PMID:27147087

Clinical and genetic analyses reveal novel pathogenic ABCA4 mutations in Stargardt disease families

PubMed Central

Lin, Bing; Cai, Xue-Bi; Zheng, Zhi-Li; Huang, Xiu-Feng; Liu, Xiao-Ling; Qu, Jia; Jin, Zi-Bing

2016-01-01

Stargardt disease (STGD1) is a juvenile macular degeneration predominantly inherited in an autosomal recessive pattern, characterized by decreased central vision in the first 2 decades of life. The condition has a genetic basis due to mutation in the ABCA4 gene, and arises from the deposition of lipofuscin-like substance in the retinal pigmented epithelium (RPE) with secondary photoreceptor cell death. In this study, we describe the clinical and genetic features of Stargardt patients from four unrelated Chinese cohorts. The targeted exome sequencing (TES) was carried out in four clinically confirmed patients and their family members using a gene panel comprising 164 known causative inherited retinal dystrophy (IRD) genes. Genetic analysis revealed eight ABCA4 mutations in all of the four pedigrees, including six mutations in coding exons and two mutations in adjacent intronic areas. All the affected individuals showed typical manifestations consistent with the disease phenotype. We disclose two novel ABCA4 mutations in Chinese patients with STGD disease, which will expand the existing spectrum of disease-causing variants and will further aid in the future mutation screening and genetic counseling, as well as in the understanding of phenotypic and genotypic correlations. PMID:27739528

RAD SNP markers as a tool for conservation of dolphinfish Coryphaena hippurus in the Mediterranean Sea: Identification of subtle genetic structure and assessment of populations sex-ratios.

PubMed

Maroso, Francesco; Franch, Rafaella; Dalla Rovere, Giulia; Arculeo, Marco; Bargelloni, Luca

2016-08-01

Dolphinfish is an important fish species for both commercial and sport fishing, but so far limited information is available on genetic variability and pattern of differentiation of dolphinfish populations in the Mediterranean basin. Recently developed techniques allow genome-wide identification of genetic markers for better understanding of population structure in species with limited genome information. Using restriction-site associated DNA analysis we successfully genotyped 140 individuals of dolphinfish from eight locations in the Mediterranean Sea at 3324 SNP loci. We identified 311 sex-related loci that were used to assess sex-ratio in dolphinfish populations. In addition, we identified a weak signature of genetic differentiation of the population closer to Gibraltar Strait in comparison to other Mediterranean populations, which might be related to introgression of individuals from Atlantic. No further genetic differentiation could be detected in the other populations sampled, as expected considering the known highly mobility of the species. The results obtained improve our knowledge of the species and can help managing dolphinfish stock in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Next-generation mammalian genetics toward organism-level systems biology.

PubMed

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.

PubMed

Revelas, Mary; Thalamuthu, Anbupalam; Oldmeadow, Christopher; Evans, Tiffany-Jane; Armstrong, Nicola J; Kwok, John B; Brodaty, Henry; Schofield, Peter R; Scott, Rodney J; Sachdev, Perminder S; Attia, John R; Mather, Karen A

2018-06-08

Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts. Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males). In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls. Copyright © 2018. Published by Elsevier B.V.

Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics

PubMed Central

Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

2015-01-01

Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains. PMID:26691589

Sex differences in genetic and environmental influences on percent body fatness and physical activity.

PubMed

White, Erin; Slane, Jennifer D; Klump, Kelly L; Burt, S Alexandra; Pivarnik, Jim

2014-08-01

Knowing the extent to which genetic and environmental factors influence percent body fatness (%Fat) and physical activity (PA) would be beneficial, since both are tightly correlated with future health outcomes. Thus, the purpose was to evaluate sex differences in genetic and environmental influences on %Fat and physical activity behavior in male and female adolescent twins. Subjects were adolescent (age range 8.3 to 16.6 yr) twins. %Fat (n = 518 twins) was assessed by bioelectrical impedance analysis (BIA) and PA (n = 296 twins) was measured using 3-Day PA Recall. Each activity was converted to total MET-minutes. Univariate twin models were used to examine sex differences in genetic and environmental factors influencing %Fat and PA. %Fat was influenced by genetic effects in both boys and girls (88% and 90%, respectively), with slightly higher heritability estimates for girls. PA was influenced solely by environmental effects for both sexes with higher shared environmental influences in boys (66%) and higher nonshared effects in girls (67%). When developing interventions to increase PA in adolescents, it is important to consider the environment in which it takes place as it is the primary contributor to PA levels.

A collection of popcorn as a reservoir of genes for the generation of lineages.

PubMed

de Carvalho, Misael Severino Nunes; Mangolin, Claudete Aparecida; Scapim, Carlos Alberto; da Silva, Teresa Aparecida; Machado, Maria de Fátima Pires da Silva

2013-03-01

In the present study, we analyze the genetic structure and diversity among accessions of popcorn obtained from the CIMMYT International Maize and Wheat Improvement Center that represent the diversity available for current use by breeding programs. The main objectives were to identify SSR loci that were the best indicators of genetic diversity, to measure the genetic diversity within popcorn genotypes, and to analyze the genetic structure of the promising populations destined for use in breeding programs. The mean gene diversity of all SSR loci was 0.6352. An extremely high population differentiation level was detected (F(st) = 0.3152) with F(st) for each locus ranging from 0.1125 (Umc1229) to 0.4870 (Umc1755). Analyzing the genetic structure of eight popcorn accessions was especially important for identifying both SSR loci with high levels of heterozygosity and genotypes showing high heterozygosity (BOYA462 and ARZM13 050). This analysis should be the medium and long-term selection goal for the generation of inbred lines and the future production of new cultivars. Plant accessions ARZM05 083, ARZM13 050, and URUG298 may also be useful varieties that exhibit important agronomic characteristics that can be used through crosses to broaden the genetic basis of popcorn.

Loss of Genetic Diversity and Increased Subdivision in an Endemic Alpine Stonefly Threatened by Climate Change

PubMed Central

Jordan, Steve; Giersch, J. Joseph; Muhlfeld, Clint C.; Hotaling, Scott; Fanning, Liz; Tappenbeck, Tyler H.; Luikart, Gordon

2016-01-01

Much remains unknown about the genetic status and population connectivity of high-elevation and high-latitude freshwater invertebrates, which often persist near snow and ice masses that are disappearing due to climate change. Here we report on the conservation genetics of the meltwater stonefly Lednia tumana (Ricker) of Montana, USA, a cold-water obligate species. We sequenced 1530 bp of mtDNA from 116 L. tumana individuals representing “historic” (>10 yr old) and 2010 populations. The dominant haplotype was common in both time periods, while the second-most-common haplotype was found only in historic samples, having been lost in the interim. The 2010 populations also showed reduced gene and nucleotide diversity and increased genetic isolation. We found lower genetic diversity in L. tumana compared to two other North American stonefly species, Amphinemura linda (Ricker) and Pteronarcys californica Newport. Our results imply small effective sizes, increased fragmentation, limited gene flow, and loss of genetic variation among contemporary L. tumana populations, which can lead to reduced adaptive capacity and increased extinction risk. This study reinforces concerns that ongoing glacier loss threatens the persistence of L. tumana, and provides baseline data and analysis of how future environmental change could impact populations of similar organisms. PMID:27348125

Loss of genetic diversity and increased subdivision in an endemic Alpine Stonefly threatened by climate change

USGS Publications Warehouse

Jordan, Steve; Giersch, J. Joseph; Muhlfeld, Clint C.; Hotalling, Scott; Fanning, Liz; Tappenbeck, Tyler H.; Luikart, Gordon

2016-01-01

Much remains unknown about the genetic status and population connectivity of high-elevation and high-latitude freshwater invertebrates, which often persist near snow and ice masses that are disappearing due to climate change. Here we report on the conservation genetics of the meltwater stonefly Lednia tumana (Ricker) of Montana, USA, a cold-water obligate species. We sequenced 1530 bp of mtDNA from 116 L. tumana individuals representing “historic” (>10 yr old) and 2010 populations. The dominant haplotype was common in both time periods, while the second-most-common haplotype was found only in historic samples, having been lost in the interim. The 2010 populations also showed reduced gene and nucleotide diversity and increased genetic isolation. We found lower genetic diversity in L. tumana compared to two other North American stonefly species, Amphinemura linda (Ricker) and Pteronarcys californica Newport. Our results imply small effective sizes, increased fragmentation, limited gene flow, and loss of genetic variation among contemporary L. tumana populations, which can lead to reduced adaptive capacity and increased extinction risk. This study reinforces concerns that ongoing glacier loss threatens the persistence of L. tumana, and provides baseline data and analysis of how future environmental change could impact populations of similar organisms.

Approach to Investigating Congenital Skeletal Abnormalities in Livestock.

PubMed

Dittmer, K E; Thompson, K G

2015-09-01

Congenital skeletal abnormalities may be genetic, teratogenic, or nutritional in origin; distinguishing among these different causes is essential in the management of the disease but may be challenging. In some cases, teratogenic or nutritional causes of skeletal abnormalities may appear very similar to genetic causes. For example, chondrodysplasia associated with intrauterine zinc or manganese deficiency and mild forms of hereditary chondrodysplasia have very similar clinical features and histologic lesions. Therefore, historical data are essential in any attempt to distinguish genetic and acquired causes of skeletal lesions; as many animals as possible should be examined; and samples should be collected for future analysis, such as genetic testing. Acquired causes of defects often show substantial variation in presentation and may improve with time, while genetic causes frequently have a consistent presentation. If a disease is determined to be of genetic origin, a number of approaches may be used to detect mutations, each with advantages and disadvantages. These approaches include sequencing candidate genes, single-nucleotide polymorphism array with genomewide association studies, and exome or whole genome sequencing. Despite advances in technology and increased cost-effectiveness of these techniques, a good clinical history and description of the pathology and a reliable diagnosis are still key components of any investigation. © The Author(s) 2015.

Resolving the Etiology of Atopic Disorders by Genetic Analysis of Racial Ancestry

PubMed Central

Gupta, Jayanta; Johansson, Elisabet; Bernstein, Jonathan A.; Chakraborty, Ranajit; Khurana Hershey, Gurjit K.; Rothenberg, Marc E.; Mersha, Tesfaye B.

2016-01-01

Atopic dermatitis (AD), food allergy (FA), allergic rhinitis (AR) and asthma are common atopic disorders of complex etiology. The frequently observed “atopic march” from early AD to asthma and/or AR later in life as well as the extensive comorbidity of atopic disorders, suggests common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a higher prevalence in African-Americans when compared to European-Americans. Whether this disparity stems from true genetic or race-specific environmental risk factors or both is unknown. Thus far, the majority of the genetic studies on atopic diseases have utilized populations of European ancestry, limiting their generalizability. Large cohort initiatives and new analytic methods such as admixture mapping are currently being employed to address this knowledge gap. Here we discuss the unique and shared genetic risk factors for atopic disorders in the context of ancestry variations, and the promise of high-throughput “-omics” based systems biology approach in providing greater insight to deconstruct into their genetic and non-genetic etiologies. Future research will also focus on deep phenotyping and genotyping of diverse racial ancestry, gene-environment, and gene-gene interactions. PMID:27297995

Heritability of Problem Drinking and the Genetic Overlap with Personality in a General Population Sample

PubMed Central

de Moor, Marleen H. M.; Vink, Jacqueline M.; van Beek, Jenny H. D. A.; Geels, Lot M.; Bartels, Meike; de Geus, Eco J. C.; Willemsen, Gonneke; Boomsma, Dorret I.

2011-01-01

This study examined the heritability of problem drinking and investigated the phenotypic and genetic relationships between problem drinking and personality. In a sample of 5,870 twins and siblings and 4,420 additional family members from the Netherlands Twin Register. Data on problem drinking (assessed with the AUDIT and CAGE; 12 items) and personality [NEO Five-Factor Inventory (FFI); 60 items] were collected in 2009/2010 by surveys. Confirmatory factor analysis on the AUDIT and CAGE items showed that the items clustered on two separate but highly correlated (r = 0.74) underlying factors. A higher-order factor was extracted that reflected those aspects of problem drinking that are common to the AUDIT and CAGE, which showed a heritability of 40%. The correlations between problem drinking and the five dimensions of personality were small but significant, ranging from 0.06 for Extraversion to −0.12 for Conscientiousness. All personality dimensions (with broad-sense heritabilities between 32 and 55%, and some evidence for non-additive genetic influences) were genetically correlated with problem drinking. The genetic correlations were small to modest (between |0.12| and |0.41|). Future studies with longitudinal data and DNA polymorphisms are needed to determine the biological mechanisms that underlie the genetic link between problem drinking and personality. PMID:22303371

[Preimplantation genetic diagnosis in order to choose a saviour sibling].

PubMed

Shenfield, F

2005-10-01

Preimplantation genetic diagnosis with HLA matching in order to bring about the birth of a saviour sibling is not mere instrumentalisation of the future child, as long as the post natal test is used and the future child will be looked after with the same love and care as if he/she had not been selected as well for the purpose.

Genetic analysis of a red tilapia (Oreochromis spp.) population undergoing three generations of selection for increased body weight at harvest.

PubMed

Hamzah, Azhar; Thoa, Ngo Phu; Nguyen, Nguyen Hong

2017-11-01

Quantitative genetic analysis was performed on 10,919 data records collected over three generations from the selection programme for increased body weight at harvest in red tilapia (Oreochromis spp.). They were offspring of 224 sires and 226 dams (50 sires and 60 dams per generation, on average). Linear mixed models were used to analyse body traits (weight, length, width and depth), whereas threshold generalised models assuming probit distribution were employed to examine genetic inheritance of survival rate, sexual maturity and body colour. The estimates of heritability for traits studied (body weight, standard length, body width, body depth, body colour, early sexual maturation and survival) across statistical models were moderate to high (0.13-0.45). Genetic correlations among body traits and survival were high and positive (0.68-0.96). Body length and width exhibited negative genetic correlations with body colour (- 0.47 to - 0.25). Sexual maturity was genetically correlated positively with measurements of body traits (weight and length). Direct and correlated genetic responses to selection were measured as estimated breeding values in each generation and expressed in genetic standard deviation units (σ G ). The cumulative improvement achieved for harvest body weight was 1.72 σ G after three generations or 12.5% per generation when the gain was expressed as a percentage of the base population. Selection for improved body weight also resulted in correlated increase in other body traits (length, width and depth) and survival rate (ranging from 0.25 to 0.81 genetic standard deviation units). Avoidance of black spot parent matings also improved the overall red colour of the selected population. It is concluded that the selective breeding programme for red tilapia has succeeded in achieving significant genetic improvement for a range of commercially important traits in this species, and the large genetic variation in body colour and survival also shows that there are prospects for future improvement of these traits in this population of red tilapia.

Raising Awareness of Pre-Symptomatic Genetic Testing

ERIC Educational Resources Information Center

Boerwinkel, Dirk Jan; Knippels, Marie-Christine; Waarlo, Arend Jan

2011-01-01

Presymptomatic genetic testing generates socioscientific issues in which decision making is complicated by several complexity factors. These factors include weighing of advantages and disadvantages, different interests of stakeholders, uncertainty of genetic information and conflicting values. Education preparing students for future decision…

The Contribution of Developmental Behavioural Genetics towards a Multifactorial Understanding of Reading Disabilities.

ERIC Educational Resources Information Center

Crawford, Shawn; And Others

1990-01-01

The utility of developmental behavioral genetics in the study of reading disability is considered. Research which has found reading disability to be partly genetically determined is cited, and future research applications are discussed. (Author/JDD)

Human germline genetic modification: scientific and bioethical perspectives.

PubMed

Smith, Kevin R; Chan, Sarah; Harris, John

2012-10-01

The latest mammalian genetic modification technology offers efficient and reliable targeting of genomic sequences, in the guise of designer genetic recombination tools. These and other improvements in genetic engineering technology suggest that human germline genetic modification (HGGM) will become a safe and effective prospect in the relatively near future. Several substantive ethical objections have been raised against HGGM including claims of unacceptably high levels of risk, damage to the status of future persons, and violations of justice and autonomy. This paper critically reviews the latest GM science and discusses the key ethical objections to HGGM. We conclude that major benefits are likely to accrue through the use of safe and effective HGGM and that it would thus be unethical to take a precautionary stance against HGGM. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Family Communication in Inherited Cardiovascular Conditions in Ireland.

PubMed

Whyte, Sinead; Green, Andrew; McAllister, Marion; Shipman, Hannah

2016-12-01

Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media.

Parents' attitudes toward genetic research in autism spectrum disorder.

PubMed

Johannessen, Jarle; Nærland, Terje; Bloss, Cinnamon; Rietschel, Marcella; Strohmaier, Jana; Gjevik, Elen; Heiberg, Arvid; Djurovic, Srdjan; Andreassen, Ole A

2016-04-01

Genetic research in autism spectrum disorder (ASD) is mainly performed in minors who are legally unable to provide consent. Thus, knowledge of the attitudes, fears, and expectations toward genetic research of the parents is important. Knowledge of the attitudes toward genetic research will improve cooperation between researchers and participants, and help establish confidence in ASD genetic research. The present study aimed to assess these attitudes. Questionnaire-based assessments of attitudes toward genetic research and toward procedures in genetic research of n=1455 parents of individuals with ASD were performed. The main motivation for participation in genetic research is to gain more knowledge of the causes and disease mechanisms of ASD (83.6%), and to contribute toward development of improved treatment in the future (63.7%). The parents also had a positive attitude towards storing genetic information (54.3%) and they requested confidentiality of data (82.9%) and expressed a need to be informed about the purpose (89%) and progress of the research (83.7%). We found a slightly more positive attitude to participation in genetic research among older parents (P=0.015), among fathers compared with mothers (P=0.01), among parents of girls compared with boys (P=0.03), and infantile autism compared with Asperger syndrome (P=0.002). However, linear regression analysis showed that parent and child characteristics seem to have too small an influence on attitudes toward genetic research to be of any relevance (R(2)=0.002-0.02). Parents of children with ASD have, in general, a very positive attitude toward genetic research. Data confidentiality is important, and they express a need for information on the purpose and progress of the research.

Pearls and pitfalls in genetic studies of migraine.

PubMed

Eising, Else; de Vries, Boukje; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M

2013-06-01

Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

Design and analysis issues in gene and environment studies

PubMed Central

2012-01-01

Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the “-omics” era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed. PMID:23253229

Design and analysis issues in gene and environment studies.

PubMed

Liu, Chen-yu; Maity, Arnab; Lin, Xihong; Wright, Robert O; Christiani, David C

2012-12-19

Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the "-omics" era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed.

Sporadic and hereditary amyotrophic lateral sclerosis (ALS).

PubMed

Ajroud-Driss, Senda; Siddique, Teepu

2015-04-01

Genetic discoveries in ALS have a significant impact on deciphering molecular mechanisms of motor neuron degeneration. The identification of SOD1 as the first genetic cause of ALS led to the engineering of the SOD1 mouse, the backbone of ALS research, and set the stage for future genetic breakthroughs. In addition, careful analysis of ALS pathology added valuable pieces to the ALS puzzle. From this joint effort, major pathogenic pathways emerged. Whereas the study of TDP43, FUS and C9ORF72 pointed to the possible involvement of RNA biology in motor neuron survival, recent work on P62 and UBQLN2 refocused research on protein degradation pathways. Despite all these efforts, the etiology of most cases of sporadic ALS remains elusive. Newly acquired genomic tools now allow the identification of genetic and epigenetic factors that can either increase ALS risk or modulate disease phenotype. These developments will certainly allow for better disease modeling to identify novel therapeutic targets for ALS. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Meta-analysis of human leukocyte antigen genetic polymorphisms and susceptibility to chronic myelogenous leukemia in Chinese population.

PubMed

Zhang, Min-Yue; Chen, Fang-Yuan; Zhong, Hua

2011-12-01

Human leukocyte antigen (HLA) genetic polymorphisms are assumed to be correlated to the risk of chronic myelogenous leukemia (CML) in various ethnicities. Up to now, no clear consensus has been reached. Our goal is to address this issue in Chinese population. By searching the data in PubMed, Embase and four Chinese databases (prior to July 2010), the association of HLA genetic polymorphisms with CML has been fixed as the research objective. We studied a totality of 12 studies, comprising 2281 CML cases and 41000 health controls. The data demonstrated that HLA-A*11, A*74, HLA-B*40, B*47, B*55 and B*81 alleles were correlated with the increasing risk of CML. Nevertheless, HLA-DRB1*13 allele seemed to contribute to the genetic protection to CML. Conclusively we suggested that certain HLA alleles might be in association with the pathogenesis of CML in Chinese population. Due to little statistical scale, larger studies and particularly in a mono-people background, our hypothesis need to be further investigated in the future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Explanatory Models of Genetics and Genetic Risk among a Selected Group of Students.

PubMed

Goltz, Heather Honoré; Bergman, Margo; Goodson, Patricia

2016-01-01

This exploratory qualitative study focuses on how college students conceptualize genetics and genetic risk, concepts essential for genetic literacy (GL) and genetic numeracy (GN), components of overall health literacy (HL). HL is dependent on both the background knowledge and culture of a patient, and lower HL is linked to increased morbidity and mortality for a number of chronic health conditions (e.g., diabetes and cancer). A purposive sample of 86 students from three Southwestern universities participated in eight focus groups. The sample ranged in age from 18 to 54 years, and comprised primarily of female (67.4%), single (74.4%), and non-White (57%) participants, none of whom were genetics/biology majors. A holistic-content approach revealed broad categories concerning participants' explanatory models (EMs) of genetics and genetic risk. Participants' EMs were grounded in highly contextualized narratives that only partially overlapped with biomedical models. While higher education levels should be associated with predominately knowledge-based EM of genetic risk, this study shows that even in well-educated populations cultural factors can dominate. Study findings reveal gaps in how this sample of young adults obtains, processes, and understands genetic/genomic concepts. Future studies should assess how individuals with low GL and GN obtain and process genetics and genetic risk information and incorporate this information into health decision making. Future work should also address the interaction of communication between health educators, providers, and genetic counselors, to increase patient understanding of genetic risk.

Multiple maternal origins of Indonesian crowing chickens revealed by mitochondrial DNA analysis.

PubMed

Ulfah, Maria; Perwitasari, Dyah; Jakaria, Jakaria; Muladno, Muhammad; Farajallah, Achmad

2017-03-01

The utilization of Indonesian crowing chickens is increasing; as such, assessing their genetic structures is important to support the conservation of their genetic resources. This study analyzes the matrilineal evolution of Indonesian crowing chickens based on the mtDNA displacement loop D-loop region to clarify their phylogenetic relationships, possible maternal origin, and possible routes of chicken dispersal. The neighbor-joining tree reveals that the majority of Indonesian crowing chickens belong to haplogroups B, D, and E, but haplogroup D harbored most of them. The Bayesian analysis also reveals that Indonesian crowing chickens derive from Bekisar chicken, a hybrid of the green junglefowl, suggesting the possible contribution of green junglefowl to chicken domestication. There appear at least three maternal lineages of Indonesian chicken origins indicated by the median network profile of mtDNA D-loop haplotypes, namely (1) Chinese; (2) Chinese, Indian, and other Southeast Asian chickens; and (3) Indian, Chinese, Southeast Asian, Japanese, and European chickens. Chicken domestication might be centered in China, India, Indonesia, and other Southeast Asian countries, supporting multiple maternal origins of Indonesian crowing chickens. A systematic breeding program of indigenous chickens will be very important to retain the genetic diversity for future use and conservation.

Prioritizing schizophrenia endophenotypes for future genetic studies: An example using data from the COGS-1 family study.

PubMed

Millard, Steven P; Shofer, Jane; Braff, David; Calkins, Monica; Cadenhead, Kristin; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel; Gur, Ruben; Lazzeroni, Laura C; Light, Gregory A; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William S; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Ming; Turetsky, Bruce; Radant, Allen; Tsuang, Debby W

2016-07-01

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially. Published by Elsevier B.V.

Identification of Multiple QTL Hotspots in Sockeye Salmon (Oncorhynchus nerka) Using Genotyping-by-Sequencing and a Dense Linkage Map.

PubMed

Larson, Wesley A; McKinney, Garrett J; Limborg, Morten T; Everett, Meredith V; Seeb, Lisa W; Seeb, James E

2016-03-01

Understanding the genetic architecture of phenotypic traits can provide important information about the mechanisms and genomic regions involved in local adaptation and speciation. Here, we used genotyping-by-sequencing and a combination of previously published and newly generated data to construct sex-specific linkage maps for sockeye salmon (Oncorhynchus nerka). We then used the denser female linkage map to conduct quantitative trait locus (QTL) analysis for 4 phenotypic traits in 3 families. The female linkage map consisted of 6322 loci distributed across 29 linkage groups and was 4082 cM long, and the male map contained 2179 loci found on 28 linkage groups and was 2291 cM long. We found 26 QTL: 6 for thermotolerance, 5 for length, 9 for weight, and 6 for condition factor. QTL were distributed nonrandomly across the genome and were often found in hotspots containing multiple QTL for a variety of phenotypic traits. These hotspots may represent adaptively important regions and are excellent candidates for future research. Comparing our results with studies in other salmonids revealed several regions with overlapping QTL for the same phenotypic trait, indicating these regions may be adaptively important across multiple species. Altogether, our study demonstrates the utility of genomic data for investigating the genetic basis of important phenotypic traits. Additionally, the linkage map created here will enable future research on the genetic basis of phenotypic traits in salmon. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prioritizing Schizophrenia Endophenotypes for Future Genetic Studies: An Example Using Data from the COGS-1 Family Study

PubMed Central

Millard, Steven P.; Shofer, Jane; Braff, David; Calkins, Monica; Cadenhead, Kristin; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Gur, Raquel; Gur, Ruben; Lazzeroni, Laura C.; Light, Gregory A.; Olincy, Ann; Nuechterlein, Keith; Seidman, Larry; Siever, Larry; Silverman, Jeremy; Stone, William; Sprock, Joyce; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Ming; Turetsky, Bruce; Radant, Allen; Tsuang, Debby W.

2016-01-01

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving statistical power of locating genetic regions associated with schizophrenia that may be the easiest to identify initially. PMID:27132484

Application of novel polymorphic microsatellite loci identified in the Korean Pacific Abalone (Haliotis diversicolor supertexta (Haliotidae)) in the genetic characterization of wild and released populations.

PubMed

An, Hye Suck; Lee, Jang Wook; Hong, Seong Wan

2012-01-01

The small abalone, Haliotis diversicolor supertexta, of the family Haliotidae, is one of the most important species of marine shellfish in eastern Asia. Over the past few decades, this species has drastically declined in Korea. Thus, hatchery-bred seeds have been released into natural coastal areas to compensate for the reduced fishery resources. However, information on the genetic background of the small abalone is scarce. In this study, 20 polymorphic microsatellite DNA markers were identified using next-generation sequencing techniques and used to compare allelic variation between wild and released abalone populations in Korea. Using high-throughput genomic sequencing, a total of 1516 (2.26%; average length of 385 bp) reads containing simple sequence repeats were obtained from 86,011 raw reads. Among the 99 loci screened, 28 amplified successfully, and 20 were polymorphic. When comparing allelic variation between wild and released abalone populations, a total of 243 different alleles were observed, with 18.7 alleles per locus. High genetic diversity (mean heterozygosity = 0.81; mean allelic number = 15.5) was observed in both populations. A statistical analysis of the fixation index (F(ST)) and analysis of molecular variance (AMOVA) indicated limited genetic differences between the two populations (F(ST) = 0.002, p > 0.05). Although no significant reductions in the genetic diversity were found in the released population compared with the wild population (p > 0.05), the genetic diversity parameters revealed that the seeds released for stock abundance had a different genetic composition. These differences are likely a result of hatchery selection and inbreeding. Additionally, all the primer pair sets were effectively amplified in another congeneric species, H. diversicolor diversicolor, indicating that these primers are useful for both abalone species. These microsatellite loci may be valuable for future aquaculture and population genetic studies aimed at developing conservation and management plans for these two abalone species.

Genetic Diversity and Demographic History of Wild and Cultivated/Naturalised Plant Populations: Evidence from Dalmatian Sage (Salvia officinalis L., Lamiaceae).

PubMed

Rešetnik, Ivana; Baričevič, Dea; Batîr Rusu, Diana; Carović-Stanko, Klaudija; Chatzopoulou, Paschalina; Dajić-Stevanović, Zora; Gonceariuc, Maria; Grdiša, Martina; Greguraš, Danijela; Ibraliu, Alban; Jug-Dujaković, Marija; Krasniqi, Elez; Liber, Zlatko; Murtić, Senad; Pećanac, Dragana; Radosavljević, Ivan; Stefkov, Gjoshe; Stešević, Danijela; Šoštarić, Ivan; Šatović, Zlatko

2016-01-01

Dalmatian sage (Salvia officinalis L., Lamiaceae) is a well-known aromatic and medicinal Mediterranean plant that is native in coastal regions of the western Balkan and southern Apennine Peninsulas and is commonly cultivated worldwide. It is widely used in the food, pharmaceutical and cosmetic industries. Knowledge of its genetic diversity and spatiotemporal patterns is important for plant breeding programmes and conservation. We used eight microsatellite markers to investigate evolutionary history of indigenous populations as well as genetic diversity and structure within and among indigenous and cultivated/naturalised populations distributed across the Balkan Peninsula. The results showed a clear separation between the indigenous and cultivated/naturalised groups, with the cultivated material originating from one restricted geographical area. Most of the genetic diversity in both groups was attributable to differences among individuals within populations, although spatial genetic analysis of indigenous populations indicated the existence of isolation by distance. Geographical structuring of indigenous populations was found using clustering analysis, with three sub-clusters of indigenous populations. The highest level of gene diversity and the greatest number of private alleles were found in the central part of the eastern Adriatic coast, while decreases in gene diversity and number of private alleles were evident towards the northwestern Adriatic coast and southern and eastern regions of the Balkan Peninsula. The results of Ecological Niche Modelling during Last Glacial Maximum and Approximate Bayesian Computation suggested two plausible evolutionary trajectories: 1) the species survived in the glacial refugium in southern Adriatic coastal region with subsequent colonization events towards northern, eastern and southern Balkan Peninsula; 2) species survived in several refugia exhibiting concurrent divergence into three genetic groups. The insight into genetic diversity and structure also provide the baseline data for conservation of S. officinalis genetic resources valuable for future breeding programmes.

