WorldWideScience

Sample records for based human genetic

  1. [Genetic Bases of Human Comorbidity].

    Science.gov (United States)

    Puzyrev, V P

    2015-04-01

    In this review, the development of ideas focused on the phenomenon of disease combination (comorbidity) in humans is discussed. The genetic bases of the three forms of the phenomenon, comorbidity (syntropias), inverse comorbidity (dystropias), and comorbidity of Mendelian and multifactorial diseases, are analyzed. The results of personal genome-wide association studies of the genetic risk profile that may predispose an individual to cardiovascular disease continuum (CDC), including coronary heart disease, type 2 diabetes, hypertension, and hypercholesterolemia (CDC syntropy), as well as the results of bioinformatic analysis of common genes and the networks of molecular interactions for two (bronchial asthma and pulmonary tuberculosis) diseases rarely found in one patient (dystropy), are presented. The importance of the diseasome and network medicine concepts in the study of comorbidity is emphasized. Promising areas in genomic studies of comorbidities for disease classification and the development of personalized medicine are designated.

  2. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    Science.gov (United States)

    Chaturvedi, Swati; Singh, Ashok K.; Maity, Siddhartha; Sarkar, Srimanta

    2016-01-01

    One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches. PMID:27051561

  3. Genetic network properties of the human cortex based on regional thickness and surface area measures

    Directory of Open Access Journals (Sweden)

    Anna R. Docherty

    2015-08-01

    Full Text Available We examined network properties of genetic covariance between average cortical thickness (CT and surface area (SA within genetically-identified cortical parcellations that we previously derived from human cortical genetic maps using vertex-wise fuzzy clustering analysis with high spatial resolution. There were 24 hierarchical parcellations based on vertex-wise CT and 24 based on vertex-wise SA expansion/contraction; in both cases the 12 parcellations per hemisphere were largely symmetrical. We utilized three techniques—biometrical genetic modeling, cluster analysis, and graph theory—to examine genetic relationships and network properties within and between the 48 parcellation measures. Biometrical modeling indicated significant shared genetic covariance between size of several of the genetic parcellations. Cluster analysis suggested small distinct groupings of genetic covariance; networks highlighted several significant negative and positive genetic correlations between bilateral parcellations. Graph theoretical analysis suggested that small world, but not rich club, network properties may characterize the genetic relationships between these regional size measures. These findings suggest that cortical genetic parcellations exhibit short characteristic path lengths across a broad network of connections. This property may be protective against network failure. In contrast, previous research with structural data has observed strong rich club properties with tightly interconnected hub networks. Future studies of these genetic networks might provide powerful phenotypes for genetic studies of normal and pathological brain development, aging, and function.

  4. Genetic network properties of the human cortex based on regional thickness and surface area measures

    Science.gov (United States)

    Docherty, Anna R.; Sawyers, Chelsea K.; Panizzon, Matthew S.; Neale, Michael C.; Eyler, Lisa T.; Fennema-Notestine, Christine; Franz, Carol E.; Chen, Chi-Hua; McEvoy, Linda K.; Verhulst, Brad; Tsuang, Ming T.; Kremen, William S.

    2015-01-01

    We examined network properties of genetic covariance between average cortical thickness (CT) and surface area (SA) within genetically-identified cortical parcellations that we previously derived from human cortical genetic maps using vertex-wise fuzzy clustering analysis with high spatial resolution. There were 24 hierarchical parcellations based on vertex-wise CT and 24 based on vertex-wise SA expansion/contraction; in both cases the 12 parcellations per hemisphere were largely symmetrical. We utilized three techniques—biometrical genetic modeling, cluster analysis, and graph theory—to examine genetic relationships and network properties within and between the 48 parcellation measures. Biometrical modeling indicated significant shared genetic covariance between size of several of the genetic parcellations. Cluster analysis suggested small distinct groupings of genetic covariance; networks highlighted several significant negative and positive genetic correlations between bilateral parcellations. Graph theoretical analysis suggested that small world, but not rich club, network properties may characterize the genetic relationships between these regional size measures. These findings suggest that cortical genetic parcellations exhibit short characteristic path lengths across a broad network of connections. This property may be protective against network failure. In contrast, previous research with structural data has observed strong rich club properties with tightly interconnected hub networks. Future studies of these genetic networks might provide powerful phenotypes for genetic studies of normal and pathological brain development, aging, and function. PMID:26347632

  5. Monkey-based research on human disease: the implications of genetic differences.

    Science.gov (United States)

    Bailey, Jarrod

    2014-11-01

    Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists.

  6. OPTIMIZATION DESIGN OF HYDRAU-LIC MANIFOLD BLOCKS BASED ON HUMAN-COMPUTER COOPERATIVE GENETIC ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    Feng Yi; Li Li; Tian Shujun

    2003-01-01

    Optimization design of hydraulic manifold blocks (HMB) is studied as a complex solid spatial layout problem. Based on comprehensive research into structure features and design rules of HMB, an optimal mathematical model for this problem is presented. Using human-computer cooperative genetic algorithm (GA) and its hybrid optimization strategies, integrated layout and connection design schemes of HMB can be automatically optimized. An example is given to testify it.

  7. Analyzing age-specific genetic effects on human extreme age survival in cohort-based longitudinal studies

    DEFF Research Database (Denmark)

    Tan, Qihua; Jacobsen, Rune; Sørensen, Mette

    2013-01-01

    The analysis of age-specific genetic effects on human survival over extreme ages is confronted with a deceleration pattern in mortality that deviates from traditional survival models and sparse genetic data available. As human late life is a distinct phase of life history, exploring the genetic...... effects on extreme age survival can be of special interest to evolutionary biology and health science. We introduce a non-parametric survival analysis approach that combines population survival information with individual genotype data in assessing the genetic effects in cohort-based longitudinal studies...

  8. Comparing ESC and iPSC—Based Models for Human Genetic Disorders

    Directory of Open Access Journals (Sweden)

    Tomer Halevy

    2014-10-01

    Full Text Available Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs from patients’ somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn’t be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.

  9. Advances in human genetics

    Energy Technology Data Exchange (ETDEWEB)

    Harris, H.; Hirschhorn, K. (eds.)

    1993-01-01

    This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.

  10. Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets

    DEFF Research Database (Denmark)

    Liu, Guo-Hua; Gasser, Robin B.; Su, Ang;

    2012-01-01

    The whipworm, Trichuris trichiura, causes trichuriasis in ~600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis...... of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig...... for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions....

  11. Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets.

    Directory of Open Access Journals (Sweden)

    Guo-Hua Liu

    Full Text Available The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis, dogs (T. vulpis and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions.

  12. Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets.

    Science.gov (United States)

    Liu, Guo-Hua; Gasser, Robin B; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

    2012-01-01

    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions.

  13. Genetics and recent human evolution.

    Science.gov (United States)

    Templeton, Alan R

    2007-07-01

    Starting with "mitochondrial Eve" in 1987, genetics has played an increasingly important role in studies of the last two million years of human evolution. It initially appeared that genetic data resolved the basic models of recent human evolution in favor of the "out-of-Africa replacement" hypothesis in which anatomically modern humans evolved in Africa about 150,000 years ago, started to spread throughout the world about 100,000 years ago, and subsequently drove to complete genetic extinction (replacement) all other human populations in Eurasia. Unfortunately, many of the genetic studies on recent human evolution have suffered from scientific flaws, including misrepresenting the models of recent human evolution, focusing upon hypothesis compatibility rather than hypothesis testing, committing the ecological fallacy, and failing to consider a broader array of alternative hypotheses. Once these flaws are corrected, there is actually little genetic support for the out-of-Africa replacement hypothesis. Indeed, when genetic data are used in a hypothesis-testing framework, the out-of-Africa replacement hypothesis is strongly rejected. The model of recent human evolution that emerges from a statistical hypothesis-testing framework does not correspond to any of the traditional models of human evolution, but it is compatible with fossil and archaeological data. These studies also reveal that any one gene or DNA region captures only a small part of human evolutionary history, so multilocus studies are essential. As more and more loci became available, genetics will undoubtedly offer additional insights and resolutions of human evolution.

  14. Next-generation human genetics

    OpenAIRE

    Shendure, Jay

    2011-01-01

    The field of human genetics is being reshaped by exome and genome sequencing. Several lessons are evident from observing the rapid development of this area over the past 2 years, and these may be instructive with respect to what we should expect from 'next-generation human genetics' in the next few years.

  15. Genetic Mapping in Human Disease

    OpenAIRE

    Altshuler, David; Daly, Mark J; Lander, Eric S.

    2008-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead.

  16. Report: Human cancer genetics

    Institute of Scientific and Technical Information of China (English)

    LI Marilyn; ALBERTSON Donna

    2006-01-01

    The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.

  17. Human cancer genetics*

    OpenAIRE

    2006-01-01

    The short report will be focused on the genetic basis and possible mechanisms of tumorigenesis, common types of cancer, the importance of genetic diagnosis of cancer, and the methodology of cancer genetic diagnosis. They will also review presymptomatic testing of hereditary cancers, and the application of expression profiling to identify patients likely to benefit from particular therapeutic approaches.

  18. Genetic Diversity of Methylotrophic Bacteria from Human Mouth Based on Amplified Ribosomal DNA Restriction Analysis (ARDRA

    Directory of Open Access Journals (Sweden)

    CINDY OKTAVIA SUSANTO

    2011-06-01

    Full Text Available Methylotrophs inhabit the human mouth. In this study, methylotrophic bacteria were isolated from the human mouth microflora of 63 subjects, especially from the tongue, gingival, and subgingival area using minimal agar supplemented with 1% methanol. The obtained isolates were subjected to biochemical assays, continued with antibiotics susceptibility testing using ampicillin (10 g, tetracycline (20 g, kanamycin (30 g, trimethoprim (5 g, and streptomycin (10 g. Genetic diversity was analyzed using ARDRA method. Isolates varying in morphology characteristics were amplified for 16S rRNA gene and continued with DNA sequencing. As many as 21 methylotrophic bacterial isolates were purified and divided into seven groups with different phenotypic profiles. A majority of the isolates were resistant to trimethoprim but sensitive to kanamycin, streptomycin, and tetracycline. Resistance to ampicillin was variable in each isolate. ARDRA showed nine different digestion profiles. DNA sequencing analysis of the 16S rRNA gene showed that six isolates with different phenotypic and digestion profiles were closely related to Methylobacterium radiotoleran (94%, Microbacterium esteraromaticum (99%, Pseudomonas sp. (100%, and three of them were exhibited 99, 99, and 98% sequence similarity with Gordonia sp., respectively. The results of this study revealed diversity among methylotrophic bacteria particularly in human mouth.

  19. Genetic variation and human longevity.

    Science.gov (United States)

    Soerensen, Mette

    2012-05-01

    The overall aim of the PhD project was to elucidate the association of human longevity with genetic variation in major candidate genes and pathways of longevity. Based on a thorough literature and database search we chose to apply a pathway approach; to explore variation in genes composing the DNA damage signaling, DNA repair, GH/IGF-1/insulin signaling and pro-/antioxidant pathways. In addition, 16 genes which did not belong to the core of either pathway, however recurrently regarded as candidate genes of longevity (e.g. APOE), were included. In this way a total of 168 genes were selected for investigation. We decided to explore the genetic variation in the form of single nucleotide polymorphisms (SNPs), a highly investigated type of genetic variation. SNPs having potential functional impact (e.g. affecting binding of transcription factors) were identified, so were specific SNPs in the candidate genes previously published to be associated with human longevity. To cover the majority of the common genetic variation in the 168 gene regions (encoding regions plus 5,000 bp upstream and 1,000 downstream) we applied the tagging SNP approach via the HapMap Consortium. Consequently 1,536 SNPs were selected. The majority of the previous publications on genetic variation and human longevity had employed a case-control study design, e.g. comparing centenarians to middle-aged controls. This type of study design is somehow prone to bias introduced by for instance cohort effects, i.e. differences in characteristics of cases and controls, a kind of bias which is avoided when a prospective cohort is under study. Therefore, we chose to investigate 1,200 individuals of the Danish 1905 birth cohort, which have been followed since 1998 when the members were 92-93 years old. The genetic contribution to human longevity has been estimated to be most profound during the late part of life, thus these oldest-old individuals are excellent for investigating such effect. The follow-up survival

  20. Understanding Tiger –Human Conflict in Corbett Tiger Reserve (CTR, India: Based on the genetic analysis

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    Sujeet Kumar Singh

    2015-06-01

    Full Text Available Attacks of tigers on humans are a common feature of human-wildlife conflicts in India, and the individual identification of such animals has been an issue for management purposes. We document a case study where we established the species, sex and genetic identity of a man-eater tiger reported from Corbett Tiger Reserve (CTR, India, using blood spots and other biological samples. A man-eater tiger killed 4 women within 2 months (December 2010 to January 2011 in different parts of CTR. The authorities decided to shoot the animal, and attempts were made to do so, but it escaped. After 16 days, a tiger was shot by the management, and biological samples were collected. The multi-locus genetic profile of an injured tiger based on blood from the injured tiger was compared with that from biological samples from the shot tiger. Our results indicate that the injured and shot tigers were the same individual. This study elucidates the potential of wildlife genetics in identification of tigers involved in fatal attacks and improves the wildlife management strategies employed where the greatest numbers of direct human- tiger conflicts are taking place.

  1. Genetic heterogeneity and phylogeny of Trichuris spp. from captive non-human primates based on ribosomal DNA sequence data.

    Science.gov (United States)

    Cavallero, Serena; De Liberato, Claudio; Friedrich, Klaus G; Di Cave, David; Masella, Valentina; D'Amelio, Stefano; Berrilli, Federica

    2015-08-01

    Nematodes of the genus Trichuris, known as whipworms, are recognized to infect numerous mammalian species including humans and non-human primates. Several Trichuris spp. have been described and species designation/identification is traditionally based on host-affiliation, although cross-infection and hybridization events may complicate species boundaries. The main aims of the present study were to genetically characterize adult Trichuris specimens from captive Japanese macaques (Macaca fuscata) and grivets (Chlorocebus aethiops), using the ribosomal DNA (ITS) as molecular marker and to investigate the phylogeny and the extent of genetic variation also by comparison with data on isolates from other humans, non-human primates and other hosts. The phylogenetic analysis of Trichuris sequences from M. fuscata and C. aethiops provided evidences of distinct clades and subclades thus advocating the existence of additional separated taxa. Neighbor Joining and Bayesian trees suggest that specimens from M. fuscata may be distinct from, but related to Trichuris trichiura, while a close relationship is suggested between the subclade formed by the specimens from C. aethiops and the subclade formed by T. suis. The tendency to associate Trichuris sp. to host species can lead to misleading taxonomic interpretations (i.e. whipworms found in primates are identified as T. trichiura). The results here obtained confirm previous evidences suggesting the existence of Trichuris spp. other than T. trichiura infecting non-human living primates.

  2. Mendelism in human genetics: 100 years on.

    Science.gov (United States)

    Majumdar, Sisir K

    2003-01-01

    Genetics (Greek word--'genes' = born) is a science without an objective past. But the genre of genetics was always roaming in the corridors of human psyche since antiquity. The account of heritable deformities in human often appears in myths and legends. Ancient Hindu Caste system was based on the assumption that both desirable and undesirable traits are passed from generation to generation. In Babylonia 60 birth defects were listed on Clay tablets written around 5,000 year ago. The Jewish Talmud contains accurate description of the inheritance of haemophilia--a human genetic disorder. The Upanisads vedant--800--200 BC provides instructions for the choice of a wife emphasizing that no heritable illness should be present and that the family should show evidence of good character for several preceding generations. These examples indicate that heritable human traits played a significant role in social customs are presented in this article.

  3. Multi-Features Encoding and Selecting Based on Genetic Algorithm for Human Action Recognition from Video

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    Chenglong Yu

    2013-05-01

    Full Text Available In this study, we proposed multiple local features encoded for recognizing the human actions. The multiple local features were obtained from the simple feature description of human actions in video. The simple features are two kinds of important features, optical flow and edge, to represent the human perception for the video behavior. As the video information descriptors, optical flow and edge, which their computing speeds are very fast and their requirement of memory consumption is very low, can represent respectively the motion information and shape information. Furthermore, key local multi-features are extracted and encoded by GA in order to reduce the computational complexity of the algorithm. After then, the Multi-SVM classifier is applied to discriminate the human actions.

  4. Segmenting the human genome based on states of neutral genetic divergence.

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    Kuruppumullage Don, Prabhani; Ananda, Guruprasad; Chiaromonte, Francesca; Makova, Kateryna D

    2013-09-03

    Many studies have demonstrated that divergence levels generated by different mutation types vary and covary across the human genome. To improve our still-incomplete understanding of the mechanistic basis of this phenomenon, we analyze several mutation types simultaneously, anchoring their variation to specific regions of the genome. Using hidden Markov models on insertion, deletion, nucleotide substitution, and microsatellite divergence estimates inferred from human-orangutan alignments of neutrally evolving genomic sequences, we segment the human genome into regions corresponding to different divergence states--each uniquely characterized by specific combinations of divergence levels. We then parsed the mutagenic contributions of various biochemical processes associating divergence states with a broad range of genomic landscape features. We find that high divergence states inhabit guanine- and cytosine (GC)-rich, highly recombining subtelomeric regions; low divergence states cover inner parts of autosomes; chromosome X forms its own state with lowest divergence; and a state of elevated microsatellite mutability is interspersed across the genome. These general trends are mirrored in human diversity data from the 1000 Genomes Project, and departures from them highlight the evolutionary history of primate chromosomes. We also find that genes and noncoding functional marks [annotations from the Encyclopedia of DNA Elements (ENCODE)] are concentrated in high divergence states. Our results provide a powerful tool for biomedical data analysis: segmentations can be used to screen personal genome variants--including those associated with cancer and other diseases--and to improve computational predictions of noncoding functional elements.

  5. Human genetics: international projects and personalized medicine.

    Science.gov (United States)

    Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina

    2016-03-01

    In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015.

  6. HmtDB, a Human Mitochondrial Genomic Resource Based on Variability Studies Supporting Population Genetics and Biomedical Research

    OpenAIRE

    Pappadà Graziano; Scioscia Gaetano; Lascaro Daniela; Santamaria Monica; Accetturo Matteo; Attimonelli Marcella; Russo Luigi; Zanchetta Luigi; Tommaseo-Ponzetta Mila

    2005-01-01

    Abstract Background Population genetics studies based on the analysis of mtDNA and mitochondrial disease studies have produced a huge quantity of sequence data and related information. These data are at present worldwide distributed in differently organised databases and web sites not well integrated among them. Moreover it is not generally possible for the user to submit and contemporarily analyse its own data comparing them with the content of a given database, both for population genetics ...

  7. Genetic aspects of human obesity.

    Science.gov (United States)

    Larder, Rachel; Lim, Chung Thong; Coll, Anthony P

    2014-01-01

    Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future.

  8. Linking yeast genetics to mammalian genomes: Identification and mapping of the human homolog of CDC27 via the expressed sequence tag (EST) data base

    Energy Technology Data Exchange (ETDEWEB)

    Tugendreich, S.; Hieter, P. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States)); Boguski, M.S. (National Institute of Health, Bethesda, MD (United States)); Seldin, M.S. (Duke Univ. Medical Center, Durham, NC (United States))

    1993-11-15

    The authors describe a strategy for quickly identifying and positionally mapping human homologs of yeast genes to cross-reference the biological and genetic information known about yeast genes to mammalian chromosomal maps. Optimized computer search methods have been developed to scan the rapidly expanding expressed sequence tag (EST) data base to find human open reading frames related to yeast protein sequence queries. These methods take advantage of the newly developed BLOSUM scoring matrices and the query masking function SEG. The corresponding human cDNA is then used to obtain a high-resolution map position on human and mouse chromosomes, providing the links between yeast genetic analysis and mapped mammalian loci. By using these methods, a human homolog of Saccharomyces cerevisiae CDC27 has been identified and mapped to human chromosome 17 and mouse chromosome 11 between the Pkca and Erbb-2 genes. Human CDC27 encodes an 823-aa protein with global similarity to its fungal homologs CDC27, nuc2+, and BimA. Comprehensive cross-referencing of genes and mutant phenotypes described in humans, mice, and yeast should accelerate the study of normal eukaryotic biology and human disease states.

  9. Genetic toxicities of human teratogens.

    Science.gov (United States)

    Bishop, J B; Witt, K L; Sloane, R A

    1997-12-12

    Birth defects cause a myriad of societal problems and place tremendous anguish on the affected individual and his or her family. Current estimates categorize about 3% of all newborn infants as having some form of birth defect or congenital anomaly. As more precise means of detecting subtle anomalies become available this estimate, no doubt, will increase. Even though birth defects have been observed in newborns throughout history, our knowledge about the causes and mechanisms through which these defects are manifested is limited. For example, it has been estimated that around 20% of all birth defects are due to gene mutations, 5-10% to chromosomal abnormalities, and another 5-10% to exposure to a known teratogenic agent or maternal factor [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis. Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500; K. Nelson, L.B. Holmes Malformations due to presumed spontaneous mutations in newborn infants, N. Engl. J. Med. 320 (1989) 19-23.]. Together, these percentages account for only 30-40%, leaving the etiology of more than half of all human birth defects unexplained. It has been speculated that environmental factors account for no more than one-tenth of all congenital anomalies [D.A. Beckman, R.L. Brent, Mechanisms of teratogenesis, Ann. Rev. Pharmacol. Toxicol. 24 (1984) 483-500]. Furthermore, since there is no evidence in humans that the exposure of an individual to any mutagen measurably increases the risk of congenital anomalies in his or her offspring' [J.F. Crow, C. Denniston, Mutation in human populations, Adv. Human Genet. 14 (1985) 59-121; J.M. Friedman, J.E. Polifka, Teratogenic Effects of Drugs: A Resource for Clinicians (TERIS). The John Hopkins University Press, Baltimore, 1994], the mutagenic activity of environmental agents and drugs as a factor in teratogenesis has been given very little attention. Epigenetic activity has also been given only limited consideration as a mechanism for teratogenesis. As new molecular

  10. Genetics of human sleep behavioral phenotypes.

    Science.gov (United States)

    Hsu, Pei-Ken; Ptáček, Louis J; Fu, Ying-Hui

    2015-01-01

    Quality sleep is critical for daily functions of human beings and thus the timing and duration of sleep are tightly controlled. However, rare genetic variants affecting sleep regulatory mechanisms can result in sleep phenotypes of extremely deviated sleep/wake onset time or duration. Using genetic analyses in families with multiple members expressing particular sleep phenotypes, these sleep-associated genetic variants can be identified. Deciphering the nature of these genetic variants using animal models or biochemical methods helps further our understanding of sleep processes. In this chapter, we describe the methods for studying genetics of human sleep behavioral phenotypes.

  11. Genetic & epigenetic approach to human obesity

    Directory of Open Access Journals (Sweden)

    K Rajender Rao

    2014-01-01

    Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  12. Genetic & epigenetic approach to human obesity.

    Science.gov (United States)

    Rao, K Rajender; Lal, Nirupama; Giridharan, N V

    2014-11-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  13. Genetic basis of human brain evolution.

    Science.gov (United States)

    Vallender, Eric J; Mekel-Bobrov, Nitzan; Lahn, Bruce T

    2008-12-01

    Human evolution is characterized by a rapid increase in brain size and complexity. Decades of research have made important strides in identifying anatomical and physiological substrates underlying the unique features of the human brain. By contrast, it has become possible only very recently to examine the genetic basis of human brain evolution. Through comparative genomics, tantalizing insights regarding human brain evolution have emerged. The genetic changes that potentially underlie human brain evolution span a wide range from single-nucleotide substitutions to large-scale structural alterations of the genome. Similarly, the functional consequences of these genetic changes vary greatly, including protein-sequence alterations, cis-regulatory changes and even the emergence of new genes and the extinction of existing ones. Here, we provide a general review of recent findings into the genetic basis of human brain evolution, highlight the most notable trends that have emerged and caution against over-interpretation of current data.

  14. Genetic enhancement, human nature, and rights.

    Science.gov (United States)

    McConnell, Terrance

    2010-08-01

    Authors such as Francis Fukuyama, the President's Council on Bioethics, and George Annas have argued that biotechnological interventions that aim to promote genetic enhancement pose a threat to human nature. This paper clarifies what conclusions these critics seek to establish, and then shows that there is no plausible account of human nature that will meet the conditions necessary to support this position. Appeals to human nature cannot establish a prohibition against the pursuit of genetic enhancement.

  15. Revertant mosaicism in human genetic disorders

    NARCIS (Netherlands)

    Jonkman, MF

    1999-01-01

    Somatic reversion of inherited mutations is known for many years in plant breeding, however it was recognized only recently in humans. The concept of revertant mosaicism is important in medical genetics. (C) 1999 Wiley-Liss, Inc.

  16. Genetic bases for glaucoma.

    Science.gov (United States)

    Fuse, Nobuo

    2010-05-01

    Glaucoma is the leading cause of visual impairment and blindness throughout the world. Primary open angle glaucoma (POAG; MIM 137760) is the main type of glaucoma in most populations, and more than 20 genetic loci for POAG have been reported. Only three causative genes have been identified in these loci, viz. myocilin (MYOC), optineurin (OPTN), and WD repeat domain 36 (WDR36). However, mutations in these genes account for only a small percentage of the patients with POAG. Some of these glaucoma cases have a Mendelian inheritance pattern, and a considerable fraction of the cases result from a large number of variants in several genes each contributing small effects. Glaucoma is considered to be a common disease such as diabetes mellitus, coronary disease, Crohn disease, and several( )common cancers. The main technological approaches used to identify the genes associated with glaucoma are the candidate gene approach, linkage analysis, case-control association study, and genome-wide association study. Association studies have found about 27 genes related to POAG, but the glaucoma-causing effects of these genes need to be investigated in more detail. The current trend is to use case-control association studies or genome-wide association studies to map the genes associated with glaucoma. Such studies are expected to greatly advance our understanding of the genetic basis of glaucoma, and to provide information on the effectiveness of glaucoma therapy. This review gives an overview on the genetic aspects of glaucoma.

  17. Genetic contributions to human brain morphology and intelligence

    DEFF Research Database (Denmark)

    Hulshoff Pol, HE; Schnack, HG; Posthuma, D

    2006-01-01

    Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...... of 54 monozygotic and 58 dizygotic twin pairs and 34 of their siblings. For genetic analyses, we used structural equation modeling and voxel-based morphometry. To explore the common genetic origin of focal GM and WM areas with intelligence, we obtained cross-trait/cross-twin correlations in which...

  18. The genetics of human obesity.

    Science.gov (United States)

    Waalen, Jill

    2014-10-01

    The heritability of obesity has long been appreciated and the genetics of obesity has been the focus of intensive study for decades. Early studies elucidating genetic factors involved in rare monogenic and syndromic forms of extreme obesity focused attention on dysfunction of hypothalamic leptin-related pathways in the control of food intake as a major contributor. Subsequent genome-wide association studies of common genetic variants identified novel loci that are involved in more common forms of obesity across populations of diverse ethnicities and ages. The subsequent search for factors contributing to the heritability of obesity not explained by these 2 approaches ("missing heritability") has revealed additional rare variants, copy number variants, and epigenetic changes that contribute. Although clinical applications of these findings have been limited to date, the increasing understanding of the interplay of these genetic factors with environmental conditions, such as the increased availability of high calorie foods and decreased energy expenditure of sedentary lifestyles, promises to accelerate the translation of genetic findings into more successful preventive and therapeutic interventions.

  19. Roles of interferon-gamma and its target genes in schizophrenia: Proteomics-based reverse genetics from mouse to human.

    Science.gov (United States)

    Kim, Hak-Jae; Eom, Chi-Yong; Kwon, Joseph; Joo, Jaesoon; Lee, Sujeong; Nah, Seong-Su; Kim, Il-Chul; Jang, Ik-Soon; Chung, Young-Ho; Kim, Seung Il; Chung, Joo-Ho; Choi, Jong-Soon

    2012-06-01

    A decreased production of interferon gamma (IFNG) has been observed in acute schizophrenia. In order to explore the possible relationship between IFNG and schizophrenia, we attempted to analyze the differentially expressed proteins in the brains of interferon-gamma knockout (Ifng-KO) mice. Five upregulated and five downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses in Ifng-KO mouse brain. Of the identified proteins, we focused on creatine kinase brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and immunohistochemistry analyses confirmed that the levels of gene expressions of Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1 were weakly associated with schizophrenia. In addition, IFNG polymorphisms were associated with schizophrenia. These results suggest that IFNG and proteins affected by IFNG may play a role in the pathogenesis of schizophrenia.

  20. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  1. The genetics of neuroticism and human values.

    Science.gov (United States)

    Zacharopoulos, George; Lancaster, Thomas M; Maio, Gregory R; Linden, David E J

    2016-04-01

    Human values and personality have been shown to share genetic variance in twin studies. However, there is a lack of evidence about the genetic components of this association. This study examined the interplay between genes, values and personality in the case of neuroticism, because polygenic scores were available for this personality trait. First, we replicated prior evidence of a positive association between the polygenic neuroticism score (PNS) and neuroticism. Second, we found that the PNS was significantly associated with the whole human value space in a sinusoidal waveform that was consistent with Schwartz's circular model of human values. These results suggest that it is useful to consider human values in the analyses of genetic contributions to personality traits. They also pave the way for an investigation of the biological mechanisms contributing to human value orientations.

  2. A lentiviral vector-based genetic sensor system for comparative analysis of permeability and activity of vitamin D3 analogues in xenotransplanted human skin.

    Science.gov (United States)

    Staunstrup, Nicklas Heine; Bak, Rasmus O; Cai, Yujia; Svensson, Lars; Petersen, Thomas K; Rosada, Cecilia; Stenderup, Karin; Bolund, Lars; Mikkelsen, Jacob Giehm

    2013-03-01

    Vitamin D3 analogues are widely used topical and oral remedies for various ailments such as psoriasis, osteoporosis and secondary hyperparathyroidism. In topical treatment, high skin permeability and cellular uptake are key criteria for beneficial effects due to the natural barrier properties of skin. In this study, we wish to establish an in vivo model that allows the comparison of permeability and activity of vitamin D3 analogues in human skin. We generate a bipartite, genetic sensor technology that combines efficient lentivirus-directed gene delivery to xenotransplanted human skin with vitamin D3-induced expression of a luciferase reporter gene and live imaging of animals by bioluminescence imaging. Based on the induction of a transcriptional activator consisting of the vitamin D receptor fused to the Gal4 DNA-binding domain, the vitamin D3-responsive sensor facilitates non-invasive and rapid assessment of permeability and functional properties of vitamin D3 analogues. By topical application of a panel of vitamin D3 analogues onto 'sensorized' human skin, the sensor produces a drug-induced readout with a magnitude and persistence that allow a direct comparative analysis of different analogues. This novel genetic tool has great potential as a non-invasive in vivo screening system for further development and refinement of vitamin D3 analogues.

  3. Human genetics of diabetic vascular complications

    Indian Academy of Sciences (India)

    Zi-Hui Tang; Zhou Fang; Linuo Zhou

    2013-12-01

    Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play important roles in the development of DVC. Genetic linkage studies have uncovered a number of genetic loci that may shape the risk of DVC. Genetic association studies have identified many common genetic variants for susceptibility to DVC. Structural variants such as copy number variation and interactions of gene × environment have also been detected by association analysis. Apart from the nuclear genome, mitochondrial DNA plays a critical role in regulation of development of DVC. Epigenetic studies have indicated epigenetic changes in chromatin affecting gene transcription in response to environmental stimuli, which provided a large body of evidence of regulating development of diabetes mellitus. Recently, a new window has opened on identifying rare and common genetic loci through next generation sequencing technologies. This review focusses on the current knowledge of the genetic and epigenetic basis of DVC. Ultimately, identification of genes or genetic loci, structural variants and epigenetic changes contributing to risk of or protection from DVC will help uncover the complex mechanism(s) underlying DVC, with crucial implications for the development of personalized medicine for diabetes mellitus and its complications.

  4. Genetic Conflict in Human Pregnancy

    OpenAIRE

    1993-01-01

    Pregnancy has commonly been viewed as a cooperative interaction between a mother and her fetus. The effects of natural selection on genes expressed in fetuses, however, may be opposed by the effects of natural selection on genes expressed in mothers. In this sense, a genetic conflict can be said to exist between maternal and fetal genes. Fetal genes will be selected to increase the transfer of nutrients to their fetus, and maternal genes will be selected to limit transfers in excess of Soma m...

  5. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

    Science.gov (United States)

    Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

    2014-04-01

    Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

  6. Human embryonic stem cells carrying mutations for severe genetic disorders.

    Science.gov (United States)

    Frumkin, Tsvia; Malcov, Mira; Telias, Michael; Gold, Veronica; Schwartz, Tamar; Azem, Foad; Amit, Ami; Yaron, Yuval; Ben-Yosef, Dalit

    2010-04-01

    Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il.

  7. MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics.

    Science.gov (United States)

    Pandey, Ram Vinay; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas

    2016-01-01

    Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK-HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid.

  8. Probability theory-based SNP association study method for identifying susceptibility loci and genetic disease models in human case-control data.

    Science.gov (United States)

    Yuan, Xiguo; Zhang, Junying; Wang, Yue

    2010-12-01

    One of the most challenging points in studying human common complex diseases is to search for both strong and weak susceptibility single-nucleotide polymorphisms (SNPs) and identify forms of genetic disease models. Currently, a number of methods have been proposed for this purpose. Many of them have not been validated through applications into various genome datasets, so their abilities are not clear in real practice. In this paper, we present a novel SNP association study method based on probability theory, called ProbSNP. The method firstly detects SNPs by evaluating their joint probabilities in combining with disease status and selects those with the lowest joint probabilities as susceptibility ones, and then identifies some forms of genetic disease models through testing multiple-locus interactions among the selected SNPs. The joint probabilities of combined SNPs are estimated by establishing Gaussian distribution probability density functions, in which the related parameters (i.e., mean value and standard deviation) are evaluated based on allele and haplotype frequencies. Finally, we test and validate the method using various genome datasets. We find that ProbSNP has shown remarkable success in the applications to both simulated genome data and real genome-wide data.