Genetic Diversity and Demographic History of Wild and Cultivated/Naturalised Plant Populations: Evidence from Dalmatian Sage (Salvia officinalis L., Lamiaceae)

PubMed Central

Rešetnik, Ivana; Baričevič, Dea; Batîr Rusu, Diana; Carović-Stanko, Klaudija; Chatzopoulou, Paschalina; Dajić-Stevanović, Zora; Gonceariuc, Maria; Grdiša, Martina; Greguraš, Danijela; Ibraliu, Alban; Jug-Dujaković, Marija; Krasniqi, Elez; Liber, Zlatko; Murtić, Senad; Pećanac, Dragana; Radosavljević, Ivan; Stefkov, Gjoshe; Stešević, Danijela; Šoštarić, Ivan; Šatović, Zlatko

2016-01-01

Dalmatian sage (Salvia officinalis L., Lamiaceae) is a well-known aromatic and medicinal Mediterranean plant that is native in coastal regions of the western Balkan and southern Apennine Peninsulas and is commonly cultivated worldwide. It is widely used in the food, pharmaceutical and cosmetic industries. Knowledge of its genetic diversity and spatiotemporal patterns is important for plant breeding programmes and conservation. We used eight microsatellite markers to investigate evolutionary history of indigenous populations as well as genetic diversity and structure within and among indigenous and cultivated/naturalised populations distributed across the Balkan Peninsula. The results showed a clear separation between the indigenous and cultivated/naturalised groups, with the cultivated material originating from one restricted geographical area. Most of the genetic diversity in both groups was attributable to differences among individuals within populations, although spatial genetic analysis of indigenous populations indicated the existence of isolation by distance. Geographical structuring of indigenous populations was found using clustering analysis, with three sub-clusters of indigenous populations. The highest level of gene diversity and the greatest number of private alleles were found in the central part of the eastern Adriatic coast, while decreases in gene diversity and number of private alleles were evident towards the northwestern Adriatic coast and southern and eastern regions of the Balkan Peninsula. The results of Ecological Niche Modelling during Last Glacial Maximum and Approximate Bayesian Computation suggested two plausible evolutionary trajectories: 1) the species survived in the glacial refugium in southern Adriatic coastal region with subsequent colonization events towards northern, eastern and southern Balkan Peninsula; 2) species survived in several refugia exhibiting concurrent divergence into three genetic groups. The insight into genetic diversity and structure also provide the baseline data for conservation of S. officinalis genetic resources valuable for future breeding programmes. PMID:27441834

The Genetic Privacy Act and commentary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annas, G.J.; Glantz, L.H.; Roche, P.A.

1995-02-28

The Genetic Privacy Act is a proposal for federal legislation. The Act is based on the premise that genetic information is different from other types of personal information in ways that require special protection. The DNA molecule holds an extensive amount of currently indecipherable information. The major goal of the Human Genome Project is to decipher this code so that the information it contains is accessible. The privacy question is, accessible to whom? The highly personal nature of the information contained in DNA can be illustrated by thinking of DNA as containing an individual`s {open_quotes}future diary.{close_quotes} A diary is perhapsmore » the most personal and private document a person can create. It contains a person`s innermost thoughts and perceptions, and is usually hidden and locked to assure its secrecy. Diaries describe the past. The information in one`s genetic code can be thought of as a coded probabilistic future diary because it describes an important part of a unique and personal future. This document presents an introduction to the proposal for federal legislation `the Genetic Privacy Act`; a copy of the proposed act; and comment.« less

Leishmania tropica isolates from non-healed and healed patients in Iran: A molecular typing and phylogenetic analysis.

PubMed

Bamorovat, Mehdi; Sharifi, Iraj; Mohammadi, Mohammad Ali; Eybpoosh, Sana; Nasibi, Saeid; Aflatoonian, Mohammad Reza; Khosravi, Ahmad

2018-03-01

The precise identification of the parasite species causing leishmaniasis is essential for selecting proper treatment modality. The present study aims to compare the nucleotide variations of the ITS1, 7SL RNA, and Hsp70 sequences between non-healed and healed anthroponotic cutaneous leishmaniasis (ACL) patients in major foci in Iran. A case-control study was carried out from September 2015 to October 2016 in the cities of Kerman and Bam, in the southeast of Iran. Randomly selected skin-scraping lesions of 40 patients (20 non-healed and 20 healed) were examined and the organisms were grown in a culture medium. Promastigotes were collected by centrifugation and kept for further molecular examinations. The extracted DNA was amplified and sequenced. After global sequence alignment with BioEdit software, maximum likelihood phylogenetic analysis was performed in PhyML for typing of Leishmania isolates. Nucleotide composition of each genetic region was also compared between non-healed and healed patients. Our results showed that all isolates belonged to the Leishmania tropica complex, with their genetic composition in the ITS1 region being different among non-healed and healed patients. 7SL RNA and Hsp70 regions were genetically identical between both groups. Variability in nucleotide patterns observed between both groups in the ITS1 region may serve to encourage future research on the function of these polymorphisms and may improve our understanding of the role of parasite genome properties on patients' response to Leishmania treatment. Our results also do not support future use of 7SL RNA and Hsp70 regions of the parasite for comparative genomic analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Variable Number of Tandem Repeats (VNTR) analysis of Flavobacterium psychrophilum from salmonids in Chile and Norway.

PubMed

Apablaza, Patricia; Brevik, Øyvind J; Mjøs, Svein; Valdebenito, Samuel; Ilardi, Pedro; Battaglia, Juan; Dalsgaard, Inger; Nylund, Are

2015-07-14

Flavobacterium psychrophilum causes serious fish diseases such RTFS and BCWD, affecting the aquaculture industry worldwide. Commercial vaccines are not available and control of the disease depends on the use of antibiotics. Reliable methods for detection and identification of different isolates of this bacterium could play an important role in the development of good management strategies. The aim of this study was to identify genetic markers for discrimination between isolates. A selection of eight VNTRs from 53 F. psychrophilum isolates from Norway, Chile, Denmark and Scotland were analyzed. The results were compared with previous work on the same pathogen using MLST for genetic differentiation. The VNTR analysis gave a separation between the F. psychrophilum isolates supporting the results of previous MLST work. A higher diversity was found among the Chilean isolates compared to those from Norway, which suggests a more homogenous reservoir in Norway. Transgenerational transmission of F. psychrophilum from other countries, exporting salmon embryos to Chile, may explain the differences in diversity. The same transmission mechanisms could also explain the wide geographical distribution of identical isolates in Norway. But, this could also be a result of movement of smolts and embryos. The selected VNTRs are stable genetic markers and no variation was observed after several passages on agar plates at different temperatures. These VNTRs are important additions for genotyping of F. psychrophilum isolates. Future studies on VNTRs of F. psychrophilum should include isolates from more host species from a wider geographical area. To get a more robust genotyping the VNTRs should be used in concert with MLST. Future studies of isolates with high and low virulence should focus on identifying virulence markers using VTNRs and MLST.

Genetics of Addiction: Future Focus on Gene × Environment Interaction?

PubMed

Vink, Jacqueline M

2016-09-01

The heritability of substance use is moderate to high. Successful efforts to find genetic variants associated with substance use (smoking, alcohol, cannabis) have been undertaken by large consortia. However, the proportion of phenotypic variance explained by the identified genetic variants is small. Interestingly, there is overlap between the genetic variants that influence different substances. Moreover, there are sets of "substance-specific" genes and sets of genes contributing to a "vulnerability for addictive behavior" in general. It is important to recognize that genes alone do not determine addiction phenotypes: Environmental factors such as parental monitoring, peer pressure, or socioeconomic status also play an important role. Despite a rich epidemiologic literature focused on the social determinants of substance use, few studies have examined the moderation of genetic influences like gene-environment (G × E) interactions. Understanding this balance may hold the key to understanding the individual differences in substance use, abuse, and addictive behavior. Recommendations for future research are described in this commentary and include increasing the power of G × E studies by using state-of-the-art methods such as polygenic risk scores instead of single genetic variants and taking genetic overlap between substances into account. Future genetic studies should also investigate environmental risk factors for addictive behavior more extensively to unravel the interaction between nature and nurture. Focusing on G × E interactions not only will give insight into the underlying biological mechanism but will also characterize subgroups (based on environmental factors) at high risk for addictive behaviors. With this information, we could bridge the gap between fundamental research and applications for society.

Epilepsy Genetics—Past, Present, and Future

PubMed Central

Poduri, Annapurna; Lowenstein, Daniel

2014-01-01

Human epilepsy is a common and heterogeneous condition in which genetics play an important etiological role. We begin by reviewing the past history of epilepsy genetics, a field that has traditionally included studies of pedigrees with epilepsy caused by defects in ion channels and neurotransmitters. We highlight important recent discoveries that have expanded the field beyond the realm of channels and neurotransmitters and that have challenged the notion that single genes produce single disorders. Finally, we project toward an exciting future for epilepsy genetics as large-scale collaborative phenotyping studies come face to face with new technologies in genomic medicine. PMID:21277190

Exploring and Harnessing Haplotype Diversity to Improve Yield Stability in Crops.

PubMed

Qian, Lunwen; Hickey, Lee T; Stahl, Andreas; Werner, Christian R; Hayes, Ben; Snowdon, Rod J; Voss-Fels, Kai P

2017-01-01

In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches. These include highly detailed assessment of population structure and genotypic diversity, facilitating the identification of selective sweeps and signatures of directional selection, dissection of genetic variants that underlie important agronomic traits, and genomic selection (GS) strategies that not only consider major-effect genes. Single-nucleotide polymorphism (SNP) markers today represent the genotyping system of choice for crop genetic studies because they occur abundantly in plant genomes and are easy to detect. SNPs are typically biallelic, however, hence their information content compared to multiallelic markers is low, limiting the resolution at which SNP-trait relationships can be delineated. An efficient way to overcome this limitation is to construct haplotypes based on linkage disequilibrium, one of the most important features influencing genetic analyses of crop genomes. Here, we give an overview of the latest advances in genomics-based haplotype analyses in crops, highlighting their importance in the context of polyploidy and genome evolution, linkage drag, and co-selection. We provide examples of how haplotype analyses can complement well-established quantitative genetics frameworks, such as quantitative trait analysis and GS, ultimately providing an effective tool to equip modern crops with environment-tailored characteristics.

A Genomic Resource for the Development, Improvement, and Exploitation of Sorghum for Bioenergy.

PubMed

Brenton, Zachary W; Cooper, Elizabeth A; Myers, Mathew T; Boyles, Richard E; Shakoor, Nadia; Zielinski, Kelsey J; Rauh, Bradley L; Bridges, William C; Morris, Geoffrey P; Kresovich, Stephen

2016-09-01

With high productivity and stress tolerance, numerous grass genera of the Andropogoneae have emerged as candidates for bioenergy production. To optimize these candidates, research examining the genetic architecture of yield, carbon partitioning, and composition is required to advance breeding objectives. Significant progress has been made developing genetic and genomic resources for Andropogoneae, and advances in comparative and computational genomics have enabled research examining the genetic basis of photosynthesis, carbon partitioning, composition, and sink strength. To provide a pivotal resource aimed at developing a comparative understanding of key bioenergy traits in the Andropogoneae, we have established and characterized an association panel of 390 racially, geographically, and phenotypically diverse Sorghum bicolor accessions with 232,303 genetic markers. Sorghum bicolor was selected because of its genomic simplicity, phenotypic diversity, significant genomic tools, and its agricultural productivity and resilience. We have demonstrated the value of sorghum as a functional model for candidate gene discovery for bioenergy Andropogoneae by performing genome-wide association analysis for two contrasting phenotypes representing key components of structural and non-structural carbohydrates. We identified potential genes, including a cellulase enzyme and a vacuolar transporter, associated with increased non-structural carbohydrates that could lead to bioenergy sorghum improvement. Although our analysis identified genes with potentially clear functions, other candidates did not have assigned functions, suggesting novel molecular mechanisms for carbon partitioning traits. These results, combined with our characterization of phenotypic and genetic diversity and the public accessibility of each accession and genomic data, demonstrate the value of this resource and provide a foundation for future improvement of sorghum and related grasses for bioenergy production. Copyright © 2016 by the Genetics Society of America.

Genetic compendium of 1511 human brains available through the UK Medical Research Council Brain Banks Network Resource.

PubMed

Keogh, Michael J; Wei, Wei; Wilson, Ian; Coxhead, Jon; Ryan, Sarah; Rollinson, Sara; Griffin, Helen; Kurzawa-Akanbi, Marzena; Santibanez-Koref, Mauro; Talbot, Kevin; Turner, Martin R; McKenzie, Chris-Anne; Troakes, Claire; Attems, Johannes; Smith, Colin; Al Sarraj, Safa; Morris, Chris M; Ansorge, Olaf; Pickering-Brown, Stuart; Ironside, James W; Chinnery, Patrick F

2017-01-01

Given the central role of genetic factors in the pathogenesis of common neurodegenerative disorders, it is critical that mechanistic studies in human tissue are interpreted in a genetically enlightened context. To address this, we performed exome sequencing and copy number variant analysis on 1511 frozen human brains with a diagnosis of Alzheimer's disease (AD, n = 289), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS, n = 252), Creutzfeldt-Jakob disease (CJD, n = 239), Parkinson's disease (PD, n = 39), dementia with Lewy bodies (DLB, n = 58), other neurodegenerative, vascular, or neurogenetic disorders (n = 266), and controls with no significant neuropathology (n = 368). Genomic DNA was extracted from brain tissue in all cases before exome sequencing (Illumina Nextera 62 Mb capture) with variants called by FreeBayes; copy number variant (CNV) analysis (Illumina HumanOmniExpress-12 BeadChip); C9orf72 repeat expansion detection; and APOE genotyping. Established or likely pathogenic heterozygous, compound heterozygous, or homozygous variants, together with the C9orf72 hexanucleotide repeat expansions and a copy number gain of APP, were found in 61 brains. In addition to known risk alleles in 349 brains (23.9% of 1461 undergoing exome sequencing), we saw an association between rare variants in GRN and DLB. Rare CNVs were found in <1.5% of brains, including copy number gains of PRPH that were overrepresented in AD. Clinical, pathological, and genetic data are available, enabling the retrieval of specific frozen brains through the UK Medical Research Council Brain Banks Network. This allows direct access to pathological and control human brain tissue based on an individual's genetic architecture, thus enabling the functional validation of known genetic risk factors and potentially pathogenic alleles identified in future studies. © 2017 Keogh et al.; Published by Cold Spring Harbor Laboratory Press.

Genetic susceptibility to bone and soft tissue sarcomas: a field synopsis and meta-analysis

PubMed Central

Benna, Clara; Simioni, Andrea; Pasquali, Sandro; De Boni, Davide; Rajendran, Senthilkumar; Spiro, Giovanna; Colombo, Chiara; Virgone, Calogero; DuBois, Steven G.; Gronchi, Alessandro; Rossi, Carlo Riccardo; Mocellin, Simone

2018-01-01

Background The genetic architecture of bone and soft tissue sarcomas susceptibility is yet to be elucidated. We aimed to comprehensively collect and meta-analyze the current knowledge on genetic susceptibility in these rare tumors. Methods We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing sarcomas through searching PubMed, The Cochrane Library, Scopus and Web of Science databases. To evaluate result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Integrative analysis of genetic and eQTL (expression quantitative trait locus) data was coupled with network and pathway analysis to explore the hypothesis that specific cell functions are involved in sarcoma predisposition. Results We retrieved 90 eligible studies comprising 47,796 subjects (cases: 14,358, 30%) and investigating 1,126 polymorphisms involving 320 distinct genes. Meta-analysis identified 55 single nucleotide polymorphisms (SNPs) significantly associated with disease risk with a high (N=9), moderate (N=38) and low (N=8) level of evidence, findings being classified as noteworthy basically only when the level of evidence was high. The estimated joint population attributable risk for three independent SNPs (rs11599754 of ZNF365/EGR2, rs231775 of CTLA4, and rs454006 of PRKCG) was 37.2%. We also identified 53 SNPs significantly associated with sarcoma risk based on single studies. Pathway analysis enabled us to propose that sarcoma predisposition might be linked especially to germline variation of genes whose products are involved in the function of the DNA repair machinery. Conclusions We built the first knowledgebase on the evidence linking DNA variation to sarcomas susceptibility, which can be used to generate mechanistic hypotheses and inform future studies in this field of oncology. PMID:29719630

Draft genome of the American Eel (Anguilla rostrata).

PubMed

Pavey, Scott A; Laporte, Martin; Normandeau, Eric; Gaudin, Jérémy; Letourneau, Louis; Boisvert, Sébastien; Corbeil, Jacques; Audet, Céline; Bernatchez, Louis

2017-07-01

Freshwater eels (Anguilla sp.) have large economic, cultural, ecological and aesthetic importance worldwide, but they suffered more than 90% decline in global stocks over the past few decades. Proper genetic resources, such as sequenced, assembled and annotated genomes, are essential to help plan sustainable recoveries by identifying physiological, biochemical and genetic mechanisms that caused the declines or that may lead to recoveries. Here, we present the first sequenced genome of the American eel. This genome contained 305 043 contigs (N50 = 7397) and 79 209 scaffolds (N50 = 86 641) for a total size of 1.41 Gb, which is in the middle of the range of previous estimations for this species. In addition, protein-coding regions, including introns and flanking regions, are very well represented in the genome, as 95.2% of the 458 core eukaryotic genes and 98.8% of the 248 ultra-conserved subset were represented in the assembly and a total of 26 564 genes were annotated for future functional genomics studies. We performed a candidate gene analysis to compare three genes among all three freshwater eel species and, congruent with the phylogenetic relationships, Japanese eel (A. japanica) exhibited the most divergence. Overall, the sequenced genome presented in this study is a crucial addition to the presently available genetic tools to help guide future conservation efforts of freshwater eels. © 2016 John Wiley & Sons Ltd.

Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction.

PubMed

Reyes-Gibby, Cielito C; Yuan, Christine; Wang, Jian; Yeung, Sai-Ching J; Shete, Sanjay

2015-06-05

Addictions to alcohol and tobacco, known risk factors for cancer, are complex heritable disorders. Addictive behaviors have a bidirectional relationship with pain. We hypothesize that the associations between alcohol, smoking, and opioid addiction observed in cancer patients have a genetic basis. Therefore, using bioinformatics tools, we explored the underlying genetic basis and identified new candidate genes and common biological pathways for smoking, alcohol, and opioid addiction. Literature search showed 56 genes associated with alcohol, smoking and opioid addiction. Using Core Analysis function in Ingenuity Pathway Analysis software, we found that ERK1/2 was strongly interconnected across all three addiction networks. Genes involved in immune signaling pathways were shown across all three networks. Connect function from IPA My Pathway toolbox showed that DRD2 is the gene common to both the list of genetic variations associated with all three addiction phenotypes and the components of the brain neuronal signaling network involved in substance addiction. The top canonical pathways associated with the 56 genes were: 1) calcium signaling, 2) GPCR signaling, 3) cAMP-mediated signaling, 4) GABA receptor signaling, and 5) G-alpha i signaling. Cancer patients are often prescribed opioids for cancer pain thus increasing their risk for opioid abuse and addiction. Our findings provide candidate genes and biological pathways underlying addiction phenotypes, which may be future targets for treatment of addiction. Further study of the variations of the candidate genes could allow physicians to make more informed decisions when treating cancer pain with opioid analgesics.

Determination of the genetic diversity of vegetable soybean [Glycine max (L.) Merr.] using EST-SSR markers*

PubMed Central

Zhang, Gu-wen; Xu, Sheng-chun; Mao, Wei-hua; Hu, Qi-zan; Gong, Ya-ming

2013-01-01

The development of expressed sequence tag-derived simple sequence repeats (EST-SSRs) provided a useful tool for investigating plant genetic diversity. In the present study, 22 polymorphic EST-SSRs from grain soybean were identified and used to assess the genetic diversity in 48 vegetable soybean accessions. Among the 22 EST-SSR loci, tri-nucleotides were the most abundant repeats, accounting for 50.00% of the total motifs. GAA was the most common motif among tri-nucleotide repeats, with a frequency of 18.18%. Polymorphic analysis identified a total of 71 alleles, with an average of 3.23 per locus. The polymorphism information content (PIC) values ranged from 0.144 to 0.630, with a mean of 0.386. Observed heterozygosity (H o) values varied from 0.0196 to 1.0000, with an average of 0.6092, while the expected heterozygosity (H e) values ranged from 0.1502 to 0.6840, with a mean value of 0.4616. Principal coordinate analysis and phylogenetic tree analysis indicated that the accessions could be assigned to different groups based to a large extent on their geographic distribution, and most accessions from China were clustered into the same groups. These results suggest that Chinese vegetable soybean accessions have a narrow genetic base. The results of this study indicate that EST-SSRs from grain soybean have high transferability to vegetable soybean, and that these new markers would be helpful in taxonomy, molecular breeding, and comparative mapping studies of vegetable soybean in the future. PMID:23549845

Genetic variation and phylogenetic relationships of the ectomycorrhizal Floccularia luteovirens on the Qinghai-Tibet Plateau.

PubMed

Xing, Rui; Gao, Qing-Bo; Zhang, Fa-Qi; Fu, Peng-Cheng; Wang, Jiu-Li; Yan, Hui-Ying; Chen, Shi-Long

2017-08-01

Floccularia luteovirens, as an ectomycorrhizal fungus, is widely distributed in the Qinghai-Tibet Plateau. As an edible fungus, it is famous for its unique flavor. Former studies mainly focus on the chemical composition and genetic structure of this species. However, the phylogenetic relationship between genotypes remains unknown. In this study, the genetic variation and phylogenetic relationship between the genotypes of F. luteovirens in Qinghai-Tibet Plateau was estimated through the analysis on two protein-coding genes (rpb1 and ef-1α) from 398 individuals collected from 24 wild populations. The sample covered the entire range of this species during all the growth seasons from 2011 to 2015. 13 genotypes were detected and moderate genetic diversity was revealed. Based on the results of network analysis, the maximum likelihood (ML), maximum parsimony (MP), and Bayesian inference (BI) analyses, the genotypes H-1, H-4, H-6, H-8, H-10, and H-11 were grouped into one clade. Additionally, a relatively higher genotype diversity (average h value is 0.722) and unique genotypes in the northeast edge of Qinghai- Tibet plateau have been found, combined with the results of mismatch analysis and neutrality tests indicated that Southeast Qinghai-Tibet plateau was a refuge for F. luteovirens during the historical geological or climatic events (uplifting of the Qinghai-Tibet Plateau or Last Glacial Maximum). Furthermore, the present distribution of the species on the Qinghai-Tibet plateau has resulted from the recent population expansion. Our findings provide a foundation for the future study of the evolutionary history and the speciation of this species.

Genetic variability in selected date palm (Phoenix dactylifera L.) cultivars of United Arab Emirates using ISSR and DAMD markers.

PubMed

Purayil, Fayas T; Robert, Gabriel A; Gothandam, Kodiveri M; Kurup, Shyam S; Subramaniam, Sreeramanan; Cheruth, Abdul Jaleel

2018-02-01

Nine (9) different date palm ( Phoenix dactylifera L.) cultivars from UAE, which differ in their flower timings were selected to determine the polymorphism and genetic relationship between these cultivars. Hereditary differences and interrelationships were assessed utilizing inter-simple sequence repeat (ISSR) and directed amplification of minisatellite DNA region (DAMD) primers. Analysis on eight DAMD and five ISSR markers produced total of 113 amplicon including 99 polymorphic and 14 monomorphic alleles with a polymorphic percentage of 85.45. The average polymorphic information content for the two-marker system was almost similar (DAMD, 0.445 and ISSR, 0.459). UPGMA based clustering of DAMD and ISSR revealed that mid-season cultivars, Mkh (Khlas) and MB (Barhee) grouped together to form a subcluster in both the marker systems. The genetic similarity analysis followed by clustering of the cumulative data from the DAMD and ISSR resulted in two major clusters with two early-season cultivars (ENg and Ekn), two mid-season cultivars (MKh and MB) and one late-season cultivar (Lkhs) in cluster 1, cluster 2 includes two late-season cultivars, one early-season cultivar and one mid-season cultivar. The cluster analysis of both DAMD and ISSR marker revealed that, the patterns of variation between some of the tested cultivars were similar in both DNA marker systems. Hence, the present study signifies the applicability of DAMD and ISSR marker system in detecting genetic diversity of date palm cultivars flowering at different seasons. This may facilitate the conservation and improvement of date palm cultivars in the future.

Population genetics of Enterocytozoon bieneusi in captive giant pandas of China.

PubMed

Li, Wei; Song, Yuan; Zhong, Zhijun; Huang, Xiangming; Wang, Chengdong; Li, Caiwu; Yang, Haidi; Liu, Haifeng; Ren, Zhihua; Lan, Jingchao; Wu, Kongju; Peng, Guangneng

2017-10-18

Most studies on Enterocytozoon bieneusi are conducted based on the internal transcribed spacer (ITS) region of the rRNA gene, whereas some have examined E. bieneusi population structures. Currently, the population genetics of this pathogen in giant panda remains unknown. The objective of this study was to determine the E. bieneusi population in captive giant pandas in China. We examined 69 E. bieneusi-positive specimens from captive giant pandas in China using five loci (ITS, MS1, MS3, MS4 and MS7) to infer E. bieneusi population genetics. For multilocus genotype (MLG) analysis of E. bieneusi-positive isolates, the MS1, MS3, MS4, and MS7 microsatellite and minisatellite loci were amplified and sequenced in 48, 45, 50 and 47 specimens, respectively, generating ten, eight, nine and five types. We successfully amplified 36 specimens and sequenced all five loci, forming 24 MLGs. Multilocus sequence analysis revealed a strong and significant linkage disequilibrium (LD), indicating a clonal population. This result was further supported by measurements of pairwise intergenic LD and a standardized index of association (I S A ) from allelic profile data. The analysis in STRUCTURE suggested three subpopulations in E. bieneusi, further confirmed using right's fixation index (F ST ). Subpopulations 1 and 2 exhibited an epidemic structure, whereas subpopulation 3 had a clonal structure. Our results describe E. bieneusi population genetics in giant pandas for the first time, improving the current understanding E. bieneusi epidemiology in the studied region. These data also benefit future studies exploring potential transmission risks from pandas to other animals, including humans.

The Legal Past, Present and Future of Prenatal Genetic Testing: Professional Liability and Other Legal Challenges Affecting Patient Access to Services.

PubMed

Pergament, Deborah; Ilijic, Katie

2014-12-15

This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments.

The Legal Past, Present and Future of Prenatal Genetic Testing: Professional Liability and Other Legal Challenges Affecting Patient Access to Services

PubMed Central

Pergament, Deborah; Ilijic, Katie

2014-01-01

This chapter is an overview of the current status of the law in the United States regarding prenatal genetic testing with an emphasis on issues related to professional liability and other challenges affecting patient access to prenatal genetic testing. The chapter discusses the roles that federal regulations, promulgated by the Centers for Medicare and Medicaid Services (CMS), the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), play in the regulation of prenatal genetic tests. The chapter discusses tort litigation based on allegations of malpractice in the provision of prenatal genetic testing and how courts have analyzed issues related to causation, damages and mitigation of damages. The chapter provides reference information regarding how individual states address causes of action under the tort theories of wrongful birth and wrongful life. The chapter concludes with a discussion of future legal issues that may affect clinical prenatal genetic testing services arising from the continued expansion of prenatal genetic testing, legal restrictions on access to abortion and the potential development of embryonic treatments. PMID:26237611

Conserving and managing the trees of the future: genetic resources for Pacific Northwest forests.

Treesearch

Sally Duncan

2003-01-01

Genetic resource management has historically called for altering the genetic structure of plant populations through selection for traits of interest such as rapid growth. Although this is still a principal component of tree breeding programs in the Pacific Northwest, managing genetic resources now also brings a clear focus on retaining a broad diversity within and...

Genetic Testing in a Drama and Discussion Workshop: Exploring Knowledge Construction

ERIC Educational Resources Information Center

Dawson, Emily; Hill, Anne; Barlow, John; Weitkamp, Emma

2009-01-01

In this pilot project, drama was used to situate genetic testing in a social and cultural context--that of the family. The drama was used to stimulate discussion about social issues relating to genetic testing, such as who has the right to know the results of the test and whether participants would want to know their "genetic future". A…

Integration of population genetic structure and plant response to climate change: sustaining genetic resources through evaluation of projected threats

Treesearch

Bryce A. Richardson; Marcus V. Warwell; Mee-Sook Kim; Ned B. Klopfenstein; Geral I. McDonald

2010-01-01

To assess threats or predict responses to disturbances, or both, it is essential to recognize and characterize the population structures of forest species in relation to changing environments. Appropriate management of these genetic resources in the future will require (1) understanding the existing genetic diversity/variation and population structure of forest trees...

A genetic investigation of Korean mummies from the Joseon Dynasty.

PubMed

Kim, Na Young; Lee, Hwan Young; Park, Myung Jin; Yang, Woo Ick; Shin, Kyoung-Jin

2011-01-01

Two Korean mummies (Danwoong-mirra and Yoon-mirra) found in medieval tombs in the central region of the Korean peninsula were genetically investigated by analysis of mitochondrial DNA (mtDNA), Y-chromosomal short tandem repeat (Y-STR) and the ABO gene. Danwoong-mirra is a male child mummy and Yoon-mirra is a pregnant female mummy, dating back about 550 and 450 years, respectively. DNA was extracted from soft tissues or bones. mtDNA, Y-STR and the ABO gene were amplified using a small size amplicon strategy and were analyzed according to the criteria of ancient DNA analysis to ensure that authentic DNA typing results were obtained from these ancient samples. Analysis of mtDNA hypervariable region sequence and coding region single nucleotide polymorphism (SNP) information revealed that Danwoong-mirra and Yoon-mirra belong to the East Asian mtDNA haplogroups D4 and M7c, respectively. The Y-STRs were analyzed in the male child mummy (Danwoong-mirra) using the AmpFlSTR® Yfiler PCR Amplification Kit and an in-house Y-miniplex plus system, and could be characterized in 4 loci with small amplicon size. The analysis of ABO gene SNPs using multiplex single base extension methods revealed that the ABO blood types of Danwoong-mirra and Yoon-mirra are AO01 and AB, respectively. The small size amplicon strategy and the authentication process in the present study will be effectively applicable to future genetic analyses of various forensic and ancient samples.

Plant genetics, sustainable agriculture and global food security.

PubMed

Ronald, Pamela

2011-05-01

The United States and the world face serious societal challenges in the areas of food, environment, energy, and health. Historically, advances in plant genetics have provided new knowledge and technologies needed to address these challenges. Plant genetics remains a key component of global food security, peace, and prosperity for the foreseeable future. Millions of lives depend upon the extent to which crop genetic improvement can keep pace with the growing global population, changing climate, and shrinking environmental resources. While there is still much to be learned about the biology of plant-environment interactions, the fundamental technologies of plant genetic improvement, including crop genetic engineering, are in place, and are expected to play crucial roles in meeting the chronic demands of global food security. However, genetically improved seed is only part of the solution. Such seed must be integrated into ecologically based farming systems and evaluated in light of their environmental, economic, and social impacts-the three pillars of sustainable agriculture. In this review, I describe some lessons learned, over the last decade, of how genetically engineered crops have been integrated into agricultural practices around the world and discuss their current and future contribution to sustainable agricultural systems.

The effects of learning about one's own genetic susceptibility to alcoholism: a randomized experiment.

PubMed

Dar-Nimrod, Ilan; Zuckerman, Miron; Duberstein, Paul R

2013-02-01

Increased accessibility of direct-to-consumer personalized genetic reports raises the question: how are people affected by information about their own genetic predispositions? Participants were led to believe that they had entered a study on the genetics of alcoholism and sleep disorders. Participants provided a saliva sample purportedly to be tested for the presence of relevant genes. While awaiting the results, they completed a questionnaire assessing their emotional state. They subsequently received a bogus report about their genetic susceptibility and completed a questionnaire about their emotional state and items assessing perceived control over drinking, relevant future drinking-related intentions, and intervention-related motivation and behavior. Participants who were led to believe that they had a gene associated with alcoholism showed an increase in negative affect, decrease in positive affect, and reduced perceived personal control over drinking. Reported intentions for alcohol consumption in the near future were not affected; however, individuals were more likely to enroll in a "responsible drinking" workshop after learning of their alleged genetic susceptibility. The first complete randomized experiment to examine the psychological and behavioral effects of receiving personalized genetic susceptibility information indicates some potential perils and benefits of direct-to-consumer genetic tests.

The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information.

PubMed

Weaver, Meaghann

2016-03-01

Genetic testing reveals information about a patient's health status and predictions about the patient's future wellness, while also potentially disclosing health information relevant to other family members. With the increasing availability and affordability of genetic testing and the integration of genetics into mainstream medicine, the importance of clarifying the scope of confidentiality and the rules regarding disclosure of genetic findings to genetic relatives is prime. The United Nations International Declaration on Human Genetic Data urges an appreciation for principles of equality, justice, solidarity and responsibility in the context of genetic testing, including a commitment to honoring the privacy and security of the person tested. Considering this global mandate and recent professional statements in the context of a legal amendment to patient privacy policies in Australia, a fresh scrutiny of the legal history of a physician's duty to warn is warranted. This article inquiries whether there may be anything ethically or socially amiss with a potential future recommendation for health professionals or patients to universally disclose particular cancer predisposition genetic diagnosis to genetic family members. While much of the discussion remains applicable to all genetic diagnosis, the article focuses on the practice of disclosure within the context of BRCA1/2 diagnosis. An 'ethic of care' interpretation of legal tradition and current practice will serve to reconcile law and medical policy on the issue of physician disclosure of genetic results to family members without patient consent. © 2015 John Wiley & Sons Ltd.

6C.04: INTEGRATED SNP ANALYSIS AND METABOLOMIC PROFILES OF METABOLIC SYNDROME.

PubMed

Marrachelli, V; Monleon, D; Morales, J M; Rentero, P; Martínez, F; Chaves, F J; Martin-Escudero, J C; Redon, J

2015-06-01

Metabolic syndrome (MS) has become a health and financial burden worldwide. Susceptibility of genetically determined metabotype of MS has not yet been investigated. We aimed to identify a distinctive metabolic profile of blood serum which might correlates to the early detection of the development of MS associated to genetic polymorphism. We applied high resolution NMR spectroscopy to profile blood serum from patients without MS (n = 945) or with (n = 291). Principal component analysis (PCA) and projection to latent structures for discriminant analysis (PLS-DA) were applied to NMR spectral datasets. Results were cross-validated using the Venetian Blinds approach. Additionally, five SNPs previously associated with MS were genotyped with SNPlex and tested for associations between the metabolic profiles and the genetic variants. Statistical analysis was performed using in-house MATLAB scripts and the PLS Toolbox statistical multivariate analysis library. Our analysis provided a PLS-DA Metabolic Syndrome discrimination model based on NMR metabolic profile (AUC = 0.86) with 84% of sensitivity and 72% specificity. The model identified 11 metabolites differentially regulated in patients with MS. Among others, fatty acids, glucose, alanine, hydroxyisovalerate, acetone, trimethylamine, 2-phenylpropionate, isobutyrate and valine, significantly contributed to the model. The combined analysis of metabolomics and SNP data revealed an association between the metabolic profile of MS and genes polymorphism involved in the adiposity regulation and fatty acids metabolism: rs2272903_TT (TFAP2B), rs3803_TT (GATA2), rs174589_CC (FADS2) and rs174577_AA (FADS2). In addition, individuals with the rs2272903-TT genotype seem to develop MS earlier than general population. Our study provides new insights on the metabolic alterations associated with a MS high-risk genotype. These results could help in future development of risk assessment and predictive models for subclinical cardiovascular disease.

A Genomic Resource for the Development, Improvement, and Exploitation of Sorghum for Bioenergy

PubMed Central

Brenton, Zachary W.; Cooper, Elizabeth A.; Myers, Mathew T.; Boyles, Richard E.; Shakoor, Nadia; Zielinski, Kelsey J.; Rauh, Bradley L.; Bridges, William C.; Morris, Geoffrey P.; Kresovich, Stephen

2016-01-01

With high productivity and stress tolerance, numerous grass genera of the Andropogoneae have emerged as candidates for bioenergy production. To optimize these candidates, research examining the genetic architecture of yield, carbon partitioning, and composition is required to advance breeding objectives. Significant progress has been made developing genetic and genomic resources for Andropogoneae, and advances in comparative and computational genomics have enabled research examining the genetic basis of photosynthesis, carbon partitioning, composition, and sink strength. To provide a pivotal resource aimed at developing a comparative understanding of key bioenergy traits in the Andropogoneae, we have established and characterized an association panel of 390 racially, geographically, and phenotypically diverse Sorghum bicolor accessions with 232,303 genetic markers. Sorghum bicolor was selected because of its genomic simplicity, phenotypic diversity, significant genomic tools, and its agricultural productivity and resilience. We have demonstrated the value of sorghum as a functional model for candidate gene discovery for bioenergy Andropogoneae by performing genome-wide association analysis for two contrasting phenotypes representing key components of structural and non-structural carbohydrates. We identified potential genes, including a cellulase enzyme and a vacuolar transporter, associated with increased non-structural carbohydrates that could lead to bioenergy sorghum improvement. Although our analysis identified genes with potentially clear functions, other candidates did not have assigned functions, suggesting novel molecular mechanisms for carbon partitioning traits. These results, combined with our characterization of phenotypic and genetic diversity and the public accessibility of each accession and genomic data, demonstrate the value of this resource and provide a foundation for future improvement of sorghum and related grasses for bioenergy production. PMID:27356613

Cheiloscopy and dermatoglyphics as genetic markers in the transmission of cleft lip and palate: A case-control study.

PubMed

Saujanya, K; Prasad, M Ghanashyam; Sushma, B; Kumar, J Raghavendra; Reddy, Y S N; Niranjani, K

2016-01-01

Determining the relative risk of cleft lip and palate (CL[P]) on the basis of lip prints and dermatoglyphics as genetic background may be useful for genetic counseling, and the development of future preventive measures. (1) To analyze the various pattern types of lip prints and dermatoglyphics in parents of CL(P) children and to detect if any specific type can be contemplated as a genetic marker in the transmission of CL(P). (2) To compare these patterns with that of parents of unaffected children. 31 parents of children with CL(P) as a study group, and 31 parents of unaffected children as control group were included. Lip prints and finger prints were collected from all subjects and analysis of both patterns was carried out followed by a comparison of the patterns of unaffected parents with the controls statistically. Among the mothers of the study group, type O followed by type IIa lip patterns were found to be significantly higher in upper and lower lips, and in fathers type IIa followed by type O were significantly higher. In the control group, type IIb followed by type III were higher in both fathers and mothers. Dermatoglyphic analysis of palm and finger prints revealed no significant difference in the pattern types and total ridge counts, but the Atd angle asymmetry was found to be significant between study and control group. Types IIa and O lip patterns, asymmetry of Atd angles can be considered as genetic markers for the transmission of CL(P) deformity to offsprings.

Visualization, documentation, analysis, and communication of large scale gene regulatory networks

PubMed Central

Longabaugh, William J.R.; Davidson, Eric H.; Bolouri, Hamid

2009-01-01

Summary Genetic regulatory networks (GRNs) are complex, large-scale, and spatially and temporally distributed. These characteristics impose challenging demands on computational GRN modeling tools, and there is a need for custom modeling tools. In this paper, we report on our ongoing development of BioTapestry, an open source, freely available computational tool designed specifically for GRN modeling. We also outline our future development plans, and give some examples of current applications of BioTapestry. PMID:18757046

Predicting fibromyalgia, a narrative review: are we better than fools and children?

PubMed

Ablin, J N; Buskila, D

2014-09-01

Fibromyalgia syndrome (FMS) is a common and intriguing condition, manifest by chronic pain and fatigue. Although the pathogenesis of FMS is not yet completely understood, predicting the future development of FMS and chronic pain is a major challenge with great potential advantages, both from an individual as well as an epidemiological standpoint. Current knowledge indicates a genetic underpinning for FMS, and as increasing data are accumulated regarding the genetics involved, the prospect of utilizing these data for prediction becomes ever more attractive. The co-existence of FMS with multiple other functional disorders indicates that the clinical identification of such symptom constellations in a patient can alert the physician to the future development of FMS. Hypermobility syndrome is another clinical (as well as genetic) phenotype that has emerged as a risk factor for the development of FMS. Stressful events, including early life trauma, are also harbingers of the future development of FMS. Functional neuroimaging may help to elucidate the neural processes involved in central sensitization, and may ultimately also evolve into markers of predictive value. Last but not least, obesity and disturbed sleep are clinical (inter-related) features relevant for this spectrum. Future efforts will aim at integrating genetic, clinical and physiological data in the prediction of FMS and chronic pain. © 2014 European Pain Federation - EFIC®

From observational to dynamic genetics

PubMed Central

Haworth, Claire M. A.; Davis, Oliver S. P.

2014-01-01

Twin and family studies have shown that most traits are at least moderately heritable. But what are the implications of finding genetic influence for the design of intervention and prevention programs? For complex traits, heritability does not mean immutability, and research has shown that genetic influences can change with age, context, and in response to behavioral and drug interventions. The most significant implications for intervention will come when we move from observational genetics to investigating dynamic genetics, including genetically sensitive interventions. Future interventions should be designed to overcome genetic risk and draw upon genetic strengths by changing the environment. PMID:24478793

Meta-analysis of quantitative pleiotropic traits for next-generation sequencing with multivariate functional linear models

PubMed Central

Chiu, Chi-yang; Jung, Jeesun; Chen, Wei; Weeks, Daniel E; Ren, Haobo; Boehnke, Michael; Amos, Christopher I; Liu, Aiyi; Mills, James L; Ting Lee, Mei-ling; Xiong, Momiao; Fan, Ruzong

2017-01-01

To analyze next-generation sequencing data, multivariate functional linear models are developed for a meta-analysis of multiple studies to connect genetic variant data to multiple quantitative traits adjusting for covariates. The goal is to take the advantage of both meta-analysis and pleiotropic analysis in order to improve power and to carry out a unified association analysis of multiple studies and multiple traits of complex disorders. Three types of approximate F -distributions based on Pillai–Bartlett trace, Hotelling–Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants. Simulation analysis is performed to evaluate false-positive rates and power of the proposed tests. The proposed methods are applied to analyze lipid traits in eight European cohorts. It is shown that it is more advantageous to perform multivariate analysis than univariate analysis in general, and it is more advantageous to perform meta-analysis of multiple studies instead of analyzing the individual studies separately. The proposed models require individual observations. The value of the current paper can be seen at least for two reasons: (a) the proposed methods can be applied to studies that have individual genotype data; (b) the proposed methods can be used as a criterion for future work that uses summary statistics to build test statistics to meta-analyze the data. PMID:28000696

Meta-analysis of quantitative pleiotropic traits for next-generation sequencing with multivariate functional linear models.

PubMed

Chiu, Chi-Yang; Jung, Jeesun; Chen, Wei; Weeks, Daniel E; Ren, Haobo; Boehnke, Michael; Amos, Christopher I; Liu, Aiyi; Mills, James L; Ting Lee, Mei-Ling; Xiong, Momiao; Fan, Ruzong

2017-02-01

To analyze next-generation sequencing data, multivariate functional linear models are developed for a meta-analysis of multiple studies to connect genetic variant data to multiple quantitative traits adjusting for covariates. The goal is to take the advantage of both meta-analysis and pleiotropic analysis in order to improve power and to carry out a unified association analysis of multiple studies and multiple traits of complex disorders. Three types of approximate F -distributions based on Pillai-Bartlett trace, Hotelling-Lawley trace, and Wilks's Lambda are introduced to test for association between multiple quantitative traits and multiple genetic variants. Simulation analysis is performed to evaluate false-positive rates and power of the proposed tests. The proposed methods are applied to analyze lipid traits in eight European cohorts. It is shown that it is more advantageous to perform multivariate analysis than univariate analysis in general, and it is more advantageous to perform meta-analysis of multiple studies instead of analyzing the individual studies separately. The proposed models require individual observations. The value of the current paper can be seen at least for two reasons: (a) the proposed methods can be applied to studies that have individual genotype data; (b) the proposed methods can be used as a criterion for future work that uses summary statistics to build test statistics to meta-analyze the data.

Modern Advances in Genetic Testing: Ethical Challenges and Training Implications for Current and Future Psychologists

PubMed Central

Richmond-Rakerd, Leah S.

2014-01-01

The ethical implications for psychological practice of genetic testing are largely unexplored. Predictive testing can have a significant impact on health and well-being, and increasing numbers of individuals with knowledge of their risk for various disorders are likely to present for psychotherapy. In addition, more people will struggle with the decision of whether to obtain information regarding their genetic material. Psychologists will need to have the appropriate knowledge and clinical skills to effectively counsel this population. This article highlights the relevant ethical issues surrounding psychological treatment of individuals pursuing or considering undergoing genetic testing. These issues are extended to psychologists working in research, education, and policy domains. Recommendations for graduate training programs to facilitate current and future practitioner competence are also discussed. PMID:24707160

Age-Related Phasic Patterns of Mitochondrial Maintenance in Adult Caenorhabditis elegans Neurons

PubMed Central

Morsci, Natalia S.; Hall, David H.

2016-01-01

Aging is associated with cognitive decline and increasing risk of neurodegeneration. Perturbation of mitochondrial function, dynamics, and trafficking are implicated in the pathogenesis of several age-associated neurodegenerative diseases. Despite this fundamental importance, the critical understanding of how organismal aging affects lifetime neuronal mitochondrial maintenance remains unknown, particularly in a physiologically relevant context. To address this issue, we performed a comprehensive in vivo analysis of age-associated changes in mitochondrial morphology, density, trafficking, and stress resistance in individual Caenorhabditis elegans neurons throughout adult life. Adult neurons display three distinct stages of increase, maintenance, and decrease in mitochondrial size and density during adulthood. Mitochondrial trafficking in the distal neuronal processes declines progressively with age starting from early adulthood. In contrast, long-lived daf-2 mutants exhibit delayed age-associated changes in mitochondrial morphology, constant mitochondrial density, and maintained trafficking rates during adulthood. Reduced mitochondrial load at late adulthood correlates with decreased mitochondrial resistance to oxidative stress. Revealing aging-associated changes in neuronal mitochondria in vivo is an essential precedent that will allow future elucidation of the mechanistic causes of mitochondrial aging. Thus, our study establishes the critical foundation for the future analysis of cellular pathways and genetic and pharmacological factors regulating mitochondrial maintenance in aging- and disease-relevant conditions. SIGNIFICANCE STATEMENT Using Caenorhabditis elegans as a model, we address long-standing questions: How does aging affect neuronal mitochondrial morphology, density, trafficking, and oxidative stress resistance? Are these age-related changes amenable to genetic manipulations that slow down the aging process? Our study illustrates that mitochondrial trafficking declines progressively from the first day of adulthood, whereas mitochondrial size, density, and resistance to oxidative stress undergo three distinct stages: increase in early adulthood, maintenance at high levels during mid-adulthood, and decline during late adulthood. Thus, our study characterizes mitochondrial aging profile at the level of a single neuron in its native environment and establishes the critical foundation for the future genetic and pharmacological dissection of factors that influence long-term mitochondrial maintenance in neurons. PMID:26818523

Genetics of Dyslipidemia and Ischemic Heart Disease.

PubMed

Sharma, Kavita; Baliga, Ragavendra R

2017-05-01

Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

Benefits and Limitations of Prenatal Screening for Prader-Willi Syndrome

PubMed Central

Butler, Merlin G.

2016-01-01

This review the status of genetic laboratory testing in Prader-Willi syndrome (PWS) due to different genetic subtypes, most often a paternally derived 15q11-q13 deletion, with benefits and limitations related to prenatal screening. Medical literature was searched for prenatal screening and genetic laboratory testing methods in use or under development and discussed in relationship to PWS. Genetic testing includes six established laboratory diagnostic approaches for PWS with direct application to prenatal screening. Ultrasonographic, obstetric and cytogenetic reports were summarized in relationship to the cause of Prader-Willi syndrome and identification of specific genetic subtypes including maternal disomy 15. Advances in genetic technology were described for diagnosing PWS specifically DNA methylation and high-resolution chromosomal SNP microarrays as current tools for genetic screening and incorporating next generation DNA sequencing for noninvasive prenatal testing (NIPT) using cell-free fetal DNA. Positive experiences are reported with NIPT for detection of numerical chromosomal problems (aneuploidies) but not for structural problems (microdeletions). These reports will be discussed along with future directions for genetic screening of PWS. In summary, this review describes and discusses the status of established and ongoing genetic testing options for PWS applicable in prenatal screening including NIPT and future directions for early diagnosis in Prader-Willi syndrome. PMID:27537837

Benefits and limitations of prenatal screening for Prader-Willi syndrome.

PubMed

Butler, Merlin G

2017-01-01

This review summarizes the status of genetic laboratory testing in Prader-Willi syndrome (PWS) with different genetic subtypes, most often a paternally derived 15q11-q13 deletion and discusses benefits and limitations related to prenatal screening. Medical literature was searched for prenatal screening and genetic laboratory testing methods in use or under development and discussed in relationship to PWS. Genetic testing includes six established laboratory diagnostic approaches for PWS with direct application to prenatal screening. Ultrasonographic, obstetric and cytogenetic reports were summarized in relationship to the cause of PWS and identification of specific genetic subtypes including maternal disomy 15. Advances in genetic technology were described for diagnosing PWS specifically DNA methylation and high-resolution chromosomal SNP microarrays as current tools for genetic screening and incorporating next generation DNA sequencing for noninvasive prenatal testing (NIPT) using cell-free fetal DNA. Positive experiences are reported with NIPT for detection of numerical chromosomal problems (aneuploidies) but not for structural problems (microdeletions). These reports will be discussed along with future directions for genetic screening of PWS. In summary, this review describes and discusses the status of established and ongoing genetic testing options for PWS applicable in prenatal screening including NIPT and future directions for early diagnosis in PWS. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Aquaculture genomics, genetics and breeding in the United States: Current status, challenges, and priorities for future research

USDA-ARS?s Scientific Manuscript database

Advancing the production efficiency and profitability of aquaculture is dependent upon the ability to utilize a diverse array of genetic resources. The ultimate goals of aquaculture genomics, genetics and breeding research are to enhance aquaculture production efficiency, sustainability, product qua...

The genetic architecture of coronary artery disease: current knowledge and future opportunities

USDA-ARS?s Scientific Manuscript database

Recent Findings Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part mod...

Current achievements and future directions in genetic engineering of european plum (Prunus domestica L.)

USDA-ARS?s Scientific Manuscript database

In most woody fruit species, transformation and regeneration are difficult. However, European plum (Prunus domestica) has been shown to be amenable to genetic improvement technologies from classical hybridization, to genetic engineering, to rapid cycle crop breeding (‘FasTrack’ breeding). Since th...

Moderating Effects of Autism on Parent Views of Genetic Screening for Aggression

ERIC Educational Resources Information Center

May, Michael E.; Brandt, Rachel C.; Bohannan, Joseph K.

2012-01-01

Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies…

gDNA enrichment by a transposase-based technology for NGS analysis of the whole sequence of BRCA1, BRCA2, and 9 genes involved in DNA damage repair.

PubMed

Chevrier, Sandy; Boidot, Romain

2014-10-06

The widespread use of Next Generation Sequencing has opened up new avenues for cancer research and diagnosis. NGS will bring huge amounts of new data on cancer, and especially cancer genetics. Current knowledge and future discoveries will make it necessary to study a huge number of genes that could be involved in a genetic predisposition to cancer. In this regard, we developed a Nextera design to study 11 complete genes involved in DNA damage repair. This protocol was developed to safely study 11 genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, PALB2, RAD50, RAD51C, RAD80, and TP53) from promoter to 3'-UTR in 24 patients simultaneously. This protocol, based on transposase technology and gDNA enrichment, gives a great advantage in terms of time for the genetic diagnosis thanks to sample multiplexing. This protocol can be safely used with blood gDNA.

Host genetic determinants of HIV pathogenesis: an immunologic perspective.

PubMed

Hunt, Peter W; Carrington, Mary

2008-05-01

The purpose of this review is to highlight recent advances in our understanding of host genetic determinants of HIV pathogenesis and to provide a theoretical framework for interpreting these studies in the context of our evolving understanding of HIV immunopathogenesis. The first genome-wide association analysis of host determinants of HIV pathogenesis and other recent studies evaluating the interaction between killer cell immunoglobulin-like receptors and human leukocyte antigen alleles have implicated both adaptive and innate immune responses in the control of HIV replication. Furthermore, genetic variation associated with the expression of CCR5 and its ligand have been strongly associated with both decreased susceptibility to HIV infection and delayed clinical progression, independent of their effects on viral replication, suggesting a potential role for CCR5 inhibitors as immune-based therapies in HIV disease. Host factors associated with the control of HIV replication may help identify important targets for vaccine design, while those associated with delayed clinical progression provide targets for future immune-based therapies against HIV infection.

Identifcation of a Novel Mutation p.I240T in the FRMD7 gene in a Family with Congenital Nystagmus

NASA Astrophysics Data System (ADS)

Zhu, Yihua; Zhuang, Jianfu; Ge, Xianglian; Zhang, Xiao; Wang, Zheng; Sun, Ji; Yang, Juhua; Gu, Feng

2013-10-01

Congenital Nystagmus (CN) is a genetically heterogeneous ocular disease, which causes a significant proportion of childhood visual impairment. To identify the underlying genetic defect of a CN family, twenty-two members were recruited. Genotype analysis showed that affected individuals shared a common haplotype with markers flanking FRMD7 locus. Sequencing FRMD7 revealed a T > C transition in exon 8, causing a conservative substitution of Isoleucine to Tyrosine at codon 240. By protein structural modeling, we found the mutation may disrupt the hydrophobic core and destabilize the protein structure. We reviewed the literature and found that exons 2, 8, and 9 (11.4% of the sequence of FRMD7 mRNA) represent the majority (55.3%) of the reported FRMD7 mutations. In summary, we identified a novel mutation in FRMD7, showed its molecular consequence, and revealed the mutation-rich exons of the FRMD7 gene. Collectively, this provides molecular insights for future CN clinical genetic diagnosis and treatment.

Genetic Dosage Compensation in a Family with Velo-cardio-facial/DiGeorge/22q11.2 Deletion Syndrome

PubMed Central

Alkalay, Avishai A.; Guo, Tingwei; Montagna, Cristina; Digilio, M. Cristina; Marino, Bruno; Dallapiccola, Bruno; Morrow, Bernice

2014-01-01

Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome revealed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carries a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as revealed by fluorescence in situ hybridization and array comparative genome hybridization analysis. The most parsimonious mechanism for the rearrangement is a mitotic non-allelic homologous recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for genetic counseling of future children. PMID:21337693

The Role of Adolescent Nutrition and Physical Activity in the Prediction of Verbal Intelligence during Early Adulthood: A Genetically Informed Analysis of Twin Pairs

PubMed Central

Jackson, Dylan B.; Beaver, Kevin M.

2015-01-01

A large body of research has revealed that nutrition and physical activity influence brain functioning at various stages of the life course. Nevertheless, very few studies have explored whether diet and exercise influence verbal intelligence as youth transition from adolescence into young adulthood. Even fewer studies have explored the link between these health behaviors and verbal intelligence while accounting for genetic and environmental factors that are shared between siblings. Employing data from the National Longitudinal Study of Adolescent Health, the current study uses a sample of same-sex twin pairs to test whether youth who engage in poorer fitness and nutritional practices are significantly more likely to exhibit reduced verbal intelligence during young adulthood. The results suggests that, independent of the effects of genetic and shared environmental factors, a number of nutritional and exercise factors during adolescence influence verbal intelligence during adulthood. Limitations are noted and suggestions for future research are outlined. PMID:25568969

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

NASA Astrophysics Data System (ADS)

McLaughlin, Russell L.; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R.; O'Brien, Margaret; Kahn, René S.; Ophoff, Roel A.; Goris, An; Bradley, Daniel G.; Al-Chalabi, Ammar; van den Berg, Leonard H.; Luykx, Jurjen J.; Hardiman, Orla; Veldink, Jan H.; Shatunov, Aleksey; Dekker, Annelot M.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; van Doormaal, Perry T. C.; Sproviero, William; Jones, Ashley R.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Bauer, Denis; Kahlke, Tim; Williams, Kelly; Eftimov, Filip; Fogh, Isabella; Ticozzi, Nicola; Lin, Kuang; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Petri, Susanne; Abdulla, Susanna; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, Nazli; Meitinger, Thomas; Lichtner, Peter; Blagojevic-Radivojkov, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safa; Dürr, Alexandra; Wood, Nicholas; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöuthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; van der Kooi, Anneke J.; de Visser, Marianne; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P.; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simon; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Blair, Ian; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Brown, Robert H.; Glass, Jonathan; Landers, John E.; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T. R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberley D.; Chan, Raymond C. K.; Chan, Ronald Y. L.; Chen, Eric Y. H.; Cheng, Wei; Cheung, Eric F. C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Lee, Jimmy; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik K. E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O'Callaghan, Eadbhard; O'Dushlaine, Colm; O'Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C. A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H. M.; Wormley, Brandon K.; Xi, Hualin Simon; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R.; Stefansson, Kari; Visscher, Peter M.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H. R.; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jönsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Riley, Brien P.; Rujescu, Dan; Sham, Pak C.; Sklar, Pamela; St Clair, David; Weinberger, Daniel R.; Wendland, Jens R.; Werge, Thomas; Daly, Mark J.; Sullivan, Patrick F.; O'Donovan, Michael C.

2017-03-01

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6 P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.

PubMed

McLaughlin, Russell L; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R; O'Brien, Margaret; Kahn, René S; Ophoff, Roel A; Goris, An; Bradley, Daniel G; Al-Chalabi, Ammar; van den Berg, Leonard H; Luykx, Jurjen J; Hardiman, Orla; Veldink, Jan H

2017-03-21

We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 × 10 -4 ) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10 -7 ). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

Identifcation of a novel mutation p.I240T in the FRMD7 gene in a family with congenital nystagmus.

PubMed

Zhu, Yihua; Zhuang, Jianfu; Ge, Xianglian; Zhang, Xiao; Wang, Zheng; Sun, Ji; Yang, Juhua; Gu, Feng

2013-10-30

Congenital Nystagmus (CN) is a genetically heterogeneous ocular disease, which causes a significant proportion of childhood visual impairment. To identify the underlying genetic defect of a CN family, twenty-two members were recruited. Genotype analysis showed that affected individuals shared a common haplotype with markers flanking FRMD7 locus. Sequencing FRMD7 revealed a T > C transition in exon 8, causing a conservative substitution of Isoleucine to Tyrosine at codon 240. By protein structural modeling, we found the mutation may disrupt the hydrophobic core and destabilize the protein structure. We reviewed the literature and found that exons 2, 8, and 9 (11.4% of the sequence of FRMD7 mRNA) represent the majority (55.3%) of the reported FRMD7 mutations. In summary, we identified a novel mutation in FRMD7, showed its molecular consequence, and revealed the mutation-rich exons of the FRMD7 gene. Collectively, this provides molecular insights for future CN clinical genetic diagnosis and treatment.

Identifcation of a Novel Mutation p.I240T in the FRMD7 gene in a Family with Congenital Nystagmus

PubMed Central

Zhu, Yihua; Zhuang, Jianfu; Ge, Xianglian; Zhang, Xiao; Wang, Zheng; Sun, Ji; Yang, Juhua; Gu, Feng

2013-01-01

Congenital Nystagmus (CN) is a genetically heterogeneous ocular disease, which causes a significant proportion of childhood visual impairment. To identify the underlying genetic defect of a CN family, twenty-two members were recruited. Genotype analysis showed that affected individuals shared a common haplotype with markers flanking FRMD7 locus. Sequencing FRMD7 revealed a T > C transition in exon 8, causing a conservative substitution of Isoleucine to Tyrosine at codon 240. By protein structural modeling, we found the mutation may disrupt the hydrophobic core and destabilize the protein structure. We reviewed the literature and found that exons 2, 8, and 9 (11.4% of the sequence of FRMD7 mRNA) represent the majority (55.3%) of the reported FRMD7 mutations. In summary, we identified a novel mutation in FRMD7, showed its molecular consequence, and revealed the mutation-rich exons of the FRMD7 gene. Collectively, this provides molecular insights for future CN clinical genetic diagnosis and treatment. PMID:24169426

AFLP markers reveal high clonal diversity and extreme longevity in four key arctic-alpine species.