  9. A global reference for human genetic variation

    DEFF Research Database (Denmark)

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David;

    2015-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals ...

  10. Genetic Manipulation of Human Embryonic Stem Cells.

    Science.gov (United States)

    Eiges, Rachel

    2016-01-01

    One of the great advantages of embryonic stem (ES) cells over other cell types is their accessibility to genetic manipulation. They can easily undergo genetic modifications while remaining pluripotent, and can be selectively propagated, allowing the clonal expansion of genetically altered cells in culture. Since the first isolation of ES cells in mice, many effective techniques have been developed for gene delivery and manipulation of ES cells. These include transfection, electroporation, and infection protocols, as well as different approaches for inserting, deleting, or changing the expression of genes. These methods proved to be extremely useful in mouse ES cells, for monitoring and directing differentiation, discovering unknown genes, and studying their function, and are now being extensively implemented in human ES cells (HESCs). This chapter describes the different approaches and methodologies that have been applied for the genetic manipulation of HESCs and their applications. Detailed protocols for generating clones of genetically modified HESCs by transfection, electroporation, and infection will be described, with special emphasis on the important technical details that are required for this purpose. All protocols are equally effective in human-induced pluripotent stem (iPS) cells.

  11. Molecular genetics of human lactase deficiencies.

    Science.gov (United States)

    Järvelä, Irma; Torniainen, Suvi; Kolho, Kaija-Leena

    2009-01-01

    Lactase non-persistence (adult-type hypolactasia) is present in more than half of the human population and is caused by the down-regulation of lactase enzyme activity during childhood. Congenital lactase deficiency (CLD) is a rare severe gastrointestinal disorder of new-borns enriched in the Finnish population. Both lactase deficiencies are autosomal recessive traits and characterized by diminished expression of lactase activity in the intestine. Genetic variants underlying both forms have been identified. Here we review the current understanding of the molecular defects of human lactase deficiencies and their phenotype-genotype correlation, the implications on clinical practice, and the understanding of their function and role in human evolution.

  12. Genetic Heterogeneity in Algerian Human Populations.

    Science.gov (United States)

    Bekada, Asmahan; Arauna, Lara R; Deba, Tahria; Calafell, Francesc; Benhamamouch, Soraya; Comas, David

    2015-01-01

    The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region.

  13. Genetic Effects on Fine-Grained Human Cortical Regionalization.

    Science.gov (United States)

    Cui, Yue; Liu, Bing; Zhou, Yuan; Fan, Lingzhong; Li, Jin; Zhang, Yun; Wu, Huawang; Hou, Bing; Wang, Chao; Zheng, Fanfan; Qiu, Chengxiang; Rao, Li-Lin; Ning, Yuping; Li, Shu; Jiang, Tianzi

    2016-09-01

    Various brain structural and functional features such as cytoarchitecture, topographic mapping, gyral/sulcal anatomy, and anatomical and functional connectivity have been used in human brain parcellation. However, the fine-grained intrinsic genetic architecture of the cortex remains unknown. In the present study, we parcellated specific regions of the cortex into subregions based on genetic correlations (i.e., shared genetic influences) between the surface area of each pair of cortical locations within the seed region. The genetic correlations were estimated by comparing the correlations of the surface area between monozygotic and dizygotic twins using bivariate twin models. Our genetic subdivisions of diverse brain regions were reproducible across 2 independent datasets and corresponded closely to fine-grained functional specializations. Furthermore, subregional genetic correlation profiles were generally consistent with functional connectivity patterns. Our findings indicate that the magnitude of the genetic covariance in brain anatomy could be used to delineate the boundaries of functional subregions of the brain and may be of value in the next generation human brain atlas.

  14. A current genetic and epigenetic view on human aging mechanisms.

    Science.gov (United States)

    Ostojić, Sala; Pereza, Nina; Kapović, Miljenko

    2009-06-01

    The process of aging is one of the most complex and intriguing biological phenomenons. Aging is a genetically regulated process in which the organism's maximum lifespan potential is pre-determined, while the rate of aging is influenced by environmental factors and lifestyle. Considering the complexity of mechanisms involved in the regulation of aging process, up to this date there isn't a major, unifying theory which could explain them. As genetic/epigenetic and environmental factors both inevitably influence the aging process, here we present a review on the genetic and epigenetic regulation of the most important molecular and cellular mechanisms involved in the process of aging. Based on the studies on oxidative stress, metabolism, genome stability, epigenetic modifications and cellular senescence in animal models and humans, we give an overview of key genetic and molecular pathways related to aging. As most of genetic manipulations which influence the aging process also affect reproduction, we discuss aging in humans as a post-reproductive genetically determined process. After the age of reproductive success, aging continously progresses which clinically coincides with the onset of most chronic diseases, cancers and dementions. As evolution shapes the genomes for reproductive success and not for post-reproductive survival, aging could be defined as a protective mechanism which ensures the preservation and progress of species through the modification, trasmission and improvement of genetic material.

  15. Articulated Human Motion Tracking Using Sequential Immune Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Yi Li

    2013-01-01

    Full Text Available We formulate human motion tracking as a high-dimensional constrained optimization problem. A novel generative method is proposed for human motion tracking in the framework of evolutionary computation. The main contribution is that we introduce immune genetic algorithm (IGA for pose optimization in latent space of human motion. Firstly, we perform human motion analysis in the learnt latent space of human motion. As the latent space is low dimensional and contents the prior knowledge of human motion, it makes pose analysis more efficient and accurate. Then, in the search strategy, we apply IGA for pose optimization. Compared with genetic algorithm and other evolutionary methods, its main advantage is the ability to use the prior knowledge of human motion. We design an IGA-based method to estimate human pose from static images for initialization of motion tracking. And we propose a sequential IGA (S-IGA algorithm for motion tracking by incorporating the temporal continuity information into the traditional IGA. Experimental results on different videos of different motion types show that our IGA-based pose estimation method can be used for initialization of motion tracking. The S-IGA-based motion tracking method can achieve accurate and stable tracking of 3D human motion.

  16. Fecal pollution source tracking in waters intended for human supply based on archaeal and bacterial genetic markers.

    Science.gov (United States)

    Bianco, Kayo; Barreto, Camila; Oliveira, Samara Sant'Anna; Pinto, Leonardo Henriques; Albano, Rodolpho Mattos; Miranda, Catia Chaia; Clementino, Maysa Mandetta

    2015-12-01

    The determination of fecal pollution sources in aquatic ecosystems is essential to estimate associated health risks. In this study, we evaluate eight microbial source tracking (MST) markers including host-specific Bacteroidales and Methanobrevibacter spp. for discrimination between human, bovine, equine, and swine fecal contamination in waters intended for human supply. Overall, the novel host-specific archaeal and bacterial primers proposed in this study demonstrated high sensitivity and specificity. Markers for the Archaea domain were more prevalent in the fecal and water samples studied. We conclude that the investigations regarding the sources of fecal pollution in public water supplies can contribute to improve the quality of human health. To our knowledge, this is the first analysis using both archaeal and bacterial fecal MST markers on tropical water bodies of Rio de Janeiro city, Brazil.

  17. Human fertility, molecular genetics, and natural selection in modern societies.

    Directory of Open Access Journals (Sweden)

    Felix C Tropf

    Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  18. Human Genetics of Diabetic Retinopathy: Current Perspectives

    Directory of Open Access Journals (Sweden)

    Daniel P. K. Ng

    2010-01-01

    Full Text Available Diabetic retinopathy (DR is a most severe microvascular complication which, if left unchecked, can be sight-threatening. With the global prevalence of diabetes being relentlessly projected to rise to 438 million subjects by 2030, DR will undoubtedly pose a major public health concern. Efforts to unravel the human genetics of DR have been undertaken using the candidate gene and linkage approaches, while GWAS efforts are still lacking. Aside from evidence for a few genes including aldose reductase and vascular endothelial growth factor, the genetics of DR remain poorly elucidated. Nevertheless, the promise of impactful scientific discoveries may be realized if concerted and collaborative efforts are mounted to identify the genes for DR. Harnessing new genetic technologies and resources such as the upcoming 1000 Genomes Project will help advance this field of research, and potentially lead to a rich harvest of insights into the biological mechanisms underlying this debilitating complication.

  19. A global reference for human genetic variation

    DEFF Research Database (Denmark)

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David

    2015-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals...... from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short...... insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications...

  20. Human Genetic Engineering: A Survey of Student Value Stances

    Science.gov (United States)

    Wilson, Sara McCormack; And Others

    1975-01-01

    Assesses the values of high school and college students relative to human genetic engineering and recommends that biology educators explore instructional strategies merging human genetic information with value clarification techniques. (LS)

  1. Advances in gene technology: Human genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.

    1984-01-01

    This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

  2. Online genetic databases informing human genome epidemiology

    Directory of Open Access Journals (Sweden)

    Higgins Julian PT

    2007-07-01

    Full Text Available Abstract Background With the advent of high throughput genotyping technology and the information available via projects such as the human genome sequencing and the HapMap project, more and more data relevant to the study of genetics and disease risk will be produced. Systematic reviews and meta-analyses of human genome epidemiology studies rely on the ability to identify relevant studies and to obtain suitable data from these studies. A first port of call for most such reviews is a search of MEDLINE. We examined whether this could be usefully supplemented by identifying databases on the World Wide Web that contain genetic epidemiological information. Methods We conducted a systematic search for online databases containing genetic epidemiological information on gene prevalence or gene-disease association. In those containing information on genetic association studies, we examined what additional information could be obtained to supplement a MEDLINE literature search. Results We identified 111 databases containing prevalence data, 67 databases specific to a single gene and only 13 that contained information on gene-disease associations. Most of the latter 13 databases were linked to MEDLINE, although five contained information that may not be available from other sources. Conclusion There is no single resource of structured data from genetic association studies covering multiple diseases, and in relation to the number of studies being conducted there is very little information specific to gene-disease association studies currently available on the World Wide Web. Until comprehensive data repositories are created and utilized regularly, new data will remain largely inaccessible to many systematic review authors and meta-analysts.

  3. Molecular genetics of human obesity: A comprehensive review.

    Science.gov (United States)

    Singh, Rajan Kumar; Kumar, Permendra; Mahalingam, Kulandaivelu

    2017-02-01

    Obesity and its related health complications is a major problem worldwide. Hypothalamus and their signalling molecules play a critical role in the intervening and coordination with energy balance and homeostasis. Genetic factors play a crucial role in determining an individual's predisposition to the weight gain and being obese. In the past few years, several genetic variants were identified as monogenic forms of human obesity having success over common polygenic forms. In the context of molecular genetics, genome-wide association studies (GWAS) approach and their findings signified a number of genetic variants predisposing to obesity. However, the last couple of years, it has also been noticed that alterations in the environmental and epigenetic factors are one of the key causes of obesity. Hence, this review might be helpful in the current scenario of molecular genetics of human obesity, obesity-related health complications (ORHC), and energy homeostasis. Future work based on the clinical discoveries may play a role in the molecular dissection of genetic approaches to find more obesity-susceptible gene loci.

  4. Fine-scaled human genetic structure revealed by SNP microarrays.

    Science.gov (United States)

    Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B

    2009-05-01

    We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure.

  5. Pervasive genetic integration directs the evolution of human skull shape.

    Science.gov (United States)

    Martínez-Abadías, Neus; Esparza, Mireia; Sjøvold, Torstein; González-José, Rolando; Santos, Mauro; Hernández, Miquel; Klingenberg, Christian Peter

    2012-04-01

    It has long been unclear whether the different derived cranial traits of modern humans evolved independently in response to separate selection pressures or whether they resulted from the inherent morphological integration throughout the skull. In a novel approach to this issue, we combine evolutionary quantitative genetics and geometric morphometrics to analyze genetic and phenotypic integration in human skull shape. We measured human skulls in the ossuary of Hallstatt (Austria), which offer a unique opportunity because they are associated with genealogical data. Our results indicate pronounced covariation of traits throughout the skull. Separate simulations of selection for localized shape changes corresponding to some of the principal derived characters of modern human skulls produced outcomes that were similar to each other and involved a joint response in all of these traits. The data for both genetic and phenotypic shape variation were not consistent with the hypothesis that the face, cranial base, and cranial vault are completely independent modules but relatively strongly integrated structures. These results indicate pervasive integration in the human skull and suggest a reinterpretation of the selective scenario for human evolution where the origin of any one of the derived characters may have facilitated the evolution of the others.

  6. Genetically engineered mouse models and human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Ng Alvin JM

    2012-10-01

    Full Text Available Abstract Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics.

  7. Social and Psychological Aspects of Applied Human Genetics: A Bibliography.

    Science.gov (United States)

    Sorenson, James R., Comp.

    This bibliography is a selective compilation of books and articles which focus on the psychological and social issues of applied human genetics. It is centered in particular around problems, issues, and discussions of genetic counseling, the primary mechanism by which human genetics has been applied to date. It includes those entries which, on the…

  8. Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

    Science.gov (United States)

    Rabino, Isaac

    2003-01-01

    Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)

  9. The influence of recombination on human genetic diversity.

    Directory of Open Access Journals (Sweden)

    Chris C A Spencer

    2006-09-01

    Full Text Available In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution.

  10. Genetic Modification of Preimplantation Embryos: Toward Adequate Human Research Policies

    OpenAIRE

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo mo...

  11. Worldwide genetic and cultural change in human evolution.

    Science.gov (United States)

    Creanza, Nicole; Feldman, Marcus W

    2016-12-01

    Both genetic variation and certain culturally transmitted phenotypes show geographic signatures of human demographic history. As a result of the human cultural predisposition to migrate to new areas, humans have adapted to a large number of different environments. Migration to new environments alters genetic selection pressures, and comparative genetic studies have pinpointed numerous likely targets of this selection. However, humans also exhibit many cultural adaptations to new environments, such as practices related to clothing, shelter, and food. Human culture interacts with genes and the environment in complex ways, and studying genes and culture together can deepen our understanding of human evolution.

  12. Genetic modification of preimplantation embryos: toward adequate human research policies.

    Science.gov (United States)

    Dresser, Rebecca

    2004-01-01

    Citing advances in transgenic animal research and setbacks in human trials of somatic cell genetic interventions, some scientists and others want to begin planning for research involving the genetic modification of human embryos. Because this form of genetic modification could affect later-born children and their offspring, the protection of human subjects should be a priority in decisions about whether to proceed with such research. Yet because of gaps in existing federal policies, embryo modification proposals might not receive adequate scientific and ethical scrutiny. This article describes current policy shortcomings and recommends policy actions designed to ensure that the investigational genetic modification of embryos meets accepted standards for research on human subjects.

  13. The human genetic history of South Asia.

    Science.gov (United States)

    Majumder, Partha P

    2010-02-23

    South Asia--comprising India, Pakistan, countries in the sub-Himalayan region and Myanmar--was one of the first geographical regions to have been peopled by modern humans. This region has served as a major route of dispersal to other geographical regions, including southeast Asia. The Indian society comprises tribal, ranked caste, and other populations that are largely endogamous. As a result of evolutionary antiquity and endogamy, populations of India show high genetic differentiation and extensive structuring. Linguistic differences of populations provide the best explanation of genetic differences observed in this region of the world. Within India, consistent with social history, extant populations inhabiting northern regions show closer affinities with Indo-European speaking populations of central Asia that those inhabiting southern regions. Extant southern Indian populations may have been derived from early colonizers arriving from Africa along the southern exit route. The higher-ranked caste populations, who were the torch-bearers of Hindu rituals, show closer affinities with central Asian, Indo-European speaking, populations.

  14. Development and validation of tools to assess genetic discrimination and genetically based racism.

    Science.gov (United States)

    Parrott, Roxanne L; Silk, Kami J; Dillow, Megan R; Krieger, Janice L; Harris, Tina M; Condit, Celeste M

    2005-07-01

    It is possible that communication from mass media, public health or consumer advertising sources about human genetics and health may reify stereotypes of racialized social groups, perhaps cueing or exacerbating discriminatory and racist attitudes. This research used a multifaceted approach to assess lay perceptions of genetic discrimination and genetically based racism (N = 644). Two tools for use in strategic planning efforts associated with communicating about human genetics and health, the genetic discrimination instrument (GDI) and the genetically based racism instrument (GBRI), were derived. The GDI emerged as having five dimensions associated with lay perceptions of genetic discrimination. The GBRI was found to be unidimensional. Scale validation activities supported the tools' concurrent and discriminant validity characteristics. Significant differences between blacks and whites on the criminal control rights, social reproductive rights and employer rights factors as well as the GBRI were found. We recommend application of these screening tools prior to national dissemination of messages associated with genes and disease susceptibility, including school and university-based curricula.

  15. Genetic diversity of human RNase 8

    Directory of Open Access Journals (Sweden)

    Chan Calvin C

    2012-01-01

    Full Text Available Abstract Background Ribonuclease 8 is a member of the RNase A family of secretory ribonucleases; orthologs of this gene have been found only in primate genomes. RNase 8 is a divergent paralog of RNase 7, which is lysine-enriched, highly conserved, has prominent antimicrobial activity, and is expressed in both normal and diseased skin; in contrast, the physiologic function of RNase 8 remains uncertain. Here, we examine the genetic diversity of human RNase 8, a subject of significant interest given the existence of functional pseudogenes (coding sequences that are otherwise intact but with mutations in elements crucial for ribonucleolytic activity in non-human primate genomes. Results RNase 8 expression was detected in adult human lung, spleen and testis tissue by quantitative reverse-transcription PCR. Only two single-nucleotide polymorphisms and four unique alleles were identified within the RNase 8 coding sequence; nucleotide sequence diversity (π = 0.00122 ± 0.00009 per site was unremarkable for a human nuclear gene. We isolated transcripts encoding RNase 8 via rapid amplification of cDNA ends (RACE and RT-PCR which included a distal potential translational start site followed by sequence encoding an additional 30 amino acids that are conserved in the genomes of several higher primates. The distal translational start site is functional and promotes RNase 8 synthesis in transfected COS-7 cells. Conclusions These results suggest that RNase 8 may diverge considerably from typical RNase A family ribonucleases and may likewise exhibit unique function. This finding prompts a reconsideration of what we have previously termed functional pseudogenes, as RNase 8 may be responding to constraints that promote significant functional divergence from the canonical structure and enzymatic activity characteristic of the RNase A family.

  16. Genetic and biomarker studies of human longevity

    NARCIS (Netherlands)

    Deelen, Joris

    2014-01-01

    The aim of this thesis was to identify novel lifespan regulating loci that influence human longevity and population mortality. To this end, we performed two genome-wide association studies, one of long-lived individuals from the family-based Leiden Longevity Study (LLS) and an extended one of long-l

  17. Genetic base of Brazilian irrigated rice cultivars

    Directory of Open Access Journals (Sweden)

    Hudson de Oliveira Rabelo

    2015-08-01

    Full Text Available The aim of this study was to estimate the genetic base of Brazilian irrigated rice cultivars released in the period from 1965 to 2012. The genealogies of the cultivars were obtained based on information from marketing folders, websites, crossings records, and scientific articles. The following factors were calculated: relative genetic contribution (RGC, accumulated genetic contribution (AGC, frequency (in percentage of each ancestor in the genealogy (FAG, number of ancestors that constitute each cultivar (NAC,number of ancestors responsible for 60%, 70%, 80% and 90% of the genetic base (NAGB, and average number of ancestor per cultivar (ANAC. The cultivars were also grouped based on the period of release (1965-1980, 1981-1990, 1991-2000 and 2001-2012. For each grouping, the previously described factors were also estimated. A total of 110 cultivars were studied and it was concluded that the genetic base of Brazilian irrigated rice cultivars is narrow.

  18. [Influence of genetic factors on human sexual orientation. Review].

    Science.gov (United States)

    Rodríguez-Larralde, Alvaro; Paradisi, Irene

    2009-09-01

    Human sexual orientation is a complex trait, influenced by several genes, experiential and sociocultural factors. These elements interact and produce a typical pattern of sexual orientation towards the opposite sex. Some exceptions exist, like bisexuality and homosexuality, which seem to be more frequent in males than females. Traditional methods for the genetic study of behavior multifactorial characteristics consist in detecting the presence of familial aggregation. In order to identify the importance of genetic and environmental factors in this aggregation, the concordance of the trait for monozygotic and dizygotic twins and for adopted sibs, reared together and apart, is compared. These types of studies have shown that familial aggregation is stronger for male than for female homosexuality. Based on the threshold method for multifactorial traits, and varying the frequency of homosexuality in the population between 4 and 10%, heritability estimates between 0.27 and 0.76 have been obtained. In 1993, linkage between homosexuality and chromosomal region Xq28 based on molecular approaches was reported. Nevertheless, this was not confirmed in later studies. Recently, a wide search of the genome has given significant or close to significant linkage values with regions 7q36, 8p12 and 10q26, which need to be studied more closely. Deviation in the proportion of X chromosome inactivation in mothers of homosexuals seems to favor the presence of genes related with sexual orientation in this chromosome. There is still much to be known about the genetics of human homosexuality.

  19. Metabolic thrift and the genetic basis of human obesity

    OpenAIRE

    O’Rourke, Robert W.

    2014-01-01

    Evolution has molded metabolic thrift within humans, a genetic heritage that, when thrust into our modern “obesogenic” environment, creates the current obesity crisis. Modern genetic analysis has identified genetic and epigenetic contributors to obesity, an understanding of which will guide the development of environmental, pharmacologic, and genetic therapeutic interventions. “The voyage was so long, food and water ran out. One hundred of the paddlers died; forty men remained. The voyager...

  20. Behavior genetic modeling of human fertility

    DEFF Research Database (Denmark)

    Rodgers, J L; Kohler, H P; Kyvik, K O;

    2001-01-01

    Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males...

  1. Evolutionary genetic bases of longevity and senescence.

    Science.gov (United States)

    Govindaraju, Diddahally R

    2015-01-01

    Senescence, as a time-dependent developmental process, affects all organisms at every stage in their development and growth. During this process, genetic, epigenetic and environmental factors are known to introduce a wide range of variation for longevity among individuals. As an important life-history trait, longevity shows ontogenetic relationships with other complex traits, and hence may be viewed as a composite trait. Factors that influence the origin and maintenance of diversity of life are ultimately governed by Darwinian processes. Here we review evolutionary genetic mechanisms underlying longevity and senescence in humans from a life-history and genotype-epigenetic-phenotype (G-E-P) map prospective. We suggest that synergistic and cascading effects of cis-ruptive mechanisms in the genome, and epigenetic disruptive processes in relation to environmental factors may lead to sequential slippage in the G-E-P space. These mechanisms accompany age, stage and individual specific senescent processes, influenced by positive pleiotropy of certain genes, superior genome integrity, negative-frequency dependent selection and other factors that universally regulate rarity in nature. Finally we interpret life span as an inherent property of self-organizing systems that, accordingly, maintain species-specific limits for the entire complex of fitness traits. We conclude that Darwinian approaches provide unique opportunities to discover the biological bases of longevity as well as devise individual specific medical or other interventions toward improving health span.

  2. Genetic differences between avian and human isolates of Candida dubliniensis.

    LENUS (Irish Health Repository)

    McManus, Brenda A

    2009-09-01

    When Candida dubliniensis isolates obtained from seabird excrement and from humans in Ireland were compared by using multilocus sequence typing, 13 of 14 avian isolates were genetically distinct from human isolates. The remaining avian isolate was indistinguishable from a human isolate, suggesting that transmission may occur between humans and birds.

  3. Inferences of Recent and Ancient Human Population History Using Genetic and Non-Genetic Data

    Science.gov (United States)

    Kitchen, Andrew

    2008-01-01

    I have adopted complementary approaches to inferring human demographic history utilizing human and non-human genetic data as well as cultural data. These complementary approaches form an interdisciplinary perspective that allows one to make inferences of human history at varying timescales, from the events that occurred tens of thousands of years…

  4. 用IGA优化的直流电机的仿人智能控制%Human-simulated intelligent control of DC motor based on Improved Genetic Algorithm.

    Institute of Scientific and Technical Information of China (English)

    李楠; 陈韶飞; 薛方正; 许威

    2011-01-01

    The paper discusses the characteristic of the robot motion control algorithm, which has important influence to the road-holding of robot. After analyzing the mathematical model and control system, the human-simulated intelligent control (HSIC) is applied to the robot DC-motor motion control system. Improved Genetic Algorithm(IGA) is used to optimize the parameters for HSIC.Compared with PID controller, the HSIC controller has more effective control on motor, improves the performance of robot.%讨论了当前足球机器人运动控制系统的控制算法对足球机器人运动性能的影响.在分析了足球机器人运动控制系统组成和电机数学模型的基础上,对足球机器人运动控制器采用多模态控制的仿人智能控制(Human-Simulated Intelligent Control,HSIC)算法,利用改进的遗传算法(Improved Genetic Algorithm,IGA)对仿人智能控制器参数进行优化.通过与目前普遍采用的常规PID控制器作对比实验,表明采用IGA参数整定后的HSIC控制器对电机具有更好的控制品质,并改善了足球机器人的运动性能.

  5. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    DEFF Research Database (Denmark)

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo;

    2016-01-01

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic v...

  6. Alu repeats as markers for human population genetics

    Energy Technology Data Exchange (ETDEWEB)

    Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Bazan, H. [Louisiana State Univ., New Orleans, LA (United States). Medical Center] [and others

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  7. Insights into the genetic foundations of human communication.

    Science.gov (United States)

    Graham, Sarah A; Deriziotis, Pelagia; Fisher, Simon E

    2015-03-01

    The human capacity to acquire sophisticated language is unmatched in the animal kingdom. Despite the discontinuity in communicative abilities between humans and other primates, language is built on ancient genetic foundations, which are being illuminated by comparative genomics. The genetic architecture of the language faculty is also being uncovered by research into neurodevelopmental disorders that disrupt the normally effortless process of language acquisition. In this article, we discuss the strategies that researchers are using to reveal genetic factors contributing to communicative abilities, and review progress in identifying the relevant genes and genetic variants. The first gene directly implicated in a speech and language disorder was FOXP2. Using this gene as a case study, we illustrate how evidence from genetics, molecular cell biology, animal models and human neuroimaging has converged to build a picture of the role of FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge the gaps between genes, brains and behavior.

  8. Fetal magnetic resonance imaging and human genetics

    Energy Technology Data Exchange (ETDEWEB)

    Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at

    2006-02-15

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.

  9. Genetic synthetic lethality screen at the single gene level in cultured human cells

    OpenAIRE

    Simons, Arnold H.; Dafni, Naomi; Dotan, Iris; Oron, Yoram; Canaani, Dan

    2001-01-01

    Recently, we demonstrated the feasibility of a chemical synthetic lethality screen in cultured human cells. We now demonstrate the principles for a genetic synthetic lethality screen. The technology employs both an immortalized human cell line deficient in the gene of interest, which is complemented by an episomal survival plasmid expressing the wild-type cDNA for the gene of interest, and the use of a novel GFP-based double-label fluorescence system. Dominant negative genetic suppressor elem...

  10. The role of genetic variants in human longevity.

    Science.gov (United States)

    Chung, Wen-Hung; Dao, Ro-Lan; Chen, Liang-Kung; Hung, Shuen-Iu

    2010-11-01

    Human longevity is a complex phenotype with a strong genetic predisposition. Increasing evidence has revealed the genetic antecedents of human longevity. This article aims to review the data of various case/control association studies that examine the difference in genetic polymorphisms between long-lived people and younger subjects across different human populations. There are more than 100 candidate genes potentially involved in human longevity; this article particularly focuses on genes of the insulin/IGF-1 pathway, FOXO3A, FOXO1A, lipoprotein metabolism (e.g., APOE and PON1), and cell-cycle regulators (e.g., TP53 and P21). Since the confirmed genetic components for human longevity are few to date, further precise assessment of the genetic contributions is required. Gaining a better understanding of the contribution of genetics to human longevity may assist in the design of improved treatment methods for age-related diseases, delay the aging process, and, ultimately, prolong the human lifespan.

  11. Global human genetics of HIV-1 infection and China

    Institute of Scientific and Technical Information of China (English)

    Tuo Fu ZHU; Tie Jian FENG; Xin XIAO; Hui WANG; Bo Ping ZHOU

    2005-01-01

    Genetic polymorphisms in human genes can influence the risk for HIV-1 infection and disease progression, although the reported effects of these alleles have been inconsistent. This review highlights the recent discoveries on global and Chinese genetic polymorphisms and their association with HIV-1 transmission and disease progression.

  12. Potential International Approaches to Ownership/Control of Human Genetic Resources.

    Science.gov (United States)

    Rhodes, Catherine

    2016-09-01

    In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented.

  13. Human Handedness: More Evidence for Genetic Involvement.

    Science.gov (United States)

    Longstreth, Langdon E.

    1980-01-01

    A series of environmental-genetical analyses of the left-handedness of 1,950 college students indicates that left-handedness is familial: it is more frequent in families in which at least one parent is left-handed. (Author/CM)

  14. Genetic Expeditions with Haploid Human Cells

    NARCIS (Netherlands)

    Jae, L.T.

    2015-01-01

    Random mutagenesis followed by phenotypic selection (forward genetics) is among the most powerful tools to elucidate the molecular basis of intricate biological processes and has been used in a suite of model organisms throughout the last century. However, its application to cultured mammalian cells

  15. A global reference for human genetic variation

    DEFF Research Database (Denmark)

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David;

    2015-01-01

    insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications...

  16. New Iris Localization Method Based on Chaos Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    Jia Dongli; Muhammad Khurram Khan; Zhang Jiashu

    2005-01-01

    This paper present a new method based on Chaos Genetic Algorithm (CGA) to localize the human iris in a given image. First, the iris image is preprocessed to estimate the range of the iris localization, and then CGA is used to extract the boundary of the iris. Simulation results show that the proposed algorithms is efficient and robust, and can achieve sub pixel precision. Because Genetic Algorithms (GAs) can search in a large space, the algorithm does not need accurate estimation of iris center for subsequent localization, and hence can lower the requirement for original iris image processing. On this point, the present localization algirithm is superior to Daugmans algorithm.

  17. Genetic engineering of human pluripotent cells using TALE nucleases.

    Science.gov (United States)

    Hockemeyer, Dirk; Wang, Haoyi; Kiani, Samira; Lai, Christine S; Gao, Qing; Cassady, John P; Cost, Gregory J; Zhang, Lei; Santiago, Yolanda; Miller, Jeffrey C; Zeitler, Bryan; Cherone, Jennifer M; Meng, Xiangdong; Hinkley, Sarah J; Rebar, Edward J; Gregory, Philip D; Urnov, Fyodor D; Jaenisch, Rudolf

    2011-07-07

    Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).

  18. Function Optimization Based on Quantum Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Ying Sun

    2014-01-01

    Full Text Available Optimization method is important in engineering design and application. Quantum genetic algorithm has the characteristics of good population diversity, rapid convergence and good global search capability and so on. It combines quantum algorithm with genetic algorithm. A novel quantum genetic algorithm is proposed, which is called Variable-boundary-coded Quantum Genetic Algorithm (vbQGA in which qubit chromosomes are collapsed into variable-boundary-coded chromosomes instead of binary-coded chromosomes. Therefore much shorter chromosome strings can be gained. The method of encoding and decoding of chromosome is first described before a new adaptive selection scheme for angle parameters used for rotation gate is put forward based on the core ideas and principles of quantum computation. Eight typical functions are selected to optimize to evaluate the effectiveness and performance of vbQGA against standard Genetic Algorithm (sGA and Genetic Quantum Algorithm (GQA. The simulation results show that vbQGA is significantly superior to sGA in all aspects and outperforms GQA in robustness and solving velocity, especially for multidimensional and complicated functions.

  19. A Model of Genetic Variation in Human Social Networks

    CERN Document Server

    Fowler, James H; Christakis, Nicholas A

    2008-01-01

    Social networks influence the evolution of cooperation and they exhibit strikingly systematic patterns across a wide range of human contexts. Both of these facts suggest that variation in the topological attributes of human social networks might have a genetic basis. While genetic variation accounts for a significant portion of the variation in many complex social behaviors, the heritability of egocentric social network attributes is unknown. Here we show that three of these attributes (in-degree, transitivity, and centrality) are heritable. We then develop a "mirror network" method to test extant network models and show that none accounts for observed genetic variation in human social networks. We propose an alternative "attract and introduce" model that generates significant heritability as well as other important network features, and we show that this model with two simple forms of heterogeneity is well suited to the modeling of real social networks in humans. These results suggest that natural selection ...

  20. Human longevity: Genetics or Lifestyle? It takes two to tango.

    Science.gov (United States)

    Passarino, Giuseppe; De Rango, Francesco; Montesanto, Alberto

    2016-01-01

    Healthy aging and longevity in humans are modulated by a lucky combination of genetic and non-genetic factors. Family studies demonstrated that about 25 % of the variation in human longevity is due to genetic factors. The search for genetic and molecular basis of aging has led to the identification of genes correlated with the maintenance of the cell and of its basic metabolism as the main genetic factors affecting the individual variation of the aging phenotype. In addition, studies on calorie restriction and on the variability of genes associated with nutrient-sensing signaling, have shown that ipocaloric diet and/or a genetically efficient metabolism of nutrients, can modulate lifespan by promoting an efficient maintenance of the cell and of the organism. Recently, epigenetic studies have shown that epigenetic modifications, modulated by both genetic background and lifestyle, are very sensitive to the aging process and can either be a biomarker of the quality of aging or influence the rate and the quality of aging. On the whole, current studies are showing that interventions modulating the interaction between genetic background and environment is essential to determine the individual chance to attain longevity.

  1. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    Science.gov (United States)

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  2. Genetic architecture for human aggression: A study of gene-phenotype relationship in OMIM.