PubMed

de Witte, Lucienne C; Armbruster, Georg F J; Gielly, Ludovic; Taberlet, Pierre; Stöcklin, Jürg

2012-03-01

We investigated clonal diversity, genet size structure and genet longevity in populations of four arctic-alpine plants (Carex curvula, Dryas octopetala, Salix herbacea and Vaccinium uliginosum) to evaluate their persistence under past climatic oscillations and their potential resistance to future climate change. The size and number of genets were determined by an analysis of amplified fragment length polymorphisms and a standardized sampling design in several European arctic-alpine populations, where these species are dominant in the vegetation. Genet age was estimated by dividing the size by the annual horizontal size increment from in situ growth measurements. Clonal diversity was generally high but differed among species, and the frequency distribution of genet size was strongly left-skewed. The largest C. curvula genet had an estimated minimum age of c. 4100 years and a maximum age of c. 5000 years, although 84.8% of the genets in this species were <200 years old. The oldest genets of D. octopetala, S. herbacea and V. uliginosum were found to be at least 500, 450 and 1400 years old, respectively. These results indicate that individuals in the studied populations have survived pronounced climatic oscillations, including the Little Ice Age and the postindustrial warming. The presence of genets in all size classes and the dominance of presumably young individuals suggest repeated recruitment over time, a precondition for adaptation to changing environmental conditions. Together, persistence and continuous genet turnover may ensure maximum ecosystem resilience. Thus, our results indicate that long-lived clonal plants in arctic-alpine ecosystems can persist, despite considerable climatic change. © 2011 Blackwell Publishing Ltd.

Inflammatory Bowel Disease: Genetics, Epigenetics, and Pathogenesis

PubMed Central

Loddo, Italia; Romano, Claudio

2015-01-01

Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although etiology remains largely unknown, recent research has suggested that genetic factors, environment, microbiota, and immune response are involved in the pathogenesis. Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn’s Disease (CD) have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to <10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci. Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early-onset IBD (before 5 years) or very early onset IBD (before 2 years). Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, ~50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice. The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is an emerging field, and future studies could provide new insight into the pathogenesis of IBD. PMID:26579126

Indirect Genetic Effects and the Spread of Infectious Disease: Are We Capturing the Full Heritable Variation Underlying Disease Prevalence?

PubMed Central

Lipschutz-Powell, Debby; Woolliams, John A.; Bijma, Piter; Doeschl-Wilson, Andrea B.

2012-01-01

Reducing disease prevalence through selection for host resistance offers a desirable alternative to chemical treatment. Selection for host resistance has proven difficult, however, due to low heritability estimates. These low estimates may be caused by a failure to capture all the relevant genetic variance in disease resistance, as genetic analysis currently is not taylored to estimate genetic variation in infectivity. Host infectivity is the propensity of transmitting infection upon contact with a susceptible individual, and can be regarded as an indirect effect to disease status. It may be caused by a combination of physiological and behavioural traits. Though genetic variation in infectivity is difficult to measure directly, Indirect Genetic Effect (IGE) models, also referred to as associative effects or social interaction models, allow the estimation of this variance from more readily available binary disease data (infected/non-infected). We therefore generated binary disease data from simulated populations with known amounts of variation in susceptibility and infectivity to test the adequacy of traditional and IGE models. Our results show that a conventional model fails to capture the genetic variation in infectivity inherent in populations with simulated infectivity. An IGE model, on the other hand, does capture some of the variation in infectivity. Comparison with expected genetic variance suggests that there is scope for further methodological improvement, and that potential responses to selection may be greater than values presented here. Nonetheless, selection using an index of estimated direct and indirect breeding values was shown to have a greater genetic selection differential and reduced future disease risk than traditional selection for resistance only. These findings suggest that if genetic variation in infectivity substantially contributes to disease transmission, then breeding designs which explicitly incorporate IGEs might help reduce disease prevalence. PMID:22768088

Cloning humans? Biological, ethical, and social considerations.

PubMed

Ayala, Francisco J

2015-07-21

There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits.

Cloning humans? Biological, ethical, and social considerations

PubMed Central

Ayala, Francisco J.

2015-01-01

There are, in mankind, two kinds of heredity: biological and cultural. Cultural inheritance makes possible for humans what no other organism can accomplish: the cumulative transmission of experience from generation to generation. In turn, cultural inheritance leads to cultural evolution, the prevailing mode of human adaptation. For the last few millennia, humans have been adapting the environments to their genes more often than their genes to the environments. Nevertheless, natural selection persists in modern humans, both as differential mortality and as differential fertility, although its intensity may decrease in the future. More than 2,000 human diseases and abnormalities have a genetic causation. Health care and the increasing feasibility of genetic therapy will, although slowly, augment the future incidence of hereditary ailments. Germ-line gene therapy could halt this increase, but at present, it is not technically feasible. The proposal to enhance the human genetic endowment by genetic cloning of eminent individuals is not warranted. Genomes can be cloned; individuals cannot. In the future, therapeutic cloning will bring enhanced possibilities for organ transplantation, nerve cells and tissue healing, and other health benefits. PMID:26195738

Mitochondrial DNA Suggests a Western Eurasian Origin for Ancient (Proto-) Bulgarians.

PubMed

Nesheva, D V; Karachanak-Yankova, S; Lari, M; Yordanov, Y; Galabov, A; Caramelli, D; Toncheva, D

2015-01-01

Ancient (proto-) Bulgarians have long been thought of as a Turkic population. However, evidence found in the past three decades shows that this is not the case. Until now, this evidence has not included ancient mitochondrial DNA (mtDNA) analysis. To fill this void, we collected human remains from the 8th to the 10th century AD located in three necropolises in Bulgaria: Nojarevo (Silistra region) and Monastery of Mostich (Shumen region), both in northeastern Bulgaria, and Tuhovishte (Satovcha region) in southwestern Bulgaria. The phylogenetic analysis of 13 ancient DNA samples (extracted from teeth) identified 12 independent haplotypes, which we further classified into mtDNA haplogroups found in present-day European and western Eurasian populations. Our results suggest a western Eurasian matrilineal origin for proto-Bulgarians, as well as a genetic similarity between proto- and modern Bulgarians. Our future work will provide additional data that will further clarify proto-Bulgarian origins, thereby adding new clues to the current understanding of European genetic evolution.

Genomic analysis reveals hidden biodiversity within colugos, the sister group to primates

PubMed Central

Mason, Victor C.; Li, Gang; Minx, Patrick; Schmitz, Jürgen; Churakov, Gennady; Doronina, Liliya; Melin, Amanda D.; Dominy, Nathaniel J.; Lim, Norman T-L.; Springer, Mark S.; Wilson, Richard K.; Warren, Wesley C.; Helgen, Kristofer M.; Murphy, William J.

2016-01-01

Colugos are among the most poorly studied mammals despite their centrality to resolving supraordinal primate relationships. Two described species of these gliding mammals are the sole living members of the order Dermoptera, distributed throughout Southeast Asia. We generated a draft genome sequence for a Sunda colugo and a Philippine colugo reference alignment, and used these to identify colugo-specific genetic changes that were enriched in sensory and musculoskeletal-related genes that likely underlie their nocturnal and gliding adaptations. Phylogenomic analysis and catalogs of rare genomic changes overwhelmingly support the contested hypothesis that colugos are the sister group to primates (Primatomorpha), to the exclusion of treeshrews. We captured ~140 kb of orthologous sequence data from colugo museum specimens sampled across their range and identified large genetic differences between many geographically isolated populations that may result in a >300% increase in the number of recognized colugo species. Our results identify conservation units to mitigate future losses of this enigmatic mammalian order. PMID:27532052

What should we want to know about our future? A Kantian view on predictive genetic testing.

PubMed

Heinrichs, Bert

2005-01-01

Recent advances in genomic research have led to the development of new diagnostic tools, including tests which make it possible to predict the future occurrence of monogenetic diseases (e.g. Chorea Huntington) or to determine increased susceptibilities to the future development of more complex diseases (e.g. breast cancer). The use of such tests raises a number of ethical, legal and social issues which are usually discussed in terms of rights. However, in the context of predictive genetic tests a key question arises which lies beyond the concept of rights, namely, What should we want to know about our future? In the following I shall discuss this question against the background of Kant's Doctrine of Virtue. It will be demonstrated that the system of duties of virtue that Kant elaborates in the second part of his Metaphysics of Morals offers a theoretical framework for addressing the question of a proper scope of future knowledge as provided by genetic tests. This approach can serve as a source of moral guidance complementary to a justice perspective. It does, however, not rest on the-rather problematic--claim to be able to define what the "good life" is.

The silencing of Kierkegaard in Habermas' critique of genetic enhancement.

PubMed

Christiansen, Karin

2009-06-01

The main purpose of this paper is to draw attention to an important part of Habermas' critique of genetic enhancement, which has been largely ignored in the discussion; namely his use of Kierkegaard's reflections on the existential conditions for becoming one-self from Either/or and the Sickness unto Death. It will be argued that, although Habermas presents some valuable and highly significant perspectives on the effect of genetic enhancement on the individual's self-understanding and ability to experience him- or herself as a free and equal individual, he does not succeed in working out a consistent argument. The claim is that he fails to explain how the existential analysis is related to his reflections on the sociological and psychological impacts of genetic enhancement in the realm of communicative action. It is this lack of theoretical clarity, which seems to render Habermas vulnerable to some of the critique which has been raised against his theory from a number of different scientific disciplines and areas of research. Hence, the first part of the paper provides some examples of the nature and variety of this critique, the second part presents Habermas' own critique of genetic enhancement in the context of a dispute between so-called 'liberal' and 'conservative' arguments, and finally, the third part discusses the limits and possibilities of his position in a future debate about genetic enhancement.

Phenotypic and genetic overlap between autistic traits at the extremes of the general population.

PubMed

Ronald, Angelica; Happé, Francesca; Price, Thomas S; Baron-Cohen, Simon; Plomin, Robert

2006-10-01

To investigate children selected from a community sample for showing extreme autistic-like traits and to assess the degree to which these individual traits--social impairments (SIs), communication impairments (CIs), and restricted repetitive behaviors and interests (RRBIs)--are caused by genes and environments, whether all of them are caused by the same genes and environments, and how often they occur together (as required by an autism diagnosis). The most extreme-scoring 5% were selected from 3,419 8-year-old pairs in the Twins Early Development Study assessed on the Childhood Asperger Syndrome Test. Phenotypic associations between extreme traits were compared with associations among the full-scale scores. Genetic associations between extreme traits were quantified using bivariate DeFries-Fulker extremes analysis. Phenotypic relationships between extreme SIs, CIs, and RRBIs were modest. There was a degree of genetic overlap between them, but also substantial genetic specificity. This first twin study assessing the links between extreme individual autistic-like traits (SIs, CIs, and RRBIs) found that all are highly heritable but show modest phenotypic and genetic overlap. This finding concurs with that of an earlier study from the same cohort that showed that a total autistic symptoms score at the extreme showed high heritability and that SIs, CIs, and RRBIs show weak links in the general population. This new finding has relevance for both clinical models and future molecular genetic studies.

Personalized translational epilepsy research - Novel approaches and future perspectives: Part I: Clinical and network analysis approaches.

PubMed

Rosenow, Felix; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Bauer, Sebastian

2017-11-01

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1]. Copyright © 2017 Elsevier Inc. All rights reserved.

Identity, prudential concern, and extended lives.

PubMed

Glannon, Walter

2002-06-01

Recent advances in human genetics suggest that it may become possible to genetically manipulate telomerase and embryonic stem cells to alter the mechanisms of aging and extend the human life span. But a life span significantly longer than the present norm would be undesirable because it would severely weaken the connections between past- and future-oriented mental states and turn the psychological grounds for personal identity and prudential concern for our future selves. In addition, the collective effects of longer lives might lower the quality of life for all people. These two problems provide reasons against genetic manipulation of cells to alter the length of the human life span.

Education Status of Oral Genetics at the Fourth Military Medical University and other Chinese Dental Schools.

PubMed

Zhang, Yan Li; Wang, Chang Ning; Fan, Zhi Peng; Jiao, Yang; Duan, Xiao Hong

To investigate the current state of genetics education at the Fourth Military Medical University (FMMU) and compare it with other dental schools of China. Detailed information about the history and current education status of Oral Genetics in the FMMU were collected and questionnaires were completed to acquire the feedback of twenty-seven students on the course. In the other thirty-five dental schools including the capitals of twenty-five provinces and four municipalities in China, information about the oral genetic course were collected by a telephone survey. The contents of survey included whether or not the Oral Genetic course is offered and some basic information about the curriculum (such as the content, hours, teachers' background and teaching methods). Among a total of thirty-six dental schools investigated, six of them (16.7%) offered the Oral Genetic course or related lectures/seminars. The length and contents of the curriculum vary among these schools. The FMMU offered the oral genetic curriculum both to undergraduates and graduated students. Their teachers had a broad range of backgrounds, such as dentistry, biology, genetics, and biochemistry. The students considered the Oral Genetics course to be helpful for their future professional careers. Genetic education in dentistry in China is still at a preliminary stage. More effort must be paid to spread the knowledge of Oral Genetics in China. In addition, domestic and international communications and networks for Oral Genetics should be set up in the near future.

Population genetic structure of Attalea vitrivir Zona (Arecaceae) in fragmented areas of southeast Brazil.

PubMed

Santos, R R M; Cavallari, M M; Pimenta, M A S; Abreu, A G; Costa, M R; Guedes, M L

2015-06-11

Attalea vitrivir Zona (synonym Orbignya oleifera) is one of the six species of Arecaceae known as "babassu". This species is used to make cosmetics, food, and detergents due to the high concentration of oil in the seeds. It is found only in fragmented areas of southern Bahia State and northern Minas Gerais State, southeast Brazil, and this fragmentation has affected both its ecological and genetic characteristics. We evaluated the genetic diversity and population genetic structure of A. vitrivir in six areas of two different regions at the extremes of its geographical range, in order to gain a better understanding of the factors that affect the distribution and partitioning of its diversity. Nine inter simple sequence repeat (ISSR) markers amplified 74 polymorphic bands, resulting in large diversity values (Shannon diversity index, 0.37-0.47; intrapopulation genetic diversity, 0.25-0.34). Analysis of molecular variance (AMOVA) revealed considerable differentiation between sampling sites (30.03%) and regions (12.08%), although most of the diversity was observed within sampling sites (69%). Further differentiation between sampling sites was noted more in the northern region than in the southern region, highlighting the genetic connectivity between the sampling sites within Rio Pandeiros Environmental Protection Area (southern region). The identification of two distinct genetic clusters (K = 2) corresponded to the northern and southern regions, and corroborated the AMOVA results. We suggest that the northern area, outside Rio Pandeiros Environmental Protection Area, must be included in future management plans for this species.

Clinical exome sequencing reports: current informatics practice and future opportunities.

PubMed

Swaminathan, Rajeswari; Huang, Yungui; Astbury, Caroline; Fitzgerald-Butt, Sara; Miller, Katherine; Cole, Justin; Bartlett, Christopher; Lin, Simon

2017-11-01

The increased adoption of clinical whole exome sequencing (WES) has improved the diagnostic yield for patients with complex genetic conditions. However, the informatics practice for handling information contained in whole exome reports is still in its infancy, as evidenced by the lack of a common vocabulary within clinical sequencing reports generated across genetic laboratories. Genetic testing results are mostly transmitted using portable document format, which can make secondary analysis and data extraction challenging. This paper reviews a sample of clinical exome reports generated by Clinical Laboratory Improvement Amendments-certified genetic testing laboratories at tertiary-care facilities to assess and identify common data elements. Like structured radiology reports, which enable faster information retrieval and reuse, structuring genetic information within clinical WES reports would help facilitate integration of genetic information into electronic health records and enable retrospective research on the clinical utility of WES. We identify elements listed as mandatory according to practice guidelines but are currently missing from some of the clinical reports, which might help to organize the data when stored within structured databases. We also highlight elements, such as patient consent, that, although they do not appear within any of the current reports, may help in interpreting some of the information within the reports. Integrating genetic and clinical information would assist the adoption of personalized medicine for improved patient care and outcomes. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders.

PubMed

Coleman, Jonathan R I; Lester, Kathryn J; Roberts, Susanna; Keers, Robert; Lee, Sang Hyuck; De Jong, Simone; Gaspar, Héléna; Teismann, Tobias; Wannemüller, André; Schneider, Silvia; Jöhren, Peter; Margraf, Jürgen; Breen, Gerome; Eley, Thalia C

2017-04-01

Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.

Population genetic characterization and family reconstruction in brood bank collections of the Indian major carp Labeo rohita (Cyprinidae:Cypriniformes).

PubMed

Ullah, Ashraf; Basak, Abhisak; Islam, Md Nazrul; Alam, Md Samsul

2015-01-01

The founder stock of a captive breeding program is prone to changes in genetic structure due to inbreeding and genetic drift. Genetic characterization of the founder population using suitable molecular markers may help monitor periodic changes in the genetic structure in future. To develop benchmark information about the genetic structure we analyzed six microsatellite loci in the Brodbank collections of rohu (Labeo rohita) originated from three major rivers-the Jamuna, the Padma and the Halda. A total of 28 alleles were detected in 90 individuals with an average of 4.6 alleles per locus. The average observed heterozygosity ranged from 0.655 to 0.705 and the expected heterozygosity ranged from 0.702 to 0.725. The mean F IS values were 0.103, 0.106 and 0.018 for the Jamuna, Padma and Halda fishes respectively. The population pair-wise F ST values ranged from 0.0057 to 0.0278. Structure analysis grouped the fishes of the three rivers into two clusters. The numbers of half-sib families were 5, 5 and 4 and the numbers of full-sib families were 12, 10 and 18 for the Halda, Jamuna and the Padma samples respectively. Bottleneck was detected in all the river samples. We recommend to collect more fish from different locations of the major rivers to broaden the genetic variability of the founder stocks of the Brood bank.

Genetic and morphological structure of a spruce hybrid (Picea sitchensis x P. glauca) zone along a climatic gradient.

PubMed

Hamilton, Jill A; Aitken, Sally N

2013-08-01

Historic colonization and contemporary evolutionary processes contribute to patterns of genetic variation and differentiation among populations. However, separating the respective influences of these processes remains a challenge, particularly for natural hybrid zones, where standing genetic variation may result from evolutionary processes both preceding and following contact, influencing the evolutionary trajectory of hybrid populations. Where adaptation to novel environments may be facilitated by interspecific hybridization, teasing apart these processes will have practical implications for forest management in changing environments. We evaluated the neutral genetic architecture of the Picea sitchensis (Sitka spruce) × P. glauca (white spruce) hybrid zone along the Nass and Skeena river valleys in northwestern British Columbia using chloroplast, mitochondrial, and nuclear microsatellite markers, in combination with cone morphological traits. Sitka spruce mitotype "capture", evidenced by this species dominating the maternal lineage, is consistent with earlier colonization of the region by Sitka spruce. This "capture" differs from the spatial distribution of chloroplast haplotypes, indicating pollen dispersal and its contribution to geographic structure. Genetic ancestry, based on nuclear markers, was strongly influenced by climate and geography. Highly parallel results for replicate transects along environmental gradients provide support for the bounded hybrid superiority model of hybrid zone maintenance. • This broad-scale analysis of neutral genetic structure indicates the importance of historic and contemporary gene flow, environmental selection, and their interaction in shaping neutral genetic variation within this hybrid zone, informative to seed transfer development and reforestation for future climates.

Reproductive Decision Making and Genetic Predisposition to Sudden Cardiac Death

PubMed Central

Barlevy, Dorit; Wasserman, David; Stolerman, Marina; Erskine, Kathleen E.; Dolan, Siobhan M.

2012-01-01

Background With current genetic technology, it is possible to detect mutations associated with long QT syndrome (LQTS), a hereditary cardiac arrhythmia syndrome. As a result, prospective parents diagnosed with LQTS will have to decide whether or not to prevent its transmission to future generations, either by not procreating or through the use of assisted reproductive technologies or prenatal testing. This paper explores how a hereditary predisposition to sudden cardiac death can influence reproductive decision making. Methods This study draws from interviews and focus groups with individuals who have personal or family histories of cardiac arrhythmia or sudden death. A keyword search was conducted on interview transcripts to identify quotes for analysis. Results Participants expressed complex, often ambivalent attitudes about the prospect of having a child with a predisposition to sudden cardiac death. Their comments reveal conflicting understandings of genetic responsibility and reflect the variable effects of personal experience on reproductive decision making. This paper compares attitudes towards LQTS and other genetic conditions in analyzing the themes that emerged in interviews and focus groups. Conclusions The “disability critique” of prenatal testing should be applied carefully to a context of genetic predisposition to sudden cardiac death in order to understand reproductive decision making. Firsthand experience with the condition, among other factors, can weigh heavily in those decisions. PMID:22822470

Genetic diversity and population structure of Plasmodium falciparum over space and time in an African archipelago.

PubMed

Salgueiro, Patrícia; Vicente, José Luís; Figueiredo, Rita Carrilho; Pinto, João

2016-09-01

The archipelago of São Tomé and Principe (STP), West Africa, has suffered the heavy burden of malaria since the 16th century. Until the last decade, when after a successful control program STP has become a low transmission country and one of the few nations with decreases of more than 90% in malaria admission and death rates. We carried out a longitudinal study to determine the genetic structure of STP parasite populations over time and space. Twelve microsatellite loci were genotyped in Plasmodium falciparum samples from two islands collected in 1997, 2000 and 2004. Analysis was performed on proportions of mixed genotype infections, allelic diversity, population differentiation, effective population size and bottleneck effects. We have found high levels of genetic diversity and minimal inter-population genetic differentiation typical of African continental regions with intense and stable malaria transmission. We detected significant differences between the years, with special emphasis for 1997 that showed the highest proportion of samples infected with P. falciparum and the highest mean number of haplotypes per isolate. This study establishes a comprehensive genetic data baseline of a pre-intervention scenario for future studies; taking into account the most recent and successful control intervention on the territory. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic engineering possibilities for CELSS: A bibliography and summary of techniques

NASA Technical Reports Server (NTRS)

Johnson, E. J.

1982-01-01

A bibliography of the most useful techniques employed in genetic engineering of higher plants, bacteria associated with plants, and plant cell cultures is provided. A resume of state-of-the-art genetic engineering of plants and bacteria is presented. The potential application of plant bacterial genetic engineering to CELSS (Controlled Ecological Life Support System) program and future research needs are discussed.

Impact of exome sequencing in inflammatory bowel disease

PubMed Central

Cardinale, Christopher J; Kelsen, Judith R; Baldassano, Robert N; Hakonarson, Hakon

2013-01-01

Approaches to understanding the genetic contribution to inflammatory bowel disease (IBD) have continuously evolved from family- and population-based epidemiology, to linkage analysis, and most recently, to genome-wide association studies (GWAS). The next stage in this evolution seems to be the sequencing of the exome, that is, the regions of the human genome which encode proteins. The GWAS approach has been very fruitful in identifying at least 163 loci as being associated with IBD, and now, exome sequencing promises to take our genetic understanding to the next level. In this review we will discuss the possible contributions that can be made by an exome sequencing approach both at the individual patient level to aid with disease diagnosis and future therapies, as well as in advancing knowledge of the pathogenesis of IBD. PMID:24187447

Trade Studies for a Manned High-Power Nuclear Electric Propulsion Vehicle

NASA Technical Reports Server (NTRS)

SanSoucie, Michael; Hull, Patrick V.; Irwin, Ryan W.; TInker, Michael L.; Patton, Bruce W.

2005-01-01

Nuclear electric propulsion (NEP) vehicles will be needed for future manned missions to Mars and beyond. Candidate vehicles must be identified through trade studies for further detailed design from a large array of possibilities. Genetic algorithms have proven their utility in conceptual design studies by effectively searching a large design space to pinpoint unique optimal designs. This research combines analysis codes for NEP subsystems with genetic algorithm-based optimization. Trade studies for a NEP reference mission to the asteroids were conducted to identify important trends, and to determine the effects of various technologies and subsystems on vehicle performance. It was found that the electric thruster type and thruster performance have a major impact on the achievable system performance, and that significant effort in thruster research and development is merited.

A Systematic Review of Genetic Testing and Lifestyle Behaviour Change: Are We Using High-Quality Genetic Interventions and Considering Behaviour Change Theory?

PubMed

Horne, Justine; Madill, Janet; O'Connor, Colleen; Shelley, Jacob; Gilliland, Jason

2018-04-10

Studying the impact of genetic testing interventions on lifestyle behaviour change has been a priority area of research in recent years. Substantial heterogeneity exists in the results and conclusions of this literature, which has yet to be explained using validated behaviour change theory and an assessment of the quality of genetic interventions. The theory of planned behaviour (TPB) helps to explain key contributors to behaviour change. It has been hypothesized that personalization could be added to this theory to help predict changes in health behaviours. This systematic review provides a detailed, comprehensive identification, assessment, and summary of primary research articles pertaining to lifestyle behaviour change (nutrition, physical activity, sleep, and smoking) resulting from genetic testing interventions. The present review further aims to provide in-depth analyses of studies conducted to date within the context of the TPB and the quality of genetic interventions provided to participants while aiming to determine whether or not genetic testing facilitates changes in lifestyle habits. This review is timely in light of a recently published "call-to-action" paper, highlighting the need to incorporate the TPB into personalized healthcare behaviour change research. Three bibliographic databases, one key website, and article reference lists were searched for relevant primary research articles. The PRISMA Flow Diagram and PRISMA Checklist were used to guide the search strategy and manuscript preparation. Out of 32,783 titles retrieved, 26 studies met the inclusion criteria. Three quality assessments were conducted and included: (1) risk of bias, (2) quality of genetic interventions, and (3) consideration of theoretical underpinnings - primarily the TPB. Risk of bias in studies was overall rated to be "fair." Consideration of the TPB was "poor," with no study making reference to this validated theory. While some studies (n = 11; 42%) made reference to other behaviour change theories, these theories were generally mentioned briefly, and were not thoroughly incorporated into the study design or analyses. The genetic interventions provided to participants were overall of "poor" quality. However, a separate analysis of studies using controlled intervention research methods demonstrated the use of higher-quality genetic interventions (overall rated to be "fair"). The provision of actionable recommendations informed by genetic testing was more likely to facilitate behaviour change than the provision of genetic information without actionable lifestyle recommendations. Several studies of good quality demonstrated changes in lifestyle habits arising from the provision of genetic interventions. The most promising lifestyle changes were changes in nutrition. It is possible to facilitate behaviour change using genetic testing as the catalyst. Future research should ensure that high-quality genetic interventions are provided to participants, and should consider validated theories such as the TPB in their study design and analyses. Further recommendations for future research are provided. © 2018 S. Karger AG, Basel.

Importance of genetic diversity assessment in crop plants and its recent advances: an overview of its analytical perspectives.

PubMed

Govindaraj, M; Vetriventhan, M; Srinivasan, M

2015-01-01

The importance of plant genetic diversity (PGD) is now being recognized as a specific area since exploding population with urbanization and decreasing cultivable lands are the critical factors contributing to food insecurity in developing world. Agricultural scientists realized that PGD can be captured and stored in the form of plant genetic resources (PGR) such as gene bank, DNA library, and so forth, in the biorepository which preserve genetic material for long period. However, conserved PGR must be utilized for crop improvement in order to meet future global challenges in relation to food and nutritional security. This paper comprehensively reviews four important areas; (i) the significance of plant genetic diversity (PGD) and PGR especially on agriculturally important crops (mostly field crops); (ii) risk associated with narrowing the genetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods in pregenomic and genomic era; and (iv) modern tools available for PGD analysis in postgenomic era. This discussion benefits the plant scientist community in order to use the new methods and technology for better and rapid assessment, for utilization of germplasm from gene banks to their applied breeding programs. With the advent of new biotechnological techniques, this process of genetic manipulation is now being accelerated and carried out with more precision (neglecting environmental effects) and fast-track manner than the classical breeding techniques. It is also to note that gene banks look into several issues in order to improve levels of germplasm distribution and its utilization, duplication of plant identity, and access to database, for prebreeding activities. Since plant breeding research and cultivar development are integral components of improving food production, therefore, availability of and access to diverse genetic sources will ensure that the global food production network becomes more sustainable. The pros and cons of the basic and advanced statistical tools available for measuring genetic diversity are briefly discussed and their source links (mostly) were provided to get easy access; thus, it improves the understanding of tools and its practical applicability to the researchers.

Genetic polymorphisms of pharmacogenomic VIP variants in the Yi population from China.

PubMed

Yan, Mengdan; Li, Dianzhen; Zhao, Guige; Li, Jing; Niu, Fanglin; Li, Bin; Chen, Peng; Jin, Tianbo

2018-03-30

Drug response and target therapeutic dosage are different among individuals. The variability is largely genetically determined. With the development of pharmacogenetics and pharmacogenomics, widespread research have provided us a wealth of information on drug-related genetic polymorphisms, and the very important pharmacogenetic (VIP) variants have been identified for the major populations around the world whereas less is known regarding minorities in China, including the Yi ethnic group. Our research aims to screen the potential genetic variants in Yi population on pharmacogenomics and provide a theoretical basis for future medication guidance. In the present study, 80 VIP variants (selected from the PharmGKB database) were genotyped in 100 unrelated and healthy Yi adults recruited for our research. Through statistical analysis, we made a comparison between the Yi and other 11 populations listed in the HapMap database for significant SNPs detection. Two specific SNPs were subsequently enrolled in an observation on global allele distribution with the frequencies downloaded from ALlele FREquency Database. Moreover, F-statistics (Fst), genetic structure and phylogenetic tree analyses were conducted for determination of genetic similarity between the 12 ethnic groups. Using the χ2 tests, rs1128503 (ABCB1), rs7294 (VKORC1), rs9934438 (VKORC1), rs1540339 (VDR) and rs689466 (PTGS2) were identified as the significantly different loci for further analysis. The global allele distribution revealed that the allele "A" of rs1540339 and rs9934438 were more frequent in Yi people, which was consistent with the most populations in East Asia. F-statistics (Fst), genetic structure and phylogenetic tree analyses demonstrated that the Yi and CHD shared a closest relationship on their genetic backgrounds. Additionally, Yi was considered similar to the Han people from Shaanxi province among the domestic ethnic populations in China. Our results demonstrated significant differences on several polymorphic SNPs and supplement the pharmacogenomic information for the Yi population, which could provide new strategies for optimizing clinical medication in accordance with the genetic determinants of drug toxicity and efficacy. Copyright © 2018 Elsevier B.V. All rights reserved.

Importance of Genetic Diversity Assessment in Crop Plants and Its Recent Advances: An Overview of Its Analytical Perspectives

PubMed Central

Govindaraj, M.; Vetriventhan, M.; Srinivasan, M.