    Science.gov (United States)

    Zhang-James, Yanli; Faraone, Stephen V

    2016-07-01

    Genetic studies of human aggression have mainly focused on known candidate genes and pathways regulating serotonin and dopamine signaling and hormonal functions. These studies have taught us much about the genetics of human aggression, but no genetic locus has yet achieved genome-significance. We here present a review based on a paradoxical hypothesis that studies of rare, functional genetic variations can lead to a better understanding of the molecular mechanisms underlying complex multifactorial disorders such as aggression. We examined all aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM), an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human disorders that have documented aggressive symptoms in at least one individual with a well-defined genetic variant. Altogether, we retrieved 86 causal genes. Although most of these genes had not been implicated in human aggression by previous studies, the most significantly enriched canonical pathways had been previously implicated in aggression (e.g., serotonin and dopamine signaling). Our findings provide strong evidence to support the causal role of these pathways in the pathogenesis of aggression. In addition, the novel genes and pathways we identified suggest additional mechanisms underlying the origins of human aggression. Genome-wide association studies with very large samples will be needed to determine if common variants in these genes are risk factors for aggression. © 2015 Wiley Periodicals, Inc.

  3. Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

    Science.gov (United States)

    Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

    2015-01-01

    This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

  4. Primer on Molecular Genetics; DOE Human Genome Program

    Science.gov (United States)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  5. Common genetic variants influence human subcortical brain structures

    OpenAIRE

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro,; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume de...

  6. Primer on molecular genetics. DOE Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  7. Web Based Genetic Algorithm Using Data Mining

    OpenAIRE

    Ashiqur Rahman; Asaduzzaman Noman; Md. Ashraful Islam; Al-Amin Gaji

    2016-01-01

    This paper presents an approach for classifying students in order to predict their final grade based on features extracted from logged data in an education web-based system. A combination of multiple classifiers leads to a significant improvement in classification performance. Through weighting the feature vectors using a Genetic Algorithm we can optimize the prediction accuracy and get a marked improvement over raw classification. It further shows that when the number of features is few; fea...

  8. Genetics of human episodic memory: dealing with complexity.

    Science.gov (United States)

    Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2011-09-01

    Episodic memory is a polygenic behavioral trait with substantial heritability estimates. Despite its complexity, recent empirical evidence supports the notion that behavioral genetic studies of episodic memory might successfully identify trait-associated molecules and pathways. The development of high-throughput genotyping methods, of elaborated statistical analyses and of phenotypic assessment methods at the neural systems level will facilitate the reliable identification of novel memory-related genes. Importantly, a necessary crosstalk between behavioral genetic studies and investigation of causality by molecular genetic studies will ultimately pave the way towards the identification of biologically important, and hopefully druggable, genes and molecular pathways related to human episodic memory.

  9. Human aggression across the lifespan: genetic propensities and environmental moderators.

    Science.gov (United States)

    Tuvblad, Catherine; Baker, Laura A

    2011-01-01

    This chapter reviews the recent evidence of genetic and environmental influences on human aggression. Findings from a large selection of the twin and adoption studies that have investigated the genetic and environmental architecture of aggressive behavior are summarized. These studies together show that about half (50%) of the variance in aggressive behavior is explained by genetic influences in both males and females, with the remaining 50% of the variance being explained by environmental factors not shared by family members. Form of aggression (reactive, proactive, direct/physical, indirect/relational), method of assessment (laboratory observation, self-report, ratings by parents and teachers), and age of the subjects-all seem to be significant moderators of the magnitude of genetic and environmental influences on aggressive behavior. Neither study design (twin vs. sibling adoption design) nor sex (male vs. female) seems to impact the magnitude of the genetic and environmental influences on aggression. There is also some evidence of gene-environment interaction (G × E) from both twin/adoption studies and molecular genetic studies. Various measures of family adversity and social disadvantage have been found to moderate genetic influences on aggressive behavior. Findings from these G × E studies suggest that not all individuals will be affected to the same degree by experiences and exposures, and that genetic predispositions may have different effects depending on the environment.

  10. Genetic and Epigenetic Discoveries in Human Retinoblastoma.

    Science.gov (United States)

    McEvoy, Justina D; Dyer, Michael A

    2015-01-01

    Retinoblastoma is a rare pediatric cancer of the retina. Nearly all retinoblastomas are initiated through the biallelic inactivation of the retinoblastoma tumor susceptibility gene (RB1). Whole-genome sequencing has made it possible to identify secondary genetic lesions following RB1 inactivation. One of the major discoveries from retinoblastoma sequencing studies is that some retinoblastoma tumors have stable genomes. Subsequent epigenetic studies showed that changes in the epigenome contribute to the rapid progression of retinoblastoma following RB1 gene inactivation. In addition, gene amplification and elevated expression of p53 antagonists, MDM2 and MDM4, may also play an important role in retinoblastoma tumorigenesis. The knowledge gained from these recent molecular, cellular, genomic, and epigenomic analyses are now being integrated to identify new therapeutic approaches that can help save lives and vision in children with retinoblastoma, with fewer long-term side effects.

  11. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    Science.gov (United States)

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-09-02

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.

  12. Toward genetics-based virus taxonomy: comparative analysis of a genetics-based classification and the taxonomy of picornaviruses.

    Science.gov (United States)

    Lauber, Chris; Gorbalenya, Alexander E

    2012-04-01

    Virus taxonomy has received little attention from the research community despite its broad relevance. In an accompanying paper (C. Lauber and A. E. Gorbalenya, J. Virol. 86:3890-3904, 2012), we have introduced a quantitative approach to hierarchically classify viruses of a family using pairwise evolutionary distances (PEDs) as a measure of genetic divergence. When applied to the six most conserved proteins of the Picornaviridae, it clustered 1,234 genome sequences in groups at three hierarchical levels (to which we refer as the "GENETIC classification"). In this study, we compare the GENETIC classification with the expert-based picornavirus taxonomy and outline differences in the underlying frameworks regarding the relation of virus groups and genetic diversity that represent, respectively, the structure and content of a classification. To facilitate the analysis, we introduce two novel diagrams. The first connects the genetic diversity of taxa to both the PED distribution and the phylogeny of picornaviruses. The second depicts a classification and the accommodated genetic diversity in a standardized manner. Generally, we found striking agreement between the two classifications on species and genus taxa. A few disagreements concern the species Human rhinovirus A and Human rhinovirus C and the genus Aphthovirus, which were split in the GENETIC classification. Furthermore, we propose a new supergenus level and universal, level-specific PED thresholds, not reached yet by many taxa. Since the species threshold is approached mostly by taxa with large sampling sizes and those infecting multiple hosts, it may represent an upper limit on divergence, beyond which homologous recombination in the six most conserved genes between two picornaviruses might not give viable progeny.

  13. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    Energy Technology Data Exchange (ETDEWEB)

    Lemaire, D. [Universidade Federal da Bahia and Universidade Estadual da Bahia, Salvador, BA (Brazil); Barbosa, T. [Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA (Brazil); Rihet, P. [TAGC-INSERM U928, Aix-Marseille Université, Marseille (France)

    2011-10-28

    Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.

  14. Canonical Genetic Signatures of the Adult Human Brain

    Science.gov (United States)

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  15. Unraveling the genetics of human obesity.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    2006-12-01

    Full Text Available The use of modern molecular biology tools in deciphering the perturbed biochemistry and physiology underlying the obese state has proven invaluable. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes (Prader-Willi and Bardet-Biedl previously assumed to be controlled by a single gene are, conversely, regulated by multiple elements. Finally, the application of comprehensive profiling technologies coupled with creative statistical analyses has revealed that interactions between genetic and environmental factors are responsible for the common obesity currently challenging many Westernized societies. As such, an improved understanding of the different "types" of obesity not only permits the development of potential therapies, but also proposes novel and often unexpected directions in deciphering the dysfunctional state of obesity.

  16. Medical and human genetics 1977: trends and directions.

    Science.gov (United States)

    Motulsky, A G

    1978-03-01

    Our field is in a rapid state of evolution. The broader concerns of human genetics not of immediate medical interest such as behavioral genetics are often investigated by persons not trained or identified as human geneticists. Both medical genetics and human genetics in general have prospered when various biologic techniques have been applied to genetic concepts. A search for novel biologic methods may provide new insights and may bridge the gulf between Mendelian and biometric approaches in studies of behavior and of common diseases. Medical geneticists need to broaden their fields of interest to encompass other fields than those of pediatric interest alone. We need to attract more basic scientists. Our field is evolving from a largely research oriented science to a service-oriented specialty. This logical development is a sign of increasing maturity and makes available to the public the results of our research. The resulting stresses and strains need careful watching to prevent their slowing the momentum of our science which can contribute continued insights into the many problems of behavior, health, and disease.

  17. Genetic alterations by human papillomaviruses in oncogenesis.

    Science.gov (United States)

    Lazo, P A; Gallego, M I; Ballester, S; Feduchi, E

    1992-03-30

    The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.

  18. A comparison of worldwide phonemic and genetic variation in human populations.

    Science.gov (United States)

    Creanza, Nicole; Ruhlen, Merritt; Pemberton, Trevor J; Rosenberg, Noah A; Feldman, Marcus W; Ramachandran, Sohini

    2015-02-03

    Worldwide patterns of genetic variation are driven by human demographic history. Here, we test whether this demographic history has left similar signatures on phonemes-sound units that distinguish meaning between words in languages-to those it has left on genes. We analyze, jointly and in parallel, phoneme inventories from 2,082 worldwide languages and microsatellite polymorphisms from 246 worldwide populations. On a global scale, both genetic distance and phonemic distance between populations are significantly correlated with geographic distance. Geographically close language pairs share significantly more phonemes than distant language pairs, whether or not the languages are closely related. The regional geographic axes of greatest phonemic differentiation correspond to axes of genetic differentiation, suggesting that there is a relationship between human dispersal and linguistic variation. However, the geographic distribution of phoneme inventory sizes does not follow the predictions of a serial founder effect during human expansion out of Africa. Furthermore, although geographically isolated populations lose genetic diversity via genetic drift, phonemes are not subject to drift in the same way: within a given geographic radius, languages that are relatively isolated exhibit more variance in number of phonemes than languages with many neighbors. This finding suggests that relatively isolated languages are more susceptible to phonemic change than languages with many neighbors. Within a language family, phoneme evolution along genetic, geographic, or cognate-based linguistic trees predicts similar ancestral phoneme states to those predicted from ancient sources. More genetic sampling could further elucidate the relative roles of vertical and horizontal transmission in phoneme evolution.

  19. The mobile genetic element Alu in the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Novick, G.E. [Florida International Univ., Miami, FL (United States); Batzer, M.A.; Deininger, P.L. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

    1996-01-01

    Genetic material has been traditionally envisioned as relatively static with the exception of occasional, often deleterious mutations. The sequence DNA-to-RNA-to-protein represented for many years the central dogma relating gene structure and function. Recently, the field of molecular genetics has provided revolutionary information on the dynamic role of repetitive elements in the function of the genetic material and the evolution of humans and other organisms. Alu sequences represent the largest family of short interspersed repetitive elements (SINEs) in humans, being present in an excess of 500,000 copies per haploid genome. Alu elements, as well as the other repetitive elements, were once considered to be useless. Today, the biology of Alu transposable elements is being widely examined in order to determine the molecular basis of a growing number of identified diseases and to provide new directions in genome mapping and biomedical research. 66 refs., 5 figs.

  20. Genetic variation and the de novo assembly of human genomes.

    Science.gov (United States)

    Chaisson, Mark J P; Wilson, Richard K; Eichler, Evan E

    2015-11-01

    The discovery of genetic variation and the assembly of genome sequences are both inextricably linked to advances in DNA-sequencing technology. Short-read massively parallel sequencing has revolutionized our ability to discover genetic variation but is insufficient to generate high-quality genome assemblies or resolve most structural variation. Full resolution of variation is only guaranteed by complete de novo assembly of a genome. Here, we review approaches to genome assembly, the nature of gaps or missing sequences, and biases in the assembly process. We describe the challenges of generating a complete de novo genome assembly using current technologies and the impact that being able to perfectly sequence the genome would have on understanding human disease and evolution. Finally, we summarize recent technological advances that improve both contiguity and accuracy and emphasize the importance of complete de novo assembly as opposed to read mapping as the primary means to understanding the full range of human genetic variation.

  1. Public Attitudes toward Human Genetic Manipulation: A Revitalization of Eugenics?

    Science.gov (United States)

    Veglia, Geremia; And Others

    The purpose of this investigation was to measure the attitudes of college students across the United States concerning the possible use of genetic manipulation, especially in terms of enhancing human physical and intellectual characteristics. The instrument used was divided into three general areas of inquiry: the first, designed to measure the…

  2. Exploring human brain lateralization with molecular genetics and genomics.

    Science.gov (United States)

    Francks, Clyde

    2015-11-01

    Lateralizations of brain structure and motor behavior have been observed in humans as early as the first trimester of gestation, and are likely to arise from asymmetrical genetic-developmental programs, as in other animals. Studies of gene expression levels in postmortem tissue samples, comparing the left and right sides of the human cerebral cortex, have generally not revealed striking transcriptional differences between the hemispheres. This is likely due to lateralization of gene expression being subtle and quantitative. However, a recent re-analysis and meta-analysis of gene expression data from the adult superior temporal and auditory cortex found lateralization of transcription of genes involved in synaptic transmission and neuronal electrophysiology. Meanwhile, human subcortical mid- and hindbrain structures have not been well studied in relation to lateralization of gene activity, despite being potentially important developmental origins of asymmetry. Genetic polymorphisms with small effects on adult brain and behavioral asymmetries are beginning to be identified through studies of large datasets, but the core genetic mechanisms of lateralized human brain development remain unknown. Identifying subtly lateralized genetic networks in the brain will lead to a new understanding of how neuronal circuits on the left and right are differently fine-tuned to preferentially support particular cognitive and behavioral functions.

  3. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic; M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); V.M. Strike (Vanessa); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (M.); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn; S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole A.); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cock); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)

    2015-01-01

    textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate h

  4. Common genetic variants influence human subcortical brain structures

    NARCIS (Netherlands)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To investigat

  5. Improved genetic manipulation of human embryonic stem cells.

    NARCIS (Netherlands)

    Braam, S.R.; Denning, C.; van den Brink, S.; Kats, P.; Hochstenbach, R.; Passier, R.; Mummery, C.L.

    2008-01-01

    Low efficiency of transfection limits the ability to genetically manipulate human embryonic stem cells (hESCs), and differences in cell derivation and culture methods require optimization of transfection protocols. We transiently transferred multiple independent hESC lines with different growth requ

  6. Human life: genetic or social construction?

    Science.gov (United States)

    Yudin, Boris

    2005-01-01

    I am going to discuss some present-day tendencies in the development of the very old debate on nature vs nurture. There is a widespread position describing the history of this debate as a pendulum-like process. Some three decades ago there was a time of overwhelming prevalence of the position stressing social factors in determining human character and behavior; now the pendulum has come to the opposite side and those who stress the role of biology, of genes are in favor. Yet in my view rather acute opposition of both positions still exists. Its existence depends not so much on new scientific discoveries as on some social and cultural factors which are more conservative than the development of science. More than that, we can even talk about competition of these two positions.

  7. Intelligent DNA-based molecular diagnostics using linked genetic markers

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

    1994-12-31

    This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

  8. Identification of susceptibility genes and genetic modifiers of human diseases

    Science.gov (United States)

    Abel, Kenneth; Kammerer, Stefan; Hoyal, Carolyn; Reneland, Rikard; Marnellos, George; Nelson, Matthew R.; Braun, Andreas

    2005-03-01

    The completion of the human genome sequence enables the discovery of genes involved in common human disorders. The successful identification of these genes is dependent on the availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform technology based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology, we generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes. We also established a large DNA sample bank comprised of more than 50,000 consented healthy and diseased individuals. This combination of reagents and technology allows the execution of large-scale genome-wide association studies. Taking advantage of MassARRAY"s capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. To compare pools as a first-pass "filtering" step is a tremendous advantage in throughput and cost over individual genotyping. We employed this approach in numerous genome-wide, hypothesis-free searches to identify genes associated with common complex diseases, such as breast cancer, osteoporosis, and osteoarthritis, and genes involved in quantitative traits like high density lipoproteins cholesterol (HDL-c) levels and central fat. Access to additional well-characterized patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our ability for early diagnosis and determination of specific disease subtype or progression stage.

  9. Genetic Algorithm Based Hybrid Fuzzy System for Assessing Morningness

    Directory of Open Access Journals (Sweden)

    Animesh Biswas

    2014-01-01

    Full Text Available This paper describes a real life case example on the assessment process of morningness of individuals using genetic algorithm based hybrid fuzzy system. It is observed that physical and mental performance of human beings in different time slots of a day are majorly influenced by morningness orientation of those individuals. To measure the morningness of people various self-reported questionnaires were developed by different researchers in the past. Among them reduced version of Morningness-Eveningness Questionnaire is mostly accepted. Almost all of the linguistic terms used in questionnaires are fuzzily defined. So, assessing them in crisp environments with their responses does not seem to be justifiable. Fuzzy approach based research works for assessing morningness of people are very few in the literature. In this paper, genetic algorithm is used to tune the parameters of a Mamdani fuzzy inference model to minimize error with their predicted outputs for assessing morningness of people.

  10. The genetics of complex human behaviour: Cannabis use, personality, sexuality and mating

    NARCIS (Netherlands)

    Verweij, K.J.H.

    2012-01-01

    I investigated the genetic and environmental etiology of individual differences in a variety of complex human behaviours, broadly captured within three domains - 1) cannabis use, 2) personality, and 3) sexuality and mating. Research questions and hypotheses are addressed with large community-based,

  11. Mapping genetic influences on the corticospinal motor system in humans

    DEFF Research Database (Denmark)

    Cheeran, B J; Ritter, C; Rothwell, J C

    2009-01-01

    It is becoming increasingly clear that genetic variations account for a certain amount of variance in the acquisition and maintenance of different skills. Until now, several levels of genetic influences were examined, ranging from global heritability estimates down to the analysis...... of the contribution of single nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the corticospinal motor system is essential to the acquisition of fine manual motor skills which require a finely tuned coordination of activity in distal forelimb muscles. Here we review recent brain mapping...

  12. 76 FR 14034 - Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

    Science.gov (United States)

    2011-03-15

    ... HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer Summary: In compliance with the requirement... included in the NCI Cancer Genetics Services Directory on NCI's Cancer.gov Web site. The...

  13. Asian Option Pricing Based on Genetic Algorithms

    Institute of Scientific and Technical Information of China (English)

    YunzhongLiu; HuiyuXuan

    2004-01-01

    The cross-fertilization between artificial intelligence and computational finance has resulted in some of the most active research areas in financial engineering. One direction is the application of machine learning techniques to pricing financial products, which is certainly one of the most complex issues in finance. In the literature, when the interest rate,the mean rate of return and the volatility of the underlying asset follow general stochastic processes, the exact solution is usually not available. In this paper, we shall illustrate how genetic algorithms (GAs), as a numerical approach, can be potentially helpful in dealing with pricing. In particular, we test the performance of basic genetic algorithms by using it to the determination of prices of Asian options, whose exact solutions is known from Black-Scholesoption pricing theory. The solutions found by basic genetic algorithms are compared with the exact solution, and the performance of GAs is ewluated accordingly. Based on these ewluations, some limitations of GAs in option pricing are examined and possible extensions to future works are also proposed.

  14. GENETIC-BASED NUTRITION RECOMMENDATION MODEL

    Directory of Open Access Journals (Sweden)

    S. A.A. Fayoumi

    2014-01-01

    Full Text Available Evolutionary computing is the collective name for a range of problem-solving techniques based on principles of biological evolution, such as natural selection and genetic inheritance. These techniques are being widely applied to a variety of problems in many vital fields. Also, Evolutionary Algorithms (EA which applied the principles of Evolutionary computations, such as genetic algorithm, particle swarm, ant colony and bees algorithm and so on play an important role in decision making process. EAs serve a lot of fields which can affect our life directly, such as medicine, engineering, transportations, communications. One of these vital fields is Nutrition which can be viewed from several points of view as medical, physical, social, environmental and psychological point of view. This study, presents a proposed model that shows how evolutionary computing generally and genetic algorithm specifically-as a powerful algorithm of evolutionary algorithms-can be used to recommend an appropriate nutrition style in a medical and physical sides only to each person according to his/her personal and medical measurements.

  15. Genetics of multifactorial disorders: proceedings of the 6th Pan Arab Human Genetics Conference

    OpenAIRE

    Nair, Pratibha; Bizzari, Sami; Rajah, Nirmal; Assaf, Nada; Al-Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak

    2016-01-01

    The 6th Pan Arab Human Genetics Conference (PAHGC), “Genetics of Multifactorial Disorders” was organized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in Dubai, United Arab Emirates from 21 to 23 January, 2016. The PAHGCs are held biennially to provide a common platform to bring together regional and international geneticists to share their knowledge and to discuss common issues. Over 800 delegates attended the first 2 days of the conference and these came from various medic...

  16. Genome-wide genetic interaction analysis of glaucoma using expert knowledge derived from human phenotype networks.

    Science.gov (United States)

    Hu, Ting; Darabos, Christian; Cricco, Maria E; Kong, Emily; Moore, Jason H

    2015-01-01

    The large volume of GWAS data poses great computational challenges for analyzing genetic interactions associated with common human diseases. We propose a computational framework for characterizing epistatic interactions among large sets of genetic attributes in GWAS data. We build the human phenotype network (HPN) and focus around a disease of interest. In this study, we use the GLAUGEN glaucoma GWAS dataset and apply the HPN as a biological knowledge-based filter to prioritize genetic variants. Then, we use the statistical epistasis network (SEN) to identify a significant connected network of pairwise epistatic interactions among the prioritized SNPs. These clearly highlight the complex genetic basis of glaucoma. Furthermore, we identify key SNPs by quantifying structural network characteristics. Through functional annotation of these key SNPs using Biofilter, a software accessing multiple publicly available human genetic data sources, we find supporting biomedical evidences linking glaucoma to an array of genetic diseases, proving our concept. We conclude by suggesting hypotheses for a better understanding of the disease.

  17. Host genetics of severe influenza: from mouse Mx1 to human IRF7.

    Science.gov (United States)

    Ciancanelli, Michael J; Abel, Laurent; Zhang, Shen-Ying; Casanova, Jean-Laurent

    2016-02-01

    Influenza viruses cause mild to moderate respiratory illness in most people, and only rarely devastating or fatal infections. The virulence factors encoded by viral genes can explain seasonal or geographic differences at the population level but are unlikely to account for inter-individual clinical variability. Inherited or acquired immunodeficiencies may thus underlie severe cases of influenza. The crucial role of host genes was first demonstrated by forward genetics in inbred mice, with the identification of interferon (IFN)-α/β-inducible Mx1 as a canonical influenza susceptibility gene. Reverse genetics has subsequently characterized the in vivo role of other mouse genes involved in IFN-α/β and -λ immunity. A series of in vitro studies with mouse and human cells have also refined the cell-intrinsic mechanisms of protection against influenza viruses. Population-based human genetic studies have not yet uncovered variants with a significant impact. Interestingly, human primary immunodeficiencies affecting T and B cells were also not found to predispose to severe influenza. Recently however, human IRF7 was shown to be essential for IFN-α/β- and IFN-λ-dependent protective immunity against primary influenza in vivo, as inferred from a patient with life-threatening influenza revealed to be IRF7-deficient by whole exome sequencing. Next generation sequencing of human exomes and genomes will facilitate the analysis of the human genetic determinism of severe influenza.

  18. Genetic Structure Analysis of Human Remains from Khitan Noble Necropolis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Ancient DNA was extracted from 13 skeletal remains from the burial groups of Khitan nobles, which were excavated in northeast China. The hypervariable segment I sequences ( HVS Ⅰ ) of the mitochondrial DNA control region, in the 13 individuals, were used as genetic markers to determine the genetic relationships between the individuals and the genetic affinity to other interrelated populations by using the known database of mtDNA. Based on the phylogenetic analysis of these ancient DNA sequences, the genetic structures of two Khitan noble kindreds were obtained, including the Yel Yuzhi's kindred and the Xiao He's kindred. Furthermore, the relationships between the Khitan nobles and some modern interrelated populations were analyzed. On the basis of the result of the analysis, the gene flows of the ancient Khitans and their demographic expansion in history was deduced.

  19. Common genetic variants influence human subcortical brain structures.

    Science.gov (United States)

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy

    2015-04-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

  20. Broadening the application of evolutionarily based genetic pest management.

    Science.gov (United States)

    Gould, Fred

    2008-02-01

    Insect- and tick-vectored diseases such as malaria, dengue fever, and Lyme disease cause human suffering, and current approaches for prevention are not adequate. Invasive plants and animals such as Scotch broom, zebra mussels, and gypsy moths continue to cause environmental damage and economic losses in agriculture and forestry. Rodents transmit diseases and cause major pre- and postharvest losses, especially in less affluent countries. Each of these problems might benefit from the developing field of Genetic Pest Management that is conceptually based on principles of evolutionary biology. This article briefly describes the history of this field, new molecular tools in this field, and potential applications of those tools. There will be a need for evolutionary biologists to interact with researchers and practitioners in a variety of other fields to determine the most appropriate targets for genetic pest management, the most appropriate methods for specific targets, and the potential of natural selection to diminish the effectiveness of genetic pest management. In addition to producing environmentally sustainable pest management solutions, research efforts in this area could lead to new insights about the evolution of selfish genetic elements in natural systems and will provide students with the opportunity to develop a more sophisticated understanding of the role of evolutionary biology in solving societal problems.

  1. Somatic retrotransposition alters the genetic landscape of the human brain

    OpenAIRE

    Baillie, J. Kenneth; Barnett, Mark W.; Upton, Kyle R; Gerhardt, Daniel J.; Richmond, Todd A.; De Sapio, Fioravante; Brennan, Paul; Rizzu, Patrizia; Smith, Sarah; Fell, Mark; Talbot, Richard T; Gustincich, Stefano; Freeman, Thomas C.; Mattick, John S.; Hume, David A

    2011-01-01

    Retrotransposons are mobile genetic elements that employ a germ line “copy-and-paste” mechanism to spread throughout metazoan genomes 1 . At least 50% of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease 2-3 . Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells 4-5 , excluding early embryo development and some malignancies 6-7 . Recent reports of L1 expressio...

  2. Molecular basis of telomere dysfunction in human genetic diseases.

    Science.gov (United States)

    Sarek, Grzegorz; Marzec, Paulina; Margalef, Pol; Boulton, Simon J

    2015-11-01

    Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

  3. Recent genetic discoveries implicating ion channels in human cardiovascular diseases.

    Science.gov (United States)

    George, Alfred L

    2014-04-01

    The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.

  4. Overview of genetic analysis of human opioid receptors.

    Science.gov (United States)

    Spampinato, Santi M

    2015-01-01

    The human μ-opioid receptor gene (OPRM1), due to its genetic and structural variation, has been a target of interest in several pharmacogenetic studies. The μ-opioid receptor (MOR), encoded by OPRM1, contributes to regulate the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic polymorphisms of opioid receptors are candidates for the variability of clinical opioid effects. The non-synonymous polymorphism A118G of the OPRM1 has been repeatedly associated with the efficacy of opioid treatments for pain and various types of dependence. Genetic analysis of human opioid receptors has evidenced the presence of numerous polymorphisms either in exonic or in intronic sequences as well as the presence of synonymous coding variants that may have important effects on transcription, mRNA stability, and splicing, thus affecting gene function despite not directly disrupting any specific residue. Genotyping of opioid receptors is still in its infancy and a relevant progress in this field can be achieved by using advanced gene sequencing techniques described in this review that allow the researchers to obtain vast quantities of data on human genomes and transcriptomes in a brief period of time and with affordable costs.

  5. Genetic Programming Neural Networks: A Powerful Bioinformatics Tool for Human Genetics.

    Science.gov (United States)

    Ritchie, Marylyn D; Motsinger, Alison A; Bush, William S; Coffey, Christopher S; Moore, Jason H

    2007-01-01

    The identification of genes that influence the risk of common, complex disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. This challenge is partly due to the limitations of parametric statistical methods for detecting genetic effects that are dependent solely or partially on interactions. We have previously introduced a genetic programming neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of genetic and gene-environment combinations associated with disease risk. Previous empirical studies suggest GPNN has excellent power for identifying gene-gene and gene-environment interactions. The goal of this study was to compare the power of GPNN to stepwise logistic regression (SLR) and classification and regression trees (CART) for identifying gene-gene and gene-environment interactions. SLR and CART are standard methods of analysis for genetic association studies. Using simulated data, we show that GPNN has higher power to identify gene-gene and gene-environment interactions than SLR and CART. These results indicate that GPNN may be a useful pattern recognition approach for detecting gene-gene and gene-environment interactions in studies of human disease.

  6. Genetic Markers of Human Evolution Are Enriched in Schizophrenia

    DEFF Research Database (Denmark)

    Srinivasan, Saurabh; Bettella, Francesco; Mattingsdal, Morten;

    2015-01-01

    and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score. RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone...... recent positive selection in humans (i.e., with a low NSS score). Variants in brain-related genes with a low NSS score confer significantly higher susceptibility than variants in other brain-related genes. The enrichment is strongest for schizophrenia, but we cannot rule out enrichment for other......BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking...

  7. Multicast Routing Based on Hybrid Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    CAO Yuan-da; CAI Gui

    2005-01-01

    A new multicast routing algorithm based on the hybrid genetic algorithm (HGA) is proposed. The coding pattern based on the number of routing paths is used. A fitness function that is computed easily and makes algorithm quickly convergent is proposed. A new approach that defines the HGA's parameters is provided. The simulation shows that the approach can increase largely the convergent ratio, and the fitting values of the parameters of this algorithm are different from that of the original algorithms. The optimal mutation probability of HGA equals 0.50 in HGA in the experiment, but that equals 0.07 in SGA. It has been concluded that the population size has a significant influence on the HGA's convergent ratio when it's mutation probability is bigger. The algorithm with a small population size has a high average convergent rate. The population size has little influence on HGA with the lower mutation probability.

  8. A Genetic Algorithm-Based Feature Selection

    Directory of Open Access Journals (Sweden)

    Babatunde Oluleye

    2014-07-01

    Full Text Available This article details the exploration and application of Genetic Algorithm (GA for feature selection. Particularly a binary GA was used for dimensionality reduction to enhance the performance of the concerned classifiers. In this work, hundred (100 features were extracted from set of images found in the Flavia dataset (a publicly available dataset. The extracted features are Zernike Moments (ZM, Fourier Descriptors (FD, Lengendre Moments (LM, Hu 7 Moments (Hu7M, Texture Properties (TP and Geometrical Properties (GP. The main contributions of this article are (1 detailed documentation of the GA Toolbox in MATLAB and (2 the development of a GA-based feature selector using a novel fitness function (kNN-based classification error which enabled the GA to obtain a combinatorial set of feature giving rise to optimal accuracy. The results obtained were compared with various feature selectors from WEKA software and obtained better results in many ways than WEKA feature selectors in terms of classification accuracy

  9. [Genetic ecological monitoring in human populations: heterozygosity, mtDNA haplotype variation, and genetic load].

    Science.gov (United States)

    Balanovskiĭ, O P; Koshel', S M; Zaporozhchenko, V V; Pshenichnov, A S; Frolova, S A; Kuznetsova, M A; Baranova, E E; Teuchezh, I E; Kuznetsova, A A; Romashkina, M V; Utevskaia, O M; Churnosov, M I; Villems, R; Balanovskaia, E V

    2011-11-01

    Yu. P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

  10. Accelerating epistasis analysis in human genetics with consumer graphics hardware

    Directory of Open Access Journals (Sweden)

    Cancare Fabio

    2009-07-01

    performance while leaving the CPU available for other tasks. The GPU workstation containing three GPUs costs $2000 while obtaining similar performance on a Beowulf cluster requires 150 CPU cores which, including the added infrastructure and support cost of the cluster system, cost approximately $82,500. Conclusion Graphics hardware based computing provides a cost effective means to perform genetic analysis of epistasis using MDR on large datasets without the infrastructure of a computing cluster.

  11. A meta-learning system based on genetic algorithms

    Science.gov (United States)

    Pellerin, Eric; Pigeon, Luc; Delisle, Sylvain

    2004-04-01

    The design of an efficient machine learning process through self-adaptation is a great challenge. The goal of meta-learning is to build a self-adaptive learning system that is constantly adapting to its specific (and dynamic) environment. To that end, the meta-learning mechanism must improve its bias dynamically by updating the current learning strategy in accordance with its available experiences or meta-knowledge. We suggest using genetic algorithms as the basis of an adaptive system. In this work, we propose a meta-learning system based on a combination of the a priori and a posteriori concepts. A priori refers to input information and knowledge available at the beginning in order to built and evolve one or more sets of parameters by exploiting the context of the system"s information. The self-learning component is based on genetic algorithms and neural Darwinism. A posteriori refers to the implicit knowledge discovered by estimation of the future states of parameters and is also applied to the finding of optimal parameters values. The in-progress research presented here suggests a framework for the discovery of knowledge that can support human experts in their intelligence information assessment tasks. The conclusion presents avenues for further research in genetic algorithms and their capability to learn to learn.

  12. Function Optimization Based on Quantum Genetic Algorithm

    OpenAIRE

    Ying Sun; Hegen Xiong

    2014-01-01

    Optimization method is important in engineering design and application. Quantum genetic algorithm has the characteristics of good population diversity, rapid convergence and good global search capability and so on. It combines quantum algorithm with genetic algorithm. A novel quantum genetic algorithm is proposed, which is called Variable-boundary-coded Quantum Genetic Algorithm (vbQGA) in which qubit chromosomes are collapsed into variable-boundary-coded chromosomes instead of binary-coded c...

  13. Function Optimization Based on Quantum Genetic Algorithm

    OpenAIRE

    Ying Sun; Yuesheng Gu; Hegen Xiong

    2013-01-01

    Quantum genetic algorithm has the characteristics of good population diversity, rapid convergence and good global search capability and so on.It combines quantum algorithm with genetic algorithm. A novel quantum genetic algorithm is proposed ,which is called variable-boundary-coded quantum genetic algorithm (vbQGA) in which qubit chromosomes are collapsed into variableboundary- coded chromosomes instead of binary-coded chromosomes. Therefore much shorter chromosome strings can be gained.The m...