2015-01-01

The importance of plant genetic diversity (PGD) is now being recognized as a specific area since exploding population with urbanization and decreasing cultivable lands are the critical factors contributing to food insecurity in developing world. Agricultural scientists realized that PGD can be captured and stored in the form of plant genetic resources (PGR) such as gene bank, DNA library, and so forth, in the biorepository which preserve genetic material for long period. However, conserved PGR must be utilized for crop improvement in order to meet future global challenges in relation to food and nutritional security. This paper comprehensively reviews four important areas; (i) the significance of plant genetic diversity (PGD) and PGR especially on agriculturally important crops (mostly field crops); (ii) risk associated with narrowing the genetic base of current commercial cultivars and climate change; (iii) analysis of existing PGD analytical methods in pregenomic and genomic era; and (iv) modern tools available for PGD analysis in postgenomic era. This discussion benefits the plant scientist community in order to use the new methods and technology for better and rapid assessment, for utilization of germplasm from gene banks to their applied breeding programs. With the advent of new biotechnological techniques, this process of genetic manipulation is now being accelerated and carried out with more precision (neglecting environmental effects) and fast-track manner than the classical breeding techniques. It is also to note that gene banks look into several issues in order to improve levels of germplasm distribution and its utilization, duplication of plant identity, and access to database, for prebreeding activities. Since plant breeding research and cultivar development are integral components of improving food production, therefore, availability of and access to diverse genetic sources will ensure that the global food production network becomes more sustainable. The pros and cons of the basic and advanced statistical tools available for measuring genetic diversity are briefly discussed and their source links (mostly) were provided to get easy access; thus, it improves the understanding of tools and its practical applicability to the researchers. PMID:25874132

Strains and stressors: an analysis of touchscreen learning in genetically diverse mouse strains.

PubMed

Graybeal, Carolyn; Bachu, Munisa; Mozhui, Khyobeni; Saksida, Lisa M; Bussey, Timothy J; Sagalyn, Erica; Williams, Robert W; Holmes, Andrew

2014-01-01

Touchscreen-based systems are growing in popularity as a tractable, translational approach for studying learning and cognition in rodents. However, while mouse strains are well known to differ in learning across various settings, performance variation between strains in touchscreen learning has not been well described. The selection of appropriate genetic strains and backgrounds is critical to the design of touchscreen-based studies and provides a basis for elucidating genetic factors moderating behavior. Here we provide a quantitative foundation for visual discrimination and reversal learning using touchscreen assays across a total of 35 genotypes. We found significant differences in operant performance and learning, including faster reversal learning in DBA/2J compared to C57BL/6J mice. We then assessed DBA/2J and C57BL/6J for differential sensitivity to an environmental insult by testing for alterations in reversal learning following exposure to repeated swim stress. Stress facilitated reversal learning (selectively during the late stage of reversal) in C57BL/6J, but did not affect learning in DBA/2J. To dissect genetic factors underlying these differences, we phenotyped a family of 27 BXD strains generated by crossing C57BL/6J and DBA/2J. There was marked variation in discrimination, reversal and extinction learning across the BXD strains, suggesting this task may be useful for identifying underlying genetic differences. Moreover, different measures of touchscreen learning were only modestly correlated in the BXD strains, indicating that these processes are comparatively independent at both genetic and phenotypic levels. Finally, we examined the behavioral structure of learning via principal component analysis of the current data, plus an archival dataset, totaling 765 mice. This revealed 5 independent factors suggestive of "reversal learning," "motivation-related late reversal learning," "discrimination learning," "speed to respond," and "motivation during discrimination." Together, these findings provide a valuable reference to inform the choice of strains and genetic backgrounds in future studies using touchscreen-based tasks.

Assessment on induced genetic variability and divergence in the mutagenized lentil populations of microsperma and macrosperma cultivars developed using physical and chemical mutagenesis

PubMed Central

2017-01-01

Induced mutagenesis was employed to create genetic variation in the lentil cultivars for yield improvement. The assessments were made on genetic variability, character association, and genetic divergence among the twelve mutagenized populations and one parent population of each of the two lentil cultivars, developed by single and combination treatments with gamma rays and hydrazine hydrates. Analysis of variance revealed significant inter-population differences for the observed quantitative phenotypic traits. The sample mean of six treatment populations in each of the cultivar exhibited highly superior quantitative phenotypic traits compared to their parent cultivars. The higher values of heritability and genetic advance with a high genotypic coefficient of variation for most of the yield attributing traits confirmed the possibilities of lentil yield improvement through phenotypic selection. The number of pods and seeds per plant appeared to be priority traits in selection for higher yield due to their strong direct association with yield. The cluster analysis divided the total populations into three divergent groups in each lentil cultivar with parent genotypes in an independent group showing the high efficacy of the mutagens. Considering the highest contribution of yield trait to the genetic divergence among the clustered population, it was confirmed that the mutagenic treatments created a wide heritable variation for the trait in the mutant populations. The selection of high yielding mutants from the mutant populations of DPL 62 (100 Gy) and Pant L 406 (100Gy + 0.1% HZ) in the subsequent generation is expected to give elite lentil cultivars. Also, hybridization between members of the divergent group would produce diverse segregants for crop improvement. Apart from this, the induced mutations at loci controlling economically important traits in the selected high yielding mutants have successfully contributed in diversifying the accessible lentil genetic base and will definitely be of immense value to the future lentil breeding programmes in India. PMID:28922405

Psychiatric genetics in China: achievements and challenges

PubMed Central

Schulze, Thomas G.; Burmeister, Margit; Sham, Pak Chung; Yao, Yong-gang; Kuo, Po-Hsiu; Chen, Chao; An, Yu; Dai, Jiapei; Yue, Weihua; Li, Miao Xin; Xue, Hong; Su, Bing; Chen, Li; Shi, Yongyong; Qiao, Mingqi; Liu, Tiebang; Xia, Kun; Chan, Raymond C.K.

2016-01-01

To coordinate research efforts in psychiatric genetics in China, a group of Chinese and foreign investigators have established an annual “Summit on Chinese Psychiatric Genetics” to present their latest research and discuss the current state and future directions of this field. To date, two Summits have been held, the first in Changsha in April, 2014, and the second in Kunming in April, 2015. The consensus of roundtable discussions held at these meetings is that psychiatric genetics in China is in need of new policies to promote collaborations aimed at creating a framework for genetic research appropriate for the Chinese population: relying solely on Caucasian population-based studies may result in missed opportunities to diagnose and treat psychiatric disorders. In addition, participants agree on the importance of promoting collaborations and data sharing in areas where China has especially strong resources, such as advanced facilities for non-human primate studies and traditional Chinese medicine: areas that may also provide overseas investigators with unique research opportunities. In this paper, we present an overview of the current state of psychiatric genetics research in China, with emphasis on genome-level studies, and describe challenges and opportunities for future advances, particularly at the dawn of “precision medicine.” Together, we call on administrative bodies, funding agencies, the research community, and the public at large for increased support for research on the genetic basis of psychiatric disorders in the Chinese population. In our opinion, increased public awareness and effective collaborative research hold the keys to the future of psychiatric genetics in China. PMID:26481319

The adequacy of informed consent forms in genetic research in Oman: a pilot study.

PubMed

Al-Riyami, Asya; Jaju, Deepali; Jaju, Sanjay; Silverman, Henry J

2011-08-01

Genetic research presents ethical challenges to the achievement of valid informed consent, especially in developing countries with areas of low literacy. During the last several years, a number of genetic research proposals involving Omani nationals were submitted to the Department of Research and Studies, Ministry of Health, Oman. The objective of this paper is to report on the results of an internal quality assurance initiative to determine the extent of the information being provided in genetic research informed consent forms. In order to achieve this, we developed checklists to assess the inclusion of basic elements of informed consent as well as elements related to the collection and future storage of biological samples. Three of the authors independently evaluated and reached consensus on seven informed consent forms that were available for review. Of the seven consent forms, four had less than half of the basic elements of informed consent. None contained any information regarding whether genetic information relevant to health would be disclosed, whether participants may share in commercial products, the extent of confidentiality protections, and the inclusion of additional consent forms for future storage and use of tissue samples. Information regarding genetic risks and withdrawal of samples were rarely mentioned (1/7), whereas limits on future use of samples were mentioned in 3 of 7 consent forms. Ultimately, consent forms are not likely to address key issues regarding genetic research that have been recommended by research ethics guidelines. We recommend enhanced educational efforts to increase awareness, on the part of researchers, of information that should be included in consent forms. © 2011 Blackwell Publishing Ltd.

Artificial intelligence applied to the automatic analysis of absorption spectra. Objective measurement of the fine structure constant

NASA Astrophysics Data System (ADS)

Bainbridge, Matthew B.; Webb, John K.

2017-06-01

A new and automated method is presented for the analysis of high-resolution absorption spectra. Three established numerical methods are unified into one `artificial intelligence' process: a genetic algorithm (Genetic Voigt Profile FIT, gvpfit); non-linear least-squares with parameter constraints (vpfit); and Bayesian model averaging (BMA). The method has broad application but here we apply it specifically to the problem of measuring the fine structure constant at high redshift. For this we need objectivity and reproducibility. gvpfit is also motivated by the importance of obtaining a large statistical sample of measurements of Δα/α. Interactive analyses are both time consuming and complex and automation makes obtaining a large sample feasible. In contrast to previous methodologies, we use BMA to derive results using a large set of models and show that this procedure is more robust than a human picking a single preferred model since BMA avoids the systematic uncertainties associated with model choice. Numerical simulations provide stringent tests of the whole process and we show using both real and simulated spectra that the unified automated fitting procedure out-performs a human interactive analysis. The method should be invaluable in the context of future instrumentation like ESPRESSO on the VLT and indeed future ELTs. We apply the method to the zabs = 1.8389 absorber towards the zem = 2.145 quasar J110325-264515. The derived constraint of Δα/α = 3.3 ± 2.9 × 10-6 is consistent with no variation and also consistent with the tentative spatial variation reported in Webb et al. and King et al.

Impact of presymptomatic genetic testing on young adults: a systematic review.

PubMed

Godino, Lea; Turchetti, Daniela; Jackson, Leigh; Hennessy, Catherine; Skirton, Heather

2016-04-01

Presymptomatic and predictive genetic testing should involve a considered choice, which is particularly true when testing is undertaken in early adulthood. Young adults are at a key life stage as they may be developing a career, forming partnerships and potentially becoming parents: presymptomatic testing may affect many facets of their future lives. The aim of this integrative systematic review was to assess factors that influence young adults' or adolescents' choices to have a presymptomatic genetic test and the emotional impact of those choices. Peer-reviewed papers published between January 1993 and December 2014 were searched using eight databases. Of 3373 studies identified, 29 were reviewed in full text: 11 met the inclusion criteria. Thematic analysis was used to identify five major themes: period before testing, experience of genetic counselling, parental involvement in decision-making, impact of test result communication, and living with genetic risk. Many participants grew up with little or no information concerning their genetic risk. The experience of genetic counselling was either reported as an opportunity for discussing problems or associated with feelings of disempowerment. Emotional outcomes of disclosure did not directly correlate with test results: some mutation carriers were relieved to know their status, however, the knowledge they may have passed on the mutation to their children was a common concern. Parents appeared to have exerted pressure on their children during the decision-making process about testing and risk reduction surgery. Health professionals should take into account all these issues to effectively assist young adults in making decisions about presymptomatic genetic testing.

Spatial and temporal genetic analysis of Walleyes in the Ohio River

USGS Publications Warehouse

Page, Kevin S.; Zweifela, Richard D.; Stott, Wendylee

2017-01-01

Previous genetic analyses have shown that Walleyes Sander vitreus in the upper Ohio River comprise two distinct genetic strains: (1) fish of Great Lakes origin that were stocked into the Ohio River basin and (2) a remnant native strain (Highlands strain). Resource agencies are developing management strategies to conserve and restore the native strain within the upper reaches of the Ohio River. Hybridization between strains has impacted the genetic integrity of the native strain. To better understand the extent and effects of hybridization on the native strain, we used mitochondrial DNA and microsatellite markers to evaluate the spatial (river sections) and temporal (pre- and poststocking) genetic diversity of Ohio River Walleyes. Contemporary Lake Erie Walleyes and archival museum specimens collected from the Ohio River basin were used for comparison to contemporary Ohio River samples. Although there was evidence of hybridization between strains, most of the genetic diversity within the Ohio River was partitioned by basin of origin (Great Lakes versus the Ohio River), with greater similarity among river sections than between strains within the same section. Results also suggested that the native strain has diverged from historical populations. Furthermore, notable decreases in measures of genetic diversity and increased relatedness among native-strain Walleyes within two sections of the Ohio River may be related to stocking aimed at restoration of the Highlands strain. Our results suggest that although the Highlands strain persists within the Ohio River, it has diverged over time, and managers should consider the potential impacts of future management practices on the genetic diversity of this native strain.

Investigating genetic diversity and habitat dynamics in Plantago brutia (Plantaginaceae), implications for the management of narrow endemics in Mediterranean mountain pastures.

PubMed

De Vita, A; Bernardo, L; Gargano, D; Palermo, A M; Peruzzi, L; Musacchio, A

2009-11-01

Many factors have contributed to the richness of narrow endemics in the Mediterranean, including long-lasting human impact on pristine landscapes. The abandonment of traditional land-use practices is causing forest recovery throughout the Mediterranean mountains, by increasing reduction and fragmentation of open habitats. We investigated the population genetic structure and habitat dynamics of Plantago brutia Ten., a narrow endemic in mountain pastures of S Italy. Some plants were cultivated in the botanical garden to explore the species' breeding system. Genetic diversity was evaluated based on inter-simple sequence repeat (ISSR) polymorphisms in 150 individuals from most of known stands. Recent dynamics in the species habitat were checked over a 14-year period. Flower phenology, stigma receptivity and experimental pollinations revealed protogyny and self-incompatibility. With the exception of very small and isolated populations, high genetic diversity was found at the species and population level. amova revealed weak differentiation among populations, and the Mantel test suggested absence of isolation-by-distance. Multivariate analysis of population and genetic data distinguished the populations based on genetic richness, size and isolation. Landscape analyses confirmed recent reduction and isolation of potentially suitable habitats. Low selfing, recent isolation and probable seed exchange may have preserved P. brutia populations from higher loss of genetic diversity. Nonetheless, data related to very small populations suggest that this species may suffer further fragmentation and isolation. To preserve most of the species' genetic richness, future management efforts should consider the large and isolated populations recognised in our analyses.

QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep

PubMed Central

Poissant, J; Davis, C S; Malenfant, R M; Hogg, J T; Coltman, D W

2012-01-01

Dissecting the genetic architecture of fitness-related traits in wild populations is key to understanding evolution and the mechanisms maintaining adaptive genetic variation. We took advantage of a recently developed genetic linkage map and phenotypic information from wild pedigreed individuals from Ram Mountain, Alberta, Canada, to study the genetic architecture of ecologically important traits (horn volume, length, base circumference and body mass) in bighorn sheep. In addition to estimating sex-specific and cross-sex quantitative genetic parameters, we tested for the presence of quantitative trait loci (QTLs), colocalization of QTLs between bighorn sheep and domestic sheep, and sex × QTL interactions. All traits showed significant additive genetic variance and genetic correlations tended to be positive. Linkage analysis based on 241 microsatellite loci typed in 310 pedigreed animals resulted in no significant and five suggestive QTLs (four for horn dimension on chromosomes 1, 18 and 23, and one for body mass on chromosome 26) using genome-wide significance thresholds (Logarithm of odds (LOD) >3.31 and >1.88, respectively). We also confirmed the presence of a horn dimension QTL in bighorn sheep at the only position known to contain a similar QTL in domestic sheep (on chromosome 10 near the horns locus; nominal P<0.01) and highlighted a number of regions potentially containing weight-related QTLs in both species. As expected for sexually dimorphic traits involved in male–male combat, loci with sex-specific effects were detected. This study lays the foundation for future work on adaptive genetic variation and the evolutionary dynamics of sexually dimorphic traits in bighorn sheep. PMID:21847139

Managing Polyploidy in Ex Situ Conservation Genetics: The Case of the Critically Endangered Adriatic Sturgeon (Acipenser naccarii)

PubMed Central

Congiu, Leonardo; Pujolar, Jose Martin; Forlani, Anna; Cenadelli, Silvia; Dupanloup, Isabelle; Barbisan, Federica; Galli, Andrea; Fontana, Francesco

2011-01-01

While the current expansion of conservation genetics enables to address more efficiently the management of threatened species, alternative methods for genetic relatedness data analysis in polyploid species are necessary. Within this framework, we present a standardized and simple protocol specifically designed for polyploid species that can facilitate management of genetic diversity, as exemplified by the ex situ conservation program for the tetraploid Adriatic sturgeon Acipenser naccarii. A critically endangered endemic species of the Adriatic Sea tributaries, its persistence is strictly linked to the ex situ conservation of a single captive broodstock currently decimated to about 25 individuals, which represents the last remaining population of Adriatic sturgeon of certain wild origin. The genetic variability of three F1 broodstocks available as future breeders was estimated based on mitochondrial and microsatellite information and compared with the variability of the parental generation. Genetic data showed that the F1 stocks have only retained part of the genetic variation present in the original stock due to the few parent pairs used as founders. This prompts for the urgent improvement of the current F1 stocks by incorporating new founders that better represent the genetic diversity available. Following parental allocation based on band sharing values, we set up a user-friendly tool for selection of candidate breeders according to relatedness between all possible parent-pairs that secures the use of non-related individuals. The approach developed here could also be applied to other endangered tetraploid sturgeon species overexploited for caviar production, particularly in regions lacking proper infrastructure and/or expertise. PMID:21483472

Elucidation of the ‘Honeycrisp’ pedigree through haplotype analysis with a multi-family integrated SNP linkage map and a large apple (Malus×domestica) pedigree-connected SNP data set

PubMed Central

Howard, Nicholas P; van de Weg, Eric; Bedford, David S; Peace, Cameron P; Vanderzande, Stijn; Clark, Matthew D; Teh, Soon Li; Cai, Lichun; Luby, James J

2017-01-01

The apple (Malus×domestica) cultivar Honeycrisp has become important economically and as a breeding parent. An earlier study with SSR markers indicated the original recorded pedigree of ‘Honeycrisp’ was incorrect and ‘Keepsake’ was identified as one putative parent, the other being unknown. The objective of this study was to verify ‘Keepsake’ as a parent and identify and genetically describe the unknown parent and its grandparents. A multi-family based dense and high-quality integrated SNP map was created using the apple 8 K Illumina Infinium SNP array. This map was used alongside a large pedigree-connected data set from the RosBREED project to build extended SNP haplotypes and to identify pedigree relationships. ‘Keepsake’ was verified as one parent of ‘Honeycrisp’ and ‘Duchess of Oldenburg’ and ‘Golden Delicious’ were identified as grandparents through the unknown parent. Following this finding, siblings of ‘Honeycrisp’ were identified using the SNP data. Breeding records from several of these siblings suggested that the previously unreported parent is a University of Minnesota selection, MN1627. This selection is no longer available, but now is genetically described through imputed SNP haplotypes. We also present the mosaic grandparental composition of ‘Honeycrisp’ for each of its 17 chromosome pairs. This new pedigree and genetic information will be useful in future pedigree-based genetic studies to connect ‘Honeycrisp’ with other cultivars used widely in apple breeding programs. The created SNP linkage map will benefit future research using the data from the Illumina apple 8 and 20 K and Affymetrix 480 K SNP arrays. PMID:28243452

Genetic Modification of Short Rotation Poplar Biomass Feedstock for Efficient Conversion to Ethanol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dinus, R.J.

2000-08-30

The Bioenergy Feedstock Development Program, Environmental Sciences Division, Oak Ridge National Laboratory is developing poplars (Populus species and hybrids) as sources of renewable energy, i.e., ethanol. Notable increases in adaptability, volume productivity, and pest/stress resistance have been achieved via classical selection and breeding and intensified cultural practices. Significant advances have also been made in the efficiencies of harvesting and handling systems. Given these and anticipated accomplishments, program leaders are considering shifting some attention to genetically modifying feedstock physical and chemical properties, so as to improve the efficiency with which feedstocks can be converted to ethanol. This report provides an in-depthmore » review and synthesis of opportunities for and feasibilities of genetically modifying feedstock qualities via classical selection and breeding, marker-aided selection and breeding, and genetic transformation. Information was collected by analysis of the literature, with emphasis on that published since 1995, and interviews with prominent scientists, breeders, and growers. Poplar research is well advanced, and literature is abundant. The report therefore primarily reflects advances in poplars, but data from other species, particularly other shortrotation hardwoods, are incorporated to fill gaps. An executive summary and recommendations for research, development, and technology transfer are provided immediately after the table of contents. The first major section of the report describes processes most likely to be used for conversion of poplar biomass to ethanol, the various physical and chemical properties of poplar feedstocks, and how such properties are expected to affect process efficiency. The need is stressed for improved understanding of the impact of change on both overall process and individual process step efficiencies. The second part documents advances in trait measurement instrumentation and methodology. The importance of these and future developments is emphasized, since trait measurement constitutes the largest cost associated with adding additional traits to improvement efforts, regardless of genetic approach. In subsequent sections, recent and projected advances in classical selection and breeding, marker-aided selection, and genetic transformation are documented and used to evaluate the feasibility of individual approaches. Interviews with specialists engaged in research and development on each approach were given particular emphasis in gauging feasibilities and defining future needs and directions. Summaries of important findings and major conclusions are presented at the end of individual sections. Closing portions describe the targeted workshop, conducted in December 1999 and list interviewees and literature cited in the text. Information obtained at the workshop was used to improve accuracy, refine conclusions, and recommend priorities for future research, development, and technology transfer.« less

Comparison of Channel Catfish and Blue Catfish Gut Microbiota Assemblages Shows Minimal Effects of Host Genetics on Microbial Structure and Inferred Function.

PubMed

Bledsoe, Jacob W; Waldbieser, Geoffrey C; Swanson, Kelly S; Peterson, Brian C; Small, Brian C

2018-01-01

The microbiota of teleost fish has gained a great deal of research attention within the past decade, with experiments suggesting that both host-genetics and environment are strong ecological forces shaping the bacterial assemblages of fish microbiomes. Despite representing great commercial and scientific importance, the catfish within the family Ictaluridae , specifically the blue and channel catfish, have received very little research attention directed toward their gut-associated microbiota using 16S rRNA gene sequencing. Within this study we utilize multiple genetically distinct strains of blue and channel catfish, verified via microsatellite genotyping, to further quantify the role of host-genetics in shaping the bacterial communities in the fish gut, while maintaining environmental and husbandry parameters constant. Comparisons of the gut microbiota among the two catfish species showed no differences in bacterial species richness (observed and Chao1) or overall composition (weighted and unweighted UniFrac) and UniFrac distances showed no correlation with host genetic distances (Rst) according to Mantel tests. The microbiota of environmental samples (diet and water) were found to be significantly more diverse than that of the catfish gut associated samples, suggesting that factors within the host were further regulating the bacterial communities, despite the lack of a clear connection between microbiota composition and host genotype. The catfish gut communities were dominated by the phyla Fusobacteria, Proteobacteria, and Firmicutes; however, differential abundance analysis between the two catfish species using analysis of composition of microbiomes detected two differential genera, Cetobacterium and Clostridium XI . The metagenomic pathway features inferred from our dataset suggests the catfish gut bacterial communities possess pathways beneficial to their host such as those involved in nutrient metabolism and antimicrobial biosynthesis, while also containing pathways involved in virulence factors of pathogens. Testing of the inferred KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways by DESeq2 revealed minor difference in microbiota function, with only two metagenomic pathways detected as differentially abundant between the two catfish species. As the first study to characterize the gut microbiota of blue catfish, our study results have direct implications on future ictalurid catfish research. Additionally, our insight into the intrinsic factors driving microbiota structure has basic implications for the future study of fish gut microbiota.

How effective are tree improvement programs in the 50 states?

Treesearch

Christopher D. Risbrudt; Stephen E. McDonald

1986-01-01

All 50 states were surveyed to determine the extent of their activities in producing genetically improved trees for timber production. Describes the funds expended, the species being improved, and the use of State and Private Forestry funds provided for genetic improvement. Projects future timber volumes attributable to genetic improvement, and estimates benefit cost...

The Role of the Family in Genetic Testing: Theoretical Perspectives, Current Knowledge, and Future Directions

ERIC Educational Resources Information Center

Peterson, Susan K.

2005-01-01

This article addresses conceptual challenges and theoretical approaches for examining the role of the family in responding and adapting to genetic testing for inherited conditions. Using a family systems perspective, family-based constructs that are relevant to genetic testing may be organized into three domains: family communication, organization…

The future of clinical cancer genomics.

PubMed

Offit, Kenneth

2016-10-01

The current and future applications of genomics to the practice of preventive oncology are being impacted by a number of challenges. These include rapid advances in genomic science and technology that allow massively parallel sequencing of both tumors and the germline, a diminishing of intellectual property restrictions on diagnostic genetic applications, rapid expansion of access to the internet which includes mobile access to both genomic data and tools to communicate and interpret genetic data in a medical context, the expansion of for-profit diagnostic companies seeking to monetize genetic information, and a simultaneous effort to depict medical professionals as barriers to rather than facilitators of understanding one's genome. Addressing each of these issues will be required to bring "personalized" germline genomics to cancer prevention and care. A profound future challenge will be whether clinical cancer genomics will be "de-medicalized" by commercial interests and their advocates, or whether the future course of this field can be modulated in a responsible way that protects the public health while implementing powerful new medical tools for cancer prevention and early detection. Copyright © 2016. Published by Elsevier Inc.

Genetic tool development underpins recent advances in thermophilic whole‐cell biocatalysts

PubMed Central

Taylor, M. P.; van Zyl, L.; Tuffin, I. M.; Leak, D. J.; Cowan, D. A.

2011-01-01

Summary The environmental value of sustainably producing bioproducts from biomass is now widely appreciated, with a primary target being the economic production of fuels such as bioethanol from lignocellulose. The application of thermophilic prokaryotes is a rapidly developing niche in this field, driven by their known catabolic versatility with lignocellulose‐derived carbohydrates. Fundamental to the success of this work has been the development of reliable genetic and molecular systems. These technical tools are now available to assist in the development of other (hyper)thermophilic strains with diverse phenotypes such as hemicellulolytic and cellulolytic properties, branched chain alcohol production and other ‘valuable bioproduct’ synthetic capabilities. Here we present an insight into the historical limitations, recent developments and current status of a number of genetic systems for thermophiles. We also highlight the value of reliable genetic methods for increasing our knowledge of thermophile physiology. We argue that the development of robust genetic systems is paramount in the evolution of future thermophilic based bioprocesses and make suggestions for future approaches and genetic targets that will facilitate this process. PMID:21310009

Complete genome sequence of probiotic Bacillus coagulans HM-08: A potential lactic acid producer.

PubMed

Yao, Guoqiang; Gao, Pengfei; Zhang, Wenyi

2016-06-20

Bacillus coagulans HM-08 is a commercialized probiotic strain in China. Its genome contains a 3.62Mb circular chromosome with an average GC content of 46.3%. In silico analysis revealed the presence of one xyl operon as well as several other genes that are correlated to xylose utilization. The genetic information provided here may help to expand its future biotechnology potential in lactic acid production. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings.

PubMed

Weissgerber, Tracey L; Turner, Stephen T; Mosley, Thomas H; Kardia, Sharon L R; Hanis, Craig L; Milic, Natasa M; Garovic, Vesna D

2016-03-01

Hypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan-Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27-2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension. Copyright © 2016 by the American Society of Nephrology.

Hypertension in Pregnancy and Future Cardiovascular Event Risk in Siblings

PubMed Central

Turner, Stephen T.; Mosley, Thomas H.; Kardia, Sharon L.R.; Hanis, Craig L.; Milic, Natasa M.; Garovic, Vesna D.

2016-01-01

Hypertension in pregnancy is a risk factor for future hypertension and cardiovascular disease. This may reflect an underlying familial predisposition or persistent damage caused by the hypertensive pregnancy. We sought to isolate the effect of hypertension in pregnancy by comparing the risk of hypertension and cardiovascular disease in women who had hypertension in pregnancy and their sisters who did not using the dataset from the Genetic Epidemiology Network of Arteriopathy study, which examined the genetics of hypertension in white, black, and Hispanic siblings. This analysis included all sibships with at least one parous woman and at least one other sibling. After gathering demographic and pregnancy data, BP and serum analytes were measured. Disease-free survival was examined using Kaplan–Meier curves and Cox proportional hazards regression. Compared with their sisters who did not have hypertension in pregnancy, women who had hypertension in pregnancy were more likely to develop new onset hypertension later in life, after adjusting for body mass index and diabetes (hazard ratio 1.75, 95% confidence interval 1.27–2.42). A sibling history of hypertension in pregnancy was also associated with an increased risk of hypertension in brothers and unaffected sisters, whereas an increased risk of cardiovascular events was observed in brothers only. These results suggest familial factors contribute to the increased risk of future hypertension in women who had hypertension in pregnancy. Further studies are needed to clarify the potential role of nonfamilial factors. Furthermore, a sibling history of hypertension in pregnancy may be a novel familial risk factor for future hypertension. PMID:26315531

Prospects for advancing defense to cereal rusts through genetical genomics

PubMed Central

Ballini, Elsa; Lauter, Nick; Wise, Roger

2013-01-01

Rusts are one of the most severe threats to cereal crops because new pathogen races emerge regularly, resulting in infestations that lead to large yield losses. In 1999, a new race of stem rust, Puccinia graminis f. sp. tritici (Pgt TTKSK or Ug99), was discovered in Uganda. Most of the wheat and barley cultivars grown currently worldwide are susceptible to this new race. Pgt TTKSK has already spread northward into Iran and will likely spread eastward throughout the Indian subcontinent in the near future. This scenario is not unique to stem rust; new races of leaf rust (Puccinia triticina) and stripe rust (Puccinia striiformis) have also emerged recently. One strategy for countering the persistent adaptability of these pathogens is to stack complete- and partial-resistance genes, which requires significant breeding efforts in order to reduce deleterious effects of linkage drag. These varied resistance combinations are typically more difficult for the pathogen to defeat, since they would be predicted to apply lower selection pressure. Genetical genomics or expression Quantitative Trait Locus (eQTL) analysis enables the identification of regulatory loci that control the expression of many to hundreds of genes. Integrated deployment of these technologies coupled with efficient phenotyping offers significant potential to elucidate the regulatory nodes in genetic networks that orchestrate host defense responses. The focus of this review will be to present advances in genetical genomic experimental designs and analysis, particularly as they apply to the prospects for discovering partial disease resistance alleles in cereals. PMID:23641250

Integrating Anisakis spp. parasites data and host genetic structure in the frame of a holistic approach for stock identification of selected Mediterranean Sea fish species.

PubMed

Mattiucci, S; Cimmaruta, R; Cipriani, P; Abaunza, P; Bellisario, B; Nascetti, G

2015-01-01

The unique environment of the Mediterranean Sea makes fish stock assessment a major challenge. Stock identification of Mediterranean fisheries has been based mostly from data on biology, morphometrics, artificial tags, otolith shape and fish genetics, with less effort on the use of parasites as biomarkers. Here we use some case studies comparing Mediterranean vs Atlantic fish stocks in a multidisciplinary framework. The generalized Procrustes Rotation (PR) was used to assess the association between host genetics and larval Anisakis spp. datasets on demersal (hake) and pelagic (horse mackerel, swordfish) species. When discordant results emerged, they were due to the different features of the data. While fish population genetics can detect changes over an evolutionary timescale, providing indications on the cohesive action of gene flow, parasites are more suitable biomarkers when considering fish stocks over smaller temporal and spatial scales, hence giving information of fish movements over their lifespan. Future studies on the phylogeographic analysis of parasites suitable as biomarkers, and that of their fish host, performed on the same genes, will represent a further tool to be included in multidisciplinary studies on fish stock structure.

Molecular Markers and Cotton Genetic Improvement: Current Status and Future Prospects

PubMed Central

Malik, Waqas; Iqbal, Muhammad Zaffar; Ali Khan, Asif; Qayyum, Abdul; Ali Abid, Muhammad; Noor, Etrat; Qadir Ahmad, Muhammad; Hasan Abbasi, Ghulam

2014-01-01

Narrow genetic base and complex allotetraploid genome of cotton (Gossypium hirsutum L.) is stimulating efforts to avail required polymorphism for marker based breeding. The availability of draft genome sequence of G. raimondii and G. arboreum and next generation sequencing (NGS) technologies facilitated the development of high-throughput marker technologies in cotton. The concepts of genetic diversity, QTL mapping, and marker assisted selection (MAS) are evolving into more efficient concepts of linkage disequilibrium, association mapping, and genomic selection, respectively. The objective of the current review is to analyze the pace of evolution in the molecular marker technologies in cotton during the last ten years into the following four areas: (i) comparative analysis of low- and high-throughput marker technologies available in cotton, (ii) genetic diversity in the available wild and improved gene pools of cotton, (iii) identification of the genomic regions within cotton genome underlying economic traits, and (iv) marker based selection methodologies. Moreover, the applications of marker technologies to enhance the breeding efficiency in cotton are also summarized. Aforementioned genomic technologies and the integration of several other omics resources are expected to enhance the cotton productivity and meet the global fiber quantity and quality demands. PMID:25401149

Genetics of Post-Traumatic Stress Disorder: Informing Clinical Conceptualizations and Promoting Future Research

PubMed Central

Nugent, Nicole R.; Amstadter, Ananda B.; Koenen, Karestan C.

2009-01-01

The purpose of this article is to provide an overview of genetic research involving post-traumatic stress disorder (PTSD). First, we summarize evidence for genetic influences on PTSD from family investigations. Second, we discuss the distinct contributions to our understanding of the genetics of PTSD permitted by twin studies. Finally, we summarize findings from molecular genetic studies, which have the potential to inform our understanding of underlying biological mechanisms for the development of PTSD. PMID:18412098

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.

PubMed

Fang, Qing; George, Akima S; Brinkmeier, Michelle L; Mortensen, Amanda H; Gergics, Peter; Cheung, Leonard Y M; Daly, Alexandre Z; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A Bilge; Kitzman, Jacob O; Mills, Ryan E; Li, Jun Z; Camper, Sally A

2016-12-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.

Metabolomic Studies in Drosophila.

PubMed

Cox, James E; Thummel, Carl S; Tennessen, Jason M

2017-07-01

Metabolomic analysis provides a powerful new tool for studies of Drosophila physiology. This approach allows investigators to detect thousands of chemical compounds in a single sample, representing the combined contributions of gene expression, enzyme activity, and environmental context. Metabolomics has been used for a wide range of studies in Drosophila , often providing new insights into gene function and metabolic state that could not be obtained using any other approach. In this review, we survey the uses of metabolomic analysis since its entry into the field. We also cover the major methods used for metabolomic studies in Drosophila and highlight new directions for future research. Copyright © 2017 by the Genetics Society of America.

Exome Array Analysis of Nuclear Lens Opacity.

PubMed

Loomis, Stephanie J; Klein, Alison P; Lee, Kristine E; Chen, Fei; Bomotti, Samantha; Truitt, Barbara; Iyengar, Sudha K; Klein, Ronald; Klein, Barbara E K; Duggal, Priya

2018-06-01

Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10 -6 ; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10 -5 ). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10 -6 ) and among never smokers (N = 790, p = 2.67 × 10 -6 ). This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

Reproductive cloning, genetic engineering and the autonomy of the child: the moral agent and the open future.

PubMed

Mameli, M

2007-02-01

Some authors have argued that the human use of reproductive cloning and genetic engineering should be prohibited because these biotechnologies would undermine the autonomy of the resulting child. In this paper, two versions of this view are discussed. According to the first version, the autonomy of cloned and genetically engineered people would be undermined because knowledge of the method by which these people have been conceived would make them unable to assume full responsibility for their actions. According to the second version, these biotechnologies would undermine autonomy by violating these people's right to an open future. There is no evidence to show that people conceived through cloning and genetic engineering would inevitably or even in general be unable to assume responsibility for their actions; there is also no evidence for the claim that cloning and genetic engineering would inevitably or even in general rob the child of the possibility to choose from a sufficiently large array of life plans.

Reproductive cloning, genetic engineering and the autonomy of the child: the moral agent and the open future

PubMed Central

Mameli, M

2007-01-01

Some authors have argued that the human use of reproductive cloning and genetic engineering should be prohibited because these biotechnologies would undermine the autonomy of the resulting child. In this paper, two versions of this view are discussed. According to the first version, the autonomy of cloned and genetically engineered people would be undermined because knowledge of the method by which these people have been conceived would make them unable to assume full responsibility for their actions. According to the second version, these biotechnologies would undermine autonomy by violating these people's right to an open future. There is no evidence to show that people conceived through cloning and genetic engineering would inevitably or even in general be unable to assume responsibility for their actions; there is also no evidence for the claim that cloning and genetic engineering would inevitably or even in general rob the child of the possibility to choose from a sufficiently large array of life plans. PMID:17264194

Genetic studies of Crohn's disease: Past, present and future

PubMed Central

Liu, Jimmy Z.; Anderson, Carl A.

2014-01-01

The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease. PMID:24913378

Are Genetic Tests for Atherosclerosis Ready for Routine Clinical Use?

PubMed

Paynter, Nina P; Ridker, Paul M; Chasman, Daniel I

2016-02-19

In this review, we lay out 3 areas currently being evaluated for incorporation of genetic information into clinical practice related to atherosclerosis. The first, familial hypercholesterolemia, is the clearest case for utility of genetic testing in diagnosis and potentially guiding treatment. Already in use for confirmatory testing of familial hypercholesterolemia and for cascade screening of relatives, genetic testing is likely to expand to help establish diagnoses and facilitate research related to most effective therapies, including new agents, such as PCSK9 inhibitors. The second area, adding genetic information to cardiovascular risk prediction for primary prevention, is not currently recommended. Although identification of additional variants may add substantially to prediction in the future, combining known variants has not yet demonstrated sufficient improvement in prediction for incorporation into commonly used risk scores. The third area, pharmacogenetics, has utility for some therapies today. Future utility for pharmacogenetics will wax or wane depending on the nature of available drugs and therapeutic strategies. © 2016 American Heart Association, Inc.

The future is now: Technology's impact on the practice of genetic counseling.

PubMed

Gordon, Erynn S; Babu, Deepti; Laney, Dawn A

2018-03-01

Smartphones, artificial intelligence, automation, digital communication, and other types of technology are playing an increasingly important role in our daily lives. It is no surprise that technology is also shaping the practice of medicine, and more specifically the practice of genetic counseling. While digital tools have been part of the practice of medical genetics for decades, such as internet- or CD-ROM-based tools like Online Mendelian Inheritance in Man and Pictures of Standard Syndromes and Undiagnosed Malformations in the 1980s, the potential for emerging tools to change how we practice and the way patients consume information is startling. Technology has the potential to aid in at-risk patient identification, assist in generating a differential diagnosis, improve efficiency in medical history collection and risk assessment, provide educational support for patients, and streamline follow-up. Here we review the historic and current uses of technology in genetic counseling, identify challenges to integration, and propose future applications of technology that can shape the practice of genetic counseling. © 2018 Wiley Periodicals, Inc.

East Greenland and Barents Sea polar bears (Ursus maritimus): adaptive variation between two populations using skull morphometrics as an indicator of environmental and genetic differences.

PubMed

Pertoldi, Cino; Sonne, Christian; Wiig, Øystein; Baagøe, Hans J; Loeschcke, Volker; Bechshøft, Thea Østergaard

2012-06-01

A morphometric study was conducted on four skull traits of 37 male and 18 female adult East Greenland polar bears (Ursus maritimus) collected 1892-1968, and on 54 male and 44 female adult Barents Sea polar bears collected 1950-1969. The aim was to compare differences in size and shape of the bear skulls using a multivariate approach, characterizing the variation between the two populations using morphometric traits as an indicator of environmental and genetic differences. Mixture analysis testing for geographic differentiation within each population revealed three clusters for Barents Sea males and three clusters for Barents Sea females. East Greenland consisted of one female and one male cluster. A principal component analysis (PCA) conducted on the clusters defined by the mixture analysis, showed that East Greenland and Barents Sea polar bear populations overlapped to a large degree, especially with regards to females. Multivariate analyses of variance (MANOVA) showed no significant differences in morphometric means between the two populations, but differences were detected between clusters from each respective geographic locality. To estimate the importance of genetics and environment in the morphometric differences between the bears, a PCA was performed on the covariance matrix derived from the skull measurements. Skull trait size (PC1) explained approx. 80% of the morphometric variation, whereas shape (PC2) defined approx. 15%, indicating some genetic differentiation. Hence, both environmental and genetic factors seem to have contributed to the observed skull differences between the two populations. Overall, results indicate that many Barents Sea polar bears are morphometrically similar to the East Greenland ones, suggesting an exchange of individuals between the two populations. Furthermore, a subpopulation structure in the Barents Sea population was also indicated from the present analyses, which should be considered with regards to future management decisions. © 2012 The Authors.

Current and future prospects for CRISPR-based tools in bacteria

PubMed Central

Luo, Michelle L.; Leenay, Ryan T.; Beisel, Chase L.

2015-01-01

CRISPR-Cas systems have rapidly transitioned from intriguing prokaryotic defense systems to powerful and versatile biomolecular tools. This article reviews how these systems have been translated into technologies to manipulate bacterial genetics, physiology, and communities. Recent applications in bacteria have centered on multiplexed genome editing, programmable gene regulation, and sequence-specific antimicrobials, while future applications can build on advances in eukaryotes, the rich natural diversity of CRISPR-Cas systems, and the untapped potential of CRISPR-based DNA acquisition. Overall, these systems have formed the basis of an ever-expanding genetic toolbox and hold tremendous potential for our future understanding and engineering of the bacterial world. PMID:26460902

A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca), Pumas (Puma concolor), and Ocelots (Leopardus pardalis) in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone.

PubMed

Wultsch, Claudia; Waits, Lisette P; Kelly, Marcella J

2016-01-01

With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca), pumas (Puma concolor), and ocelots (Leopardus pardalis). We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09), followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16), and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08). We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes.

A Comparative Analysis of Genetic Diversity and Structure in Jaguars (Panthera onca), Pumas (Puma concolor), and Ocelots (Leopardus pardalis) in Fragmented Landscapes of a Critical Mesoamerican Linkage Zone

PubMed Central

Wultsch, Claudia; Waits, Lisette P.; Kelly, Marcella J.

2016-01-01

With increasing anthropogenic impact and landscape change, terrestrial carnivore populations are becoming more fragmented. Thus, it is crucial to genetically monitor wild carnivores and quantify changes in genetic diversity and gene flow in response to these threats. This study combined the use of scat detector dogs and molecular scatology to conduct the first genetic study on wild populations of multiple Neotropical felids coexisting across a fragmented landscape in Belize, Central America. We analyzed data from 14 polymorphic microsatellite loci in 1053 scat samples collected from wild jaguars (Panthera onca), pumas (Puma concolor), and ocelots (Leopardus pardalis). We assessed levels of genetic diversity, defined potential genetic clusters, and examined gene flow for the three target species on a countrywide scale using a combination of individual- and population-based analyses. Wild felids in Belize showed moderate levels of genetic variation, with jaguars having the lowest diversity estimates (HE = 0.57 ± 0.02; AR = 3.36 ± 0.09), followed by pumas (HE = 0.57 ± 0.08; AR = 4.20 ± 0.16), and ocelots (HE = 0.63 ± 0.03; AR = 4.16 ± 0.08). We observed low to moderate levels of genetic differentiation for all three target species, with jaguars showing the lowest degree of genetic subdivision across the country, followed by ocelots and pumas. Although levels of genetic diversity and gene flow were still fairly high, we detected evidence of fine-scale genetic subdivision, indicating that levels of genetic connectivity for wild felids in Belize are likely to decrease if habitat loss and fragmentation continue at the current rate. Our study demonstrates the value of understanding fine-scale patterns of gene flow in multiple co-occurring felid species of conservation concern, which is vital for wildlife movement corridor planning and prioritizing future conservation and management efforts within human-impacted landscapes. PMID:26974968

The genetic tale of a recovering lion population (Panthera leo) in the Savé Valley region (Zimbabwe): A better understanding of the history and managing the future

PubMed Central

Groom, Rosemary J.; Khuzwayo, Joy; Jansen van Vuuren, Bettine

2018-01-01

The rapid decline of the African lion (Panthera leo) has raised conservation concerns. In the Savé Valley Conservancy (SVC), in the Lowveld of Zimbabwe, lions were presumably reduced to approximately 5 to 10 individuals. After ten lions were reintroduced in 2005, the population has recovered to over 200 lions in 2016. Although the increase of lions in the SVC seems promising, a question remains whether the population is genetically viable, considering their small founding population. In this study, we document the genetic diversity in the SVC lion population using both mitochondrial and nuclear genetic markers, and compare our results to literature from other lion populations across Africa. We also tested whether genetic diversity is spatially structured between lion populations residing on several reserves in the Lowveld of Zimbabwe. A total of 42 lions were genotyped successfully for 11 microsatellite loci. We confirmed that the loss of allelic richness (probably resulting from genetic drift and small number of founders) has resulted in low genetic diversity and inbreeding. The SVC lion population was also found to be genetically differentiated from surrounding population, as a result of genetic drift and restricted natural dispersal due to anthropogenic barriers. From a conservation perspective, it is important to avoid further loss of genetic variability in the SVC lion population and maintain evolutionary potential required for future survival. Genetic restoration through the introduction of unrelated individuals is recommended, as this will increase genetic heterozygosity and improve survival and reproductive fitness in populations. PMID:29415031

The genetic tale of a recovering lion population (Panthera leo) in the Savé Valley region (Zimbabwe): A better understanding of the history and managing the future.

PubMed

Tensen, Laura; Groom, Rosemary J; Khuzwayo, Joy; Jansen van Vuuren, Bettine

2018-01-01

The rapid decline of the African lion (Panthera leo) has raised conservation concerns. In the Savé Valley Conservancy (SVC), in the Lowveld of Zimbabwe, lions were presumably reduced to approximately 5 to 10 individuals. After ten lions were reintroduced in 2005, the population has recovered to over 200 lions in 2016. Although the increase of lions in the SVC seems promising, a question remains whether the population is genetically viable, considering their small founding population. In this study, we document the genetic diversity in the SVC lion population using both mitochondrial and nuclear genetic markers, and compare our results to literature from other lion populations across Africa. We also tested whether genetic diversity is spatially structured between lion populations residing on several reserves in the Lowveld of Zimbabwe. A total of 42 lions were genotyped successfully for 11 microsatellite loci. We confirmed that the loss of allelic richness (probably resulting from genetic drift and small number of founders) has resulted in low genetic diversity and inbreeding. The SVC lion population was also found to be genetically differentiated from surrounding population, as a result of genetic drift and restricted natural dispersal due to anthropogenic barriers. From a conservation perspective, it is important to avoid further loss of genetic variability in the SVC lion population and maintain evolutionary potential required for future survival. Genetic restoration through the introduction of unrelated individuals is recommended, as this will increase genetic heterozygosity and improve survival and reproductive fitness in populations.

Biology of lung cancer: genetic mutation, epithelial-mesenchymal transition, and cancer stem cells.

PubMed

Aoi, Takashi

2016-09-01

At present, most cases of unresectable cancer cannot be cured. Genetic mutations, EMT, and cancer stem cells are three major issues linked to poor prognosis in such cases, all connected by inter- and intra-tumor heterogeneity. Issues on inter-/intra-tumor heterogeneity of genetic mutation could be resolved with recent and future technologies of deep sequencers, whereas, regarding such issues as the "same genome, different epigenome/phenotype", we expect to solve many of these problems in the future through further research in stem cell biology. We herein review and discuss the three major issues in the biology of cancers, especially from the standpoint of stem cell biology.

The ROOTS study: a 10-year review of findings on adolescent depression, and recommendations for future longitudinal research.

PubMed

Lewis, Gemma; Jones, Peter B; Goodyer, Ian M

2016-02-01

The purpose of this study is to review longitudinal findings on adolescent mental health from the 'ROOTS study', and provide directions and recommendations for future longitudinal research. To do this, we discuss relevant findings from the ROOTS study, and review its strengths and limitations. We examined all publications from the ROOTS study up to July 2015, selected those examining adolescent mental health, and classified them as investigating (a) childhood risk factors for adolescent depression, (b) genetic and cognitive vulnerability to depression in adolescence, (c) genetic markers, childhood adversities, and neuroendophenotypes, (d) morning cortisol and depression, (e) physical activity and depression symptoms, and (f) the underlying structure of mental health in adolescence. We reviewed the strengths and limitations of the ROOTS study, and how they feed into recommendations for future longitudinal research. There was evidence supporting a putative hormonal biomarker for the emergence of depression in boys. Environmental pathways from child adversity to adolescent depression were confirmed in girls, partly accounted for by negative life events in early adolescence. The preceding role of automatic cognitive biases assessed using behavioural tasks was substantiated, with evidence for genetic susceptibility. Novel latent statistical models of child adversity, depression, anxiety, and psychotic experiences were produced, with concurrent and prospective validity. Our experiences conducting the ROOTS study resulted in a set of strengths, limitations, and recommendations for future longitudinal studies. The ROOTS study has advanced knowledge on the aetiology of adolescent depression by investigating environmental, genetic, hormonal, and neural risk factors. Findings provide a foundation for future research integrating cognitive neuroscience with epidemiology.

Molecular typing of Sarcocystis neurona: current status and future trends.

PubMed

Elsheikha, Hany M; Mansfield, Linda S

2007-10-21

Sarcocystis neurona is an important protozoal pathogen because it causes the serious neurological disease equine protozoal myeloencephalitis (EPM). The capacity of this organism to cause a wide spectrum of neurological signs in horses and the broad geographic distribution of observed cases in the Americas drive the need for sensitive, reliable and rapid typing methods to characterize strains. Various molecular methods have been developed and used to diagnose EPM due to S. neurona, to identify S. neurona isolates and to determine the heterogeneity and evolutionary relatedness within this species and related Sarcocystis spp. These methods included sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immuno-fluorescent assay (IFA), slide agglutination test (SAT), SnSAG-specific ELISA, random amplified polymorphic DNA (RAPD), PCR-based restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP) fingerprinting, and sequence analysis of surface protein genes, ribosomal genes, microsatellite alleles and other molecular markers. Here, the utility of these molecular methods is reviewed and evaluated with respect to the need for molecular approaches that utilize well-characterized polymorphic, simple, independent, and stable genetic markers. These tools have the potential to add to knowledge of the genetic population structure of S. neurona and to provide new insights into the pathogenesis of EPM and S. neurona epidemiology. In particular, these methods provide new tools to address the hypothesis that particular genetic variants are associated with adverse clinical outcomes (severe pathotypes). The ultimate goal is to utilize them in future studies to improve treatment and prevention strategies.

Phylogeography and origin of Chinese domestic chicken.

PubMed

Wu, Y P; Huo, J H; Xie, J F; Liu, L X; Wei, Q P; Xie, M G; Kang, Z F; Ji, H Y; Ma, Y H

2014-04-01

The loss of local chicken breeds as result of replacement with cosmopolitan breeds indicates the need for conservation measures to protect the future of local genetic stocks. The aim of this study is to describe the patterns of polymorphism of the hypervariable control region of mitochondrial DNA (HVR1) in domestic chicken in China's Jiangxi province to investigate genetic diversity, genetic structure and phylo-dynamics. To this end, we sequenced the mtDNA HVR1 in 231 chickens including 22 individuals which belonged to previously published sequences. A neighbor-joining tree revealed that these samples clustered into five lineages (Lineages A, B, C, E and G). The highest haplotype diversity and nucleotide diversity were both found in Anyi tile-liked gray breed. We estimated that the most recent common ancestor of the local chicken existed approximately 16 million years ago. The mismatch distribution analysis showed two major peaks at positions 4 and 9, while the neutrality test (Tajima's D = -2.19, p < 0.05) and Fu's F-statistics (-8.59, p < 0.05) revealed a significant departure from the neutrality assumption. These results support the idea that domestication of chickens facilitated population increases. Results of a global AMOVA indicated that there was no obvious geographic structure among the local chicken breeds analyzed in this study. The data obtained in this study will assist future conservation management of local breeds and also reveals intriguing implications for the history of human population movements and commerce.

Diabetic macular oedema: under-represented in the genetic analysis of diabetic retinopathy.

PubMed

Broadgate, Suzanne; Kiire, Christine; Halford, Stephanie; Chong, Victor

2018-04-01

Diabetic retinopathy, a complication of both type 1 and type 2 diabetes, is a complex disease and is one of the leading causes of blindness in adults worldwide. It can be divided into distinct subclasses, one of which is diabetic macular oedema. Diabetic macular oedema can occur at any time in diabetic retinopathy and is the most common cause of vision loss in patients with type 2 diabetes. The purpose of this review is to summarize the large number of genetic association studies that have been performed in cohorts of patients with type 2 diabetes and published in English-language journals up to February 2017. Many of these studies have produced positive associations with gene polymorphisms and diabetic retinopathy. However, this review highlights that within this large body of work, studies specifically addressing a genetic association with diabetic macular oedema, although present, are vastly under-represented. We also highlight that many of the studies have small patient numbers and that meta-analyses often inappropriately combine patient data sets. We conclude that there will continue to be conflicting results and no meaningful findings will be achieved if the historical approach of combining all diabetic retinopathy disease states within patient cohorts continues in future studies. This review also identifies several genes that would be interesting to analyse in large, well-defined cohorts of patients with diabetic macular oedema in future candidate gene association studies. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Recommendations for developing and applying genetic tools to assess and manage biological invasions in marine ecosystems

PubMed Central

Darling, John A.; Galil, Bella S.; Carvalho, Gary R.; Rius, Marc; Viard, Frédérique; Piraino, Stefano

2018-01-01

The European Union’s Marine Strategy Framework Directive (MSFD) aims to adopt integrated ecosystem management approaches to achieve or maintain “Good Environmental Status” for marine waters, habitats and resources, including mitigation of the negative effects of non-indigenous species (NIS). The Directive further seeks to promote broadly standardized monitoring efforts and assessment of temporal trends in marine ecosystem condition, incorporating metrics describing the distribution and impacts of NIS. Accomplishing these goals will require application of advanced tools for NIS surveillance and risk assessment, particularly given known challenges associated with surveying and monitoring with traditional methods. In the past decade, a host of methods based on nucleic acids (DNA and RNA) analysis have been developed or advanced that promise to dramatically enhance capacity in assessing and managing NIS. However, ensuring that these rapidly evolving approaches remain accessible and responsive to the needs of resource managers remains a challenge. This paper provides recommendations for future development of these genetic tools for assessment and management of NIS in marine systems, within the context of the explicit requirements of the MSFD. Issues considered include technological innovation, methodological standardization, data sharing and collaboration, and the critical importance of shared foundational resources, particularly integrated taxonomic expertise. Though the recommendations offered here are not exhaustive, they provide a basis for future intentional (and international) collaborative development of a genetic toolkit for NIS research, capable of fulfilling the immediate and long term goals of marine ecosystem and resource conservation. PMID:29681680

Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.

PubMed

Unemo, Magnus

2015-08-21

Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus azithromycin 1-2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed, randomized controlled clinical trials evaluating efficacy, ideal dose, toxicity, adverse effects, cost, and pharmacokinetic/pharmacodynamics data for anogenital and, importantly, also pharyngeal gonorrhoea, i.e. because treatment failures initially emerge at this anatomical site. Finally, in the future treatment at first health care visit will ideally be individually-tailored, i.e. by novel rapid phenotypic AMR tests and/or genetic point of care AMR tests, including detection of gonococci, which will improve the management and public health control of gonorrhoea and AMR. Nevertheless, now is certainly the right time to readdress the challenges of developing a gonococcal vaccine.

The future: genetics advances in MEN1 therapeutic approaches and management strategies.

PubMed

Agarwal, Sunita K

2017-10-01

The identification of the multiple endocrine neoplasia type 1 ( MEN1 ) gene in 1997 has shown that germline heterozygous mutations in the MEN1 gene located on chromosome 11q13 predisposes to the development of tumors in the MEN1 syndrome. Tumor development occurs upon loss of the remaining normal copy of the MEN1 gene in MEN1-target tissues. Therefore, MEN1 is a classic tumor suppressor gene in the context of MEN1. This tumor suppressor role of the protein encoded by the MEN1 gene, menin, holds true in mouse models with germline heterozygous Men1 loss, wherein MEN1-associated tumors develop in adult mice after spontaneous loss of the remaining non-targeted copy of the Men1 gene. The availability of genetic testing for mutations in the MEN1 gene has become an essential part of the diagnosis and management of MEN1. Genetic testing is also helping to exclude mutation-negative cases in MEN1 families from the burden of lifelong clinical screening. In the past 20 years, efforts of various groups world-wide have been directed at mutation analysis, molecular genetic studies, mouse models, gene expression studies, epigenetic regulation analysis, biochemical studies and anti-tumor effects of candidate therapies in mouse models. This review will focus on the findings and advances from these studies to identify MEN1 germline and somatic mutations, the genetics of MEN1-related states, several protein partners of menin, the three-dimensional structure of menin and menin-dependent target genes. The ongoing impact of all these studies on disease prediction, management and outcomes will continue in the years to come. © 2017 Society for Endocrinology.

Determination of Genetic Structure and Signatures of Selection in Three Strains of Tanzania Shorthorn Zebu, Boran and Friesian Cattle by Genome-Wide SNP Analyses

PubMed Central

Msalya, George; Kim, Eui-Soo; Laisser, Emmanuel L. K.; Kipanyula, Maulilio J.; Karimuribo, Esron D.; Kusiluka, Lughano J. M.; Chenyambuga, Sebastian W.; Rothschild, Max F.

2017-01-01

Background More than 90 percent of cattle in Tanzania belong to the indigenous Tanzania Short Horn Zebu (TSZ) population which has been classified into 12 strains based on historical evidence, morphological characteristics, and geographic distribution. However, specific genetic information of each TSZ population has been lacking and has caused difficulties in designing programs such as selection, crossbreeding, breed improvement or conservation. This study was designed to evaluate the genetic structure, assess genetic relationships, and to identify signatures of selection among cattle of Tanzania with the main goal of understanding genetic relationship, variation and uniqueness among them. Methodology/Principal findings The Illumina Bos indicus SNP 80K BeadChip was used to genotype genome wide SNPs in 168 DNA samples obtained from three strains of TSZ cattle namely Maasai, Tarime and Sukuma as well as two comparative breeds; Boran and Friesian. Population structure and signatures of selection were examined using principal component analysis (PCA), admixture analysis, pairwise distances (FST), integrated haplotype score (iHS), identical by state (IBS) and runs of homozygosity (ROH). There was a low level of inbreeding (F~0.01) in the TSZ population compared to the Boran and Friesian breeds. The analyses of FST, IBS and admixture identified no considerable differentiation between TSZ trains. Importantly, common ancestry in Boran and TSZ were revealed based on admixture and IBD, implying gene flow between two populations. In addition, Friesian ancestry was found in Boran. A few common significant iHS were detected, which may reflect influence of recent selection in each breed or strain. Conclusions Population admixture and selection signatures could be applied to develop conservation plan of TSZ cattle as well as future breeding programs in East African cattle. PMID:28129396

The nature of individual differences in inhibited temperament and risk for psychiatric disease: a review and meta-analysis

PubMed Central

Clauss, J. A.; Avery, S. N.; Blackford, J. U.

2015-01-01

What makes us different from one another? Why does one person jump out of airplanes for fun while another prefers to stay home and read? Why are some babies born with a predisposition to become anxious? Questions about individual differences in temperament have engaged the minds of scientists, psychologists, and philosophers for centuries. Recent technological advances in neuroimaging and genetics provide an unprecedented opportunity to answer these questions. Here we review the literature on the neurobiology of one of the most basic individual differences—the tendency to approach or avoid novelty. This trait, called inhibited temperament, is innate, heritable, and observed across species. Importantly, inhibited temperament also confers risk for psychiatric disease. Here, we provide a comprehensive review of inhibited temperament including neuroimaging and genetic studies in human and non-human primates. We conducted a meta-analysis of neuroimaging findings in inhibited humans that points to alterations in a fronto-limbic-basal ganglia circuit; these findings provide the basis of a model of inhibited temperament neurocircuitry. Lesion and neuroimaging studies in non-human primate models of inhibited temperament highlight roles for the amygdala, hippocampus, orbitofrontal cortex, and dorsal prefrontal cortex. Genetic studies highlight a role for genes that regulate neurotransmitter function, such as the serotonin transporter polymorphisms (5-HTTLPR), as well as genes that regulate stress response, such as corticotropin-releasing hormone (CRH). Together these studies provide a foundation of knowledge about the genetic and neural substrates of this most basic of temperament traits. Future studies using novel imaging methods and genetic approaches promise to expand upon these biological bases of inhibited temperament and inform our understanding of risk for psychiatric disease. PMID:25784645

The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis.