  14. Genetic and phenotypic consequences of introgression between humans and Neanderthals.

    Science.gov (United States)

    Wills, Christopher

    2011-01-01

    Strong evidence for introgression of Neanderthal genes into parts of the modern human gene pool has recently emerged. The evidence indicates that some populations of modern humans have received infusions of genes from two different groups of Neanderthals. One of these Neanderthal groups lived in the Middle East and Central Europe and the other group (the Denisovans) is known to have lived in Central Asia and was probably more widespread. This review examines two questions. First, how were these introgressions detected and what does the genetic evidence tell us about their nature and extent? We will see that an unknown but possibly large fraction of the entire Neanderthal gene complement may have survived in modern humans. Even though each modern European and Asian carries only a few percent of genes that can be traced back to Neanderthals, different individuals carry different subgroups of these introgressed genes. Second, what is the likelihood that this Neanderthal genetic legacy has had phenotypic effects on modern humans? We examine evidence for and against the possibility that some of the surviving fragments of Neanderthal genomes have been preserved by natural selection, and we explore the ways in which more evidence bearing on this question will become available in the future.

  15. Scaling up: human genetics as a Cold War network.

    Science.gov (United States)

    Lindee, Susan

    2014-09-01

    In this commentary I explore how the papers here illuminate the processes of collection that have been so central to the history of human genetics since 1945. The development of human population genetics in the Cold War period produced databases and biobanks that have endured into the present, and that continue to be used and debated. In the decades after the bomb, scientists collected and transferred human biological materials and information from populations of interest, and as they moved these biological resources or biosocial resources acquired new meanings and uses. The papers here collate these practices and map their desires and ironies. They explore how a large international network of geneticists, biological anthropologists, virologists and other physicians and scientists interacted with local informants, research subjects and public officials. They also track the networks and standards that mobilized the transfer of information, genealogies, tissue and blood samples. As Joanna Radin suggests here, the massive collections of human biological materials and data were often understood to be resources for an "as-yet-unknown" future. The stories told here contain elements of surveillance, extraction, salvage and eschatology.

  16. Human genetic differentiation across the Strait of Gibraltar

    Directory of Open Access Journals (Sweden)

    Sanchez-Mazas Alicia

    2010-08-01

    Full Text Available Abstract Background The Strait of Gibraltar is a crucial area in the settlement history of modern humans because it represents a possible connection between Africa and Europe. So far, genetic data were inconclusive about the fact that this strait constitutes a barrier to gene flow, as previous results were highly variable depending on the genetic locus studied. The present study evaluates the impact of the Gibraltar region in reducing gene flow between populations from North-Western Africa and South-Western Europe, by comparing formally various genetic loci. First, we compute several statistics of population differentiation. Then, we use an original simulation approach in order to infer the most probable evolutionary scenario for the settlement of the area, taking into account the effects of both demography and natural selection at some loci. Results We show that the genetic patterns observed today in the region of the Strait of Gibraltar may reflect an ancient population genetic structure which has not been completely erased by more recent events such as Neolithic migrations. Moreover, the differences observed among the loci (i.e. a strong genetic boundary revealed by the Y-chromosome polymorphism and, at the other extreme, no genetic differentiation revealed by HLA-DRB1 variation across the strait suggest specific evolutionary histories like sex-mediated migration and natural selection. By considering a model of balancing selection for HLA-DRB1, we here estimate a coefficient of selection of 2.2% for this locus (although weaker in Europe than in Africa, which is in line with what was estimated from synonymous versus non-synonymous substitution rates. Selection at this marker thus appears strong enough to leave a signature not only at the DNA level, but also at the population level where drift and migration processes were certainly relevant. Conclusions Our multi-loci approach using both descriptive analyses and Bayesian inferences lead to

  17. Common genetic variants influence human subcortical brain structures

    Science.gov (United States)

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  18. Cognitive radio resource allocation based on coupled chaotic genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    Zu Yun-Xiao; Zhou Jie; Zeng Chang-Chang

    2010-01-01

    A coupled chaotic genetic algorithm for cognitive radio resource allocation which is based on genetic algorithm and coupled Logistic map is proposed. A fitness function for cognitive radio resource allocation is provided. Simulations are conducted for cognitive radio resource allocation by using the coupled chaotic genetic algorithm, simple genetic algorithm and dynamic allocation algorithm respectively. The simulation results show that, compared with simple genetic and dynamic allocation algorithm, coupled chaotic genetic algorithm reduces the total transmission power and bit error rate in cognitive radio system, and has faster convergence speed.

  19. Cognitive radio resource allocation based on coupled chaotic genetic algorithm

    Science.gov (United States)

    Zu, Yun-Xiao; Zhou, Jie; Zeng, Chang-Chang

    2010-11-01

    A coupled chaotic genetic algorithm for cognitive radio resource allocation which is based on genetic algorithm and coupled Logistic map is proposed. A fitness function for cognitive radio resource allocation is provided. Simulations are conducted for cognitive radio resource allocation by using the coupled chaotic genetic algorithm, simple genetic algorithm and dynamic allocation algorithm respectively. The simulation results show that, compared with simple genetic and dynamic allocation algorithm, coupled chaotic genetic algorithm reduces the total transmission power and bit error rate in cognitive radio system, and has faster convergence speed.

  20. [Exploration on human blood type case in teaching practice of genetics].

    Science.gov (United States)

    Pi, Yan; Li, Xiao-Ying; Huai, Cong; Wang, Shi-Ming; Qiao, Shou-Yi; Lu, Da-Ru

    2013-08-01

    Blood type, which harbors abundant genetics meaning, is one of the most common phenotypes in human life. With the development of science and technology, its significance is unceasingly updated and new finding is increasingly emerging, which constantly attracts people to decipher the heredity mechanism of blood type. In addition to four main associated contents, i.e., Mendelian inheritance, genetic linkage, gene mutations, and chromosome abnormalities, the blood type case also covers many other aspects of the genetics knowledge. Based on the genetic knowledge context, we can interest the students and improve the teaching output in genetic teaching practice by combining with explaining ABO blood type case and heredity mechanism, expanding leucocyte groups, and introducing infrequent blood type such as Bombay blood, Rh and MN. By carrying out the related experimental teaching, we could drive the student to integrate theory with practice. In genetic experimental teaching, 80% of the students chose this optional experiment, molecular identification of ABO blood type, and it greatly interested them. Using appropriate blood type case in teaching related knowledge, organizing PPT exhi-bition and the debating discussion activities, it could provide opportunities for student to propose their own opinions, guide the student to thinking deeply, and develop their abilities to analyze and solve problem. Afterwards, students will gain in-depth comprehension about the fundamental knowledge of genetics.

  1. Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

    Directory of Open Access Journals (Sweden)

    D. Lemaire

    2012-05-01

    Full Text Available Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii population genetic differences that are a rationale behind group-targeted vaccines; iv an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data.

  2. Human copy number variation and complex genetic disease.

    Science.gov (United States)

    Girirajan, Santhosh; Campbell, Catarina D; Eichler, Evan E

    2011-01-01

    Copy number variants (CNVs) play an important role in human disease and population diversity. Advancements in technology have allowed for the analysis of CNVs in thousands of individuals with disease in addition to thousands of controls. These studies have identified rare CNVs associated with neuropsychiatric diseases such as autism, schizophrenia, and intellectual disability. In addition, copy number polymorphisms (CNPs) are present at higher frequencies in the population, show high diversity in copy number, sequence, and structure, and have been associated with multiple phenotypes, primarily related to immune or environmental response. However, the landscape of copy number variation still remains largely unexplored, especially for smaller CNVs and those embedded within complex regions of the human genome. An integrated approach including characterization of single nucleotide variants and CNVs in a large number of individuals with disease and normal genomes holds the promise of thoroughly elucidating the genetic basis of human disease and diversity.

  3. Genetic engineering of human embryonic stem cells with lentiviral vectors.

    Science.gov (United States)

    Xiong, Chen; Tang, Dong-Qi; Xie, Chang-Qing; Zhang, Li; Xu, Ke-Feng; Thompson, Winston E; Chou, Wayne; Gibbons, Gary H; Chang, Lung-Ji; Yang, Li-Jun; Chen, Yuqing E

    2005-08-01

    Human embryonic stem (hES) cells present a valuable source of cells with a vast therapeutic potential. However, the low efficiency of directed differentiation of hES cells remains a major obstacle in their uses for regenerative medicine. While differentiation may be controlled by the genetic manipulation, effective and efficient gene transfer into hES cells has been an elusive goal. Here, we show stable and efficient genetic manipulations of hES cells using lentiviral vectors. This method resulted in the establishment of stable gene expression without loss of pluripotency in hES cells. In addition, lentiviral vectors were effective in conveying the expression of an U6 promoter-driven small interfering RNA (siRNA), which was effective in silencing its specific target. Taken together, our results suggest that lentiviral gene delivery holds great promise for hES cell research and application.

  4. Oxytocin receptor genetic variation promotes human trust behavior

    Directory of Open Access Journals (Sweden)

    Frank eKrueger

    2012-02-01

    Full Text Available Given that human trust behavior is heritable and intranasal administration of oxytocin enhances trust, the oxytocin receptor (OXTR gene is an excellent candidate to investigate genetic contributions to individual variations in trust behavior. Although a single-nucleotide polymorphism involving an adenine (A/ guanine (G transition (rs53576 has been associated with socio-emotional phenotypes, its link to trust behavior is unclear. We combined genotyping of healthy male students with the administration of a trust game experiment. Our results show that a naturally occurring genetic variation (rs53576 in the OXTR gene is reliably associated with trust behavior rather than a general increase in trustworthy or risk behaviors. Individuals homozygous for the G allele (GG showed higher trust behavior than individuals with A allele carriers (AA/AG. Although the molecular functionality of this polymorphism is still unknown, future research should clarify how the OXTR gene interacts with other genes and the environment in promoting socio-emotional behaviors.

  5. Genetics of the dentofacial variation in human malocclusion.

    Science.gov (United States)

    Moreno Uribe, L M; Miller, S F

    2015-04-01

    Malocclusions affect individuals worldwide, resulting in compromised function and esthetics. Understanding the etiological factors contributing to the variation in dentofacial morphology associated with malocclusions is the key to develop novel treatment approaches. Advances in dentofacial phenotyping, which is the comprehensive characterization of hard and soft tissue variation in the craniofacial complex, together with the acquisition of large-scale genomic data have started to unravel genetic mechanisms underlying facial variation. Knowledge on the genetics of human malocclusion is limited even though results attained thus far are encouraging, with promising opportunities for future research. This review summarizes the most common dentofacial variations associated with malocclusions and reviews the current knowledge of the roles of genes in the development of malocclusions. Lastly, this review will describe ways to advance malocclusion research, following examples from the expanding fields of phenomics and genomic medicine, which aim to better patient outcomes.

  6. Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

    Directory of Open Access Journals (Sweden)

    Shuji Mizumoto

    2014-01-01

    Full Text Available Glycosaminoglycans (GAGs are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs.

  7. Genetic variation in lipid desaturases and its impact on the development of human disease

    Directory of Open Access Journals (Sweden)

    Mutch David M

    2010-06-01

    Full Text Available Abstract Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2 and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

  8. Predicting human genetic interactions from cancer genome evolution.

    Directory of Open Access Journals (Sweden)

    Xiaowen Lu

    Full Text Available Synthetic Lethal (SL genetic interactions play a key role in various types of biological research, ranging from understanding genotype-phenotype relationships to identifying drug-targets against cancer. Despite recent advances in empirical measuring SL interactions in human cells, the human genetic interaction map is far from complete. Here, we present a novel approach to predict this map by exploiting patterns in cancer genome evolution. First, we show that empirically determined SL interactions are reflected in various gene presence, absence, and duplication patterns in hundreds of cancer genomes. The most evident pattern that we discovered is that when one member of an SL interaction gene pair is lost, the other gene tends not to be lost, i.e. the absence of co-loss. This observation is in line with expectation, because the loss of an SL interacting pair will be lethal to the cancer cell. SL interactions are also reflected in gene expression profiles, such as an under representation of cases where the genes in an SL pair are both under expressed, and an over representation of cases where one gene of an SL pair is under expressed, while the other one is over expressed. We integrated the various previously unknown cancer genome patterns and the gene expression patterns into a computational model to identify SL pairs. This simple, genome-wide model achieves a high prediction power (AUC = 0.75 for known genetic interactions. It allows us to present for the first time a comprehensive genome-wide list of SL interactions with a high estimated prediction precision, covering up to 591,000 gene pairs. This unique list can potentially be used in various application areas ranging from biotechnology to medical genetics.

  9. Genetic tracking of mice and other bioproxies to infer human history.

    Science.gov (United States)

    Jones, Eleanor P; Eager, Heidi M; Gabriel, Sofia I; Jóhannesdóttir, Fríða; Searle, Jeremy B

    2013-05-01

    The long-distance movements made by humans through history are quickly erased by time but can be reconstructed by studying the genetic make-up of organisms that travelled with them. The phylogeography of the western house mouse (Mus musculus domesticus), whose current widespread distribution around the world has been caused directly by the movements of (primarily) European people, has proved particularly informative in a series of recent studies. The geographic distributions of genetic lineages in this commensal have been linked to the Iron Age movements within the Mediterranean region and Western Europe, the extensive maritime activities of the Vikings in the 9th to 11th centuries, and the colonisation of distant landmasses and islands by the Western European nations starting in the 15th century. We review here recent insights into human history based on phylogeographic studies of mice and other species that have travelled with humans, and discuss how emerging genomic methodologies will increase the precision of these inferences.

  10. A genetic basis for mechanosensory traits in humans.

    Science.gov (United States)

    Frenzel, Henning; Bohlender, Jörg; Pinsker, Katrin; Wohlleben, Bärbel; Tank, Jens; Lechner, Stefan G; Schiska, Daniela; Jaijo, Teresa; Rüschendorf, Franz; Saar, Kathrin; Jordan, Jens; Millán, José M; Gross, Manfred; Lewin, Gary R

    2012-01-01

    In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.

  11. A genetic basis for mechanosensory traits in humans.

    Directory of Open Access Journals (Sweden)

    Henning Frenzel

    Full Text Available In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.

  12. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation.

  13. Liberal or Conservative? Genetic Rhetoric, Disability, and Human Species Modification

    Directory of Open Access Journals (Sweden)

    Christopher F. Goodey

    2016-11-01

    Full Text Available A certain political rhetoric is implicit and sometimes explicit in the advocacy of human genetic modification (indicating here both the enhancement and the prevention of disability. The main claim is that it belongs to a liberal tradition. From a perspective supplied by the history and philosophy of science rather than by ethics, the content of that claim is examined to see if such a self-description is justified. The techniques are analyzed by which apparently liberal arguments get to be presented as “reasonable” in a juridical sense that draws on theories of law and rhetoric.

  14. Genetics and Human Agency: Comment on Dar-Nimrod and Heine (2011)

    Science.gov (United States)

    Turkheimer, Eric

    2011-01-01

    Dar-Nimrod and Heine (2011) decried genetic essentialism without denying the importance of genetics in the genesis of human behavior, and although I agree on both counts, a deeper issue remains unaddressed: how should we adjust our cognitions about our own behavior in light of genetic influence, or is it perhaps not necessary to take genetics into…

  15. Web Based Genetic Algorithm Using Data Mining

    Directory of Open Access Journals (Sweden)

    Ashiqur Rahman

    2016-09-01

    Full Text Available This paper presents an approach for classifying students in order to predict their final grade based on features extracted from logged data in an education web-based system. A combination of multiple classifiers leads to a significant improvement in classification performance. Through weighting the feature vectors using a Genetic Algorithm we can optimize the prediction accuracy and get a marked improvement over raw classification. It further shows that when the number of features is few; feature weighting is works better than just feature selection. Many leading educational institutions are working to establish an online teaching and learning presence. Several systems with different capabilities and approaches have been developed to deliver online education in an academic setting. In particular, Michigan State University (MSU has pioneered some of these systems to provide an infrastructure for online instruction. The research presented here was performed on a part of the latest online educational system developed at MSU, the Learning Online Network with Computer-Assisted Personalized Approach (LON-CAPA

  16. Indiana Health Science Teachers: Their Human Genetics/Bioethics Educational Needs.

    Science.gov (United States)

    Hendrix, Jon R.; And Others

    1982-01-01

    Results from a human genetics/bioethics needs assessment questionnaire (N = 124 out of 300) mailed to Indiana health teachers are reported. Genetic topics and human genetic diseases/defects included in health science instruction are listed in two tables. Responses to 16 science/society statements (and statements themselves) are also reported. (SK)

  17. Design and analysis in genetic studies of human ageing and longevity.

    Science.gov (United States)

    Tan, Qihua; Kruse, Torben A; Christensen, Kaare

    2006-11-01

    With the success of the Human Genome Project and taking advantage of the recent developments in high-throughput genotyping techniques as well as in functional genomics, it is now feasible to collect vast quantities of genetic data with the aim of deciphering the genetics of human complex traits. As a result, the amount of research on human ageing and longevity has been growing rapidly in recent years. The situation raises questions concerning efficient choice of study population, sampling schemes, and methods of data analysis. In this article, we summarize the key issues in genetic studies of human ageing and longevity ranging from research design to statistical analyses. We discuss the virtues and drawbacks of the multidisciplinary approaches including the population-based cross-sectional and cohort studies, family-based linkage analysis, and functional genomics studies. Different analytical approaches are illustrated with their performances compared. In addition, important research topics are highlighted together with experiment design and data analyzing issues to serve as references for future studies.

  18. Genetic mapping of complex discrete human diseases by discriminant analysis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The objective of the present study is to propose and evaluate a novel multivariate approach for genetic mapping of complex categorical diseases. This approach results from an application of standard stepwise discriminant analysis to detect linkage based on the differential marker identity-by-descent (IBD) distributions among the different groups of sib pairs. Two major advantages of this method are that it allows for simultaneously testing all markers, together with other genetic and environmental factors in a single multivariate setting and it avoids explicitly modeling the complex relationship between the affection status of sib pairs and the underlying genetic determinants. The efficiency and properties of the method are demonstrated via simulations. The proposed multivariate approach has successfully located the true position(s) under various genetic scenarios. The more important finding is that using highly densely spaced markers (1~2 cM) leads to only a marginal loss of statistical efficiency of the proposed methods in terms of gene localization and statistical power. These results have well established its utility and advantages as a fine-mapping tool. A unique property of the proposed method is the ability to map multiple linked trait loci to their precise positions due to its sequential nature, as demonstrated via simulations.

  19. Genetic control of human brain transcript expression in Alzheimer disease.

    Science.gov (United States)

    Webster, Jennifer A; Gibbs, J Raphael; Clarke, Jennifer; Ray, Monika; Zhang, Weixiong; Holmans, Peter; Rohrer, Kristen; Zhao, Alice; Marlowe, Lauren; Kaleem, Mona; McCorquodale, Donald S; Cuello, Cindy; Leung, Doris; Bryden, Leslie; Nath, Priti; Zismann, Victoria L; Joshipura, Keta; Huentelman, Matthew J; Hu-Lince, Diane; Coon, Keith D; Craig, David W; Pearson, John V; Heward, Christopher B; Reiman, Eric M; Stephan, Dietrich; Hardy, John; Myers, Amanda J

    2009-04-01

    We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

  20. Complement regulators in human disease: lessons from modern genetics.

    Science.gov (United States)

    K Liszewski, M; Atkinson, J P

    2015-03-01

    First identified in human serum in the late 19th century as a 'complement' to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating 'hyperinflammatory complement phenotypes'. To treat these 'complementopathies', a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.

  1. Psychological aspects of human cloning and genetic manipulation: the identity and uniqueness of human beings.

    Science.gov (United States)

    Morales, N M

    2009-01-01

    Human cloning has become one of the most controversial debates about reproduction in Western civilization. Human cloning represents asexual reproduction, but the critics of human cloning argue that the result of cloning is not a new individual who is genetically unique. There is also awareness in the scientific community, including the medical community, that human cloning and the creation of clones are inevitable. Psychology and other social sciences, together with the natural sciences, will need to find ways to help the healthcare system, to be prepared to face the new challenges introduced by the techniques of human cloning. One of those challenges is to help the healthcare system to find specific standards of behaviour that could be used to help potential parents to interact properly with cloned babies or children created through genetic manipulation. In this paper, the concepts of personality, identity and uniqueness are discussed in relationship to the contribution of twin studies in these areas. The author argues that an individual created by human cloning techniques or any other type of genetic manipulation will not show the donor's characteristics to the extent of compromising uniqueness. Therefore, claims to such an effect are needlessly alarmist.

  2. Enfermedades de base genética Genetically based diseases

    Directory of Open Access Journals (Sweden)

    D. González-Lamuño

    2008-01-01

    Full Text Available La genética constituye uno de los mayores avances científicos del siglo XX, que comienza con el redescubrimiento de las leyes de Mendel y termina con la elaboración del primer "borrador" de la secuencia completa del genoma humano. La genética utiliza diferentes estrategias de investigación, como los estudios de gemelos y de adopción, que investigan la influencia de los factores genéticos y ambientales, y las estrategias para identificar genes específicos (genética molecular. Además del importante grado de discapacidad que generan, el impacto social de las enfermedades hereditarias es enorme, por su carácter potencialmente recurrente en una misma familia y por el elevado coste socio-sanitario derivado de la enorme carga de cuidados que requiere. El diagnóstico de las enfermedades hereditarias presenta características diferenciadoras muy significativas ya que el resultado de un diagnóstico genético tiene no sólo efectos sobre el paciente sino también sobre todos los individuos emparentados. Por tanto, la unidad de estudio en el diagnóstico genético es la familia y todo proceso de diagnóstico implica una investigación familiar. También conviene tener en cuenta que los protocolos de diagnóstico se desarrollan de forma paralela a la investigación básica y generalmente están poco estandarizados. Los resultados obtenidos en los estudios genéticos y el tipo de información que se facilita al paciente y a su familia deben ser matizados dentro del proceso del "consejo genético".Genetics is one of the greatest scientific advances of the XX century, which begins with the rediscovery of Mendel’s laws and culminates in the elaboration of the first "draft" of the complete sequence of the human genome. Genetics employs different research strategies, such as the study of twins and adoption, investigating the influence of genetic and environmental factors, and strategies for identifying specific genes (molecular genetics. Besides the

  3. Blood groups and human groups: collecting and calibrating genetic data after World War Two.

    Science.gov (United States)

    Bangham, Jenny

    2014-09-01

    Arthur Mourant's The Distribution of the Human Blood Groups (1954) was an "indispensable" reference book on the "anthropology of blood groups" containing a vast collection of human genetic data. It was based on the results of blood-grouping tests carried out on half-a-million people and drew together studies on diverse populations around the world: from rural communities, to religious exiles, to volunteer transfusion donors. This paper pieces together sequential stages in the production of a small fraction of the blood-group data in Mourant's book, to examine how he and his colleagues made genetic data from people. Using sources from several collecting projects, I follow how blood was encountered, how it was inscribed, and how it was turned into a laboratory resource. I trace Mourant's analytical and representational strategies to make blood groups both credibly 'genetic' and understood as relevant to human ancestry, race and history. In this story, 'populations' were not simply given, but were produced through public health, colonial and post-colonial institutions, and by the labour and expertise of subjects, assistants and mediators. Genetic data were not self-evidently 'biological', but were shaped by existing historical and geographical identities, by political relationships, and by notions of kinship and belonging.

  4. G protein-coupled receptor mutations and human genetic disease.

    Science.gov (United States)

    Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

    2014-01-01

    Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

  5. Human KIR repertoires: shaped by genetic diversity and evolution.

    Science.gov (United States)

    Manser, Angela R; Weinhold, Sandra; Uhrberg, Markus

    2015-09-01

    Killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals' immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I-encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types.

  6. Somatic retrotransposition alters the genetic landscape of the human brain.

    Science.gov (United States)

    Baillie, J Kenneth; Barnett, Mark W; Upton, Kyle R; Gerhardt, Daniel J; Richmond, Todd A; De Sapio, Fioravante; Brennan, Paul M; Rizzu, Patrizia; Smith, Sarah; Fell, Mark; Talbot, Richard T; Gustincich, Stefano; Freeman, Thomas C; Mattick, John S; Hume, David A; Heutink, Peter; Carninci, Piero; Jeddeloh, Jeffrey A; Faulkner, Geoffrey J

    2011-10-30

    Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.

  7. Human impact on genetic diversity of Toxoplasma gondii: example of the anthropized environment from French Guiana.

    Science.gov (United States)

    Mercier, A; Ajzenberg, D; Devillard, S; Demar, M P; de Thoisy, B; Bonnabau, H; Collinet, F; Boukhari, R; Blanchet, D; Simon, S; Carme, B; Dardé, M-L

    2011-08-01

    In French Guiana, severe cases of toxoplasmosis in immunocompetent patients are associated with atypical strains of Toxoplasma gondii linked to a wild neotropical rainforest cycle and a higher genetic diversity than usually observed for T. gondii isolates from anthropized environment. This raises the question of the impact of anthropization of the natural environment, on genetic diversity and on the population structure of T. gondii. However, few data are available on strains circulating in the anthropized areas from French Guiana. Seropositive animals originating mainly from anthropized sub-urban areas and punctually from wild environment in French Guiana were analyzed for T. gondii isolation and genotyping. Thirty-three strains were obtained by bioassay in mice and compared with 18 previously reported isolates chiefly originating from the Amazon rainforest. The genotyping analysis performed with 15 microsatellite markers located on 12 different chromosomes revealed a lower genetic diversity in the anthropized environment. Results were analyzed in terms of population structure by clustering methods, Neighbor-joining trees reconstruction based on genetic distances, F(ST,) Mantel's tests and linkage disequilibrium. They clearly showed a genetic differentiation between strains associated to the anthropized environment and those associated to the wild, but with some inbreeding between them. The majority of strains from the anthropized environment were clustered into additional lineages of T. gondii that are common in the Caribbean. In conclusion the two environmental populations "wild" and "anthropized" were genetically well differentiated. The anthropization of the environment seems to be accompanied with a decreased diversity of T. gondii associated with a greater structure of the populations. We detected potential interpenetration and genetic exchanges between these two environmental populations. As a higher pathogenicity in human of "wild" genotypes has been

  8. Soybean parent selection based on genetic diversity

    Directory of Open Access Journals (Sweden)

    Valéria Carpentieri-Pípolo

    2000-01-01

    Full Text Available Thirty-four soybean lines were assessed for twelve traits. The genetic distances were estimates using multivariate techniques, to identify parents to be included in breeding programs for hybridization. Grouping by the Tocher method, from generalized Mahalanobis distances, divided the 34 lines into four groups. The most important agronomic traits, weight of seeds per plot, plant height, height of first pod and days to maturity were considered when recommending for crossing. The following crosses were recommended based on the genetic divergence and the key agronomic traits: lines 23, 10, 2, 27 and 25 (group I with genotype 6 (group II and genotype 16 (group III. Thus only ten crosses would be made, representing only 2% of the total crosses which could be made in the partial diallel among the 34 lines assessed, which would allow up to 561 combinations.Trinta e quatro linhagens de soja foram avaliadas para doze características. As distâncias genéticas foram estimadas utilizando técnicas multivariadas com objetivo de identificar parentais a serem incluidos em um programa de melhoramento envolvendo hibridação. O agrupamento pelo método de Tocher, a partir das distâncias generalizadas de Mahalanobis, dividiu as 34 linhagens em 4 grupos. As caracterísiticas agronômicas mais importantes, peso de sementes por parcela, altura de planta, altura da primeira vagem e dias para maturação foram consideradas para a recomendação dos cruzamentos. Os seguintes cruzamentos foram recomendados baseado na divergência genética e nas características agronômicas chave: linhagens 23, 10, 2, 27 e 25 (grupo I com genótipo 6 (grupoII e com o genótipo 16 (grupo III. Portanto somente 10 cruzamentos poderiam ser realizados representando somente 2% do total de cruzamentos qu poderiam ser realizados em um dialelo parcial entre as 34 linhagens avaliadas as quais admitiriam até 561 combinações.

  9. 76 FR 28439 - Submission for OMB Review; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

    Science.gov (United States)

    2011-05-17

    ... HUMAN SERVICES National Institutes of Health Submission for OMB Review; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer Summary: Under the provisions of... Collection: Title: NCI Cancer Genetics Services Directory Web-based Application Form and Update Mailer....

  10. Efficient derivation and genetic modifications of human pluripotent stem cells on engineered human feeder cell lines.

    Science.gov (United States)

    Zou, Chunlin; Chou, Bin-Kuan; Dowey, Sarah N; Tsang, Kitman; Huang, Xiaosong; Liu, Cyndi F; Smith, Cory; Yen, Jonathan; Mali, Prashant; Zhang, Yu Alex; Cheng, Linzhao; Ye, Zhaohui

    2012-08-10

    Derivation of pluripotent stem cells (iPSCs) induced from somatic cell types and the subsequent genetic modifications of disease-specific or patient-specific iPSCs are crucial steps in their applications for disease modeling as well as future cell and gene therapies. Conventional procedures of these processes require co-culture with primary mouse embryonic fibroblasts (MEFs) to support self-renewal and clonal growth of human iPSCs as well as embryonic stem cells (ESCs). However, the variability of MEF quality affects the efficiencies of all these steps. Furthermore, animal sourced feeders may hinder the clinical applications of human stem cells. In order to overcome these hurdles, we established immortalized human feeder cell lines by stably expressing human telomerase reverse transcriptase, Wnt3a, and drug resistance genes in adult mesenchymal stem cells. Here, we show that these immortalized human feeders support efficient derivation of virus-free, integration-free human iPSCs and long-term expansion of human iPSCs and ESCs. Moreover, the drug-resistance feature of these feeders also supports nonviral gene transfer and expression at a high efficiency, mediated by piggyBac DNA transposition. Importantly, these human feeders exhibit superior ability over MEFs in supporting homologous recombination-mediated gene targeting in human iPSCs, allowing us to efficiently target a transgene into the AAVS1 safe harbor locus in recently derived integration-free iPSCs. Our results have great implications in disease modeling and translational applications of human iPSCs, as these engineered human cell lines provide a more efficient tool for genetic modifications and a safer alternative for supporting self-renewal of human iPSCs and ESCs.

  11. Genetic and Environmental Bases of Reading and Spelling: A Unified Genetic Dual Route Model

    Science.gov (United States)

    Bates, Timothy C.; Castles, Anne; Luciano, Michelle; Wright, Margaret J.; Coltheart, Max; Martin, Nicholas G.

    2007-01-01

    We develop and test a dual-route model of genetic effects on reading aloud and spelling, based on irregular and non-word reading and spelling performance assessed in 1382 monozygotic and dizygotic twins. As in earlier research, most of the variance in reading was due to genetic effects. However, there were three more specific conclusions: the…

  12. Building capacity for human genetics and genomics research in Trinidad and Tobago

    Science.gov (United States)

    Roach, Allana; Warner, Wayne A.; Llanos, Adana A. M.

    2016-01-01

    Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well-known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations) that is informed by public health needs and contextual realities of the nation. PMID:26837529

  13. Human teratogens and genetic phenocopies. Understanding pathogenesis through human genes mutation.

    Science.gov (United States)

    Cassina, Matteo; Cagnoli, Giulia A; Zuccarello, Daniela; Di Gianantonio, Elena; Clementi, Maurizio

    2017-01-01

    Exposure to teratogenic drugs during pregnancy is associated with a wide range of embryo-fetal anomalies and sometimes results in recurrent and recognizable patterns of malformations; however, the comprehension of the mechanisms underlying the pathogenesis of drug-induced birth defects is difficult, since teratogenesis is a multifactorial process which is always the result of a complex interaction between several environmental factors and the genetic background of both the mother and the fetus. Animal models have been extensively used to assess the teratogenic potential of pharmacological agents and to study their teratogenic mechanisms; however, a still open issue concerns how the information gained through animal models can be translated to humans. Instead, significant information can be obtained by the identification and analysis of human genetic syndromes characterized by clinical features overlapping with those observed in drug-induced embryopathies. Until now, genetic phenocopies have been reported for the embryopathies/fetopathies associated with prenatal exposure to warfarin, leflunomide, mycophenolate mofetil, fluconazole, thalidomide and ACE inhibitors. In most cases, genetic phenocopies are caused by mutations in genes encoding for the main targets of teratogens or for proteins belonging to the same molecular pathways. The aim of this paper is to review the proposed teratogenic mechanisms of these drugs, by the analysis of human monogenic disorders and their molecular pathogenesis.

  14. UNDERSTANDING THE HIGH MIND: HUMANS ARE STILL EVOLVING GENETICALLY

    Directory of Open Access Journals (Sweden)

    Blum K et al

    2011-01-01

    Full Text Available The total population of the United States at the turn of the 21 st century was 281,421,906. The total number of people above the age of 12 years old was estimated at 249 million. The National Institutes on Drug Abuse and the Substance Abuse and Mental Health Services Administration (SAMHSA have surveyed persons age 12 and older and found that in the year 2001, a total of 104 million people have used illegal drugs in their life (ever used, 32 million used a psychoactive drug in the past year (2000-2001 and 18 million used a psychoactive drug in the past 30 days. Interestingly this does not include Alcohol. We must ask then, who are the people that could just say NO? When almost half-of the US population have indulged in illegal drug practices, when our presidential candidates are forced to dodge the tricky question of their past history involving illegal drug use, and when almost every American has sloshed down a martini or two in their life time, there must be a reason, there must be a need, there must be a natural response for humans to imbibe at such high rates. There is even a more compelling question surrounding the millions who seek out high risk novelty. Why do millions have this innate drive in face of putting themselves in harms-way? Why are millions paying the price of their indiscretions in our jails, in hospitals, in wheel chairs and are lying dead in our cemeteries. What price must we pay for pleasure seeking or just plain getting “HIGH”? Maybe the answer lies within our brain. Maybe it is in our genome? Utilization of the candidate vs the common variant approach may be parsimonious as it relates to unraveling the addiction riddle. In this commentary we have discussed evidence, theories and conjecture about the “High Mind” and its relationship to evolutionary genetics and drug seeking behavior as impacted by genetic polymorphisms. We consider the meaning of recent findings in genetic research including an exploration of the

  15. Stable genetic modification of human embryonic stem cells by lentiviral vectors.

    Science.gov (United States)

    Gropp, Michal; Itsykson, Pavel; Singer, Orna; Ben-Hur, Tamir; Reinhartz, Etti; Galun, Eithan; Reubinoff, Benjamin E

    2003-02-01

    Human embryonic stem (hES) cells are pluripotent cells derived from the inner cell mass of the early preimplantation embryo. An efficient strategy for stable genetic modification of hES cells may be highly valuable for manipulating the cells in vitro and may promote the study of hES cell biology, human embryogenesis, and the development of cell-based therapies. Here, we demonstrate that vectors derived from self-inactivating (SIN) human immunodeficiency virus type 1 (HIV-1) are efficient tools for stable genetic modification of hES cells. Transduction of hES cells by a modified vector derived from SIN HIV-1 and containing the woodchuck hepatitis regulatory element (WPRE) and the central polypurine tract (cPPT) sequence facilitated stable transgene expression during prolonged (38 weeks) undifferentiated proliferation in vitro. Southern blot analysis revealed that the viral vector had integrated into the host cells' DNA. Transgene expression was maintained throughout differentiation into progeny of all three germ layers both in vitro and in vivo in teratomas. Thus, the transduced hES cells retained the capability for self-renewal and their pluripotent potential. Genetic modification of hES cells by lentiviral vectors provides a powerful tool for basic and applied research in the area of human ES cells.

  16. [The genetic bases of neurodevelopmental disorders].

    Science.gov (United States)

    Artigas-Pallarés, Josep; Guitart, Miriam; Gabau-Vila, Elisabeth

    2013-02-22

    In the last decade, progress made in genetics is questioning the current implicit nosological model in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) and the International Classification of Diseases, tenth revision. Both the categorical nature and the comorbidity detected on applying diagnostic criteria become unsustainable in the light of the genetic architecture that is emerging from studies being conducted on the genetics of mental disorders. The classical paradigms -one gene for one disease- or even a specific distinctive genetic pattern for each condition, are concepts restricted to specific cases. In this review the objective is to describe the current scenario that has arisen following the latest advances in genetics. The lines of work being traced by research both in the present and in the near future include: the identification of variations in the number of copies (both frequent and rare), indiscriminately linked to different disorders; the concurrence of multiple variants for a single disorder; the double hit phenomenon; and epigenetic modulation. The new version of the DSM, fully aware of the deficiencies in the current model, will mark a turning point that, while somewhat timid, is decidedly oriented towards incorporating a dimensional conception of mental disorders.

  17. Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

    Directory of Open Access Journals (Sweden)

    Hilda Montero

    2012-01-01

    Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.

  18. Genetic diversity of human blastocystis isolates in khorramabad, central iran.

    Directory of Open Access Journals (Sweden)

    Ebrahim Badparva

    2014-03-01

    Full Text Available There are some genetic differences in Blastocystis that show the existence of species or genotypes. One of these genes that help in identifying Blastocystis is SSUrRNA. The aim of this study was assessment of genetic diversity of Blastocystis by PCR with seven pairs of STS primers.This study was done on 511 stool samples collected from patients referred to the health care centers of Khorramabad, Central Iran, in 2012. Genomic DNA was extracted and in order to determine the Blastocystis subtype in contaminated samples, seven pairs of primers STS (subtype specific sequence-tagged site were used.Out of 511 samples, 33 (6.5% samples were infected with Blastocystis. Subtype (ST of 30 samples was identified and three subtypes 2, 3 and 4 were determined. Mix infection was reported 10% which 3.33% of the infection was for the mixture of ST 3 and ST5 and 6.67% was for the mixture of ST 2 and ST 3.The predominant subtype was ST3 that is the main human subtype. The dominance of ST2 and 5 are important in this study. This superiority has been reported in some of the studies in ST 2 which is different from the studies in other countries, because they have announced priorities of the ST1 and ST6 after ST3.

  19. Correlation of physical and genetic maps of human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, G.R.

    1991-01-01

    This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentially 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.

  20. A personification heuristic Genetic Algorithm for Digital Microfluidics-based Biochips Placement

    Directory of Open Access Journals (Sweden)

    Jingsong Yang

    2013-06-01

    Full Text Available A personification heuristic Genetic Algorithm is established for the placement of digital microfluidics-based biochips, in which, the personification heuristic algorithm is used to control the packing process, while the genetic algorithm is designed to be used in multi-objective placement results optimizing. As an example, the process of microfluidic module physical placement in multiplexed in-vitro diagnostics on human physiological fluids is simulated. The experiment results show that personification heuristic genetic algorithm can achieve better results in multi-objective optimization, compare to the parallel recombinative simulated annealing algorithm.

  1. Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation

    Directory of Open Access Journals (Sweden)

    Shriver Mark D

    2005-06-01

    Full Text Available Abstract Understanding the distribution of human genetic variation is an important foundation for research into the genetics of common diseases. Some of the alleles that modify common disease risk are themselves likely to be common and, thus, amenable to identification using gene-association methods. A problem with this approach is that the large sample sizes required for sufficient statistical power to detect alleles with moderate effect make gene-association studies susceptible to false-positive findings as the result of population stratification 12. Such type I errors can be eliminated by using either family-based association tests or methods that sufficiently adjust for population stratification 345. These methods require the availability of genetic markers that can detect and, thus, control for sources of genetic stratification among populations. In an effort to investigate population stratification and identify appropriate marker panels, we have analysed 11,555 single nucleotide polymorphisms in 203 individuals from 12 diverse human populations. Individuals in each population cluster to the exclusion of individuals from other populations using two clustering methods. Higher-order branching and clustering of the populations are consistent with the geographic origins of populations and with previously published genetic analyses. These data provide a valuable resource for the definition of marker panels to detect and control for population stratification in population-based gene identification studies. Using three US resident populations (European-American, African-American and Puerto Rican, we demonstrate how such studies can proceed, quantifying proportional ancestry levels and detecting significant admixture structure in each of these populations.

  2. Pigmentation, pleiotropy, and genetic pathways in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Barsh, G.S. [Stanford Univ., CA (United States)

    1995-10-01

    Some of the most striking polymorphisms in human populations affect the color of our eyes, hair, or skin. Despite some simple lessons from high school biology (blue eyes are recessive; brown are dominant), the genetic basis of such phenotypic variability has, for the most part, eluded Mendelian description. A logical place to search for the keys to understanding common variation in human pigmentation are genes in which defects cause uncommon conditions such as albinism or piebaldism. The area under this lamppost has recently gotten larger, with two articles, one in this issue of the Journal, that describe the map position for Hermansky-Pudlak syndrome (HPS) and with the recent cloning of a gene that causes X-linked ocular albinism (OA1). In addition, a series of three recent articles in Cell demonstrate (1) that defects in the gene encoding the endothelin B (ET{sub B}) receptor cause hypopigmentation and Hirschsprung disease in a Mennonite population and the mouse mutation piebald(s) and (2) that a defect in the edn3 gene, which encodes one of the ligands for the ET{sub B} receptor, causes the lethal spotting (ls) mouse mutation. 47 refs., 1 fig.

  3. Cat Mammary Tumors: Genetic Models for the Human Counterpart

    Directory of Open Access Journals (Sweden)

    Filomena Adega

    2016-08-01

    Full Text Available The records are not clear, but Man has been sheltering the cat inside his home for over 12,000 years. The close proximity of this companion animal, however, goes beyond sharing the same roof; it extends to the great similarity found at the cellular and molecular levels. Researchers have found a striking resemblance between subtypes of feline mammary tumors and their human counterparts that goes from the genes to the pathways involved in cancer initiation and progression. Spontaneous cat mammary pre-invasive intraepithelial lesions (hyperplasias and neoplasias and malignant lesions seem to share a wide repertoire of molecular features with their human counterparts. In the present review, we tried to compile all the genetics aspects published (i.e., chromosomal alterations, critical cancer genes and their expression regarding cat mammary tumors, which support the cat as a valuable alternative in vitro cell and animal model (i.e., cat mammary cell lines and the spontaneous tumors, respectively, but also to present a critical point of view of some of the issues that really need to be investigated in future research.

  4. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum.

    Science.gov (United States)

    Gieger, Christian; Geistlinger, Ludwig; Altmaier, Elisabeth; Hrabé de Angelis, Martin; Kronenberg, Florian; Meitinger, Thomas; Mewes, Hans-Werner; Wichmann, H-Erich; Weinberger, Klaus M; Adamski, Jerzy; Illig, Thomas; Suhre, Karsten

    2008-11-01

    The rapidly evolving field of metabolomics aims at a comprehensive measurement of ideally all endogenous metabolites in a cell or body fluid. It thereby provides a functional readout of the physiological state of the human body. Genetic variants that associate with changes in the homeostasis of key lipids, carbohydrates, or amino acids are not only expected to display much larger effect sizes due to their direct involvement in metabolite conversion modification, but should also provide access to the biochemical context of such variations, in particular when enzyme coding genes are concerned. To test this hypothesis, we conducted what is, to the best of our knowledge, the first GWA study with metabolomics based on the quantitative measurement of 363 metabolites in serum of 284 male participants of the KORA study. We found associations of frequent single nucleotide polymorphisms (SNPs) with considerable differences in the metabolic homeostasis of the human body, explaining up to 12% of the observed variance. Using ratios of certain metabolite concentrations as a proxy for enzymatic activity, up to 28% of the variance can be explained (p-values 10(-16) to 10(-21)). We identified four genetic variants in genes coding for enzymes (FADS1, LIPC, SCAD, MCAD) where the corresponding metabolic phenotype (metabotype) clearly matches the biochemical pathways in which these enzymes are active. Our results suggest that common genetic polymorphisms induce major differentiations in the metabolic make-up of the human population. This may lead to a novel approach to personalized health care based on a combination of genotyping and metabolic characterization. These genetically determined metabotypes may subscribe the risk for a certain medical phenotype, the response to a given drug treatment, or the reaction to a nutritional intervention or environmental challenge.

  5. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum.

    Directory of Open Access Journals (Sweden)

    Christian Gieger

    2008-11-01

    Full Text Available The rapidly evolving field of metabolomics aims at a comprehensive measurement of ideally all endogenous metabolites in a cell or body fluid. It thereby provides a functional readout of the physiological state of the human body. Genetic variants that associate with changes in the homeostasis of key lipids, carbohydrates, or amino acids are not only expected to display much larger effect sizes due to their direct involvement in metabolite conversion modification, but should also provide access to the biochemical context of such variations, in particular when enzyme coding genes are concerned. To test this hypothesis, we conducted what is, to the best of our knowledge, the first GWA study with metabolomics based on the quantitative measurement of 363 metabolites in serum of 284 male participants of the KORA study. We found associations of frequent single nucleotide polymorphisms (SNPs with considerable differences in the metabolic homeostasis of the human body, explaining up to 12% of the observed variance. Using ratios of certain metabolite concentrations as a proxy for enzymatic activity, up to 28% of the variance can be explained (p-values 10(-16 to 10(-21. We identified four genetic variants in genes coding for enzymes (FADS1, LIPC, SCAD, MCAD where the corresponding metabolic phenotype (metabotype clearly matches the biochemical pathways in which these enzymes are active. Our results suggest that common genetic polymorphisms induce major differentiations in the metabolic make-up of the human population. This may lead to a novel approach to personalized health care based on a combination of genotyping and metabolic characterization. These genetically determined metabotypes may subscribe the risk for a certain medical phenotype, the response to a given drug treatment, or the reaction to a nutritional intervention or environmental challenge.

  6. [Constant or break? On the relations between human genetics and eugenics in the Twentieth Century].

    Science.gov (United States)

    Germann, Pascal

    2015-07-01

    The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations.

  7. Deterministic Pattern Classifier Based on Genetic Programming

    Institute of Scientific and Technical Information of China (English)

    LI Jian-wu; LI Min-qiang; KOU Ji-song

    2001-01-01

    This paper proposes a supervised training-test method with Genetic Programming (GP) for pattern classification. Compared and contrasted with traditional methods with regard to deterministic pattern classifiers, this method is true for both linear separable problems and linear non-separable problems. For specific training samples, it can formulate the expression of discriminate function well without any prior knowledge. At last, an experiment is conducted, and the result reveals that this system is effective and practical.

  8. Inconsistencies in pedigree symbols in human genetics publications: A need for standardization

    Energy Technology Data Exchange (ETDEWEB)

    Steinhaus, K.A.; Bennett, R.L.; Resta, R.G. [Univ. of California at Irvine, Orange, CA (United States)] [and others

    1995-04-10

    To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree`s basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations. 5 refs., 11 figs., 2 tabs.

  9. Recollections of J.B.S. Haldane, with special reference to Human Genetics in India

    Directory of Open Access Journals (Sweden)

    Krishna R Dronamraju

    2012-01-01

    Full Text Available This paper is a brief account of the scientific work of J.B.S. Haldane (1892-1964, with special reference to early research in Human Genetics. Brief descriptions of Haldane′s background, his important contributions to the foundations of human genetics, his move to India from Great Britain and the research carried out in Human Genetics in India under his direction are outlined. Population genetic research on Y-linkage in man, inbreeding, color blindness and other aspects are described.

  10. Perspectives on human genetic variation from the HapMap Project.

    Science.gov (United States)

    McVean, Gil; Spencer, Chris C A; Chaix, Raphaelle

    2005-10-01

    The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human genetic diversity. In this review we focus on what the HapMap Project has taught us about the structure of human genetic variation and the fundamental molecular and evolutionary processes that shape it.

  11. The New Human Genetics. How Gene Splicing Helps Researchers Fight Inherited Disease.

    Science.gov (United States)

    Pines, Maya

    The science of genetics is perceived to offer hope that a large number of the 3,000 inherited diseases which afflict human beings may be prevented or controlled. This document addresses some of the advances that have been made in this field. It includes an introduction and sections on: "The Beginning of Human Genetics"; "Unlocking the Secrets of…

  12. Atlas of the clinical genetics of human dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Haas, Jan; Frese, Karen S; Peil, Barbara;

    2015-01-01

    : This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide...... a sound database of the genetic causes of DCM....

  13. Human gene therapy: a brief overview of the genetic revolution.

    Science.gov (United States)

    Misra, Sanjukta

    2013-02-01

    Advances in biotechnology have brought gene therapy to the forefront of medical research. The prelude to successful gene therapy i.e. the efficient transfer and expression of a variety of human gene into target cells has already been accomplished in several systems. Safe methods have been devised to do this, using several viral and no-viral vectors. Two main approaches emerged: in vivo modification and ex vivo modification. Retrovirus, adenovirus, adeno-associated virus are suitable for gene therapeutic approaches which are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and their large capacity for therapeutic DNA. To improve the function of non-viral vectors, the addition of viral functions such as receptor mediated uptake and nuclear translocation of DNA may finally lead to the development of an artificial virus. Gene transfer protocols have been approved for human use in inherited diseases, cancers and acquired disorders. In 1990, the first successful clinical trial of gene therapy was initiated for adenosine deaminase deficiency. Since then, the number of clinical protocols initiated worldwide has increased exponentially. Although preliminary results of these trials are somewhat disappointing, but human gene therapy dreams of treating diseases by replacing or supplementing the product of defective or introducing novel therapeutic genes. So definitely human gene therapy is an effective addition to the arsenal of approaches to many human therapies in the 21st century.

  14. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

    Directory of Open Access Journals (Sweden)

    Amr T. M. Saeb

    2016-01-01

    Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

  15. Parameters optimization on DHSVM model based on a genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    Changqing YAO; Zhifeng YANG

    2009-01-01

    Due to the multiplicity of factors including weather, the underlying surface and human activities, the complexity of parameter optimization for a distributed hydrological model of a watershed land surface goes far beyond the capability of traditional optimization methods. The genetic algorithm is a new attempt to find a solution to this problem. A genetic algorithm design on the Distributed-Hydrology-Soil-Vegetation model (DHSVM) parameter optimization is illustrated in this paper by defining the encoding method, designing the fitness value function, devising the genetic operators, selecting the arithmetic parameters and identifying the arithmetic termination conditions. Finally, a case study of the optimization method is implemented on the Lushi Watershed of the Yellow River Basin and achieves satisfactory results of parameter estimation. The result shows that the genetic algorithm is feasible in optimizing parameters of the DHSVM model.

  16. Grammar Based Genetic Programming Using Linear Representations

    Institute of Scientific and Technical Information of China (English)

    ZHANGHong; LUYinan; WANGFei

    2003-01-01

    In recent years,there has been a great interest in genetic programming(GP),which is used to solve many applications such as data mining,electronic engineering and pattern recognition etc.. Genetic programming paradigm as a from of adaptive learning is a functional approach to many problems that require a nonfixed representation and GP typically operates on a population of parse which usually represent computer programs whose nodes have single data type.In this paper GP using context-free grammars(CFGs) is described.This technique separates search space from solution space through a genotype to phenotype mapping.The genotypes and phenotypes of the individuals both act on different linear representations.A phenotype is postfix expression,a new method of representing which is described by making use of the definition and related features of a context-free grammar,i.e.a genotype is a variable length,linear valid genome determined by a simplifled derivation tree(SDT) generated from a context-free grammar.A CFG is used to specify how the possible solutions are created according to experiential knowledge and to direct legal crossover(ormutation)operations without any explicit reference to the process of program generation and parsing,and automatically ensuring typing and syntax correctness.Some related definitions involving genetic operators are described.Fitness evaluation is given.This technique is applied to a symbol regression problem-the identification of nonlinear dynamic characteristics of cushioning packaging.Experimental results show this method can flnd good relations between variables and is better than basic GP without a grammar.Future research on it is outlined.

  17. Genetic bases of the evolution of organisms

    Directory of Open Access Journals (Sweden)

    Marinković Dragoslav M.

    2002-01-01

    Full Text Available Biological progress consists of the continuous increase of divergence with simultaneous maintenance and the increase of conformance (harmoniousness of living systems. A mutual balance between divergence of forms and the degree of perfection of their structure and function indicates a level of the evolutionary development of a particular group of organisms, i.e. a level and prospects of their evolutionary progress. An enormous potential of combined genetic polymorphousness is reduced to adaptive landscapes of a limited number of developmental programmes that make actual units of inheritance and variability within each species.

  18. Analysis of protein-coding genetic variation in 60,706 humans.

    Science.gov (United States)

    Lek, Monkol; Karczewski, Konrad J; Minikel, Eric V; Samocha, Kaitlin E; Banks, Eric; Fennell, Timothy; O'Donnell-Luria, Anne H; Ware, James S; Hill, Andrew J; Cummings, Beryl B; Tukiainen, Taru; Birnbaum, Daniel P; Kosmicki, Jack A; Duncan, Laramie E; Estrada, Karol; Zhao, Fengmei; Zou, James; Pierce-Hoffman, Emma; Berghout, Joanne; Cooper, David N; Deflaux, Nicole; DePristo, Mark; Do, Ron; Flannick, Jason; Fromer, Menachem; Gauthier, Laura; Goldstein, Jackie; Gupta, Namrata; Howrigan, Daniel; Kiezun, Adam; Kurki, Mitja I; Moonshine, Ami Levy; Natarajan, Pradeep; Orozco, Lorena; Peloso, Gina M; Poplin, Ryan; Rivas, Manuel A; Ruano-Rubio, Valentin; Rose, Samuel A; Ruderfer, Douglas M; Shakir, Khalid; Stenson, Peter D; Stevens, Christine; Thomas, Brett P; Tiao, Grace; Tusie-Luna, Maria T; Weisburd, Ben; Won, Hong-Hee; Yu, Dongmei; Altshuler, David M; Ardissino, Diego; Boehnke, Michael; Danesh, John; Donnelly, Stacey; Elosua, Roberto; Florez, Jose C; Gabriel, Stacey B; Getz, Gad; Glatt, Stephen J; Hultman, Christina M; Kathiresan, Sekar; Laakso, Markku; McCarroll, Steven; McCarthy, Mark I; McGovern, Dermot; McPherson, Ruth; Neale, Benjamin M; Palotie, Aarno; Purcell, Shaun M; Saleheen, Danish; Scharf, Jeremiah M; Sklar, Pamela; Sullivan, Patrick F; Tuomilehto, Jaakko; Tsuang, Ming T; Watkins, Hugh C; Wilson, James G; Daly, Mark J; MacArthur, Daniel G

    2016-08-18

    Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

  19. Genetic interaction mapping with microfluidic-based single cell sequencing

    Science.gov (United States)

    Haliburton, John R.; Shao, Wenjun; Deutschbauer, Adam; Arkin, Adam; Abate, Adam R.

    2017-01-01

    Genetic interaction mapping is useful for understanding the molecular basis of cellular decision making, but elucidating interactions genome-wide is challenging due to the massive number of gene combinations that must be tested. Here, we demonstrate a simple approach to thoroughly map genetic interactions in bacteria using microfluidic-based single cell sequencing. Using single cell PCR in droplets, we link distinct genetic information into single DNA sequences that can be decoded by next generation sequencing. Our approach is scalable and theoretically enables the pooling of entire interaction libraries to interrogate multiple pairwise genetic interactions in a single culture. The speed, ease, and low-cost of our approach makes genetic interaction mapping viable for routine characterization, allowing the interaction network to be used as a universal read out for a variety of biology experiments, and for the elucidation of interaction networks in non-model organisms. PMID:28170417

  20. 论人的思想政治教育需要的产生--基于发生学视角%On the Generation of Human Needs for Political and Ideological Education---Bases on Genetic Perspective

    Institute of Scientific and Technical Information of China (English)

    侯丹娟

    2016-01-01

    As a human activity with the objectivity ans the regularity,the reason why iseological ans political esucation can emerge ans sevelops unceasingly lies in people’s nees for it. So,how soes it generate?Accorsing to the theory of genetics,the paper siscusses the founsation,the consition ans the process of insivisual nees for iseological ans political esucation from microscopic angle.%作为一项具有客观性和规律性的人类活动,思想政治教育之所以能够出现并不断发展,其根本原因在于人需要它。根据发生学的理论,从微观角度探讨个体思想政治教育需要产生的基础、条件和过程是非常必要的。

  1. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    DEFF Research Database (Denmark)

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo;

    2016-01-01

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic...... variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height...... variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent...

  2. Feeder-free culture of human embryonic stem cells in conditioned medium for efficient genetic modification.

    Science.gov (United States)

    Braam, Stefan R; Denning, Chris; Matsa, Elena; Young, Lorraine E; Passier, Robert; Mummery, Christine L

    2008-01-01

    Realizing the potential of human embryonic stem cells (hESCs) in research and commercial applications requires generic protocols for culture, expansion and genetic modification that function between multiple lines. Here we describe a feeder-free hESC culture protocol that was tested in 13 independent hESC lines derived in five different laboratories. The procedure is based on Matrigel adaptation in mouse embryonic fibroblast conditioned medium (CM) followed by monolayer culture of hESC. When combined, these techniques provide a robust hESC culture platform, suitable for high-efficiency genetic modification via plasmid transfection (using lipofection or electroporation), siRNA knockdown and viral transduction. In contrast to other available protocols, it does not require optimization for individual lines. hESC transiently expressing ectopic genes are obtained within 9 d and stable transgenic lines within 3 weeks.

  3. Morphological and Genetic Diversity of Trichuris spp. recovered from Humans and Pigs

    DEFF Research Database (Denmark)

    Nissen, Sofie; Nejsum, Peter; Christensen, Henrik;

    2009-01-01

    The nematodes, Trichuris suis and Trichuris trichiura are believed to be two separate but closely related species. The aim of our study was to examine the morphological and genetic diversity of Trichuris spp. recovered from pigs and humans. Sympatric worm material isolated from 10 humans and 5 pigs...... found in pig-derived worms (31% of the human-derived worms, consensus sequence 531 nucleotides long). The results indicated that the nematodes found in pigs belong to a genetically distinct species (T. suis) whereas the nematodes in humans showed considerable genetic variability either related...

  4. The human genetic history of the Americas: the final frontier.

    Science.gov (United States)

    O'Rourke, Dennis H; Raff, Jennifer A

    2010-02-23

    The Americas, the last continents to be entered by modern humans, were colonized during the late Pleistocene via a land bridge across what is now the Bering strait. However, the timing and nature of the initial colonization events remain contentious. The Asian origin of the earliest Americans has been amply established by numerous classical marker studies of the mid-twentieth century. More recently, mtDNA sequences, Y-chromosome and autosomal marker studies have provided a higher level of resolution in confirming the Asian origin of indigenous Americans and provided more precise time estimates for the emergence of Native Americans. But these data raise many additional questions regarding source populations, number and size of colonizing groups and the points of entry to the Americas. Rapidly accumulating molecular data from populations throughout the Americas, increased use of demographic models to test alternative colonization scenarios, and evaluation of the concordance of archaeological, paleoenvironmental and genetic data provide optimism for a fuller understanding of the initial colonization of the Americas.

  5. Faecal carriage of Pseudomonas aeruginosa in healthy humans: antimicrobial susceptibility and global genetic lineages.

    Science.gov (United States)

    Estepa, Vanesa; Rojo-Bezares, Beatriz; Torres, Carmen; Sáenz, Yolanda

    2014-07-01

    The aim of this study was to analyse the Pseudomonas aeruginosa faecal carriage rate in 98 healthy humans and to perform the phenotypic and genotypic characterization of recovered isolates. The genetic relatedness among the isolates was analysed by pulsed-field gel electrophoresis and multilocus sequence typing that was compared with worldwide epidemic clones. Pseudomonas aeruginosa was isolated from eight healthy individuals (8.2%), and two of them remained colonized after 5 months (in one case by the same clone). All 10 isolates (one/sample) were susceptible to 14 tested antipseudomonal agents and lacked integron structures. Six pulsed-field gel electrophoresis patterns and six sequence types (ST245, ST253, ST254, ST274, ST663 and the new one, ST1059) were identified among them. Four groups of OprD alterations were detected based on mutations and deletions related to PAO1 reference strain in our carbapenem-susceptible strains. This is the first study focused on P. aeruginosa from faecal samples of healthy humans that provides additional insights into the antimicrobial resistance and genetic diversity of P. aeruginosa. Although the isolates were antimicrobial susceptible, most of the sequence types detected were genetically related to Spanish epidemic clones or globally spread sequence types, such as ST274 and ST253.

  6. Using Fuzzy Gaussian Inference and Genetic Programming to Classify 3D Human Motions

    Science.gov (United States)

    Khoury, Mehdi; Liu, Honghai

    This research introduces and builds on the concept of Fuzzy Gaussian Inference (FGI) (Khoury and Liu in Proceedings of UKCI, 2008 and IEEE Workshop on Robotic Intelligence in Informationally Structured Space (RiiSS 2009), 2009) as a novel way to build Fuzzy Membership Functions that map to hidden Probability Distributions underlying human motions. This method is now combined with a Genetic Programming Fuzzy rule-based system in order to classify boxing moves from natural human Motion Capture data. In this experiment, FGI alone is able to recognise seven different boxing stances simultaneously with an accuracy superior to a GMM-based classifier. Results seem to indicate that adding an evolutionary Fuzzy Inference Engine on top of FGI improves the accuracy of the classifier in a consistent way.

  7. Human thromboxane A2 receptor genetic variants: in silico, in vitro and "in platelet" analysis.

    Directory of Open Access Journals (Sweden)

    Scott Gleim

    Full Text Available Thromboxane and its receptor have emerged as key players in modulating vascular thrombotic events. Thus, a dysfunctional hTP genetic variant may protect against (hypoactivity or promote (hyperactivity vascular events, based upon its activity on platelets. After extensive in silico analysis, six hTP-α variants were selected (C(68S, V(80E, E(94V, A(160T, V(176E, and V(217I for detailed biochemical studies based on structural proximity to key regions involved in receptor function and in silico predictions. Variant biochemical profiles ranged from severe instability (C(68S to normal (V(217I, with most variants demonstrating functional alteration in binding, expression or activation (V(80E, E(94V, A(160T, and V(176E. In the absence of patient platelet samples, we developed and validated a novel megakaryocyte based system to evaluate human platelet function in the presence of detected dysfunctional genetic variants. Interestingly, variant V80E exhibited reduced platelet activation whereas A160T demonstrated platelet hyperactivity. This report provides the most comprehensive in silico, in vitro and "in platelet" evaluation of hTP variants to date and highlightscurrent inherent problems in evaluating genetic variants, with possible solutions. The study additionally provides clinical relevance to characterized dysfunctional hTP variants.

  8. Genetic Characterization of Atypical Mansonella (Mansonella) ozzardi Microfilariae in Human Blood Samples from Northeastern Peru

    Science.gov (United States)

    Marcos, Luis A.; Arrospide, Nancy; Recuenco, Sergio; Cabezas, Cesar; Weil, Gary J.; Fischer, Peter U.

    2012-01-01

    DNA sequence comparisons are useful for characterizing proposed new parasite species or strains. Microfilariae with an atypical arrangement of nuclei behind the cephalic space have been recently described in human blood samples from the Amazon region of Peru. Three blood specimens containing atypical microfilariae were genetically characterized using three DNA markers (5S ribosomal DNA, 12S ribosomal DNA, and cytochrome oxidase I). All atypical microfilariae were clustered into the Mansonella group and indistinguishable from M. ozzardi based on these DNA markers. PMID:22826497

  9. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints.

    Science.gov (United States)

    Sessions, October M; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients' sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses.

  10. Warehouse Optimization Model Based on Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Guofeng Qin

    2013-01-01

    Full Text Available This paper takes Bao Steel logistics automated warehouse system as an example. The premise is to maintain the focus of the shelf below half of the height of the shelf. As a result, the cost time of getting or putting goods on the shelf is reduced, and the distance of the same kind of goods is also reduced. Construct a multiobjective optimization model, using genetic algorithm to optimize problem. At last, we get a local optimal solution. Before optimization, the average cost time of getting or putting goods is 4.52996 s, and the average distance of the same kinds of goods is 2.35318 m. After optimization, the average cost time is 4.28859 s, and the average distance is 1.97366 m. After analysis, we can draw the conclusion that this model can improve the efficiency of cargo storage.

  11. Genetic Algorithm Based Microscale Vehicle Emissions Modelling

    Directory of Open Access Journals (Sweden)

    Sicong Zhu

    2015-01-01

    Full Text Available There is a need to match emission estimations accuracy with the outputs of transport models. The overall error rate in long-term traffic forecasts resulting from strategic transport models is likely to be significant. Microsimulation models, whilst high-resolution in nature, may have similar measurement errors if they use the outputs of strategic models to obtain traffic demand predictions. At the microlevel, this paper discusses the limitations of existing emissions estimation approaches. Emission models for predicting emission pollutants other than CO2 are proposed. A genetic algorithm approach is adopted to select the predicting variables for the black box model. The approach is capable of solving combinatorial optimization problems. Overall, the emission prediction results reveal that the proposed new models outperform conventional equations in terms of accuracy and robustness.

  12. Topology control based on quantum genetic algorithm in sensor networks

    Institute of Scientific and Technical Information of China (English)

    SUN Lijuan; GUO Jian; LU Kai; WANG Ruchuan

    2007-01-01

    Nowadays,two trends appear in the application of sensor networks in which both multi-service and quality of service (QoS)are supported.In terms of the goal of low energy consumption and high connectivity,the control on topology is crucial.The algorithm of topology control based on quantum genetic algorithm in sensor networks is proposed.An advantage of the quantum genetic algorithm over the conventional genetic algorithm is demonstrated in simulation experiments.The goals of high connectivity and low consumption of energy are reached.

  13. Restart-Based Genetic Algorithm for the Quadratic Assignment Problem

    Science.gov (United States)

    Misevicius, Alfonsas

    The power of genetic algorithms (GAs) has been demonstrated for various domains of the computer science, including combinatorial optimization. In this paper, we propose a new conceptual modification of the genetic algorithm entitled a "restart-based genetic algorithm" (RGA). An effective implementation of RGA for a well-known combinatorial optimization problem, the quadratic assignment problem (QAP), is discussed. The results obtained from the computational experiments on the QAP instances from the publicly available library QAPLIB show excellent performance of RGA. This is especially true for the real-life like QAPs.

  14. A review of approaches to the detection of genetic damage in the human fetus.

    OpenAIRE

    Everson, R B

    1987-01-01

    Studies in experimental animals suggest links between genetic damage to the fetus and the etiology of several disorders, including fetal loss, teratogenesis, and cancer. Methods for measuring genetic damage directly in the human fetus could provide epidemiologists and clinical researchers with powerful tools for investigating similar associations in humans. Current methods potentially available for such studies include assays for mutagenic substances in human body fluids and for measuring mod...

  15. Neuron-Based Heredity and Human Evolution

    Directory of Open Access Journals (Sweden)

    Don Marshall Gash

    2015-06-01

    Full Text Available Abstract:Abstract: It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes are in line with Neolamarckian concepts of evolution (Packard, 1901. Evidence is presented of bipartite evolutionary processes – Darwinian and Neolamarckian – driving human descent from a common ancestor shared with the great apes.

  16. The concept of human dignity in the ethics of genetic research.

    Science.gov (United States)

    Chan, David K

    2015-05-01

    Despite criticism that dignity is a vague and slippery concept, a number of international guidelines on bioethics have cautioned against research that is contrary to human dignity, with reference specifically to genetic technology. What is the connection between genetic research and human dignity? In this article, I investigate the concept of human dignity in its various historical forms, and examine its status as a moral concept. Unlike Kant's ideal concept of human dignity, the empirical or relational concept takes human dignity as something that is affected by one's circumstances and what others do. I argue that the dignity objection to some forms of genetic research rests on a view of human nature that gives humans a special status in nature - one that is threatened by the potential of genetic research to reduce individuals to their genetic endowment. I distinguish two main philosophical accounts of human nature. One of these, the Aristotelian view, is compatible with the use of genetic technology to help humans realize their inherent potential to a fuller extent.

  17. Genetic recombination pathways and their application for genome modification of human embryonic stem cells.

    Science.gov (United States)

    Nieminen, Mikko; Tuuri, Timo; Savilahti, Harri

    2010-10-01

    Human embryonic stem cells are pluripotent cells derived from early human embryo and retain a potential to differentiate into all adult cell types. They provide vast opportunities in cell replacement therapies and are expected to become significant tools in drug discovery as well as in the studies of cellular and developmental functions of human genes. The progress in applying different types of DNA recombination reactions for genome modification in a variety of eukaryotic cell types has provided means to utilize recombination-based strategies also in human embryonic stem cells. Homologous recombination-based methods, particularly those utilizing extended homologous regions and those employing zinc finger nucleases to boost genomic integration, have shown their usefulness in efficient genome modification. Site-specific recombination systems are potent genome modifiers, and they can be used to integrate DNA into loci that contain an appropriate recombination signal sequence, either naturally occurring or suitably pre-engineered. Non-homologous recombination can be used to generate random integrations in genomes relatively effortlessly, albeit with a moderate efficiency and precision. DNA transposition-based strategies offer substantially more efficient random strategies and provide means to generate single-copy insertions, thus potentiating the generation of genome-wide insertion libraries applicable in genetic screens.