PubMed

Clauss, J A; Avery, S N; Blackford, J U

2015-04-01

What makes us different from one another? Why does one person jump out of airplanes for fun while another prefers to stay home and read? Why are some babies born with a predisposition to become anxious? Questions about individual differences in temperament have engaged the minds of scientists, psychologists, and philosophers for centuries. Recent technological advances in neuroimaging and genetics provide an unprecedented opportunity to answer these questions. Here we review the literature on the neurobiology of one of the most basic individual differences-the tendency to approach or avoid novelty. This trait, called inhibited temperament, is innate, heritable, and observed across species. Importantly, inhibited temperament also confers risk for psychiatric disease. Here, we provide a comprehensive review of inhibited temperament, including neuroimaging and genetic studies in human and non-human primates. We conducted a meta-analysis of neuroimaging findings in inhibited humans that points to alterations in a fronto-limbic-basal ganglia circuit; these findings provide the basis of a model of inhibited temperament neurocircuitry. Lesion and neuroimaging studies in non-human primate models of inhibited temperament highlight roles for the amygdala, hippocampus, orbitofrontal cortex, and dorsal prefrontal cortex. Genetic studies highlight a role for genes that regulate neurotransmitter function, such as the serotonin transporter polymorphisms (5-HTTLPR), as well as genes that regulate stress response, such as corticotropin-releasing hormone (CRH). Together these studies provide a foundation of knowledge about the genetic and neural substrates of this most basic of temperament traits. Future studies using novel imaging methods and genetic approaches promise to expand upon these biological bases of inhibited temperament and inform our understanding of risk for psychiatric disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Natural Genetic Variation for Acclimation of Photosynthetic Light Use Efficiency to Growth Irradiance in Arabidopsis1[OPEN

PubMed Central

Harbinson, Jeremy

2015-01-01

Plants are known to be able to acclimate their photosynthesis to the level of irradiance. Here, we present the analysis of natural genetic variation for photosynthetic light use efficiency (ΦPSII) in response to five light environments among 12 genetically diverse Arabidopsis (Arabidopsis thaliana) accessions. We measured the acclimation of ΦPSII to constant growth irradiances of four different levels (100, 200, 400, and 600 µmol m−2 s−1) by imaging chlorophyll fluorescence after 24 d of growth and compared these results with acclimation of ΦPSII to a step-wise change in irradiance where the growth irradiance was increased from 100 to 600 µmol m−2 s−1 after 24 d of growth. Genotypic variation for ΦPSII is shown by calculating heritability for the short-term ΦPSII response to different irradiance levels as well as for the relation of ΦPSII measured at light saturation (a measure of photosynthetic capacity) to growth irradiance level and for the kinetics of the response to a step-wise increase in irradiance from 100 to 600 µmol m−2 s−1. A genome-wide association study for ΦPSII measured 1 h after a step-wise increase in irradiance identified several new candidate genes controlling this trait. In conclusion, the different photosynthetic responses to a changing light environment displayed by different Arabidopsis accessions are due to genetic differences, and we have identified candidate genes for the photosynthetic response to an irradiance change. The genetic variation for photosynthetic acclimation to irradiance found in this study will allow future identification and analysis of the causal genes for the regulation of ΦPSII in plants. PMID:25670817

The effects of Medieval dams on genetic divergence and demographic history in brown trout populations

PubMed Central

2014-01-01

Background Habitat fragmentation has accelerated within the last century, but may have been ongoing over longer time scales. We analyzed the timing and genetic consequences of fragmentation in two isolated lake-dwelling brown trout populations. They are from the same river system (the Gudenå River, Denmark) and have been isolated from downstream anadromous trout by dams established ca. 600–800 years ago. For reference, we included ten other anadromous populations and two hatchery strains. Based on analysis of 44 microsatellite loci we investigated if the lake populations have been naturally genetically differentiated from anadromous trout for thousands of years, or have diverged recently due to the establishment of dams. Results Divergence time estimates were based on 1) Approximate Bayesian Computation and 2) a coalescent-based isolation-with-gene-flow model. Both methods suggested divergence times ca. 600–800 years bp, providing strong evidence for establishment of dams in the Medieval as the factor causing divergence. Bayesian cluster analysis showed influence of stocked trout in several reference populations, but not in the focal lake and anadromous populations. Estimates of effective population size using a linkage disequilibrium method ranged from 244 to > 1,000 in all but one anadromous population, but were lower (153 and 252) in the lake populations. Conclusions We show that genetic divergence of lake-dwelling trout in two Danish lakes reflects establishment of water mills and impassable dams ca. 600–800 years ago rather than a natural genetic population structure. Although effective population sizes of the two lake populations are not critically low they may ultimately limit response to selection and thereby future adaptation. Our results demonstrate that populations may have been affected by anthropogenic disturbance over longer time scales than normally assumed. PMID:24903056

The effects of Medieval dams on genetic divergence and demographic history in brown trout populations.

PubMed

Hansen, Michael M; Limborg, Morten T; Ferchaud, Anne-Laure; Pujolar, José-Martin

2014-06-05

Habitat fragmentation has accelerated within the last century, but may have been ongoing over longer time scales. We analyzed the timing and genetic consequences of fragmentation in two isolated lake-dwelling brown trout populations. They are from the same river system (the Gudenå River, Denmark) and have been isolated from downstream anadromous trout by dams established ca. 600-800 years ago. For reference, we included ten other anadromous populations and two hatchery strains. Based on analysis of 44 microsatellite loci we investigated if the lake populations have been naturally genetically differentiated from anadromous trout for thousands of years, or have diverged recently due to the establishment of dams. Divergence time estimates were based on 1) Approximate Bayesian Computation and 2) a coalescent-based isolation-with-gene-flow model. Both methods suggested divergence times ca. 600-800 years bp, providing strong evidence for establishment of dams in the Medieval as the factor causing divergence. Bayesian cluster analysis showed influence of stocked trout in several reference populations, but not in the focal lake and anadromous populations. Estimates of effective population size using a linkage disequilibrium method ranged from 244 to > 1,000 in all but one anadromous population, but were lower (153 and 252) in the lake populations. We show that genetic divergence of lake-dwelling trout in two Danish lakes reflects establishment of water mills and impassable dams ca. 600-800 years ago rather than a natural genetic population structure. Although effective population sizes of the two lake populations are not critically low they may ultimately limit response to selection and thereby future adaptation. Our results demonstrate that populations may have been affected by anthropogenic disturbance over longer time scales than normally assumed.

De novo transcriptomic analysis and development of EST-SSRs for Sorbus pohuashanensis (Hance) Hedl.

PubMed Central

Guan, Xuelian; Fu, Qiang; Zhang, Ze; Hu, Zenghui; Zheng, Jian; Lu, Yizeng; Li, Wei

2017-01-01

Sorbus pohuashanensis is a native tree species of northern China that is used for a variety of ecological purposes. The species is often grown as an ornamental landscape tree because of its beautiful form, silver flowers in early summer, attractive pinnate leaves in summer, and red leaves and fruits in autumn. However, development and further utilization of the species are hindered by the lack of comprehensive genetic information, which impedes research into its genetics and molecular biology. Recent advances in de novo transcriptome sequencing (RNA-seq) technology have provided an effective means to obtain genomic information from non-model species. Here, we applied RNA-seq for sequencing S. pohuashanensis leaves and obtained a total of 137,506 clean reads. After assembly, 96,213 unigenes with an average length of 770 bp were obtained. We found that 64.5% of the unigenes could be annotated using bioinformatics tools to analyze gene function and alignment with the NCBI database. Overall, 59,089 unigenes were annotated using the Nr database(non-redundant protein database), 35,225 unigenes were annotated using the GO (Gene Ontology categories) database, and 33,168 unigenes were annotated using COG (Cluster of Orthologous Groups). Analysis of the unigenes using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database indicated that 13,953 unigenes were involved in 322 metabolic pathways. Finally, simple sequence repeat (SSR) site detection identified 6,604 unigenes that included EST-SSRs and a total of 7,473 EST-SSRs in the unigene sequences. Fifteen polymorphic SSRs were screened and found to be of use for future genetic research. These unigene sequences will provide important genetic resources for genetic improvement and investigation of biochemical processes in S. pohuashanensis. PMID:28614366

Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks.

PubMed

Ramanan, Vijay K; Kim, Sungeun; Holohan, Kelly; Shen, Li; Nho, Kwangsik; Risacher, Shannon L; Foroud, Tatiana M; Mukherjee, Shubhabrata; Crane, Paul K; Aisen, Paul S; Petersen, Ronald C; Weiner, Michael W; Saykin, Andrew J

2012-12-01

Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value < 0.05) against this composite memory score. Processes classically understood to be involved in memory consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions.

Wild European apple (Malus sylvestris (L.) Mill.) population dynamics: insight from genetics and ecology in the Rhine Valley. Priorities for a future conservation programme.

PubMed

Schnitzler, Annik; Arnold, Claire; Cornille, Amandine; Bachmann, Olivier; Schnitzler, Christophe

2014-01-01

The increasing fragmentation of forest habitats and the omnipresence of cultivars potentially threaten the genetic integrity of the European wild apple (Malus sylvestris (L.) Mill). However, the conservation status of this species remains unclear in Europe, other than in Belgium and the Czech Republic, where it has been declared an endangered species. The population density of M. sylvestris is higher in the forests of the upper Rhine Valley (France) than in most European forests, with an unbalanced age-structure, an overrepresentation of adults and a tendency to clump. We characterize here the ecology, age-structure and genetic diversity of wild apple populations in the Rhine Valley. We use these data to highlight links to the history of this species and to propose guidelines for future conservation strategies. In total, 255 individual wild apple trees from six forest stands (five floodplain forests and one forest growing in drier conditions) were analysed in the field, collected and genotyped on the basis of data for 15 microsatellite markers. Genetic analyses showed no escaped cultivars and few hybrids with the cultivated apple. Excluding the hybrids, the genetically "pure" populations displayed high levels of genetic diversity and a weak population structure. Age-structure and ecology studies of wild apple populations identified four categories that were not randomly distributed across the forests, reflecting the history of the Rhine forest over the last century. The Rhine wild apple populations, with their ecological strategies, high genetic diversity, and weak traces of crop-to-wild gene flow associated with the history of these floodplain forests, constitute candidate populations for inclusion in future conservation programmes for European wild apple.

Wild European Apple (Malus sylvestris (L.) Mill.) Population Dynamics: Insight from Genetics and Ecology in the Rhine Valley. Priorities for a Future Conservation Programme

PubMed Central

Schnitzler, Annik; Arnold, Claire; Cornille, Amandine; Bachmann, Olivier; Schnitzler, Christophe

2014-01-01

The increasing fragmentation of forest habitats and the omnipresence of cultivars potentially threaten the genetic integrity of the European wild apple (Malus sylvestris (L.) Mill). However, the conservation status of this species remains unclear in Europe, other than in Belgium and the Czech Republic, where it has been declared an endangered species. The population density of M. sylvestris is higher in the forests of the upper Rhine Valley (France) than in most European forests, with an unbalanced age-structure, an overrepresentation of adults and a tendency to clump. We characterize here the ecology, age-structure and genetic diversity of wild apple populations in the Rhine Valley. We use these data to highlight links to the history of this species and to propose guidelines for future conservation strategies. In total, 255 individual wild apple trees from six forest stands (five floodplain forests and one forest growing in drier conditions) were analysed in the field, collected and genotyped on the basis of data for 15 microsatellite markers. Genetic analyses showed no escaped cultivars and few hybrids with the cultivated apple. Excluding the hybrids, the genetically “pure” populations displayed high levels of genetic diversity and a weak population structure. Age-structure and ecology studies of wild apple populations identified four categories that were not randomly distributed across the forests, reflecting the history of the Rhine forest over the last century. The Rhine wild apple populations, with their ecological strategies, high genetic diversity, and weak traces of crop-to-wild gene flow associated with the history of these floodplain forests, constitute candidate populations for inclusion in future conservation programmes for European wild apple. PMID:24827575

A genomic scale map of genetic diversity in Trypanosoma cruzi

PubMed Central

2012-01-01

Background Trypanosoma cruzi, the causal agent of Chagas Disease, affects more than 16 million people in Latin America. The clinical outcome of the disease results from a complex interplay between environmental factors and the genetic background of both the human host and the parasite. However, knowledge of the genetic diversity of the parasite, is currently limited to a number of highly studied loci. The availability of a number of genomes from different evolutionary lineages of T. cruzi provides an unprecedented opportunity to look at the genetic diversity of the parasite at a genomic scale. Results Using a bioinformatic strategy, we have clustered T. cruzi sequence data available in the public domain and obtained multiple sequence alignments in which one or two alleles from the reference CL-Brener were included. These data covers 4 major evolutionary lineages (DTUs): TcI, TcII, TcIII, and the hybrid TcVI. Using these set of alignments we have identified 288,957 high quality single nucleotide polymorphisms and 1,480 indels. In a reduced re-sequencing study we were able to validate ~ 97% of high-quality SNPs identified in 47 loci. Analysis of how these changes affect encoded protein products showed a 0.77 ratio of synonymous to non-synonymous changes in the T. cruzi genome. We observed 113 changes that introduce or remove a stop codon, some causing significant functional changes, and a number of tri-allelic and tetra-allelic SNPs that could be exploited in strain typing assays. Based on an analysis of the observed nucleotide diversity we show that the T. cruzi genome contains a core set of genes that are under apparent purifying selection. Interestingly, orthologs of known druggable targets show statistically significant lower nucleotide diversity values. Conclusions This study provides the first look at the genetic diversity of T. cruzi at a genomic scale. The analysis covers an estimated ~ 60% of the genetic diversity present in the population, providing an essential resource for future studies on the development of new drugs and diagnostics, for Chagas Disease. These data is available through the TcSNP database (http://snps.tcruzi.org). PMID:23270511

Restoration seed reserves for assisted gene flow within seed orchards

Treesearch

C.S. Echt; B.S. Crane

2017-01-01

Changing climate and declining forest populations imperil the future of certain forest tree species. To complement forest management and genetic conservation plans, we propose a new paradigm for seedling seed orchards: foster genetic mixing among a variety of seed sources to increase genetic diversity and adaptive potential of seed supplies used for forest restoration...

The GENET Project--The Discussion of Biotechnology and Genetics Controversies at Internet.

ERIC Educational Resources Information Center

Rocha dos Reis, Pedro

The GENET (gene + net) Forum was designed as a contribution to help teachers and pupils to develop critical thinking, creativity, and values capable of assuring to future citizens an active and responsible involvement in societal evolution. This project (which includes a chat and online discussion forum) explores the ethical, legal, and social…

Banking on the future: progress, challenges and opportunities for the genetic conservation of forest trees

Treesearch

Kevin M. Potter; Robert M. Jetton; Andrew Bower; Douglass F. Jacobs; Gary Man; Valerie D. Hipkins; Murphy Westwood

2017-01-01

Genetic diversity provides the essential basis for the adaptation and resilience of tree species to environmental stress and change. The genetic conservation of tree species is an urgent global necessity as forest conversion and fragmentation continue apace, damaging insects and pathogens are transported between continents, and climate change alters local habitat...

Proteomics and Systems Biology: Current and Future Applications in the Nutritional Sciences1

PubMed Central

Moore, J. Bernadette; Weeks, Mark E.

2011-01-01

In the last decade, advances in genomics, proteomics, and metabolomics have yielded large-scale datasets that have driven an interest in global analyses, with the objective of understanding biological systems as a whole. Systems biology integrates computational modeling and experimental biology to predict and characterize the dynamic properties of biological systems, which are viewed as complex signaling networks. Whereas the systems analysis of disease-perturbed networks holds promise for identification of drug targets for therapy, equally the identified critical network nodes may be targeted through nutritional intervention in either a preventative or therapeutic fashion. As such, in the context of the nutritional sciences, it is envisioned that systems analysis of normal and nutrient-perturbed signaling networks in combination with knowledge of underlying genetic polymorphisms will lead to a future in which the health of individuals will be improved through predictive and preventative nutrition. Although high-throughput transcriptomic microarray data were initially most readily available and amenable to systems analysis, recent technological and methodological advances in MS have contributed to a linear increase in proteomic investigations. It is now commonplace for combined proteomic technologies to generate complex, multi-faceted datasets, and these will be the keystone of future systems biology research. This review will define systems biology, outline current proteomic methodologies, highlight successful applications of proteomics in nutrition research, and discuss the challenges for future applications of systems biology approaches in the nutritional sciences. PMID:22332076

The Three Domains of Conservation Genetics: Case Histories from Hawaiian Waters.

PubMed

Bowen, Brian W

2016-07-01

The scientific field of conservation biology is dominated by 3 specialties: phylogenetics, ecology, and evolution. Under this triad, phylogenetics is oriented towards the past history of biodiversity, conserving the divergent branches in the tree of life. The ecological component is rooted in the present, maintaining the contemporary life support systems for biodiversity. Evolutionary conservation (as defined here) is concerned with preserving the raw materials for generating future biodiversity. All 3 domains can be documented with genetic case histories in the waters of the Hawaiian Archipelago, an isolated chain of volcanic islands with 2 types of biodiversity: colonists, and new species that arose from colonists. This review demonstrates that 1) phylogenetic studies have identified previously unknown branches in the tree of life that are endemic to Hawaiian waters; 2) population genetic surveys define isolated marine ecosystems as management units, and 3) phylogeographic analyses illustrate the pathways of colonization that can enhance future biodiversity. Conventional molecular markers have advanced all 3 domains in conservation biology over the last 3 decades, and recent advances in genomics are especially valuable for understanding the foundations of future evolutionary diversity. © The American Genetic Association. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experiences from the National Institute of Nursing Research: Summer Genetics Institute 2004.

PubMed

Whitt, Karen J

2005-02-01

The National Institute of Nursing Research (NINR) Summer Genetics Institute (SGI) prepares nurses with training in molecular genetics for use in clinical practice, research, and education. Experiences from the SGI 2004 are recounted. More than 35 genetic experts from National Institutes of Health and surrounding universities in Washington, D.C., provided lecture and laboratory experiences. The lecture portion of the SGI focused on the molecular aspect of genetics and the laboratory component included experiments designed to provide an understanding of genetic approaches for diagnostic and research purposes. The SGI prepares nurses with the genetic foundation to meet the healthcare challenges of the future.

Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use.

PubMed

Hammond, Elizabeth R; Shelling, Andrew N; Cree, Lynsey M

2016-08-01

The ability to screen embryos for aneuploidy or inherited disorders in a minimally invasive manner may represent a major advancement for the future of embryo viability assessment. Recent studies have demonstrated that both blastocoele fluid and embryo culture medium contain genetic material, which can be isolated and subjected to downstream genetic analysis. The blastocoele fluid may represent an alternative source of nuclear DNA for aneuploidy testing, although the degree to which the isolated genetic material is solely representative of the developing embryo is currently unclear. In addition to nuclear DNA, mitochondrial DNA (mtDNA) can be detected in the embryo culture medium. Currently, the origin of this nuclear and mtDNA has not been fully evaluated and there are several potential sources of contamination that may contribute to the genetic material detected in the culture medium. There is however evidence that the mtDNA content of the culture medium is related to embryo fragmentation levels and its presence is predictive of blastulation, indicating that embryo development may influence the levels of genetic material detected. If the levels of genetic material are strongly related to aspects of embryo quality, then this may be a novel biomarker of embryo viability. If the genetic material does have an embryo origin, the mechanisms by which DNA may be released into the blastocoele fluid and embryo culture medium are unknown, although apoptosis may play a role. While the presence of this genetic material is an exciting discovery, the DNA in the blastocoele fluid and embryo culture medium appears to be of low yield and integrity, which makes it challenging to study. Further research aimed at assessing the methodologies used for both isolating and analysing this genetic material, as well as tracing its origin, are needed in order to evaluate its potential for clinical use. Should such methodologies prove to be routinely successful and the DNA recovered demonstrated to be embryonic in origin, then they may be used in a minimally invasive and less technical methodology for genetic analysis and embryo viability assessment than those currently available. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

USEPA Resistance Management Research

EPA Science Inventory

A significant increase in genetically modified corn planting driven by biofuel demand is expected for future planted acreages approaching 80% of total corn plantings in 2009. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is...

Analysis of Geographic and Pairwise Distances among Chinese Cashmere Goat Populations

PubMed Central

Liu, Jian-Bin; Wang, Fan; Lang, Xia; Zha, Xi; Sun, Xiao-Ping; Yue, Yao-Jing; Feng, Rui-Lin; Yang, Bo-Hui; Guo, Jian

2013-01-01

This study investigated the geographic and pairwise distances of nine Chinese local Cashmere goat populations through the analysis of 20 microsatellite DNA markers. Fluorescence PCR was used to identify the markers, which were selected based on their significance as identified by the Food and Agriculture Organization of the United Nations (FAO) and the International Society for Animal Genetics (ISAG). In total, 206 alleles were detected; the average allele number was 10.30; the polymorphism information content of loci ranged from 0.5213 to 0.7582; the number of effective alleles ranged from 4.0484 to 4.6178; the observed heterozygosity was from 0.5023 to 0.5602 for the practical sample; the expected heterozygosity ranged from 0.5783 to 0.6464; and Allelic richness ranged from 4.7551 to 8.0693. These results indicated that Chinese Cashmere goat populations exhibited rich genetic diversity. Further, the Wright’s F-statistics of subpopulation within total (FST) was 0.1184; the genetic differentiation coefficient (GST) was 0.0940; and the average gene flow (Nm) was 2.0415. All pairwise FST values among the populations were highly significant (p<0.01 or p<0.001), suggesting that the populations studied should all be considered to be separate breeds. Finally, the clustering analysis divided the Chinese Cashmere goat populations into at least four clusters, with the Hexi and Yashan goat populations alone in one cluster. These results have provided useful, practical, and important information for the future of Chinese Cashmere goat breeding. PMID:25049794

Investigating Factors that Generate and Maintain Variation in Migratory Orientation: A Primer for Recent and Future Work.

PubMed

Delmore, Kira E; Liedvogel, Miriam

2016-01-01

The amazing accuracy of migratory orientation performance across the animal kingdom is facilitated by the use of magnetic and celestial compass systems that provide individuals with both directional and positional information. Quantitative genetics analyses in several animal systems suggests that migratory orientation has a strong genetic component. Nevertheless, the exact identity of genes controlling orientation remains largely unknown, making it difficult to obtain an accurate understanding of this fascinating behavior on the molecular level. Here, we provide an overview of molecular genetic techniques employed thus far, highlight the pros and cons of various approaches, generalize results from species-specific studies whenever possible, and evaluate how far the field has come since early quantitative genetics studies. We emphasize the importance of examining different levels of molecular control, and outline how future studies can take advantage of high-resolution tracking and sequencing techniques to characterize the genomic architecture of migratory orientation.

Genetic variability in the Florida manatee (Trichechus manatus)

USGS Publications Warehouse

McClenaghan, Leroy R.; O'Shea, Thomas J.

1988-01-01

Tissue was obtained from 59 manatee (Trichechus manatus) carcasses salvaged from 20 counties in Florida. Allozyme phenotypes at 24 structural loci were determined by gel electrophoresis. Averages for the proportion of polymorphic loci and mean heterozygosity were 0.300 (range, 0.167-0.417) and 0.050 (range, 0.028-0.063), respectively. These estimates are equivalent to or higher than those generally reported for other species of marine mammals and do not support the hypothesis that body size and heterozygosity in mammals are related inversely. Among-region gene diversity accounted for only 4% of the total diversity. High rates of gene flow probably account for genetic homogeneity across regions. An F-statistic analysis revealed a general tendency toward excess homozygosity within regions. Management efforts to prevent future reductions in population size that would erode existing genic diversity should continue.

ECUT: Energy Conversion and Utilization Technologies program - Biocatalysis research activity

NASA Technical Reports Server (NTRS)

Wilcox, R.

1984-01-01

The activities of the Biocatalysis Research Activity are organized into the Biocatalysis and Molecular Modeling work elements and a supporting planning and analysis function. In the Biocatalysis work element, progress is made in developing a method for stabilizing genetically engineered traits in microorganisms, refining a technique for monitoring cells that are genetically engineered, and identifying strains of fungi for highly efficient preprocessing of biomass for optimizing the efficiency of bioreactors. In the Molecular Modeling work element, a preliminary model of the behavior of enzymes is developed. A preliminary investigation of the potential for synthesizing enzymes for use in electrochemical processes is completed. Contact with industry and universities is made to define key biocatalysis technical issues and to broaden the range of potential participants in the activity. Analyses are conducted to identify and evaluate potential concepts for future research funding.

Human Germline Genome Editing.

PubMed

Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

2017-08-03

With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

Genetic Assessments and Parentage Analysis of Captive Bolson Tortoises (Gopherus flavomarginatus) Inform Their “Rewilding” in New Mexico

PubMed Central

Edwards, Taylor; Cox, Elizabeth Canty; Buzzard, Vanessa; Wiese, Christiane; Hillard, L. Scott; Murphy, Robert W.

2014-01-01

The Bolson tortoise (Gopherus flavomarginatus) is the first species of extirpated megafauna to be repatriated into the United States. In September 2006, 30 individuals were translocated from Arizona to New Mexico with the long-term objective of restoring wild populations via captive propagation. We evaluated mtDNA sequences and allelic diversity among 11 microsatellite loci from the captive population and archived samples collected from wild individuals in Durango, Mexico (n = 28). Both populations exhibited very low genetic diversity and the captive population captured roughly 97.5% of the total wild diversity, making it a promising founder population. Genetic screening of other captive animals (n = 26) potentially suitable for reintroduction uncovered multiple hybrid G. flavomarginatus×G. polyphemus, which were ineligible for repatriation; only three of these individuals were verified as purebred G. flavomarginatus. We used these genetic data to inform mate pairing, reduce the potential for inbreeding and to monitor the maintenance of genetic diversity in the captive population. After six years of successful propagation, we analyzed the parentage of 241 hatchlings to assess the maintenance of genetic diversity. Not all adults contributed equally to successive generations. Most yearly cohorts of hatchlings failed to capture the diversity of the parental population. However, overlapping generations of tortoises helped to alleviate genetic loss because the entire six-year cohort of hatchlings contained the allelic diversity of the parental population. Polyandry and sperm storage occurred in the captives and future management strategies must consider such events. PMID:25029369

The memory remains: application of historical DNA for scaling biodiversity loss.

PubMed

Nielsen, Einar E; Bekkevold, Dorte

2012-04-01

Few species worldwide have attracted as much attention in relation to conservation and sustainable management as Pacific salmon. Most populations have suffered significant reductions, many have disappeared, and even entire evolutionary significant units (ESUs) are believed to have been lost. Until now, no 'smoking gun' in terms of direct genetic evidence of the loss of a salmon ESU has been produced. In this issue of Molecular Ecology, Iwamoto et al. (2012) use microsatellite analysis of historical scale samples of Columbia River sockeye salmon (Oncorhynchus nerka) from 1924 (Fig. 1) to ask the pertinent question: Do the historical samples contain salmon from extirpated populations or ESUs? They identified four genetic groups in the historical samples of which two were almost genetically identical to contemporary ESUs in the river, one showed genetic relationship with a third ESU, but one group was not related to any of the contemporary populations. In association with ecological data, the genetic results suggest that an early migrating Columbia River headwater sockeye salmon ESU has been extirpated. The study has significant importance for conservation and reestablishment of sockeye populations in the Columbia River, but also underpins the general significance of shifting baselines in conservation biology, and how to assess loss of genetic biodiversity. The results clearly illustrate the huge and versatile potential of using historical DNA in population and conservation genetics. Because of the extraordinarily plentiful historical samples and rapid advances in fish genomics, fishes are likely to spearhead future studies of temporal ecological and population genomics in non-model organisms. [Figure: see text]. © 2012 Blackwell Publishing Ltd.

The Y chromosome as the most popular marker in genetic genealogy benefits interdisciplinary research.

PubMed

Calafell, Francesc; Larmuseau, Maarten H D

2017-05-01

The Y chromosome is currently by far the most popular marker in genetic genealogy that combines genetic data and family history. This popularity is based on its haploid character and its close association with the patrilineage and paternal inherited surname. Other markers have not been found (yet) to overrule this status due to the low sensitivity and precision of autosomal DNA for genetic genealogical applications, given the vagaries of recombination, and the lower capacities of mitochondrial DNA combined with an in general much lower interest in maternal lineages. The current knowledge about the Y chromosome and the availability of markers with divergent mutation rates make it possible to answer questions on relatedness levels which differ in time depth; from the individual and familial level to the surnames, clan and population level. The use of the Y chromosome in genetic genealogy has led to applications in several well-established research disciplines; namely in, e.g., family history, demography, anthropology, forensic sciences, population genetics and sex chromosome evolution. The information obtained from analysing this chromosome is not only interesting for academic scientists but also for the huge and lively community of amateur genealogists and citizen-scientists, fascinated in analysing their own genealogy or surname. This popularity, however, has also some drawbacks, mainly for privacy reasons related to the DNA donor, his close family and far-related namesakes. In this review paper we argue why Y-chromosomal analysis and its genetic genealogical applications will still perform an important role in future interdisciplinary research.

Genetic effects influencing risk for major depressive disorder in China and Europe.

PubMed

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-03-28

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log 10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Genetic effects influencing risk for major depressive disorder in China and Europe

PubMed Central

Bigdeli, T B; Ripke, S; Peterson, R E; Trzaskowski, M; Bacanu, S-A; Abdellaoui, A; Andlauer, T F M; Beekman, A T F; Berger, K; Blackwood, D H R; Boomsma, D I; Breen, G; Buttenschøn, H N; Byrne, E M; Cichon, S; Clarke, T-K; Couvy-Duchesne, B; Craddock, N; de Geus, E J C; Degenhardt, F; Dunn, E C; Edwards, A C; Fanous, A H; Forstner, A J; Frank, J; Gill, M; Gordon, S D; Grabe, H J; Hamilton, S P; Hardiman, O; Hayward, C; Heath, A C; Henders, A K; Herms, S; Hickie, I B; Hoffmann, P; Homuth, G; Hottenga, J-J; Ising, M; Jansen, R; Kloiber, S; Knowles, J A; Lang, M; Li, Q S; Lucae, S; MacIntyre, D J; Madden, P A F; Martin, N G; McGrath, P J; McGuffin, P; McIntosh, A M; Medland, S E; Mehta, D; Middeldorp, C M; Milaneschi, Y; Montgomery, G W; Mors, O; Müller-Myhsok, B; Nauck, M; Nyholt, D R; Nöthen, M M; Owen, M J; Penninx, B W J H; Pergadia, M L; Perlis, R H; Peyrot, W J; Porteous, D J; Potash, J B; Rice, J P; Rietschel, M; Riley, B P; Rivera, M; Schoevers, R; Schulze, T G; Shi, J; Shyn, S I; Smit, J H; Smoller, J W; Streit, F; Strohmaier, J; Teumer, A; Treutlein, J; Van der Auwera, S; van Grootheest, G; van Hemert, A M; Völzke, H; Webb, B T; Weissman, M M; Wellmann, J; Willemsen, G; Witt, S H; Levinson, D F; Lewis, C M; Wray, N R; Flint, J; Sullivan, P F; Kendler, K S

2017-01-01

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30–40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies. PMID:28350396

Low Genetic Diversity and Structuring of the Arapaima (Osteoglossiformes, Arapaimidae) Population of the Araguaia-Tocantins Basin.