  18. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  19. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  20. Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.

    Directory of Open Access Journals (Sweden)

    Zhi Xu

    Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.

  1. Genetic bases of arrhythmogenic right ventricular cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Alessandra Rampazzo

    2010-05-01

    Full Text Available Arrhythmogenic right ventricular cardiomyopathy (ARVC is a heart muscle disease in which the pathological substrate is a fibro-fatty replacement of the right ventricular myocardium. The major clinical features are different types of arrhythmias with a left branch block pattern. ARVC shows autosomal dominant inheritance with incomplete penetrance. Recessive forms were also described, although in association with skin disorders. Ten genetic loci have been discovered so far and mutations were reported in five different genes. ARVD1 was associated with regulatory mutations of transforming growth factor beta-3 (TGFβ3, whereas ARVD2, characterized by effort-induced polymorphic arrhythmias, was associated with mutations in cardiac ryanodine receptor-2 (RYR2. All other mutations identified to date have been detected in genes encoding desmosomal proteins: plakoglobin (JUP which causes Naxos disease (a recessive form of ARVC associated with palmoplantar keratosis and woolly hair; desmoplakin (DSP which causes the autosomal dominant ARVD8 and plakophilin-2 (PKP2 involved in ARVD9. Desmosomes are important cell-to-cell adhesion junctions predominantly found in epidermis and heart; they are believed to couple cytoskeletal elements to plasma membrane in cell-to-cell or cell-to-substrate adhesions.

  2. Genetic polymorphisms and lipid response to dietary changes in humans

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Ordovas, J.M.; Ramos-Galluzzi, J.; Katan, M.B.

    2001-01-01

    Previous studies on the effects of genetic polymorphisms on the serum cholesterol response to dietary treatments were often inconsistent and frequently involved small numbers of subjects. We studied the effect of 10 genetic polymorphisms on the responses of serum cholesterol to saturated and trans f

  3. Inter-chromosomal variation in the pattern of human population genetic structure

    Directory of Open Access Journals (Sweden)

    Baye Tesfaye M

    2011-05-01

    Full Text Available Abstract Emerging technologies now make it possible to genotype hundreds of thousands of genetic variations in individuals, across the genome. The study of loci at finer scales will facilitate the understanding of genetic variation at genomic and geographic levels. We examined global and chromosomal variations across HapMap populations using 3.7 million single nucleotide polymorphisms to search for the most stratified genomic regions of human populations and linked these regions to ontological annotation and functional network analysis. To achieve this, we used five complementary statistical and genetic network procedures: principal component (PC, cluster, discriminant, fixation index (FST and network/pathway analyses. At the global level, the first two PC scores were sufficient to account for major population structure; however, chromosomal level analysis detected subtle forms of population structure within continental populations, and as many as 31 PCs were required to classify individuals into homogeneous groups. Using recommended population ancestry differentiation measures, a total of 126 regions of the genome were catalogued. Gene ontology and networks analyses revealed that these regions included the genes encoding oculocutaneous albinism II (OCA2, hect domain and RLD 2 (HERC2, ectodysplasin A receptor (EDAR and solute carrier family 45, member 2 (SLC45A2. These genes are associated with melanin production, which is involved in the development of skin and hair colour, skin cancer and eye pigmentation. We also identified the genes encoding interferon-γ (IFNG and death-associated protein kinase 1 (DAPK1, which are associated with cell death, inflammatory and immunological diseases. An in-depth understanding of these genomic regions may help to explain variations in adaptation to different environments. Our approach offers a comprehensive strategy for analysing chromosome-based population structure and differentiation, and demonstrates the

  4. An atlas of genetic correlations across human diseases and traits

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri;

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods...... are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample...... overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses...

  5. Numeral eddy current sensor modelling based on genetic neural network

    Institute of Scientific and Technical Information of China (English)

    Yu A-Long

    2008-01-01

    This paper presents a method used to the numeral eddy current sensor modelling based on the genetic neural network to settle its nonlinear problem. The principle and algorithms of genetic neural network are introduced. In this method, the nonlinear model parameters of the numeral eddy current sensor are optimized by genetic neural network (GNN) according to measurement data. So the method remains both the global searching ability of genetic algorithm and the good local searching ability of neural network. The nonlinear model has the advantages of strong robustness,on-line modelling and high precision.The maximum nonlinearity error can be reduced to 0.037% by using GNN.However, the maximum nonlinearity error is 0.075% using the least square method.

  6. OPTIMIZATION BASED ON LMPROVED REAL—CODED GENETIC ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    ShiYu; YuShenglin

    2002-01-01

    An improved real-coded genetic algorithm is pro-posed for global optimization of functionsl.The new algo-rithm is based om the judgement of the searching perfor-mance of basic real-coded genetic algorithm.The opera-tions of basic real-coded genetic algorithm are briefly dis-cussed and selected.A kind of chaos sequence is described in detail and added in the new algorithm ad a disturbance factor.The strategy of field partition is also used to im-prove the strcture of the new algorithm.Numerical ex-periment shows that the mew genetic algorithm can find the global optimum of complex funtions with satistaiting precision.

  7. Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers.

    Science.gov (United States)

    Sinkovics, Joseph G; Horvath, Joseph C

    2008-12-01

    Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a

  8. MS-based analytical methodologies to characterize genetically modified crops.

    Science.gov (United States)

    García-Cañas, Virginia; Simó, Carolina; León, Carlos; Ibáñez, Elena; Cifuentes, Alejandro

    2011-01-01

    The development of genetically modified crops has had a great impact on the agriculture and food industries. However, the development of any genetically modified organism (GMO) requires the application of analytical procedures to confirm the equivalence of the GMO compared to its isogenic non-transgenic counterpart. Moreover, the use of GMOs in foods and agriculture faces numerous criticisms from consumers and ecological organizations that have led some countries to regulate their production, growth, and commercialization. These regulations have brought about the need of new and more powerful analytical methods to face the complexity of this topic. In this regard, MS-based technologies are increasingly used for GMOs analysis to provide very useful information on GMO composition (e.g., metabolites, proteins). This review focuses on the MS-based analytical methodologies used to characterize genetically modified crops (also called transgenic crops). First, an overview on genetically modified crops development is provided, together with the main difficulties of their analysis. Next, the different MS-based analytical approaches applied to characterize GM crops are critically discussed, and include "-omics" approaches and target-based approaches. These methodologies allow the study of intended and unintended effects that result from the genetic transformation. This information is considered to be essential to corroborate (or not) the equivalence of the GM crop with its isogenic non-transgenic counterpart.

  9. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  10. Manufacturing Resource Planning Technology Based on Genetic Programming Simulation

    Institute of Scientific and Technical Information of China (English)

    GAO Shiwen; LIAO Wenhe; GUO Yu; LIU Jinshan; SU Yan

    2009-01-01

    Network-based manufacturing is a kind of distributed system, which enables manufacturers to finish production tasks as well as to grasp the opportunities in the market, even if manufacturing resources are insufficient. One of the main problems in network-based manufacturing is the allocation of resources and the assignment of tasks rationally, according to flexible resource distribution. The mapping rules and relations between production techniques and resources are proposed, followed by the definition of the resource unit. Ultimately, the genetic programming method for the optimization of the manufacturing system is put forward. A set of software for the optimization system of simulation process using genetic programming techniques has been developed, and the problems of manufacturing resource planning in network-based manufacturing are solved with the simulation of optimizing methods by genetic programming. The optimum proposal of hardware planning, selection of company and scheduling will be obtained in theory to help company managers in scientific decision-making.

  11. Retrospective analysis of main and interaction effects in genetic association studies of human complex traits

    DEFF Research Database (Denmark)

    Tan, Qihua; Christiansen, Lene; Brasch-Andersen, Charlotte;

    2007-01-01

    BACKGROUND: The etiology of multifactorial human diseases involves complex interactions between numerous environmental factors and alleles of many genes. Efficient statistical tools are demanded in identifying the genetic and environmental variants that affect the risk of disease development....... This paper introduces a retrospective polytomous logistic regression model to measure both the main and interaction effects in genetic association studies of human discrete and continuous complex traits. In this model, combinations of genotypes at two interacting loci or of environmental exposure...... regression model can be used as a convenient tool for assessing both main and interaction effects in genetic association studies of human multifactorial diseases involving genetic and non-genetic factors as well as categorical or continuous traits....

  12. Using human genetics to predict the effects and side-effects of drugs

    DEFF Research Database (Denmark)

    Stender, Stefan; Tybjærg-Hansen, Anne

    2016-01-01

    PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG...... that inhibit these targets. Both mutations in PCSK9 and PCSK9-inhibition seem without adverse effects. Mutations in APOC3 cause low triglycerides and protect against IHD, and recent pharmacological APOC3-inhibition reported major reductions in plasma triglycerides. Human genetics support that low lipoprotein......(a) protects against IHD, without adverse effects, and the first trial of lipoprotein(a) inhibition reduced lipoprotein(a) up to 78%. SUMMARY: Recent genetic studies have confirmed the efficacy of statins and ezetimibe in protecting against IHD. Results from human genetics support that several lipid...

  13. Generation and genetic engineering of human induced pluripotent stem cells using designed zinc finger nucleases.

    Science.gov (United States)

    Ramalingam, Sivaprakash; London, Viktoriya; Kandavelou, Karthikeyan; Cebotaru, Liudmila; Guggino, William; Civin, Curt; Chandrasegaran, Srinivasan

    2013-02-15

    Zinc finger nucleases (ZFNs) have become powerful tools to deliver a targeted double-strand break at a pre-determined chromosomal locus in order to insert an exogenous transgene by homology-directed repair. ZFN-mediated gene targeting was used to generate both single-allele chemokine (C-C motif) receptor 5 (CCR5)-modified human induced pluripotent stem cells (hiPSCs) and biallele CCR5-modified hiPSCs from human lung fibroblasts (IMR90 cells) and human primary cord blood mononuclear cells (CBMNCs) by site-specific insertion of stem cell transcription factor genes flanked by LoxP sites into the endogenous CCR5 locus. The Oct4 and Sox2 reprogramming factors, in combination with valproic acid, induced reprogramming of human lung fibroblasts to form CCR5-modified hiPSCs, while 5 factors, Oct4/Sox2/Klf4/Lin28/Nanog, induced reprogramming of CBMNCs. Subsequent Cre recombinase treatment of the CCR5-modified IMR90 hiPSCs resulted in the removal of the Oct4 and Sox2 transgenes. Further genetic engineering of the single-allele CCR5-modified IMR90 hiPSCs was achieved by site-specific addition of the large CFTR transcription unit to the remaining CCR5 wild-type allele, using CCR5-specific ZFNs and a donor construct containing tdTomato and CFTR transgenes flanked by CCR5 homology arms. CFTR was expressed efficiently from the endogenous CCR5 locus of the CCR5-modified tdTomato/CFTR hiPSCs. These results suggest that it might be feasible to use ZFN-evoked strategies to (1) generate precisely targeted genetically well-defined patient-specific hiPSCs, and (2) then to reshape their function by targeted addition and expression of therapeutic genes from the CCR5 chromosomal locus for autologous cell-based transgene-correction therapy to treat various recessive monogenic human diseases in the future.

  14. The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

    OpenAIRE

    2009-01-01

    Summary: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination—a copy choice mechanism involving the migration of reverse transcr...

  15. A Songbird Animal Model for Dissecting the Genetic Bases of Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    S. Carmen Panaitof

    2012-01-01

    Full Text Available The neural and genetic bases of human language development and associated neurodevelopmental disorders, including autism spectrum disorder (ASD, in which language impairment represents a core deficit, are poorly understood. Given that no single animal model can fully capture the behavioral and genetic complexity of ASD, work in songbird, an experimentally tractable animal model of vocal learning, can complement the valuable tool of rodent genetic models and contribute important insights to our understanding of the communication deficits observed in ASD. Like humans, but unlike traditional laboratory animals such as rodents or non-human primates, songbirds exhibit the capacity of vocal learning, a key subcomponent of language. Human speech and birdsong reveal important parallels, highlighting similar developmental critical periods, a homologous cortico-basal ganglia-thalamic circuitry, and a critical role for social influences in the learning of vocalizations. Here I highlight recent advances in using the songbird model to probe the cellular and molecular mechanisms underlying the formation and function of neural circuitry for birdsong and, by analogy, human language, with the ultimate goal of identifying any shared or human unique biological pathways underscoring language development and its disruption in ASD.

  16. Range expansion of house sparrows (Passer domesticus) in Kenya: evidence of genetic admixture and human-mediated dispersal.

    Science.gov (United States)

    Schrey, Aaron W; Liebl, Andrea L; Richards, Christina L; Martin, Lynn B

    2014-01-01

    Introduced species offer an opportunity to study the ecological process of range expansions. Recently, 3 mechanisms have been identified that may resolve the genetic paradox (the seemingly unlikely success of introduced species given the expected reduction in genetic diversity through bottlenecks or founder effects): multiple introductions, high propagule pressure, and epigenetics. These mechanisms are probably also important in range expansions (either natural or anthropogenic), yet this possibility remains untested in vertebrates. We used microsatellite variation (7 loci) in house sparrows (Passer domesticus), an introduced species that has been spreading across Kenya for ~60 years, to determine if patterns of variation could explain how this human commensal overcame the genetic paradox and expresses such considerable phenotypic differentiation across this new range. We note that in some cases, polygenic traits and epistasis among genes, for example, may not have negative effects on populations. House sparrows arrived in Kenya by a single introduction event (to Mombasa, ~1950) and have lower genetic diversity than native European and introduced North American populations. We used Bayesian clustering of individuals (n = 233) to detect that at least 2 types of range expansion occurred in Kenya: one with genetic admixture and one with little to no admixture. We also found that genetic diversity increased toward a range edge, and the range expansion was consistent with long-distance dispersal. Based on these data, we expect that the Kenyan range expansion was anthropogenically influenced, as the expansions of other introduced human commensals may also be.

  17. Biological bases of human musicality.

    Science.gov (United States)

    Perrone-Capano, Carla; Volpicelli, Floriana; di Porzio, Umberto

    2017-01-20

    Music is a universal language, present in all human societies. It pervades the lives of most human beings and can recall memories and feelings of the past, can exert positive effects on our mood, can be strongly evocative and ignite intense emotions, and can establish or strengthen social bonds. In this review, we summarize the research and recent progress on the origins and neural substrates of human musicality as well as the changes in brain plasticity elicited by listening or performing music. Indeed, music improves performance in a number of cognitive tasks and may have beneficial effects on diseased brains. The emerging picture begins to unravel how and why particular brain circuits are affected by music. Numerous studies show that music affects emotions and mood, as it is strongly associated with the brain's reward system. We can therefore assume that an in-depth study of the relationship between music and the brain may help to shed light on how the mind works and how the emotions arise and may improve the methods of music-based rehabilitation for people with neurological disorders. However, many facets of the mind-music connection still remain to be explored and enlightened.

  18. Optimal design of steel portal frames based on genetic algorithms

    Institute of Scientific and Technical Information of China (English)

    Yue CHEN; Kai HU

    2008-01-01

    As for the optimal design of steel portal frames, due to both the complexity of cross selections of beams and columns and the discreteness of design variables, it is difficult to obtain satisfactory results by traditional optimization. Based on a set of constraints of the Technical Specification for Light-weighted Steel Portal Frames of China, a genetic algorithm (GA) optimization program for portal frames, written in MATLAB code, was proposed in this paper. The graph user interface (GUI) is also developed for this optimal program, so that it can be used much more conveniently. Finally, some examples illustrate the effectiveness and efficiency of the genetic-algorithm-based optimal program.

  19. An integrated map of genetic variation from 1.092 human genomes

    DEFF Research Database (Denmark)

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination...

  20. THE MEANING OF GENOMIC IMPRINTING IN HUMAN GENETIC AND DEFECTOLOGY

    OpenAIRE

    Anastas LAKOSKI

    2000-01-01

    Several genetic phenomena do not appear to conform the Mendel's low in the sense that they are not inherited in simple way through the generations. Such exceptions to Mendel's laws include new mutations, changes in chromosomes, expanded triplet sequences, and genomic imprinting. Many genetic diseases involve spontaneous mutations that are not inherited from generation to generation. Changes in chromosomes include nondisjunction, which is the most important cause of mental retardation, the tri...

  1. GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

    Directory of Open Access Journals (Sweden)

    Khoury Muin J

    2008-04-01

    Full Text Available Abstract Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM, a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.

  2. Genetic Engineering of Mesenchymal Stem Cells and Its Application in Human Disease Therapy

    OpenAIRE

    Hodgkinson, Conrad P; Gomez, José A.; Mirotsou, Maria; Dzau, Victor J.

    2010-01-01

    Hodgkinson and colleagues review the current status of knowledge with respect to the genetic modifications being explored as a means to improve mesenchymal stem cell therapy for human diseases, with a particular focus on cardiovascular diseases.

  3. Precision Medicine and Advancing Genetic Technologies—Disability and Human Rights Perspectives

    Directory of Open Access Journals (Sweden)

    Aisling de Paor

    2016-08-01

    Full Text Available Scientific and technological developments are propelling genetics and genetic technologies into the public sphere. Scientific and technological innovation is becoming more refined, resulting in an increase in the availability and use of genetic testing, and other cutting edge genetic technologies, including gene editing. These genetic advances not only signal a growing trend towards precision medicine, but also provoke consideration of the protection of genetic information as an emerging human rights concern. Particular ethical and legal issues arise from a disability perspective, including the potential for discrimination and privacy violations. In consideration of the intersection of genetics and disability, this article highlights the significant concerns raised as genetic science and technology advances, and the consequences for disability rights, particularly the core concepts of non-discrimination, and respect for diversity and difference. On examining international human rights perspectives, it looks particularly at the UN Convention on the Rights of Persons with Disabilities and how it may be used to guide best practice in this area. With an acknowledgement of historical abuses of genetic science, this article highlights the need to maintain caution as to the potential consequences of advancing genetic technologies on persons with disabilities and indeed on society as a whole.

  4. Human genetics education for middle and secondary science teachers. Third annual report, April 1, 1994--March 30, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Collins, D.L.; Segebrecht, L.; Schimke, R.N.

    1994-12-01

    This project is designed to increase teachers` knowledge of the Human Genome Project (HGP) with a focus on the ethical, legal and social implications of genetic technology. The project provides educators with the newest information on human genetics including applications of genetic technology, updated teaching resources and lesson plans, peer teaching ideas to disseminate genetic information to students and other educators, and established liaisons with genetic professionals.

  5. Knee Joint Optimization Design of Intelligent Bionic Leg Based on Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Hualong Xie

    2014-09-01

    Full Text Available Intelligent bionic leg (IBL is an advanced prosthesis which can maximum functionally simulate and approach the motion trajectory of human leg. Knee joint is the most important bone of human leg and its bionic design has great significance to prosthesis performance. The structural components of IBL are introduced and virtual prototype is given. The advantages of 4-bar knee joint are analyzed and are adopted in IBL design. The kinematics model of 4-bar knee joint is established. The objective function, constraint condition, parameters selection and setting of genetic algorithm are discussed in detail. Based on genetic algorithm, the optimization design of IBL knee joint is done. The optimization results indicate that the 4-bar mechanism can achieve better anthropomorphic characteristics of human knee joint.

  6. Incorporating privileged genetic information for fundus image based glaucoma detection.

    Science.gov (United States)

    Duan, Lixin; Xu, Yanwu; Li, Wen; Chen, Lin; Wing, Damon Wing Kee; Wong, Tien Yin; Liu, Jiang

    2014-01-01

    Visual features extracted from retinal fundus images have been increasingly used for glaucoma detection, as those images are generally easy to acquire. In recent years, genetic researchers have found that some single nucleic polymorphisms (SNPs) play important roles in the manifestation of glaucoma and also show superiority over fundus images for glaucoma detection. In this work, we propose to use the SNPs to form the so-called privileged information and deal with a practical problem where both fundus images and privileged genetic information exist for the training subjects, while the test objects only have fundus images. To solve this problem, we present an effective approach based on the learning using privileged information (LUPI) paradigm to train a predictive model for the image visual features. Extensive experiments demonstrate the usefulness of our approach in incorporating genetic information for fundus image based glaucoma detection.

  7. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans

    NARCIS (Netherlands)

    Verloop, H.; Dekkers, O.M.; Peeters, R.P.; Schoones, J.W.; Smit, J.W.

    2014-01-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clini

  8. Genetic engineering of human ES and iPS cells using TALE nucleases

    OpenAIRE

    Hockemeyer, Dirk; Wang, Haoyi; Kiani, Samira; Lai, Christine S.; Gao, Qing; Cassady, John P.; Cost, Gregory J.; Zhang, Lei; Santiago, Yolanda; Miller, Jeffrey C; Zeitler, Bryan; Cherone, Jennifer M.; Meng, Xiangdong; Hinkley, Sarah J; Rebar, Edward J.

    2011-01-01

    Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator–like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that T...

  9. Methods of Sports Genetics: dermatoglyphic analysis of human fingerprints (information 1

    Directory of Open Access Journals (Sweden)

    Serhiyenko L.P.

    2010-02-01

    Full Text Available The article provides data on the dermatoglyphic analysis of human fingerprints. The most informative dermatoglyphic traits of fingerprints are defined. They can be used as genetic markers to prognosticate sports endowments. The recommendations to use the technology of dermatoglyphic analysis of human fingerprints in sports genetics are given. There are certain national and racial differences in phenotypical expressed of dermatoglyphics of digit patterns.

  10. Perspectives on human genetic variation from the HapMap Project.

    OpenAIRE

    2005-01-01

    ABSTRACT The completion of the International HapMap Project marks the start of a new phase in human genetics. The aim of the project was to provide a resource that facilitates the design of efficient genome-wide association studies, through characterising patterns of genetic variation and linkage disequilibrium in a sample of 270 individuals across four geographical populations. In total, over one million SNPs have been typed across these genomes, providing an unprecedented view of human gene...

  11. Legal Regulation of Human Trials of Genetically Modified Foods:A Constitutional Analysis Based on the Golden Rice Case%转基因食品人体试验的法律规制--基于“黄金大米”事件的宪法分析

    Institute of Scientific and Technical Information of China (English)

    吕方圆

    2015-01-01

    The exposure of Golden Rice Case caused people to think about human trials of genetically modified foods.In this human trial,human dignity,right to life,right to health,and privacy of students participating in the trial were violated.At present,there are plenty of illegal biomedical human trials in China,which invade the interests of the subjects.There are not any specified laws regulating of human trials.The subjects’rights are vulnerable.However,by the external regulation of market,it is impossible to regulate human trials effectively and protect subjects’interests.Therefore,it is necessary to enact Human Trails Act and make special provisions for human trials of genetically modified food.The law bases on the principle of human dignity,with the protection of subjects’human rights at it’s core.By reviewing of the Institutional Review Board and license system executed by health administrative departments,the law aims to protect the subjects’human rights.%“黄金大米”事件的曝光引发了人们对于转基因食品人体试验的法学思考。在该转基因食品人体试验中,参与试验学生的尊严、生命权、健康权、知情同意权都受到了一定的侵害。现阶段,我国存在着许多违法的生物医学人体试验,这严重侵害了受试者的权益。目前,我国尚未有专门的法律对人体试验进行规制,人体试验中受试者权利易受侵害,而通过市场的外在调节,难以达到有效规范人体实验、保护受试者的人权的目的,因而需要制定专门的《人体试验法》。该法律应该以保障人的尊严为原则,以受试者人权保护为核心,同时在程序上应执行伦理委员会审查和卫生行政部门许可的双审制度。

  12. Human Genome Epidemiology : A scientific foundation for using genetic information to improve health and prevent disease

    Directory of Open Access Journals (Sweden)

    Stefania Boccia

    2005-03-01

    Full Text Available

    Human health is determined by the interplay of genetic factors and the environment. In this context the recent advances in human genomics are expected to play a central role in medicine and public health by providing genetic information for disease prediction and prevention.

    After the completion of the human genome sequencing, a fundamental step will be represented by the translation of these discoveries into meaningful actions to improve health and prevent diseases, and the field of epidemiology plays a central role in this effort. These are some of the issues addressed by Human Genome Epidemiology –A scientific foundation for using genetic information to improve health and prevent disease, a volume edited by Prof. M. Khoury, Prof. J. Little, Prof.W. Burke and published by Oxford university Press 2004.

    This book describes the important role that epidemiological methods play in the continuum from gene discovery to the development and application of genetic tests. The Authors calls this continuum human genome epidemiology (HuGE to denote an evolving field of inquiry that uses systematic applications of epidemiological methods to assess the impact of human genetic variation on health and disease.

    The book is divided into four sections and it is structured to allow readers to proceed systematically from the fundamentals of genome technology and discovery, to the epidemiological approaches, to gene characterisation, to the evaluation of genetic tests and their use in health services and public health.

  13. Computational dissection of human episodic memory reveals mental process-specific genetic profiles.

    Science.gov (United States)

    Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2015-09-01

    Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

  14. Human genetic variation: new challenges and opportunities for doping control.

    Science.gov (United States)

    Schneider, Angela J; Fedoruk, Matthew N; Rupert, Jim L

    2012-01-01

    Sport celebrates differences in competitors that lead to the often razor-thin margins between victory and defeat. The source of this variation is the interaction between the environment in which the athletes develop and compete and their genetic make-up. However, a darker side of sports may also be genetically influenced: some anti-doping tests are affected by the athlete's genotype. Genetic variation is an issue that anti-doping authorities must address as more is learned about the interaction between genotype and the responses to prohibited practices. To differentiate between naturally occurring deviations in indirect blood and urine markers from those potentially caused by doping, the "biological-passport" program uses intra-individual variability rather than population values to establish an athlete's expected physiological range. The next step in "personalized" doping control may be the inclusion of genetic data, both for the purposes of documenting an athlete's responses to doping agents and doping-control assays as well facilitating athlete and sample identification. Such applications could benefit "clean" athletes but will come at the expense of risks to privacy. This article reviews the instances where genetics has intersected with doping control, and briefly discusses the potential role, and ethical implications, of genotyping in the struggle to eliminate illicit ergogenic practices.

  15. Discovering Pair-Wise Genetic Interactions: An Information Theory-Based Approach

    Science.gov (United States)

    Ignac, Tomasz M.; Skupin, Alexander; Sakhanenko, Nikita A.; Galas, David J.

    2014-01-01

    Phenotypic variation, including that which underlies health and disease in humans, results in part from multiple interactions among both genetic variation and environmental factors. While diseases or phenotypes caused by single gene variants can be identified by established association methods and family-based approaches, complex phenotypic traits resulting from multi-gene interactions remain very difficult to characterize. Here we describe a new method based on information theory, and demonstrate how it improves on previous approaches to identifying genetic interactions, including both synthetic and modifier kinds of interactions. We apply our measure, called interaction distance, to previously analyzed data sets of yeast sporulation efficiency, lipid related mouse data and several human disease models to characterize the method. We show how the interaction distance can reveal novel gene interaction candidates in experimental and simulated data sets, and outperforms other measures in several circumstances. The method also allows us to optimize case/control sample composition for clinical studies. PMID:24670935

  16. GeneNetwork: framework for web-based genetics

    NARCIS (Netherlands)

    Sloan, Zachary; Arends, Danny; Broman, Karl W.; Centeno, Arthur; Furlotte, Nicholas; Nijveen, H.; Yan, Lei; Zhou, Xiang; Williams, Robert W.; Prins, Pjotr

    2016-01-01

    GeneNetwork (GN) is a free and open source (FOSS) framework for web-based genetics that can be deployed anywhere. GN allows biologists to upload high-throughput experimental data, such as expression data from microarrays and RNA-seq, and also `classic' phenotypes, such as disease phenotypes. These p

  17. THE MEANING OF GENOMIC IMPRINTING IN HUMAN GENETIC AND DEFECTOLOGY

    Directory of Open Access Journals (Sweden)

    Anastas LAKOSKI

    2000-12-01

    Full Text Available Several genetic phenomena do not appear to conform the Mendel's low in the sense that they are not inherited in simple way through the generations. Such exceptions to Mendel's laws include new mutations, changes in chromosomes, expanded triplet sequences, and genomic imprinting. Many genetic diseases involve spontaneous mutations that are not inherited from generation to generation. Changes in chromosomes include nondisjunction, which is the most important cause of mental retardation, the trisomy of Dowen syndrome. Expanded triplet repeats are responsible for the next important cause of mental retardation, fragile X, and for Huntington's disease. Genomic imprinting occurs when the expression of a gene depends on whether it is inherited from the mother or from the father. In this paper the phenomenon of genomic imprinting is explained on the occurrence of Angelman and Prader-Willi syndromes. It's essential for the counselor to be able during the genetic counseling to recognize this phenomenon and to make a proper decision.

  18. Human Genetic Variation and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sun Ju Chung

    2010-05-01

    Full Text Available Parkinson’s disease (PD is a chronic neurodegenerative disorder with multifactorial etiology. In the past decade, the genetic causes of monogenic forms of familial PD have been defined. However, the etiology and pathogenesis of the majority of sporadic PD cases that occur in outbred populations have yet to be clarified. The recent development of resources such as the International HapMap Project and technological advances in high-throughput genotyping have provided new basis for genetic association studies of common complex diseases, including PD. A new generation of genome-wide association studies will soon offer a potentially powerful approach for mapping causal genes and will likely change treatment and alter our perception of the genetic determinants of PD. However, the execution and analysis of such studies will require great care.

  19. Stellar Population Analysis of Galaxies based on Genetic Algorithms

    Institute of Scientific and Technical Information of China (English)

    Abdel-Fattah Attia; H.A.Ismail; I.M.Selim; A.M.Osman; I.A.Isaa; M.A.Marie; A.A.Shaker

    2005-01-01

    We present a new method for determining the age and relative contribution of different stellar populations in galaxies based on the genetic algorithm.We apply this method to the barred spiral galaxy NGC 3384, using CCD images in U, B, V, R and I bands. This analysis indicates that the galaxy NGC 3384 is mainly inhabited by old stellar population (age > 109 yr). Some problems were encountered when numerical simulations are used for determining the contribution of different stellar populations in the integrated color of a galaxy. The results show that the proposed genetic algorithm can search efficiently through the very large space of the possible ages.

  20. Optimizing Combination of Units Commitment Based on Improved Genetic Algorithms

    Institute of Scientific and Technical Information of China (English)

    LAI Yifei; ZHANG Qianhua; JIA Junping

    2007-01-01

    GAs are general purpose optimization techniques based on principles inspired from the biological evolution using metaphors of mechanisms, such as natural selection, genetic recombination and survival of the fittest. By use of coding betterment, the dynamic changes of the mutation rate and the crossover probability, the dynamic choice of subsistence, the reservation of the optimal fitness value, a modified genetic algorithm for optimizing combination of units in thermal power plants is proposed.And through taking examples, test result are analyzed and compared with results of some different algorithms. Numerical results show available value for the unit commitment problem with examples.

  1. [The application of genetic risk score in genetic studies of complex human diseases].

    Science.gov (United States)

    Dayan, Niu; Weili, Yan

    2015-12-01

    Complex diseases such as cardiovascular disease, type 2 diabetes, essential hypertension, asthma, obesity and cancer have spread across the globe and become the predominant cause of death. There are growing concerns over the role of genetic susceptibility in pathogenesis of complex diseases. However, the related susceptibility genes and sequence variations are still unknown. To elucidate the genetic basis of complex diseases, researchers have identified a large number of genetic variants associated with complex diseases through genome-wide association studies (GWAS) and candidate gene studies recently. The identification of these causal and/or associated variants promotes the development of approaches for complex diseases prediction and prevention. Genetic risk score (GRS), an emerging method for exploring correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes of complex diseases, integrates weak effects of multiple SNPs and dramatically enhances predictability of complex diseases by gene polymorphisms. This method has been applied successfully in genetic studies of many complex diseases. Here we focus on the introduction of the computational methods and evaluation criteria of GRS, enumerate a series of achievements through GRS application, discuss some limitations during application, and finally prospect the future of GRS.

  2. Immune and Genetic Algorithm Based Assembly Sequence Planning

    Institute of Scientific and Technical Information of China (English)

    YANG Jian-guo; LI Bei-zhi; YU Lei; JIN Yu-song

    2004-01-01

    In this paper an assembly sequence planning model inspired by natural immune and genetic algorithm (ASPIG) based on the part degrees of freedom matrix (PDFM) is proposed, and a proto system - DSFAS based on the ASPIG is introduced to solve assembly sequence problem. The concept and generation of PDFM and DSFAS are also discussed. DSFAS can prevent premature convergence, and promote population diversity, and can accelerate the learning and convergence speed in behavior evolution problem.

  3. [Improvement of genetics teaching using literature-based learning model].

    Science.gov (United States)

    Liang, Liang; Shiqian, Liang; Hongyan, Qin; Yong, Ji; Hua, Han

    2015-06-01

    Genetics is one of the most important courses for undergraduate students majoring in life science. In recent years, new knowledge and technologies are continually updated with deeper understanding of life science. However, the teaching model of genetics is still based on theoretical instruction, which makes the abstract principles hard to understand by students and directly affects the teaching effect. Thus, exploring a new teaching model is necessary. We have carried out a new teaching model, literature-based learning, in the course on Microbial Genetics for undergraduate students majoring in biotechnology since 2010. Here we comprehensively analyzed the implementation and application value of this model including pre-course knowledge, how to choose professional literature, how to organize teaching process and the significance of developing this new teaching model for students and teachers. Our literature-based learning model reflects the combination of "cutting-edge" and "classic" and makes book knowledge easy to understand, which improves students' learning effect, stimulates their interests, expands their perspectives and develops their ability. This practice provides novel insight into exploring new teaching model of genetics and cultivating medical talents capable of doing both basic and clinical research in the "precision medicine" era.

  4. Method of stereo matching based on genetic algorithm

    Science.gov (United States)

    Lu, Chaohui; An, Ping; Zhang, Zhaoyang

    2003-09-01

    A new stereo matching scheme based on image edge and genetic algorithm (GA) is presented to improve the conventional stereo matching method in this paper. In order to extract robust edge feature for stereo matching, infinite symmetric exponential filter (ISEF) is firstly applied to remove the noise of image, and nonlinear Laplace operator together with local variance of intensity are then used to detect edges. Apart from the detected edge, the polarity of edge pixels is also obtained. As an efficient search method, genetic algorithm is applied to find the best matching pair. For this purpose, some new ideas are developed for applying genetic algorithm to stereo matching. Experimental results show that the proposed methods are effective and can obtain good results.

  5. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui;

    2011-01-01

    throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has......A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  6. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui;

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...... of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address...

  7. Genetic control of the alternative pathway of complement in humans and age-related macular degeneration.

    Science.gov (United States)

    Hecker, Laura A; Edwards, Albert O; Ryu, Euijung; Tosakulwong, Nirubol; Baratz, Keith H; Brown, William L; Charbel Issa, Peter; Scholl, Hendrik P; Pollok-Kopp, Beatrix; Schmid-Kubista, Katharina E; Bailey, Kent R; Oppermann, Martin

    2010-01-01

    Activation of the alternative pathway of complement is implicated in common neurodegenerative diseases including age-related macular degeneration (AMD). We explored the impact of common variation in genes encoding proteins of the alternative pathway on complement activation in human blood and in AMD. Genetic variation across the genes encoding complement factor H (CFH), factor B (CFB) and component 3 (C3) was determined. The influence of common haplotypes defining transcriptional and translational units on complement activation in blood was determined in a quantitative genomic association study. Individual haplotypes in CFH and CFB were associated with distinct and novel effects on plasma levels of precursors, regulators and activation products of the alternative pathway of complement in human blood. Further, genetic variation in CFH thought to influence cell surface regulation of complement did not alter plasma complement levels in human blood. Plasma markers of chronic activation (split-products Ba and C3d) and an activating enzyme (factor D) were elevated in AMD subjects. Most of the elevation in AMD was accounted for by the genetic variation controlling complement activation in human blood. Activation of the alternative pathway of complement in blood is under genetic control and increases with age. The genetic variation associated with increased activation of complement in human blood also increased the risk of AMD. Our data are consistent with a disease model in which genetic variation in the complement system increases the risk of AMD by a combination of systemic complement activation and abnormal regulation of complement activation in local tissues.

  8. Human genetic susceptibility and infection with Leishmania peruviana

    Energy Technology Data Exchange (ETDEWEB)

    Shaw, M.A.; Davis, C.R.; Collins, A. [and others

    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. 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.

  9. Comparison of French and Estonian Students' Conceptions in Genetic Determinism of Human Behaviours

    Science.gov (United States)

    Castera, Jeremy; Sarapuu, Tago; Clement, Pierre

    2013-01-01

    Innatism is the belief that most of the human personality can be determined by genes. This ideology is dangerous, especially when it claims to be scientific. The present study investigates conceptions of 1060 students from Estonia and France related to genetic determinism of some human behaviours. Factors taken into account included students'…

  10. Genetic factors in human reproduction : a trade off between procreation and longevity

    NARCIS (Netherlands)

    Dunné, Frédérique Margo van

    2006-01-01

    Genetic factors play an important role in the regulation of human life span but the exact pathways remain to be elucidated, however they may be interrelated with the regulation of human reproduction. It is argued that an innate cytokine profile supportive of Th1-type T cells favors survival of infec

  11. The impact of recent events on human genetic diversity.

    Science.gov (United States)

    Jobling, Mark A

    2012-03-19

    The historical record tells us stories of migrations, population expansions and colonization events in the last few thousand years, but what was their demographic impact? Genetics can throw light on this issue, and has mostly done so through the maternally inherited mitochondrial DNA (mtDNA) and the male-specific Y chromosome. However, there are a number of problems, including marker ascertainment bias, possible influences of natural selection, and the obscuring layers of the palimpsest of historical and prehistorical events. Y-chromosomal lineages are particularly affected by genetic drift, which can be accentuated by recent social selection. A diversity of approaches to expansions in Europe is yielding insights into the histories of Phoenicians, Roma, Anglo-Saxons and Vikings, and new methods for producing and analysing genome-wide data hold much promise. The field would benefit from more consensus on appropriate methods, and better communication between geneticists and experts in other disciplines, such as history, archaeology and linguistics.

  12. The dynamic human brain : Genetic aspects in schizophrenia and health

    OpenAIRE

    Brans, R.G.H.

    2009-01-01

    The general aim of this thesis is to explore the possible mechanisms underlying the individual differences in brain structure and brain structure change in healthy adults and schizophrenia patients. For this purpose, Magnetic Resonance Imaging scans of the brain were acquired in schizophrenia patients, their relatives and healthy comparison subjects. Since all studies are conducted in relatives, we were able to disentangle genetic and environmental influences on the studied phenotypes. Taken ...

  13. An Exercise in Molecular Epidemiology: Human Rhinovirus Prevalence and Genetics

    Science.gov (United States)

    Albright, Catherine J.; Hall, David J.

    2011-01-01

    Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques…

  14. Genetics and epigenetics of repeat derepression in human disease

    NARCIS (Netherlands)

    Thijssen, P.E.

    2016-01-01

    A large part of the human genome consists of repetitive DNA. In this thesis two human diseases have been studied in which deregulation of repetitive DNA is a central feature: facioscapulohumeral muscular dystrophy (FSHD) and immunodeficiency, centromere instability and facial anomalies (ICF) syndrom

  15. Molecular genetic analysis of Dongzhou-period ancient human of Helingeer in Inner Mongolia, China

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The mtDNA hypervariable region I (HVR-I) of 10 ancient individuals from Dongzhou-period ancient human populations in Helingeer county of Inner Mongolia were amplified and sequenced to investigate the genetic structure. The relationships between the ancient population and related extant populations, as well as its possible origin at the molecular level, were also studied. Moreover, phylogenetic analysis and multi-dimensional scaling analysis were also performed based on the mtDNA data of the ancient population in Helingeer and the related Eurasian population. The results showed that the ancient population in Helingeer were closer to the northern Asian populations than to the other compared populations in matrilineal lineage. Combining the research results of archaeology and anthropology as well as molecular biology, we inferred that they were nomads who migrated from Mongolia plateau and cis-Baikal region to Helingeer in Inner Mongolia, China.

  16. Evolutionary anthropology and genes: investigating the genetics of human evolution from excavated skeletal remains.

    Science.gov (United States)

    Anastasiou, Evilena; Mitchell, Piers D

    2013-10-01

    The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution.

  17. The Bifidobacterium dentium Bd1 genome sequence reflects its genetic adaptation to the human oral cavity.

    Directory of Open Access Journals (Sweden)

    Marco Ventura

    2009-12-01

    Full Text Available Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria. However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from

  18. Genetic Algorithm based PID controller for Frequency Regulation Ancillary services

    Directory of Open Access Journals (Sweden)

    Sandeep Bhongade

    2010-12-01

    Full Text Available In this paper, the parameters of Proportional, Integral and Derivative (PID controller for Automatic Generation Control (AGC suitable in restructured power system is tuned according to Generic Algorithms (GAs based performance indices. The key idea of the proposed method is to use the fitness function based on Area Control Error (ACE. The functioning of the proposed Genetic Algorithm based PID (GAPID controller has been demonstrated on a 75-bus Indian power system network and the results have been compared with those obtained by using Least Square Minimization method.

  19. Transplantation of human hepatocytes into tolerized genetically immunocompetent rats

    Institute of Scientific and Technical Information of China (English)

    Edwin C. Ouyang; Catherine H. Wu; Cherie Walton; Kittichai Promrat; George Y. Wu

    2001-01-01

    AIM To determine whether normal geneticallyirnmunocornpetent rodent hosts could bemanipulated to accept human hepatocytetransplants with long term survival withoutirnrnunosuppression.METHODS Tolerance towards humanhepatocytes was established by injection ofprimary human hepatocytes or Huh7 humanhepatoma cells into the peritoneal cavities offetal rats. Corresponding cells weresubsequently transplanted into newborn rats viaintrasplenic injection within 24 h after birth.RESULTS Mixed lymphocyte assays showedthat spleen cells from non-tolerized rats werestimulated to proliferate when exposed to humanhepatocytes, while cells from tolerized ratswere not. Injections made between 15 d and 17 dof gestation produced optimal tolerizaton.Transplanted human hepatocytes in rat liverswere visualized by immunohistochemicalstaining of human albumin. By dot blotting ofgenomic DNA in livers of tolerized rats 16 weeksafter hepatocyte transplantation, it was foundthat approximately 2.5 × 105 human hepatocytessurvived per rat liver. Human albumin mRNA wasdetected in rat livers by RT-PCR for 15 wk, andhuman albumin protein was also detectable in ratserum.CONCLUSION Tolerization of an immuno-competent rat can permit transplantation, andsurvival of functional human hepatocytes.

  20. Genetic algorithm for network cost minimization using threshold based discounting

    Directory of Open Access Journals (Sweden)

    Hrvoje Podnar

    2003-01-01

    Full Text Available We present a genetic algorithm for heuristically solving a cost minimization problem applied to communication networks with threshold based discounting. The network model assumes that every two nodes can communicate and offers incentives to combine flow from different sources. Namely, there is a prescribed threshold on every link, and if the total flow on a link is greater than the threshold, the cost of this flow is discounted by a factor α. A heuristic algorithm based on genetic strategy is developed and applied to a benchmark set of problems. The results are compared with former branch and bound results using the CPLEX® solver. For larger data instances we were able to obtain improved solutions using less CPU time, confirming the effectiveness of our heuristic approach.

  1. Genetic algorithm-based evaluation of spatial straightness error

    Institute of Scientific and Technical Information of China (English)

    崔长彩; 车仁生; 黄庆成; 叶东; 陈刚

    2003-01-01

    A genetic algorithm ( GA ) -based approach is proposed to evaluate the straightness error of spatial lines. According to the mathematical definition of spatial straightness, a verification model is established for straightness error, and the fitness function of GA is then given and the implementation techniques of the proposed algorithm is discussed in detail. The implementation techniques include real number encoding, adaptive variable range choosing, roulette wheel and elitist combination selection strategies, heuristic crossover and single point mutation schemes etc. An application example is quoted to validate the proposed algorithm. The computation result shows that the GA-based approach is a superior nonlinear parallel optimization method. The performance of the evolution population can be improved through genetic operations such as reproduction, crossover and mutation until the optimum goal of the minimum zone solution is obtained. The quality of the solution is better and the efficiency of computation is higher than other methods.

  2. Human genetic deficiencies reveal the roles of complement in the inflammatory network: lessons from nature

    DEFF Research Database (Denmark)

    Lappegård, Knut Tore; Christiansen, Dorte; Pharo, Anne;

    2009-01-01

    Complement component C5 is crucial for experimental animal inflammatory tissue damage; however, its involvement in human inflammation is incompletely understood. The responses to gram-negative bacteria were here studied taking advantage of human genetic complement-deficiencies--nature's own...... of complement and CD14. The present study provides important insight into the comprehensive role of complement in human inflammatory responses to gram-negative bacteria....

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

    Science.gov (United States)

    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 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. PMID:28003435

  4. Migration distance rather than migration rate explains genetic diversity in human patrilocal groups.

    Science.gov (United States)

    Marks, Sarah J; Levy, Hila; Martinez-Cadenas, Conrado; Montinaro, Francesco; Capelli, Cristian

    2012-10-01

    In patrilocal groups, females preferentially move to join their mate's paternal relatives. The gender-biased gene flow generated by this cultural practice is expected to affect genetic diversity across human populations. Greater female than male migration is predicted to result in a larger decrease in between-group differentiation for mitochondrial DNA (mtDNA) than for the non-recombining part of the Y chromosome (NRY). We address the question of how patrilocality affects the distribution of genetic variation in human populations controlling for confounding factors such as ethno-linguistic heterogeneity and geographic distance which possibly explain the contradictory results observed in previous studies. By combining genetic and bio-demographic data from Lesotho and Spain, we show that preferential female migration over short distances appears to minimize the impact of a generally higher female migration rate in patrilocal communities, suggesting patrilocality might influence genetic variation only at short ranges.

  5. Genetics and human rights. Two histories : restoring genetic identify after forced disappearance and identify suppression in Argentina and after compulsory isolation for leprosy in Brazil

    OpenAIRE

    Penchaszadeh, Victor; Faccini, Lavinia Schuler

    2014-01-01

    Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to i...

  6. Genetics and human rights: Two histories: restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil

    OpenAIRE

    Penchaszadeh,Victor B.; Lavinia Schuler-Faccini

    2014-01-01

    Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to i...

  7. The New World of Human Genetics: A dialogue between Practitioners & the General Public on Ethical, Legal & Social Implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Schofield, Amy

    2014-12-08

    The history and reasons for launching the Human Genome project and the current uses of genetic human material; Identifying and discussing the major issues stemming directly from genetic research and therapy-including genetic discrimination, medical/ person privacy, allocation of government resources and individual finances, and the effect on the way in which we perceive the value of human life; Discussing the sometimes hidden ethical, social and legislative implications of genetic research and therapy such as informed consent, screening and preservation of genetic materials, efficacy of medical procedures, the role of the government, and equal access to medical coverage.

  8. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis.

    Science.gov (United States)

    Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O

    2015-04-09

    Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.

  9. Progress report on research on human genetics in Iceland

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-10-31

    Records of the Icelandic population are being used to investigate the possible inheritance of disabilities and diseases as well as other characteristics and the effect of environment on man. The progress report of research covers the period from 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  10. Research on human genetics in Iceland. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-10-31

    Records of the Icelandic Population are being used to investigate the possible inheritance of disabilities and diseases as well as other characters and the effect of environment on man. The progress report of research covers the period 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  11. Support Vector Machine Ensemble Based on Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    LI Ye; YIN Ru-po; CAI Yun-ze; XU Xiao-ming

    2006-01-01

    Support vector machines (SVMs) have been introduced as effective methods for solving classification problems.However, due to some limitations in practical applications,their generalization performance is sometimes far from the expected level. Therefore, it is meaningful to study SVM ensemble learning. In this paper, a novel genetic algorithm based ensemble learning method, namely Direct Genetic Ensemble (DGE), is proposed. DGE adopts the predictive accuracy of ensemble as the fitness function and searches a good ensemble from the ensemble space. In essence, DGE is also a selective ensemble learning method because the base classifiers of the ensemble are selected according to the solution of genetic algorithm. In comparison with other ensemble learning methods, DGE works on a higher level and is more direct. Different strategies of constructing diverse base classifiers can be utilized in DGE.Experimental results show that SVM ensembles constructed by DGE can achieve better performance than single SVMs,bagged and boosted SVM ensembles. In addition, some valuable conclusions are obtained.

  12. Comparison of morphological and molecular genetic sex-typing on mediaeval human skeletal remains☆

    Science.gov (United States)

    Bauer, Christiane Maria; Niederstätter, Harald; McGlynn, George; Stadler, Harald; Parson, Walther

    2013-01-01

    Archaeological excavations conducted at an early mediaeval cemetery in Volders (Tyrol, Austria) produced 141 complete skeletal remains dated between the 5th/6th and 12th/13th centuries. These skeletons represent one of the largest historical series of human remains ever discovered in the East Alpine region. Little historical information is available for this region and time period. The good state of preservation of these bioarchaeological finds offered the opportunity of performing molecular genetic investigations. Adequate DNA extraction methods were tested in the attempt to obtain as high DNA yields as possible for further analyses. Molecular genetic sex-typing using a dedicated PCR multiplex (“Genderplex”) gave interpretable results in 88 remains, 78 of which had previously been sexed based on morphological features. We observed a discrepancy in sex determination between the two methods in 21 cases. An unbiased follow-up morphological examination of these finds showed congruence with the DNA results in all but five samples. PMID:23941903

  13. Genetic manipulation of human embryonic stem cells in serum and feeder-free media.

    Science.gov (United States)

    Braam, Stefan R; Denning, Chris; Mummery, Christine L

    2010-01-01

    Generic methods for genetic manipulation of human embryonic stem cells (hESCs) are important for both present research and future commercial applications. To date, differences in cell derivation and culture have required independent optimization of transfection and transduction protocols and some lines have remained refractile to all methods. Here we describe a culture protocol that has been extensively tested in 12 different hESC lines (1, 2) and shown to support efficient gene transfer independent of the method of gene delivery or history of the cell line. The system is based on Matrigel monolayer culture and conditioned medium from mouse embryonic feeder cells (MEFs) and entails transient high-density culture followed by rapid adaptation to low density for gene transfer. Under these conditions, plasmid transfection, virus infection, and siRNA transfection are highly effective. Stable genetically modified hESC lines can be generated with plasmid transfection, viral infection, or electroporation without loss of pluripotency or differentiation potential. The majority of lines generated in this system display a normal karyotype.

  14. Genetic Evaluation of Schizophrenia Using the Illumina HumanExome Chip

    Science.gov (United States)

    Moons, Tim; De Hert, Marc; Gellens, Edith; Gielen, Leen; Sweers, Kim; Jacqmaert, Sigrun; van Winkel, Ruud; Vandekerckhove, Philippe; Claes, Stephan

    2016-01-01

    Introduction Schizophrenia is a genetically heterogeneous disorder that is associated with several common and rare genetic variants. As technology involved, cost advantages of chip based genotyping was combined with information about rare variants, resulting in the Infinium HumanExome Beadchip. Using this chip, a sample of 493 patients with schizophrenia or schizoaffective disorder and 484 healthy controls was genotyped. Results From the initial 242901 SNVs, 88306 had at least one minor allele and passed quality control. No variant reached genomewide-significant results (p<10-8). The SNP with the lowest p-value was rs1230345 in WISP3 (p = 3.05*10−6), followed by rs9311525 in CACNA2D3 (p = 1.03*10−5) and rs1558557 (p = 3.85*10−05) on chromosome 7. At the gene level, 3 genes were of interest: WISP3, on chromosome 6q21, a signally protein from the extracellular matrix. A second candidate gene is CACNA2D3, a regulator of the intracerebral calcium pathway. A third gene is TNFSF10, associated with p53 mediated apoptosis. PMID:27028512

  15. Genetically Engineered Corn Rootworm Resistance: Potential for Reduction of Human Health Effects From Pesticides

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective and Methods Insecticide use, grower preferences regarding genetically engineered (GE) corn resistant to corn rootworm (CRW), and the health effects of using various CRW insecticides (organophosphates, pyrethroids, fipronil and carbamates) are reviewed for current and future farm practices. Results Pest damage to corn has been reduced only one-third by insecticide applications. Health costs from insecticide use appear significant, but costs attributable to CRW control are not quantifiable from available data. Methods reducing health-related costs of insecticide-based CRW control should be evaluated. As a first step, organophosphate insecticide use has been reduced as they have high acute toxicity and risk of long-term neurological consequences. A second step is to use agents which more specifically target the CRW. Conclusion Whereas current insecticides may be poisonous to many species of insects, birds, mammals and humans, a protein derived from Bacillus thurigiensis and produced in plants via genetic modification can target the specific insect of CRW (Coleoptra), sparing other insect and non-insect species from injury.

  16. Genomic and Network Patterns of Schizophrenia Genetic Variation in Human Evolutionary Accelerated Regions

    OpenAIRE

    Xu, Ke; Schadt, Eric E.; Pollard, Katherine S.; Roussos, Panos; Joel T Dudley

    2015-01-01

    The population persistence of schizophrenia despite associated reductions in fitness and fecundity suggests that the genetic basis of schizophrenia has a complex evolutionary history. A recent meta-analysis of schizophrenia genome-wide association studies offers novel opportunities for assessment of the evolutionary trajectories of schizophrenia-associated loci. In this study, we hypothesize that components of the genetic architecture of schizophrenia are attributable to human lineage-specifi...

  17. Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): Reassignment to human chromosome 12q

    Energy Technology Data Exchange (ETDEWEB)

    Howard, T.D.; Akots, G.; Bowden, D.W. [Bowman Gray School of Medicine of Wake Forest Univ., Winston-Salem, NC (United States)

    1996-05-15

    Phosphofructokinase (PFK) is a key rate-limiting enzyme in glycolysis and represents a major control point in the metabolism of glucose. There are at least three known isoforms of PFK in humans, referred to as the muscle, platelet, and liver forms, each of which is differentially expressed in various tissues. The gene for muscle phosphofructokinase, PFKM, is mutated in Tarui disease and conceivably contributes to non-insulin-dependent diabetes mellitus (NIDDM). Based on physical and genetic mapping, we have found that the gene for PFKM does not map to chromosome 1 as previously described, but instead maps to chromosome 12. PCR analysis with a somatic cell hybrid mapping panel using primers derived from intron 6 and exon 18 of the PFKM gene showed consistent amplification of cell lines containing chromosome 12 (concordance, 100%). Fluorescence in situ hybridization analysis with CEPH YAC 762G4, isolated with exon 18 primers, indicated that this clone maps to 12q13, centromeric to the diacylglycerol kinase gene (DAGK) at 12q13.3. A highly informative genetic marker isolated from YAC 762G4 was used to map PFKM genetically between the CHLC framework markers D12S1090 and D12S390. This placement for 762G4 was significantly proximal to the recently reported locus for a third gene for maturity onset diabetes of the young (MODY). The PFKM-associated microsatellite will be a valuable tool in the evaluation of PFKM in diabetic populations as well as in linkage analysis in families with Tarui disease. 23 refs., 3 figs., 2 tabs.

  18. Characterization of large structural genetic mosaicism in human autosomes.

    Science.gov (United States)

    Machiela, Mitchell J; Zhou, Weiyin; Sampson, Joshua N; Dean, Michael C; Jacobs, Kevin B; Black, Amanda; Brinton, Louise A; Chang, I-Shou; Chen, Chu; Chen, Constance; Chen, Kexin; Cook, Linda S; Crous Bou, Marta; De Vivo, Immaculata; Doherty, Jennifer; Friedenreich, Christine M; Gaudet, Mia M; Haiman, Christopher A; Hankinson, Susan E; Hartge, Patricia; Henderson, Brian E; Hong, Yun-Chul; Hosgood, H Dean; Hsiung, Chao A; Hu, Wei; Hunter, David J; Jessop, Lea; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Robert; Kraft, Peter; Lan, Qing; Lin, Dongxin; Liu, Jianjun; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M; Matsuo, Keitaro; Olson, Sara H; Orlow, Irene; Park, Jae Yong; Pooler, Loreall; Prescott, Jennifer; Rastogi, Radhai; Risch, Harvey A; Schumacher, Fredrick; Seow, Adeline; Setiawan, Veronica Wendy; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; VanDen Berg, David; Wang, Jiu-Cun; Wentzensen, Nicolas; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Yi-Long; Xia, Lucy; Yang, Hannah P; Yang, Pan-Chyr; Zheng, Wei; Zhou, Baosen; Abnet, Christian C; Albanes, Demetrius; Aldrich, Melinda C; Amos, Christopher; Amundadottir, Laufey T; Berndt, Sonja I; Blot, William J; Bock, Cathryn H; Bracci, Paige M; Burdett, Laurie; Buring, Julie E; Butler, Mary A; Carreón, Tania; Chatterjee, Nilanjan; Chung, Charles C; Cook, Michael B; Cullen, Michael; Davis, Faith G; Ding, Ti; Duell, Eric J; Epstein, Caroline G; Fan, Jin-Hu; Figueroa, Jonine D; Fraumeni, Joseph F; Freedman, Neal D; Fuchs, Charles S; Gao, Yu-Tang; Gapstur, Susan M; Patiño-Garcia, Ana; Garcia-Closas, Montserrat; Gaziano, J Michael; Giles, Graham G; Gillanders, Elizabeth M; Giovannucci, Edward L; Goldin, Lynn; Goldstein, Alisa M; Greene, Mark H; Hallmans, Goran; Harris, Curtis C; Henriksson, Roger; Holly, Elizabeth A; Hoover, Robert N; Hu, Nan; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Koh, Woon-Puay; Kolonel, Laurence N; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C; LaCroix, Andrea; Landgren, Annelie; Landi, Maria Teresa; Li, Donghui; Liao, Linda M; Malats, Nuria; McGlynn, Katherine A; McNeill, Lorna H; McWilliams, Robert R; Melin, Beatrice S; Mirabello, Lisa; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M; Prokunina-Olsson, Ludmila; Purdue, Mark; Qiao, You-Lin; Rabe, Kari G; Rajaraman, Preetha; Real, Francisco X; Riboli, Elio; Rodríguez-Santiago, Benjamín; Rothman, Nathaniel; Ruder, Avima M; Savage, Sharon A; Schwartz, Ann G; Schwartz, Kendra L; Sesso, Howard D; Severi, Gianluca; Silverman, Debra T; Spitz, Margaret R; Stevens, Victoria L; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R; Teras, Lauren R; Tobias, Geoffrey S; Viswanathan, Kala; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J; Wheeler, William; White, Emily; Wiencke, John K; Wolpin, Brian M; Wu, Xifeng; Wunder, Jay S; Yu, Kai; Zanetti, Krista A; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G; de Andrade, Mariza; Barnes, Kathleen C; Beaty, Terri H; Bierut, Laura J; Desch, Karl C; Doheny, Kimberly F; Feenstra, Bjarke; Ginsburg, David; Heit, John A; Kang, Jae H; Laurie, Cecilia A; Li, Jun Z; Lowe, William L; Marazita, Mary L; Melbye, Mads; Mirel, Daniel B; Murray, Jeffrey C; Nelson, Sarah C; Pasquale, Louis R; Rice, Kenneth; Wiggs, Janey L; Wise, Anastasia; Tucker, Margaret; Pérez-Jurado, Luis A; Laurie, Cathy C; Caporaso, Neil E; Yeager, Meredith; Chanock, Stephen J

    2015-03-05

    Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

  19. A genetic study of the human low-voltage electroencephalogram.

    Science.gov (United States)

    Anokhin, A; Steinlein, O; Fischer, C; Mao, Y; Vogt, P; Schalt, E; Vogel, F

    1992-01-01

    The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studying new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given.

  20. Searching Online Mendelian Inheritance in Man (OMIM) for information on genetic loci involved in human disease.

    Science.gov (United States)

    Baxevanis, Andreas D

    2012-04-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of information on human genes and genetic disorders, with a particular emphasis on the interplay between observed phenotypes and underlying genotypes. This unit focuses on the basic methodology for formulating OMIM searches and illustrates the types of information that can be retrieved from OMIM, including descriptions of clinical manifestations resulting from genetic abnormalities. This unit also provides information on additional relevant medical and molecular biology databases. A basic knowledge of OMIM should be part of the armamentarium of physicians and scientists with an interest in research on the clinical aspects of genetic disorders.

  1. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.

    Science.gov (United States)

    Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A

    2005-01-01

    Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.

  2. Human genetics for non-scientists: Practical workshops for policy makers and opinion leaders

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    These workshops form part of a series of workshops that the Banbury and the DNA Learning Centers of Cold Spring Harbor Laboratory have held for a number of years, introducing genetics, and the ways in which scientific research is done, to non-scientists. The purpose of the workshops as stated in the grant application was: {open_quotes}Our objective is to foster a better understanding of the societal impact of human genome research by providing basic information on genetics to non-scientists whose professions or special interests interface with genetic technology.... Participants will be chosen for their interest in human genetics and for their roles as opinion leaders in their own communities. Primary care physicians are of particular interest to us for this series of workshops.{close_quotes} Two workshops were held under this grant. The first was held in 21-24 April, 1994 and attended by 20 participants, and the second was held 16-19 November, 1995, and attended by 16 participants. In each case, there was a combination of concept lectures on the foundations of human molecular genetics; lectures by invited specialists; and laboratory experiments to introduce non-scientists to the techniques used in molecular genetics.

  3. Human Variome Project country nodes: documenting genetic information within a country.

    Science.gov (United States)

    Patrinos, George P; Smith, Timothy D; Howard, Heather; Al-Mulla, Fahd; Chouchane, Lotfi; Hadjisavvas, Andreas; Hamed, Sherifa A; Li, Xi-Tao; Marafie, Makia; Ramesar, Rajkumar S; Ramos, Feliciano J; de Ravel, Thomy; El-Ruby, Mona O; Shrestha, Tilak Ram; Sobrido, María-Jesús; Tadmouri, Ghazi; Witsch-Baumgartner, Martina; Zilfalil, Bin Alwi; Auerbach, Arleen D; Carpenter, Kevin; Cutting, Garry R; Dung, Vu Chi; Grody, Wayne; Hasler, Julia; Jorde, Lynn; Kaput, Jim; Macek, Milan; Matsubara, Yoichi; Padilla, Carmancita; Robinson, Helen; Rojas-Martinez, Augusto; Taylor, Graham R; Vihinen, Mauno; Weber, Tom; Burn, John; Qi, Ming; Cotton, Richard G H; Rimoin, David

    2012-11-01

    The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project's aims and goals because they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up-to-date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on 12th December 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country-specific clinical genetics resources and summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects.

  4. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

    Directory of Open Access Journals (Sweden)

    Ruth Hershberg

    2008-12-01

    Full Text Available Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC. However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.

  5. Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice.

    Science.gov (United States)

    Wu, Min; Jung, Lina; Cooper, Adrian B; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Richardson, Andrea; Bosenburg, Marcus; Naber, Stephen P; DePinho, Ronald A; Kuperwasser, Charlotte; Robinson, Murray O

    2009-04-28

    Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.

  6. [The development of molecular human genetics and its significance for perspectives of modern medicine].

    Science.gov (United States)

    Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

    1989-01-01

    The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

  7. Identification of a genetic cluster influencing memory performance and hippocampal activity in humans.

    Science.gov (United States)

    de Quervain, Dominique J-F; Papassotiropoulos, Andreas

    2006-03-14

    Experimental work in animals has shown that memory formation depends on a cascade of molecular events. Here we show that variability of human memory performance is related to variability in genes encoding proteins of this signaling cascade, including the NMDA and metabotrobic glutamate receptors, adenylyl cyclase, CAMKII, PKA, and PKC. The individual profile of genetic variability in these signaling molecules correlated significantly with episodic memory performance (P < 0.00001). Moreover, functional MRI during memory formation revealed that this genetic profile correlated with activations in memory-related brain regions, including the hippocampus and parahippocampal gyrus. The present study indicates that genetic variability in the human homologues of memory-related signaling molecules contributes to interindividual differences in human memory performance and memory-related brain activations.

  8. The regulatory effect of miRNAs is a heritable genetic trait in humans

    Directory of Open Access Journals (Sweden)

    Geeleher Paul

    2012-08-01

    Full Text Available Abstract Background microRNAs (miRNAs have been shown to regulate the expression of a large number of genes and play key roles in many biological processes. Several previous studies have quantified the inhibitory effect of a miRNA indirectly by considering the expression levels of genes that are predicted to be targeted by the miRNA and this approach has been shown to be robust to the choice of prediction algorithm. Given a gene expression dataset, Cheng et al. defined the regulatory effect score (RE-score of a miRNA as the difference in the gene expression rank of targets of the miRNA compared to non-targeted genes. Results Using microarray data from parent-offspring trios from the International HapMap project, we show that the RE-score of most miRNAs is correlated between parents and offspring and, thus, inter-individual variation in RE-score has a genetic component in humans. Indeed, the mean RE-score across miRNAs is correlated between parents and offspring, suggesting genetic differences in the overall efficiency of the miRNA biogenesis pathway between individuals. To explore the genetics of this quantitative trait further, we carried out a genome-wide association study of the mean RE-score separately in two HapMap populations (CEU and YRI. No genome-wide significant associations were discovered; however, a SNP rs17409624, in an intron of DROSHA, was significantly associated with mean RE-score in the CEU population following permutation-based control for multiple testing based on all SNPs mapped to the canonical miRNA biogenesis pathway; of 244 individual miRNA RE-scores assessed in the CEU, 214 were associated (p p = 0.04 with mean RE-score in the YRI population. Interestingly, the same SNP was associated with 17 (8.5% of all expressed miRNA expression levels in the CEU. We also show here that the expression of the targets of most miRNAs is more highly correlated with global changes in miRNA regulatory effect than with the expression of

  9. Genetic Algorithm based Decentralized PI Type Controller: Load Frequency Control

    Science.gov (United States)

    Dwivedi, Atul; Ray, Goshaidas; Sharma, Arun Kumar

    2016-12-01

    This work presents a design of decentralized PI type Linear Quadratic (LQ) controller based on genetic algorithm (GA). The proposed design technique allows considerable flexibility in defining the control objectives and it does not consider any knowledge of the system matrices and moreover it avoids the solution of algebraic Riccati equation. To illustrate the results of this work, a load-frequency control problem is considered. Simulation results reveal that the proposed scheme based on GA is an alternative and attractive approach to solve load-frequency control problem from both performance and design point of views.

  10. Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.

    Science.gov (United States)

    Lindee, Susan

    2016-02-01

    In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention.

  11. Ancient Humans Influenced the Current Spatial Genetic Structure of Common Walnut Populations in Asia.

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    Paola Pollegioni

    Full Text Available Common walnut (Juglans regia L is an economically important species cultivated worldwide for its wood and nuts. It is generally accepted that J. regia survived and grew spontaneously in almost completely isolated stands in its Asian native range after the Last Glacial Maximum. Despite its natural geographic isolation, J. regia evolved over many centuries under the influence of human management and exploitation. We evaluated the hypothesis that the current distribution of natural genetic resources of common walnut in Asia is, at least in part, the product of ancient anthropogenic dispersal, human cultural interactions, and afforestation. Genetic analysis combined with ethno-linguistic and historical data indicated that ancient trade routes such as the Persian Royal Road and Silk Road enabled long-distance dispersal of J. regia from Iran and Trans-Caucasus to Central Asia, and from Western to Eastern China. Ancient commerce also disrupted the local spatial genetic structure of autochthonous walnut populations between Tashkent and Samarkand (Central-Eastern Uzbekistan, where the northern and central routes of the Northern Silk Road converged. A significant association between ancient language phyla and the genetic structure of walnut populations is reported even after adjustment for geographic distances that could have affected both walnut gene flow and human commerce over the centuries. Beyond the economic importance of common walnut, our study delineates an alternative approach for understanding how the genetic resources of long-lived perennial tree species may be affected by the interaction of geography and human history.