PubMed

Vitorino, Carla A; Nogueira, Fabrícia; Souza, Issakar L; Araripe, Juliana; Venere, Paulo C

2017-01-01

The arapaima, Arapaima gigas , is a fish whose populations are threatened by both overfishing and the ongoing destruction of its natural habitats. In the Amazon basin, varying levels of population structure have been found in A. gigas , although no data are available on the genetic diversity or structure of the populations found in the Araguaia-Tocantins basin, which has a topographic profile, hydrological regime, and history of fishing quite distinct from those of the Amazon. In this context, microsatellite markers were used to assess the genetic diversity and connectivity of five wild A. gigas populations in the Araguaia-Tocantins basin. The results of the analysis indicated low levels of genetic diversity in comparison with other A. gigas populations, studied in the Amazon basin. The AMOVA revealed that the Arapaima populations of the Araguaia-Tocantins basin are structured significantly. No correlation was found between pairwise F ST values and the geographical distance among populations. The low level of genetic variability and the evidence of restricted gene flow may both be accounted for by overfishing, as well as the other human impacts that these populations have been exposed to over the years. The genetic fragility of these populations demands attention, given that future environmental changes (natural or otherwise) may further reduce these indices and eventually endanger these populations. The results of this study emphasize the need to take the genetic differences among the study populations into account when planning management measures and conservation strategies for the arapaima stocks of the Araguaia-Tocantins basin.

Low Genetic Diversity and Structuring of the Arapaima (Osteoglossiformes, Arapaimidae) Population of the Araguaia-Tocantins Basin

PubMed Central

Vitorino, Carla A.; Nogueira, Fabrícia; Souza, Issakar L.; Araripe, Juliana; Venere, Paulo C.

2017-01-01

The arapaima, Arapaima gigas, is a fish whose populations are threatened by both overfishing and the ongoing destruction of its natural habitats. In the Amazon basin, varying levels of population structure have been found in A. gigas, although no data are available on the genetic diversity or structure of the populations found in the Araguaia-Tocantins basin, which has a topographic profile, hydrological regime, and history of fishing quite distinct from those of the Amazon. In this context, microsatellite markers were used to assess the genetic diversity and connectivity of five wild A. gigas populations in the Araguaia-Tocantins basin. The results of the analysis indicated low levels of genetic diversity in comparison with other A. gigas populations, studied in the Amazon basin. The AMOVA revealed that the Arapaima populations of the Araguaia-Tocantins basin are structured significantly. No correlation was found between pairwise FST values and the geographical distance among populations. The low level of genetic variability and the evidence of restricted gene flow may both be accounted for by overfishing, as well as the other human impacts that these populations have been exposed to over the years. The genetic fragility of these populations demands attention, given that future environmental changes (natural or otherwise) may further reduce these indices and eventually endanger these populations. The results of this study emphasize the need to take the genetic differences among the study populations into account when planning management measures and conservation strategies for the arapaima stocks of the Araguaia-Tocantins basin. PMID:29114261

Genetic diversity of wild germplasm of "yerba mate" (Ilex paraguariensis St. Hil.) from Uruguay.

PubMed

Cascales, Jimena; Bracco, Mariana; Poggio, Lidia; Gottlieb, Alexandra Marina

2014-12-01

The "yerba mate" tree, Ilex paraguariensis St. Hil., is a crop native to subtropical South America, marketed for the elaboration of the highly popular "mate" beverage. The Uruguayan germplasm occupies the southernmost area of the species distribution range and carries adaptations to environments that considerably differ from the current production area. We characterized the genetic variability of the germplasm from this unexplored area by jointly analyzing individuals from the diversification center (ABP, Argentina, Brazil and Paraguay) with 19 nuclear and 11 plastidic microsatellite markers. For the Uruguayan germplasm, we registered 55 alleles (18 % private), and 80 genotypes (44 % exclusive), whereas 63 alleles (28.6 % private) and 81 genotypes (42 % exclusive) were recorded for individuals from ABP. Only two plastidic haplotypes were detected. Distance-based and multilocus genotype analyses showed that individuals from ABP intermingle and that the Uruguayan germplasm is differentiated in three gene-pools. Significant positive correlations between genetic and geographic distances were detected. Our results concur in that ABP individuals harbor greater genetic variation than those from the tail of the distribution, as to the number of alleles (1.15-fold), He (1.19-fold), Rs (1.39-fold), and the between-group genetic distances (1.16-fold). Also the shape of the genetic landscape interpolation analysis suggests that the genetic variation decays southward towards the Uruguayan territory. We showed that Uruguayan germplasm hosts a combination of nuclear alleles not present in the central region, constituting a valuable breeding resource. Future conservation efforts should concentrate in collecting numerous individuals of "yerba mate" per site to gather the existent variation.

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England

PubMed Central

2010-01-01

Background As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Methods Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Results Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can be customised for reuse by other services. Conclusions Healthcare services need to translate advances in genetics into benefits for patients. Consideration of the issues presented here when incorporating genetics into mainstream medical services will help ensure that new service developments build on the body of experience gained by the pilots, to provide high quality services for patients with or at risk of genetic conditions. PMID:20470377

A toolkit for incorporating genetics into mainstream medical services: Learning from service development pilots in England.

PubMed

Bennett, Catherine L; Burke, Sarah E; Burton, Hilary; Farndon, Peter A

2010-05-14

As advances in genetics are becoming increasingly relevant to mainstream healthcare, a major challenge is to ensure that these are integrated appropriately into mainstream medical services. In 2003, the Department of Health for England announced the availability of start-up funding for ten 'Mainstreaming Genetics' pilot services to develop models to achieve this. Multiple methods were used to explore the pilots' experiences of incorporating genetics which might inform the development of new services in the future. A workshop with project staff, an email questionnaire, interviews and a thematic analysis of pilot final reports were carried out. Seven themes relating to the integration of genetics into mainstream medical services were identified: planning services to incorporate genetics; the involvement of genetics departments; the establishment of roles incorporating genetic activities; identifying and involving stakeholders; the challenges of working across specialty boundaries; working with multiple healthcare organisations; and the importance of cultural awareness of genetic conditions. Pilots found that the planning phase often included the need to raise awareness of genetic conditions and services and that early consideration of organisational issues such as clinic location was essential. The formal involvement of genetics departments was crucial to success; benefits included provision of clinical and educational support for staff in new roles. Recruitment and retention for new roles outside usual career pathways sometimes proved difficult. Differences in specialties' working practices and working with multiple healthcare organisations also brought challenges such as the 'genetic approach' of working with families, incompatible record systems and different approaches to health professionals' autonomous practice. 'Practice points' have been collated into a Toolkit which includes resources from the pilots, including job descriptions and clinical tools. These can be customised for reuse by other services. Healthcare services need to translate advances in genetics into benefits for patients. Consideration of the issues presented here when incorporating genetics into mainstream medical services will help ensure that new service developments build on the body of experience gained by the pilots, to provide high quality services for patients with or at risk of genetic conditions.

Genotype-Specific Minimal Residual Disease Interpretation Improves Stratification in Pediatric Acute Lymphoblastic Leukemia

PubMed Central

O’Connor, David; Enshaei, Amir; Bartram, Jack; Hancock, Jeremy; Harrison, Christine J.; Hough, Rachael; Samarasinghe, Sujith; Schwab, Claire; Vora, Ajay; Wade, Rachel; Moppett, John; Moorman, Anthony V.; Goulden, Nick

2018-01-01

Purpose Minimal residual disease (MRD) and genetic abnormalities are important risk factors for outcome in acute lymphoblastic leukemia. Current risk algorithms dichotomize MRD data and do not assimilate genetics when assigning MRD risk, which reduces predictive accuracy. The aim of our study was to exploit the full power of MRD by examining it as a continuous variable and to integrate it with genetics. Patients and Methods We used a population-based cohort of 3,113 patients who were treated in UKALL2003, with a median follow-up of 7 years. MRD was evaluated by polymerase chain reaction analysis of Ig/TCR gene rearrangements, and patients were assigned to a genetic subtype on the basis of immunophenotype, cytogenetics, and fluorescence in situ hybridization. To examine response kinetics at the end of induction, we log-transformed the absolute MRD value and examined its distribution across subgroups. Results MRD was log normally distributed at the end of induction. MRD distributions of patients with distinct genetic subtypes were different (P < .001). Patients with good-risk cytogenetics demonstrated the fastest disease clearance, whereas patients with high-risk genetics and T-cell acute lymphoblastic leukemia responded more slowly. The risk of relapse was correlated with MRD kinetics, and each log reduction in disease level reduced the risk by 20% (hazard ratio, 0.80; 95% CI, 0.77 to 0.83; P < .001). Although the risk of relapse was directly proportional to the MRD level within each genetic risk group, absolute relapse rate that was associated with a specific MRD value or category varied significantly by genetic subtype. Integration of genetic subtype–specific MRD values allowed more refined risk group stratification. Conclusion A single threshold for assigning patients to an MRD risk group does not reflect the response kinetics of the different genetic subtypes. Future risk algorithms should integrate genetics with MRD to accurately identify patients with the lowest and highest risk of relapse. PMID:29131699

Psychosocial impact of prognostic genetic testing in the care of uveal melanoma patients: protocol of a controlled prospective clinical observational study.

PubMed

Erim, Yesim; Scheel, Jennifer; Breidenstein, Anja; Metz, Claudia Hd; Lohmann, Dietmar; Friederich, Hans-Christoph; Tagay, Sefik

2016-07-07

Uveal melanoma patients with a poor prognosis can be detected through genetic analysis of the tumor, which has a very high sensitivity. A large number of patients with uveal melanoma decide to receive information about their individual risk and therefore routine prognostic genetic testing is being carried out on a growing number of patients. It is obvious that a positive prediction for recidivism in the future will emotionally burden the respective patients, but research on the psychosocial impact of this innovative method is lacking. The aim of the current study is therefore to investigate the psychosocial impact (psychological distress and quality of life) of prognostic genetic testing in patients with uveal melanoma. This study is a non-randomized controlled prospective clinical observational trial. Subjects are patients with uveal melanoma, in whom genetic testing is possible. Patients who consent to genetic testing are allocated to the intervention group and patients who refuse genetic testing form the observational group. Both groups receive cancer therapy and psycho-oncological intervention when needed. The psychosocial impact of prognostic testing is investigated with the following variables: resilience, social support, fear of tumor progression, depression, general distress, cancer-specific and general health-related quality of life, attitude towards genetic testing, estimation of the perceived risk of metastasis, utilization and satisfaction with psycho-oncological crisis intervention, and sociodemographic data. Data are assessed preoperatively (at initial admission in the clinic) and postoperatively (at discharge from hospital after surgery, 6-12 weeks, 6 and 12 months after initial admission). Genetic test results are communicated 6-12 weeks after initial admission to the clinic. We created optimal conditions for investigation of the psychosocial impact of prognostic genetic testing. This study will provide information on the course of disease and psychosocial outcomes after prognostic genetic testing. We expect that empirical data from our study will give a scientific basis for medico-ethical considerations.

Understanding invasion history and predicting invasive niches using genetic sequencing technology in Australia: case studies from Cucurbitaceae and Boraginaceae.

PubMed

Shaik, Razia S; Zhu, Xiaocheng; Clements, David R; Weston, Leslie A

2016-01-01

Part of the challenge in dealing with invasive plant species is that they seldom represent a uniform, static entity. Often, an accurate understanding of the history of plant introduction and knowledge of the real levels of genetic diversity present in species and populations of importance is lacking. Currently, the role of genetic diversity in promoting the successful establishment of invasive plants is not well defined. Genetic profiling of invasive plants should enhance our understanding of the dynamics of colonization in the invaded range. Recent advances in DNA sequencing technology have greatly facilitated the rapid and complete assessment of plant population genetics. Here, we apply our current understanding of the genetics and ecophysiology of plant invasions to recent work on Australian plant invaders from the Cucurbitaceae and Boraginaceae. The Cucurbitaceae study showed that both prickly paddy melon ( Cucumis myriocarpus ) and camel melon ( Citrullus lanatus ) were represented by only a single genotype in Australia, implying that each was probably introduced as a single introduction event. In contrast, a third invasive melon, Citrullus colocynthis , possessed a moderate level of genetic diversity in Australia and was potentially introduced to the continent at least twice. The Boraginaceae study demonstrated the value of comparing two similar congeneric species; one, Echium plantagineum , is highly invasive and genetically diverse, whereas the other, Echium vulgare , exhibits less genetic diversity and occupies a more limited ecological niche. Sequence analysis provided precise identification of invasive plant species, as well as information on genetic diversity and phylogeographic history. Improved sequencing technologies will continue to allow greater resolution of genetic relationships among invasive plant populations, thereby potentially improving our ability to predict the impact of these relationships upon future spread and better manage invaders possessing potentially diverse biotypes and exhibiting diverse breeding systems, life histories and invasion histories.

Field-based detection of biological samples for forensic analysis: Established techniques, novel tools, and future innovations.

PubMed

Morrison, Jack; Watts, Giles; Hobbs, Glyn; Dawnay, Nick

2018-04-01

Field based forensic tests commonly provide information on the presence and identity of biological stains and can also support the identification of species. Such information can support downstream processing of forensic samples and generate rapid intelligence. These approaches have traditionally used chemical and immunological techniques to elicit the result but some are known to suffer from a lack of specificity and sensitivity. The last 10 years has seen the development of field-based genetic profiling systems, with specific focus on moving the mainstay of forensic genetic analysis, namely STR profiling, out of the laboratory and into the hands of the non-laboratory user. In doing so it is now possible for enforcement officers to generate a crime scene DNA profile which can then be matched to a reference or database profile. The introduction of these novel genetic platforms also allows for further development of new molecular assays aimed at answering the more traditional questions relating to body fluid identity and species detection. The current drive for field-based molecular tools is in response to the needs of the criminal justice system and enforcement agencies, and promises a step-change in how forensic evidence is processed. However, the adoption of such systems by the law enforcement community does not represent a new strategy in the way forensic science has integrated previous novel approaches. Nor do they automatically represent a threat to the quality control and assurance practices that are central to the field. This review examines the historical need and subsequent research and developmental breakthroughs in field-based forensic analysis over the past two decades with particular focus on genetic methods Emerging technologies from a range of scientific fields that have potential applications in forensic analysis at the crime scene are identified and associated issues that arise from the shift from laboratory into operational field use are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Beliefs and Perceptions about the Future: A Measurement of Future Time Perspective

ERIC Educational Resources Information Center

Husman, Jenefer; Shell, Duane F.

2008-01-01

Human's ability to consider the future, willingness to make sacrifices in the present to obtain something better in the future has been a significant part of our success as a species (Suddendorf, T., & Corballis, M. C. (1997). "Mental time travel and the evolution of the human mind." "Genetic, social, and general psychology monographs" 123,…

MTHFR genetic polymorphisms may contribute to the risk of chronic myelogenous leukemia in adults: a meta-analysis of 12 genetic association studies.

PubMed

Li, Bin; Zhang, Jian; Wang, Lei; Li, Yan; Jin, Juping; Ai, Limei; Li, Chong; Li, Zhe; Mao, Shudan

2014-05-01

Chronic myelogenous leukemia (CML) is a complex disease with a genetic basis. The genetic association studies (GASs) that have investigated the association between adult CML and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have produced contradictory and inconclusive results. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the association of these polymorphisms with adult CML risk. A literature search for eligible GAS published before September 15, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using the Stata software, version 12.0. Twelve case-control studies were included in this meta-analysis with a total of 932 CML patients and 3,465 healthy controls. For MTHFR C677T (dbSNP: rs1801133, C>T), though the pooled ORs were not significant in the overall population, all the ORs greater than 1 suggested an increased risk of CML for carriers of the risk allele. However, stratified analysis based on genotyping method revealed a significant association in the PCR-restriction fragment length polymorphism (RFLP) subgroup, possibly as a result of heterogeneity. For MTHFR A1298C (dbSNP: rs1801131, A>C), the combined results showed that carriers of the C allele may be associated with a decreased risk of adult CML. Stratified analysis showed that the magnitude of this effect was especially significant among Asians, indicating ethnicity differences in adult CML susceptibility. This meta-analysis shows that the C allele of MTHFR A1298C may be associated with a decreased risk in adult CML, especially among Asians, while MTHFR C677T may not be associated with adult CML risk. However, the development of adult CML may be the result of gene-gene and gene-environment interactions, which should be considered in future individual GAS and subsequent meta-analyses.

Progress and Prospects for Genetic Modification of Nonhuman Primate Models in Biomedical Research

PubMed Central

Chan, Anthony W. S.

2013-01-01

The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model. PMID:24174443

Genetic Testing in the Multidisciplinary Management of Melanoma.

PubMed

Rashid, Omar M; Zager, Jonathan S

2015-10-01

Melanoma is increasing in incidence and represents an aggressive type of cancer. Efforts have focused on identifying genetic factors in melanoma carcinogenesis to guide prevention, screening, early detection, and targeted therapy. This article reviews the hereditary risk factors associated with melanoma and the known molecular pathways and genetic mutations associated with this disease. This article also explores the controversies associated with genetic testing and the latest advances in identifying genetic targets in melanoma, which offer promise for future application in the multidisciplinary management of melanoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Medical mistrust influences black women's level of engagement in BRCA 1/2 genetic counseling and testing.

PubMed

Sheppard, Vanessa B; Mays, Darren; LaVeist, Thomas; Tercyak, Kenneth P

2013-01-01

Clinical evidence supports the value of BRCA1/2 genetic counseling and testing for managing hereditary breast and ovarian cancer risk; however, BRCA1/2 genetic counseling and testing are underutilized among black women, and reasons for low use remain elusive. We examined the potential influence of sociocultural factors (medical mistrust, concerns about genetic discrimination) on genetic counseling and testing engagement in a sample of 100 black women at increased risk for carrying a BRCA1/2 mutation. Eligible participants fell into 1 of 3 groups: (1) healthy women with at least 1 first-degree relative affected by breast and/or ovarian cancer, (2) women diagnosed with breast cancer at age less than or equal to 50 years; and (3) women diagnosed with breast and/or ovarian cancer at age greater than or equal to 50 years with either 1 first-degree relative or 2 second-degree relatives with breast and/or ovarian cancer. Participants were recruited from clinical anid community settings and completed a semistructured interview. Study variable relationships were examined using bivariate tests and multivariate regression analysis. As expected, genetic counseling and testing engagement among this sample was low (28%). After accounting for;sociodemographic factors and self-efficacy (beta=0.37, p<.001), women with higher medical mistrust had lower genetic counseling and testing engagement (beta=-0.26, p<.01). Community-level and individual interventions are needed to improve utilization of genetic counseling and testing among underserved women. Along with trust building between patients and providers, strategies should enhance women's personal confidence. The impact of medical mistrust on the realization of the benefits of personalized medicine in minority populations should be further examined in future studies.

Polygenic risk accelerates the developmental progression to heavy, persistent smoking and nicotine dependence: Evidence from a 4-Decade Longitudinal Study

PubMed Central

Moffitt, Terrie E; Baker, Timothy B; Biddle, Andrea K; Evans, James P; Harrington, HonaLee; Houts, Renate; Meier, Madeline; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom

2013-01-01

OBJECTIVE To test how genomic loci identified in genome-wide association studies (GWAS) influence the developmental progression of smoking behavior. DESIGN A 38-year prospective longitudinal study of a representative birth-cohort. SETTING The Dunedin Multidisciplinary Health and Development Study, New Zealand. PARTICIPANTS N=1037 male and female study members. MAIN EXPOSURES We assessed genetic risk with a multi-locus genetic risk score (GRS). The GRS was composed of single-nucleotide polymorphisms identified in three meta-analyses of GWAS of smoking quantity phenotypes. OUTCOME MEASURES Smoking initiation, conversion to daily smoking, progression to heavy smoking, nicotine dependence (Fagerstrom Test of Nicotine Dependence), and cessation difficulties were evaluated at eight assessments spanning ages 11-38 years. RESULTS Genetic risk score was unrelated to smoking initiation. However, individuals at higher genetic risk were more likely to convert to daily smoking as teenagers, progressed more rapidly from smoking initiation to heavy smoking, persisted longer in smoking heavily, developed nicotine dependence more frequently, were more reliant on smoking to cope with stress, and were more likely to fail in their cessation attempts. Further analysis revealed that two adolescent developmental phenotypes—early conversion to daily smoking and rapid progression to heavy smoking--mediated associations between the genetic risk score and mature phenotypes of persistent heavy smoking, nicotine dependence, and cessation failure. The genetic risk score predicted smoking risk over and above family history. CONCLUSIONS Initiatives that disrupt the developmental progression of smoking behavior among adolescents may mitigate genetic risks for developing adult smoking problems. Future genetic research may maximize discovery potential by focusing on smoking behavior soon after smoking initiation and by studying young smokers. PMID:23536134

Farm-by-farm analysis of microsatellite, mtDNA and SNP genotype data reveals inbreeding and crossbreeding as threats to the survival of a native Spanish pig breed.

PubMed

Herrero-Medrano, J M; Megens, H J; Crooijmans, R P; Abellaneda, J M; Ramis, G

2013-06-01

The Chato Murciano (CM), a pig breed from the Murcia region in the southeastern region of Spain, is a good model for endangered livestock populations. The remaining populations are bred on approximately 15 small farms, and no herdbook exists. To assess the genetic threats to the integrity and survival of the CM breed, and to aid in designing a conservation program, three genetic marker systems - microsatellites, SNPs and mtDNA - were applied across the majority of the total breeding stock. In addition, mtDNA and SNPs were genotyped in breeds that likely contributed genetically to the current CM gene pool. The analyses revealed the levels of genetic diversity within the range of other European local breeds (H(e) = 0.53). However, when the eight farms that rear at least 10 CM pigs were independently analyzed, high levels of inbreeding were found in some. Despite the evidence for recent crossbreeding with commercial breeds on a few farms, the entire breeding stock remains readily identifiable as CM, facilitating the design of traceability assays. The genetic management of the breed is consistent with farm size, farm owner and presence of other pig breeds on the farm, demonstrating the highly ad hoc nature of current CM breeding. The results of genetic diversity and substructure of the entire breed, as well as admixture and crossbreeding obtained in the present study, provide a benchmark to develop future conservation strategies. Furthermore, this study demonstrates that identifying farm-based practices and farm-based breeding stocks can aid in the design of a sustainable breeding program for minority breeds. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Consequences of a demographic bottleneck on genetic structure and variation in the Scandinavian brown bear.

PubMed

Xenikoudakis, G; Ersmark, E; Tison, J-L; Waits, L; Kindberg, J; Swenson, J E; Dalén, L

2015-07-01

The Scandinavian brown bear went through a major decline in population size approximately 100 years ago, due to intense hunting. After being protected, the population subsequently recovered and today numbers in the thousands. The genetic diversity in the contemporary population has been investigated in considerable detail, and it has been shown that the population consists of several subpopulations that display relatively high levels of genetic variation. However, previous studies have been unable to resolve the degree to which the demographic bottleneck impacted the contemporary genetic structure and diversity. In this study, we used mitochondrial and microsatellite DNA markers from pre- and postbottleneck Scandinavian brown bear samples to investigate the effect of the bottleneck. Simulation and multivariate analysis suggested the same genetic structure for the historical and modern samples, which are clustered into three subpopulations in southern, central and northern Scandinavia. However, the southern subpopulation appears to have gone through a marked change in allele frequencies. When comparing the mitochondrial DNA diversity in the whole population, we found a major decline in haplotype numbers across the bottleneck. However, the loss of autosomal genetic diversity was less pronounced, although a significant decline in allelic richness was observed in the southern subpopulation. Approximate Bayesian computations provided clear support for a decline in effective population size during the bottleneck, in both the southern and northern subpopulations. These results have implications for the future management of the Scandinavian brown bear because they indicate a recent loss in genetic diversity and also that the current genetic structure may have been caused by historical ecological processes rather than recent anthropogenic persecution. © 2015 John Wiley & Sons Ltd.

Unique genetic variation at a species' rear edge is under threat from global climate change

PubMed Central

Provan, Jim; Maggs, Christine A.

2012-01-01

Global climate change is having a significant effect on the distributions of a wide variety of species, causing both range shifts and population extinctions. To date, however, no consensus has emerged on how these processes will affect the range-wide genetic diversity of impacted species. It has been suggested that species that recolonized from low-latitude refugia might harbour high levels of genetic variation in rear-edge populations, and that loss of these populations could cause a disproportionately large reduction in overall genetic diversity in such taxa. In the present study, we have examined the distribution of genetic diversity across the range of the seaweed Chondrus crispus, a species that has exhibited a northward shift in its southern limit in Europe over the last 40 years. Analysis of 19 populations from both sides of the North Atlantic using mitochondrial single nucleotide polymorphisms (SNPs), sequence data from two single-copy nuclear regions and allelic variation at eight microsatellite loci revealed unique genetic variation for all marker classes in the rear-edge populations in Iberia, but not in the rear-edge populations in North America. Palaeodistribution modelling and statistical testing of alternative phylogeographic scenarios indicate that the unique genetic diversity in Iberian populations is a result not only of persistence in the region during the last glacial maximum, but also because this refugium did not contribute substantially to the recolonization of Europe after the retreat of the ice. Consequently, loss of these rear-edge populations as a result of ongoing climate change will have a major effect on the overall genetic diversity of the species, particularly in Europe, and this could compromise the adaptive potential of the species as a whole in the face of future global warming. PMID:21593035

Resistance Management Research for PIP Crops

EPA Science Inventory

A significant increase in genetically modified corn planting driven by biofuel demand is expected for future planted acreages approaching 80% of total corn plantings in 2009. As demand increases, incidence of farmer non-compliance with mandated non-genetically modified refuge is...

MOLECULAR GENETIC TOOLS FOR ASSESSING THE STATUS AND VULNERABILITY OF AQUATIC RESOURCES

EPA Science Inventory

Development of ecological indicators that efficiently capture the present condition and project future vulnerabilities of biological resources is critical to sound environmental management. For this reason, the ORD's Ecological Research Program is developing genetic methodologies...

Evolutionary and genetic analysis of the VP2 gene of canine parvovirus.

PubMed

Li, Gairu; Ji, Senlin; Zhai, Xiaofeng; Zhang, Yuxiang; Liu, Jie; Zhu, Mengyan; Zhou, Jiyong; Su, Shuo

2017-07-17

Canine parvovirus (CPV) type 2 emerged in 1978 in the USA and quickly spread among dog populations all over the world with high morbidity. Although CPV is a DNA virus, its genomic substitution rate is similar to some RNA viruses. Therefore, it is important to trace the evolution of CPV to monitor the appearance of mutations that might affect vaccine effectiveness. Our analysis shows that the VP2 genes of CPV isolated from 1979 to 2016 are divided into six groups: GI, GII, GIII, GIV, GV, and GVI. Amino acid mutation analysis revealed several undiscovered important mutation sites: F267Y, Y324I, and T440A. Of note, the evolutionary rate of the CPV VP2 gene from Asia and Europe decreased. Codon usage analysis showed that the VP2 gene of CPV exhibits high bias with an ENC ranging from 34.93 to 36.7. Furthermore, we demonstrate that natural selection plays a major role compared to mutation pressure driving CPV evolution. There are few studies on the codon usage of CPV. Here, we comprehensively studied the genetic evolution, codon usage pattern, and evolutionary characterization of the VP2 gene of CPV. The novel findings revealing the evolutionary process of CPV will greatly serve future CPV research.

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era

PubMed Central

Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; Cheung, Leonard Y. M.; Daly, Alexandre Z.; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A. Bilge; Kitzman, Jacob O.; Mills, Ryan E.; Li, Jun Z.

2016-01-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD. PMID:27828722

Increased genetic variation and evolutionary potential drive the success of an invasive grass.

PubMed

Lavergne, Sébastien; Molofsky, Jane

2007-03-06

Despite the increasing biological and economic impacts of invasive species, little is known about the evolutionary mechanisms that favor geographic range expansion and evolution of invasiveness in introduced species. Here, we focus on the invasive wetland grass Phalaris arundinacea L. and document the evolutionary consequences that resulted from multiple and uncontrolled introductions into North America of genetic material native to different European regions. Continental-scale genetic variation occurring in reed canarygrass' European range has been reshuffled and recombined within North American introduced populations, giving rise to a number of novel genotypes. This process alleviated genetic bottlenecks throughout reed canarygrass' introduced range, including in peripheral populations, where depletion of genetic diversity is expected and is observed in the native range. Moreover, reed canarygrass had higher genetic diversity and heritable phenotypic variation in its invasive range relative to its native range. The resulting high evolutionary potential of invasive populations allowed for rapid selection of genotypes with higher vegetative colonization ability and phenotypic plasticity. Our results show that repeated introductions of a single species may inadvertently create harmful invaders with high adaptive potential. Such invasive species may be able to evolve in response to changing climate, allowing them to have increasing impact on native communities and ecosystems in the future. More generally, multiple immigration events may thus trigger future adaptation and geographic spread of a species population by preventing genetic bottlenecks and generating genetic novelties through recombination.

Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

PubMed

Zhang, Ying; Xiong, Chi; Kudelko, Mateusz; Li, Yan; Wang, Cheng; Wong, Yuk Lun; Tam, Vivian; Rai, Muhammad Farooq; Cheverud, James; Lawson, Heather A; Sandell, Linda; Chan, Wilson C W; Cheah, Kathryn S E; Sham, Pak C; Chan, Danny

2018-04-09

Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784. Copyright © 2017. Published by Elsevier B.V.