  12. Human Genetic Marker for Resistance to Radiation and Chemicals

    Energy Technology Data Exchange (ETDEWEB)

    DR. Howard B. Lieberman

    2001-05-11

    TO characterize the human HRDAD9 gene and evaluate its potential as a biomarker to predict susceptibility to the deleterious health effects potentially caused by exposure to radiations or chemicals present at DOE hazardous waste cleanup sites. HRAD9 is a human gene that is highly conserved throughout evolution. Related genes have been isolated from yeasts and mice, underscoring its biological significance. Most of our previous work involved characterization of the yeast gene cognate, wherein it was determined that the corresponding protein plays a significant role in promoting resistance of cells to radiations and chemicals, and in particular, controlling cell growth in response to DNA damage.

  13. Human genetic variation database, a reference database of genetic variations in the Japanese population

    Science.gov (United States)

    Higasa, Koichiro; Miyake, Noriko; Yoshimura, Jun; Okamura, Kohji; Niihori, Tetsuya; Saitsu, Hirotomo; Doi, Koichiro; Shimizu, Masakazu; Nakabayashi, Kazuhiko; Aoki, Yoko; Tsurusaki, Yoshinori; Morishita, Shinichi; Kawaguchi, Takahisa; Migita, Osuke; Nakayama, Keiko; Nakashima, Mitsuko; Mitsui, Jun; Narahara, Maiko; Hayashi, Keiko; Funayama, Ryo; Yamaguchi, Daisuke; Ishiura, Hiroyuki; Ko, Wen-Ya; Hata, Kenichiro; Nagashima, Takeshi; Yamada, Ryo; Matsubara, Yoichi; Umezawa, Akihiro; Tsuji, Shoji; Matsumoto, Naomichi; Matsuda, Fumihiko

    2016-01-01

    Whole-genome and -exome resequencing using next-generation sequencers is a powerful approach for identifying genomic variations that are associated with diseases. However, systematic strategies for prioritizing causative variants from many candidates to explain the disease phenotype are still far from being established, because the population-specific frequency spectrum of genetic variation has not been characterized. Here, we have collected exomic genetic variation from 1208 Japanese individuals through a collaborative effort, and aggregated the data into a prevailing catalog. In total, we identified 156 622 previously unreported variants. The allele frequencies for the majority (88.8%) were lower than 0.5% in allele frequency and predicted to be functionally deleterious. In addition, we have constructed a Japanese-specific major allele reference genome by which the number of unique mapping of the short reads in our data has increased 0.045% on average. Our results illustrate the importance of constructing an ethnicity-specific reference genome for identifying rare variants. All the collected data were centralized to a newly developed database to serve as useful resources for exploring pathogenic variations. Public access to the database is available at http://www.genome.med.kyoto-u.ac.jp/SnpDB/. PMID:26911352

  14. Statistical genetics with application to population-based study design: a primer for clinicians.

    Science.gov (United States)

    Beyene, Joseph; Pare, Guillaume

    2014-02-01

    With the completion of the entire human genome sequence and remarkable advances in genotyping technologies, there has been an increased interest in the application of genetics and genomics in biomedical research over the last decade. Large-scale population-based genetic association studies have now become routine and their application to several multifactorial diseases such as cardiovascular disorders has led to the identification of a number of novel susceptibility genes. However, to be able to interpret results from such studies, clinicians need to have a basic understanding of unique concepts and issues related to this fast-moving area of research. In this primer, we provide a broad overview of design, analysis, and methodological issues with a focus on population-based study design.

  15. Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women.

    Directory of Open Access Journals (Sweden)

    Thomas R Hawn

    Full Text Available BACKGROUND: Although several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early in vivo urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria. METHODOLOGY: We conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines. PRINCIPAL FINDINGS: Polymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65-7.17. Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P< or =0.0001. Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P< or =0.0001. In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004. CONCLUSIONS: TLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early in vivo human bladder immune responses prior to the development of symptomatic UTIs.

  16. A dynamic fuzzy clustering method based on genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yan; ZHOU Chunguang; LIANG Yanchun; GUO Dongwei

    2003-01-01

    A dynamic fuzzy clustering method is presented based on the genetic algorithm. By calculating the fuzzy dissimilarity between samples the essential associations among samples are modeled factually. The fuzzy dissimilarity between two samples is mapped into their Euclidean distance, that is, the high dimensional samples are mapped into the two-dimensional plane. The mapping is optimized globally by the genetic algorithm, which adjusts the coordinates of each sample, and thus the Euclidean distance, to approximate to the fuzzy dissimilarity between samples gradually. A key advantage of the proposed method is that the clustering is independent of the space distribution of input samples, which improves the flexibility and visualization. This method possesses characteristics of a faster convergence rate and more exact clustering than some typical clustering algorithms. Simulated experiments show the feasibility and availability of the proposed method.

  17. Healing Temperature of Hybrid Structures Based on Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    赵中伟; 陈志华; 刘红波

    2016-01-01

    The healing temperature of suspen-dome with stacked arches(SDSA)and arch-supported single-layer lattice shell structures was investigated based on the genetic algorithm. The temperature field of arch under solar radiation was derived by FLUENT to investigate the influence of solar radiation on the determination of the healing temperature. Moreover, a multi-scale model was established to apply the complex temperature field under solar radiation. The change in the mechanical response of these two kinds of structures with the healing temperature was discussed. It can be concluded that solar radiation has great influence on the healing temperature, and the genetic algorithm can be effectively used in the optimization of the healing temperature for hybrid structures.

  18. Characterization of Large Structural Genetic Mosaicism in Human Autosomes

    Science.gov (United States)

    Machiela, Mitchell J.; Zhou, Weiyin; Sampson, Joshua N.; Dean, Michael C.; Jacobs, Kevin B.; Black, Amanda; Brinton, Louise A.; Chang, I-Shou; Chen, Chu; Chen, Constance; Chen, Kexin; Cook, Linda S.; Crous Bou, Marta; De Vivo, Immaculata; Doherty, Jennifer; Friedenreich, Christine M.; Gaudet, Mia M.; Haiman, Christopher A.; Hankinson, Susan E.; Hartge, Patricia; Henderson, Brian E.; Hong, Yun-Chul; Hosgood, H. Dean; Hsiung, Chao A.; Hu, Wei; Hunter, David J.; Jessop, Lea; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Robert; Kraft, Peter; Lan, Qing; Lin, Dongxin; Liu, Jianjun; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Matsuo, Keitaro; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Pooler, Loreall; Prescott, Jennifer; Rastogi, Radhai; Risch, Harvey A.; Schumacher, Fredrick; Seow, Adeline; Setiawan, Veronica Wendy; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; VanDen Berg, David; Wang, Jiu-Cun; Wentzensen, Nicolas; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Yi-Long; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Zheng, Wei; Zhou, Baosen; Abnet, Christian C.; Albanes, Demetrius; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Berndt, Sonja I.; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Carreón, Tania; Chatterjee, Nilanjan; Chung, Charles C.; Cook, Michael B.; Cullen, Michael; Davis, Faith G.; Ding, Ti; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Freedman, Neal D.; Fuchs, Charles S.; Gao, Yu-Tang; Gapstur, Susan M.; Patiño-Garcia, Ana; Garcia-Closas, Montserrat; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Greene, Mark H.; Hallmans, Goran; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hoover, Robert N.; Hu, Nan; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Landgren, Annelie; Landi, Maria Teresa; Li, Donghui; Liao, Linda M.; Malats, Nuria; McGlynn, Katherine A.; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Prokunina-Olsson, Ludmila; Purdue, Mark; Qiao, You-Lin; Rabe, Kari G.; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Rodríguez-Santiago, Benjamín; Rothman, Nathaniel; Ruder, Avima M.; Savage, Sharon A.; Schwartz, Ann G.; Schwartz, Kendra L.; Sesso, Howard D.; Severi, Gianluca; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Viswanathan, Kala; Wacholder, Sholom; Wang, Zhaoming; Weinstein, Stephanie J.; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wu, Xifeng; Wunder, Jay S.; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G.; de Andrade, Mariza; Barnes, Kathleen C.; Beaty, Terri H.; Bierut, Laura J.; Desch, Karl C.; Doheny, Kimberly F.; Feenstra, Bjarke; Ginsburg, David; Heit, John A.; Kang, Jae H.; Laurie, Cecilia A.; Li, Jun Z.; Lowe, William L.; Marazita, Mary L.; Melbye, Mads; Mirel, Daniel B.; Murray, Jeffrey C.; Nelson, Sarah C.; Pasquale, Louis R.; Rice, Kenneth; Wiggs, Janey L.; Wise, Anastasia; Tucker, Margaret; Pérez-Jurado, Luis A.; Laurie, Cathy C.; Caporaso, Neil E.; Yeager, Meredith; Chanock, Stephen J.

    2015-01-01

    Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10−31) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. PMID:25748358

  19. Genetic microheterogeneity of human transthyretin detected by IEF

    NARCIS (Netherlands)

    Altland, Klaus; Benson, Merrill D.; Costello, Catherine E.; Ferlini, Alessandra; Hazenberg, Bouke R. C.; Hund, Ernst; Kristen, Arnt V.; Linke, Reinhold P.; Merlini, Giampaolo; Salvi, Fabrizio; Saraiva, Maria J.; Singer, Reinhard; Skinner, Martha; Winter, Pia

    2007-01-01

    Mutations of the human transthyretin (TTR) gene have attracted medical interest as a cause of amyloidosis. Recently, we have described in detail an electrophoretic procedure with PAGE followed by IEF in urea gradients for the study of the microheterogeneity of TTR monomers (Altland, K., Winter, P.,

  20. A Trio of Human Molecular Genetics PCR Assays

    Science.gov (United States)

    Reinking, Jeffrey L.; Waldo, Jennifer T.; Dinsmore, Jannett

    2013-01-01

    This laboratory exercise demonstrates three different analytical forms of the polymerase chain reaction (PCR) that allow students to genotype themselves at four different loci. Here, we present protocols to allow students to a) genotype a non-coding polymorphic Variable Number of Tandem Repeat (VNTR) locus on human chromosome 5 using conventional…

  1. The (epi)genetics of human synovial sarcoma

    NARCIS (Netherlands)

    de Bruijn, Diederik R. H.; Nap, Jan-Peter; van Kessel, Ad Geurts

    2007-01-01

    Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy. For the development of novel diagnostic, prognostic, and therapeutic approaches, deta

  2. The (epi)genetics of human synovial sarcoma.

    NARCIS (Netherlands)

    Bruijn, D.R.H. de; Nap, J.P.; Geurts van Kessel, A.H.M.

    2007-01-01

    Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy. For the development of novel diagnostic, prognostic, and therapeutic approaches, deta

  3. First genetic analysis of Cryptosporidium from humans from Tasmania, and identification of a new genotype from a traveller to Bali.

    Science.gov (United States)

    Koehler, Anson V; Whipp, Margaret; Hogg, Geoff; Haydon, Shane R; Stevens, Melita A; Jex, Aaron R; Gasser, Robin B

    2014-09-01

    Little is known about the molecular composition of Cryptosporidium species from humans living in the insular state of Tasmania, Australia. In the present study, we genetically characterized 82 samples of Cryptosporidium from humans following conventional coproscopic testing in a routine, diagnostic laboratory. Using a PCR-coupled single-strand conformation polymorphism (SSCP) technique, targeting portions of the small subunit rRNA (SSU), and 60 kDa glycoprotein (gp60) loci, we identified two species of Cryptosporidium, including C. hominis (subgenotypes IbA10G2, IdA16, IeA12G3T3, and IfA19G1) and C. parvum (IIaA16G1R1 and IIaA18G3), and a new operational taxonomic unit (OTU) that genetically closely resembled C. wrairi. This OTU was further characterized using markers in the actin, Cryptosporidium oocyst wall protein (COWP), and 70 kDa heat shock protein (hsp70) genes. This study provides the first characterization of species and genotypes of Cryptosporidium from Tasmania, and presents clear genetic evidence, using five independent genetic loci, for a new genotype or species of Cryptosporidium in a Tasmanian person with a recent history of travelling to Bali, Indonesia. It would be interesting to undertake detailed molecular-based studies of Cryptosporidium in Indonesia and neighbouring countries, in conjunction with morphological and experimental investigations of new genotypes.

  4. Neanderthal and Denisova genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.

    Science.gov (United States)

    Lowery, Robert K; Uribe, Gabriel; Jimenez, Eric B; Weiss, Mark A; Herrera, Kristian J; Regueiro, Maria; Herrera, Rene J

    2013-11-01

    Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations.

  5. A genetic linkage map of quinoa ( Chenopodium quinoa) based on AFLP, RAPD, and SSR markers.

    Science.gov (United States)

    Maughan, P J; Bonifacio, A; Jellen, E N; Stevens, M R; Coleman, C E; Ricks, M; Mason, S L; Jarvis, D E; Gardunia, B W; Fairbanks, D J

    2004-10-01

    Quinoa ( Chenopodium quinoa Willd.) is an important seed crop for human consumption in the Andean region of South America. It is the primary staple in areas too arid or saline for the major cereal crops. The objective of this project was to build the first genetic linkage map of quinoa. Selection of the mapping population was based on a preliminary genetic similarity analysis of four potential mapping parents. Breeding lines 'Ku-2' and '0654', a Chilean lowland type and a Peruvian Altiplano type, respectively, showed a low similarity coefficient of 0.31 and were selected to form an F(2) mapping population. The genetic map is based on 80 F(2) individuals from this population and consists of 230 amplified length polymorphism (AFLP), 19 simple-sequence repeat (SSR), and six randomly amplified polymorphic DNA markers. The map spans 1,020 cM and contains 35 linkage groups with an average marker density of 4.0 cM per marker. Clustering of AFLP markers was not observed. Additionally, we report the primer sequences and map locations for 19 SSR markers that will be valuable tools for future quinoa genome analysis. This map provides a key starting point for genetic dissection of agronomically important characteristics of quinoa, including seed saponin content, grain yield, maturity, and resistance to disease, frost, and drought. Current efforts are geared towards the generation of more than 200 mapped SSR markers and the development of several recombinant-inbred mapping populations.

  6. Temporal differentiation across a West-European Y-chromosomal cline: genealogy as a tool in human population genetics.

    Science.gov (United States)

    Larmuseau, Maarten H D; Ottoni, Claudio; Raeymaekers, Joost A M; Vanderheyden, Nancy; Larmuseau, Hendrik F M; Decorte, Ronny

    2012-04-01

    The pattern of population genetic variation and allele frequencies within a species are unstable and are changing over time according to different evolutionary factors. For humans, it is possible to combine detailed patrilineal genealogical records with deep Y-chromosome (Y-chr) genotyping to disentangle signals of historical population genetic structures because of the exponential increase in genetic genealogical data. To test this approach, we studied the temporal pattern of the 'autochthonous' micro-geographical genetic structure in the region of Brabant in Belgium and the Netherlands (Northwest Europe). Genealogical data of 881 individuals from Northwest Europe were collected, from which 634 family trees showed a residence within Brabant for at least one generation. The Y-chr genetic variation of the 634 participants was investigated using 110 Y-SNPs and 38 Y-STRs and linked to particular locations within Brabant on specific time periods based on genealogical records. Significant temporal variation in the Y-chr distribution was detected through a north-south gradient in the frequencies distribution of sub-haplogroup R1b1b2a1 (R-U106), next to an opposite trend for R1b1b2a2g (R-U152). The gradient on R-U106 faded in time and even became totally invisible during the Industrial Revolution in the first half of the nineteenth century. Therefore, genealogical data for at least 200 years are required to study small-scale 'autochthonous' population structure in Western Europe.

  7. Isolation and genetic characteristics of human genotype 1 Japanese encephalitis virus, China, 2009.

    Directory of Open Access Journals (Sweden)

    Jiu-Song Zhang

    Full Text Available BACKGROUND: Several studies have shown that the predominant genotype of Chinese Japanese encephalitis virus (JEV is evolving from genotype 3 to genotype 1. However, in recent years, almost all genotype 1 isolates were from mosquitoes, and genotype 1 has been less associated with human disease than genotype 3. This study reports the isolation of human genotype 1 JEV and its genetic characteristics to provide additional insights into human JE pathogens that are currently circulating in China. METHODS AND RESULTS: In 2009, 31 cerebrospinal fluid samples were collected from patients living in Yunnan and Shanxi provinces and were used to inoculate Aedes albopictus C6/36 cells for virus isolation. The JEV strains were identified using immunofluorescent assays and the reverse transcription-polymerase chain reaction. Phylogenetic analyses based on the partial capsid/pre-membrane and full envelope (E sequences were performed using Clustalx 1.8 software. Three JEV isolates were obtained from a 4-year-old girl and a 2-year-old boy living in Yunnan and an 82-year-old woman in Shanxi. The boy had been immunized with one dose of JE live attenuated vaccine. New isolates were grouped into genotype 1. Amino acid sequence for the viral E protein indicated 95% to 100% identity with each other and with other JEV strains. When compared with a consensus sequence of E protein, two amino acid substitutions were found: Ser(E-123-Asn in the two Yunnan isolates and Lys(E-166-Arg in the Shanxi isolate. CONCLUSIONS: Our findings indicate that the genotype 1 of JEV is causing human infections in China. Our observation of a previously vaccinated boy developing JE from genotype 1 virus infection also calls for more detailed studies, both in vitro and in vivo neutralization tests as well as active surveillance, to examine the possibility of a lack of complete protection conferred by the live attenuated JE vaccine against genotype 1 virus.

  8. New genetic and linguistic analyses show ancient human influence on baobab evolution and distribution in Australia.

    Science.gov (United States)

    Rangan, Haripriya; Bell, Karen L; Baum, David A; Fowler, Rachael; McConvell, Patrick; Saunders, Thomas; Spronck, Stef; Kull, Christian A; Murphy, Daniel J

    2015-01-01

    This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia.

  9. New genetic and linguistic analyses show ancient human influence on baobab evolution and distribution in Australia.

    Directory of Open Access Journals (Sweden)

    Haripriya Rangan

    Full Text Available This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia.

  10. Statement of the ESHG on direct-to-consumer genetic testing for health-related purposes European Society of Human Genetics

    OpenAIRE

    Borry, Pascal

    2010-01-01

    Many private companies offer direct-to-consumer (DTC) genetic testing services. Some tests may detect severe and highly penetrant monogenic disorders, while other tests are for genetic variants found associated with increased susceptibility for common and complex diseases in large-scale population studies. Through its Public and Professional Policy committee followed by member and expert consultation, the European Society of Human Genetics has developed the following policy on advertising and...

  11. Drosophila as a genetic model for studying pathogenic human viruses.

    Science.gov (United States)

    Hughes, Tamara T; Allen, Amanda L; Bardin, Joseph E; Christian, Megan N; Daimon, Kansei; Dozier, Kelsey D; Hansen, Caom L; Holcomb, Lisa M; Ahlander, Joseph

    2012-02-05

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area.

  12. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Neven, Bénédicte; Stolzenberg, Marie-Claude; Daussy, Cécile; Arkwright, Peter D; Lanzarotti, Nina; Schaffner, Catherine; Cluet-Dennetiere, Sophie; Haerynck, Filomeen; Michel, Gérard; Bole-Feysot, Christine; Zarhrate, Mohammed; Radford-Weiss, Isabelle; Romana, Serge P; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2011-01-01

    Autoimmune diseases develop in approximately 5% of humans. They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved in lymphocyte activation, survival, or death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects in self-tolerance checkpoints as a consequence of mutations in the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as FAS). However, some mutation carriers remain asymptomatic throughout life. We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele. Analysis of the patients' CD4(-)CD8(-) (double negative) T cells--accumulation of which is a hallmark of ALPS--revealed that in these cells, 3 patients had somatic mutations in their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10. This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases.

  13. Striatal dopamine mediates the interface between motivational and cognitive control in humans: evidence from genetic imaging.

    Science.gov (United States)

    Aarts, Esther; Roelofs, Ardi; Franke, Barbara; Rijpkema, Mark; Fernández, Guillén; Helmich, Rick C; Cools, Roshan

    2010-08-01

    Dopamine has been hypothesized to provide the basis for the interaction between motivational and cognitive control. However, there is no evidence for this hypothesis in humans. We fill this gap by using fMRI, a novel behavioral paradigm and a common polymorphism in the DAT1 gene (SLC6A3). Carriers of the 9-repeat (9R) allele of a 40 base pair repeat polymorphism in the 3' untranslated region of DAT1, associated with high striatal dopamine, showed greater activity in the ventromedial striatum during reward anticipation than homozygotes for the 10-repeat allele, replicating previous genetic imaging studies. The crucial novel finding is that 9R carriers also exhibited a greater influence of anticipated reward on switch costs, as well as greater activity in the dorsomedial striatum during task switching in anticipation of high reward relative to low reward. These data establish a crucial role for human striatal dopamine in the modulation of cognitive flexibility by reward anticipation, thus, elucidating the neurochemical mechanism of the interaction between motivation and cognitive control.

  14. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    Full Text Available Abstract Background Signaling by the vitamin A-derived morphogen retinoic acid (RA is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2 is critical for cardiac development, we screened patients with congenital heart disease (CHDs for genetic variation at the ALDH1A2 locus. Methods One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430 at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay. Results We describe in Tetralogy of Fallot (TOF the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT design using single marker genotype, or haplotype information do not show differences between cases and controls. Conclusion In summary, our screen indicates that

  15. Parameter Optimization of Linear Quadratic Controller Based on Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    LI Jimin; SHANG Chaoxuan; ZOU Minghu

    2007-01-01

    The selection of weighting matrix in design of the linear quadratic optimal controller is an important topic in the control theory. In this paper, an approach based on genetic algorithm is presented for selecting the weighting matrix for the optimal controller. Genetic algorithm is adaptive heuristic search algorithm premised on the evolutionary ideas of natural selection and genetic. In this algorithm, the fitness function is used to evaluate individuals and reproductive success varies with fitness. In the design of the linear quadratic optimal controller, the fitness function has relation to the anticipated step response of the system. Not only can the controller designed by this approach meet the demand of the performance indexes of linear quadratic controller, but also satisfy the anticipated step response of close-loop system. The method possesses a higher calculating efficiency and provides technical support for the optimal controller in engineering application. The simulation of a three-order single-input single-output (SISO) system has demonstrated the feasibility and validity of the approach.

  16. A novel pipeline based FPGA implementation of a genetic algorithm

    Science.gov (United States)

    Thirer, Nonel

    2014-05-01

    To solve problems when an analytical solution is not available, more and more bio-inspired computation techniques have been applied in the last years. Thus, an efficient algorithm is the Genetic Algorithm (GA), which imitates the biological evolution process, finding the solution by the mechanism of "natural selection", where the strong has higher chances to survive. A genetic algorithm is an iterative procedure which operates on a population of individuals called "chromosomes" or "possible solutions" (usually represented by a binary code). GA performs several processes with the population individuals to produce a new population, like in the biological evolution. To provide a high speed solution, pipelined based FPGA hardware implementations are used, with a nstages pipeline for a n-phases genetic algorithm. The FPGA pipeline implementations are constraints by the different execution time of each stage and by the FPGA chip resources. To minimize these difficulties, we propose a bio-inspired technique to modify the crossover step by using non identical twins. Thus two of the chosen chromosomes (parents) will build up two new chromosomes (children) not only one as in classical GA. We analyze the contribution of this method to reduce the execution time in the asynchronous and synchronous pipelines and also the possibility to a cheaper FPGA implementation, by using smaller populations. The full hardware architecture for a FPGA implementation to our target ALTERA development card is presented and analyzed.

  17. Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

    Science.gov (United States)

    Bakken, Trygve E; Roddey, J Cooper; Djurovic, Srdjan; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Casey, B J; Chang, Linda; Ernst, Thomas M; Gruen, Jeffrey R; Jernigan, Terry L; Kaufmann, Walter E; Kenet, Tal; Kennedy, David N; Kuperman, Joshua M; Murray, Sarah S; Sowell, Elizabeth R; Rimol, Lars M; Mattingsdal, Morten; Melle, Ingrid; Agartz, Ingrid; Andreassen, Ole A; Schork, Nicholas J; Dale, Anders M; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R; Jagust, William; Trojanowki, John Q; Toga, Arthur W; Beckett, Laurel; Green, Robert C; Saykin, Andrew J; Morris, John; Liu, Enchi; Montine, Tom; Gamst, Anthony; Thomas, Ronald G; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Harvey, Danielle; Kornak, John; Dale, Anders; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; DeCarli, Charles; Bandy, Dan; Koeppe, Robert A; Foster, Norm; Reiman, Eric M; Chen, Kewei; Mathis, Chet; Cairns, Nigel J; Taylor-Reinwald, Lisa; Trojanowki, J Q; Shaw, Les; Lee, Virginia M Y; Korecka, Magdalena; Crawford, Karen; Neu, Scott; Foroud, Tatiana M; Potkin, Steven; Shen, Li; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Dolen, Sara; Schneider, Lon S; Pawluczyk, Sonia; Spann, Bryan M; Brewer, James; Vanderswag, Helen; Heidebrink, Judith L; Lord, Joanne L; Johnson, Kris; Doody, Rachelle S; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S; Bell, Karen L; Morris, John C; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Clark, David; Grossman, Hillel; Mitsis, Effie; Romirowsky, Aliza; deToledo-Morrell, Leyla; Shah, Raj C; Duara, Ranjan; Varon, Daniel; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; Kielb, Stephanie; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P Murali; Petrella, Jeffrey R; Coleman, R Edward; Arnold, Steven E; Karlawish, Jason H; Wolk, David; Smith, Charles D; Jicha, Greg; Hardy, Peter; Lopez, Oscar L; Oakley, MaryAnn; Simpson, Donna M; Porsteinsson, Anton P; Goldstein, Bonnie S; Martin, Kim; Makino, Kelly M; Ismail, M Saleem; Brand, Connie; Mulnard, Ruth A; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I; Lah, James J; Cellar, Janet S; Burns, Jeffrey M; Anderson, Heather S; Swerdlow, Russell H; Apostolova, Liana; Lu, Po H; Bartzokis, George; Silverman, Daniel H S; Graff-Radford, Neill R; Parfitt, Francine; Johnson, Heather; Farlow, Martin R; Hake, Ann Marie; Matthews, Brandy R; Herring, Scott; van Dyck, Christopher H; Carson, Richard E; MacAvoy, Martha G; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Ging-Yuek; Hsiung, Robin; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristina; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Turner, Raymond Scott; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan; Belden, Christine; Jacobson, Sandra; Kowall, Neil; Killiany, Ronald; Budson, Andrew E; Norbash, Alexander; Johnson, Patricia Lynn; Obisesan, Thomas O; Wolday, Saba; Bwayo, Salome K; Lerner, Alan; Hudson, Leon; Ogrocki, Paula; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M; Potkin, Steven G; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Fleisher, Adam; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W; Kataki, Maria; Zimmerman, Earl A; Celmins, Dzintra; Brown, Alice D; Pearlson, Godfrey D; Blank, Karen; Anderson, Karen; Santulli, Robert B; Schwartz, Eben S; Sink, Kaycee M; Williamson, Jeff D; Garg, Pradeep; Watkins, Franklin; Ott, Brian R; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J; Miller, Bruce L; Mintzer, Jacobo; Longmire, Crystal Flynn; Spicer, Kenneth; Finger, Elizabether; Rachinsky, Irina; Drost, Dick; Jernigan, Terry; McCabe, Connor; Grant, Ellen; Ernst, Thomas; Kuperman, Josh; Chung, Yoon; Murray, Sarah; Bloss, Cinnamon; Darst, Burcu; Pritchett, Lexi; Saito, Ashley; Amaral, David; DiNino, Mishaela; Eyngorina, Bella; Sowell, Elizabeth; Houston, Suzanne; Soderberg, Lindsay; Kaufmann, Walter; van Zijl, Peter; Rizzo-Busack, Hilda; Javid, Mohsin; Mehta, Natasha; Ruberry, Erika; Powers, Alisa; Rosen, Bruce; Gebhard, Nitzah; Manigan, Holly; Frazier, Jean; Kennedy, David; Yakutis, Lauren; Hill, Michael; Gruen, Jeffrey; Bosson-Heenan, Joan; Carlson, Heatherly

    2012-03-06

    Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

  18. Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Scott G Kitchen

    Full Text Available There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR. Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

  19. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene

    Institute of Scientific and Technical Information of China (English)

    CAI Pei-qiang; TANG Xun; LIN Yue-qiu; Oudega Martin; SUN Guang-yun; XU Lin; YANG Yun-kang; ZHOU Tian-hua

    2006-01-01

    Objective:To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs)mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI).Methods: Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3(NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot.Results: Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot.Conclusions: Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  20. Genetic population structure accounts for contemporary ecogeographic patterns in tropic and subtropic-dwelling humans.

    Science.gov (United States)

    Hruschka, Daniel J; Hadley, Craig; Brewis, Alexandra A; Stojanowski, Christopher M

    2015-01-01

    Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R2 = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R2 = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

  1. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    Science.gov (United States)

    2015-10-01

    Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...SUBTITLE Developiing Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER Carcinoma Using Genetically Engineered Mouse Models and 5b...biomarkers. 15. SUBJECT TERMS Small cell lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis

  2. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals.

    Science.gov (United States)

    Elliot, Michael G; Crespi, Bernard J

    2015-03-05

    The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification.

  3. Statistical inference on genetic data reveals the complex demographic history of human populations in central Asia.

    Science.gov (United States)

    Palstra, Friso P; Heyer, Evelyne; Austerlitz, Frédéric

    2015-06-01

    The demographic history of modern humans constitutes a combination of expansions, colonizations, contractions, and remigrations. The advent of large scale genetic data combined with statistically refined methods facilitates inference of this complex history. Here we study the demographic history of two genetically admixed ethnic groups in Central Asia, an area characterized by high levels of genetic diversity and a history of recurrent immigration. Using Approximate Bayesian Computation, we infer that the timing of admixture markedly differs between the two groups. Admixture in the traditionally agricultural Tajiks could be dated back to the onset of the Neolithic transition in the region, whereas admixture in Kyrgyz is more recent, and may have involved the westward movement of Turkic peoples. These results are confirmed by a coalescent method that fits an isolation-with-migration model to the genetic data, with both Central Asian groups having received gene flow from the extremities of Eurasia. Interestingly, our analyses also uncover signatures of gene flow from Eastern to Western Eurasia during Paleolithic times. In conclusion, the high genetic diversity currently observed in these two Central Asian peoples most likely reflects the effects of recurrent immigration that likely started before historical times. Conversely, conquests during historical times may have had a relatively limited genetic impact. These results emphasize the need for a better understanding of the genetic consequences of transmission of culture and technological innovations, as well as those of invasions and conquests.

  4. Genetic regulation of recurrent spontaneous abortion in humans

    Directory of Open Access Journals (Sweden)

    Daniel Vaiman

    2015-02-01

    Full Text Available Recurrent pregnancy loss, defined as a pregnancy failure occurring before 24 weeks of gestation more than two or three times according to most definitions, is a fertility defect encountered in 1-5% of the patients. This defect is of course of multifactorial origin. Among the possible origins of recurrent pregnancy loss are uterine structural defaults, defective ploidy control of the embryo, defective immunological dialog between the embryo (or the fetus and the uterus sometimes in relation with immunological disorders (such as autoimmune diseases, thrombophilia, and free radical metabolism imbalance. Numerous studies attempted to correlate variants of genes supposed to be intervening in the different facets of the early maternal-fetal or maternal-embryonic dialog, and eventually modify the outcome of fertilization, leading to success or failure of post-implantation development. The objective of the present review is to portray the major genes and gene polymorphisms studied for their putative association with recurrent pregnancy loss. Most of these genes have been studied as candidate genes for which strong biological arguments were put forward as to their putative involvement in recurrent pregnancy loss. They were mostly studied by genetic analysis, often in various populations of different ethnic origins, throughout the world. Some of these studies were available only in English as abstracts and were nevertheless used if the information was given with enough detail. With the space being too short to depict all the available literature, different major pathways releva nt to the scientific question are presented without any attempt to hide the fact that discordant views often aroused for a given gene.

  5. Application layer multicast routing solution based on genetic algorithms

    Institute of Scientific and Technical Information of China (English)

    Peng CHENG; Qiufeng WU; Qionghai DAI

    2009-01-01

    Application layer multicast routing is a multi-objective optimization problem.Three routing con-straints,tree's cost,tree's balance and network layer load distribution are analyzed in this paper.The three fitness functions are used to evaluate a multicast tree on the three indexes respectively and one general fitness function is generated.A novel approach based on genetic algorithms is proposed.Numerical simulations show that,compared with geometrical routing rules,the proposed algorithm improve all three indexes,especially on cost and network layer load distribution indexes.

  6. Genetic-evolution-based optimization methods for engineering design

    Science.gov (United States)

    Rao, S. S.; Pan, T. S.; Dhingra, A. K.; Venkayya, V. B.; Kumar, V.

    1990-01-01

    This paper presents the applicability of a biological model, based on genetic evolution, for engineering design optimization. Algorithms embodying the ideas of reproduction, crossover, and mutation are developed and applied to solve different types of structural optimization problems. Both continuous and discrete variable optimization problems are solved. A two-bay truss for maximum fundamental frequency is considered to demonstrate the continuous variable case. The selection of locations of actuators in an actively controlled structure, for minimum energy dissipation, is considered to illustrate the discrete variable case.

  7. Improved Adaptive LSB Steganography Based on Chaos and Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Yu Lifang

    2010-01-01

    Full Text Available We propose a novel steganographic method in JPEG images with high performance. Firstly, we propose improved adaptive LSB steganography, which can achieve high capacity while preserving the first-order statistics. Secondly, in order to minimize visual degradation of the stego image, we shuffle bits-order of the message based on chaos whose parameters are selected by the genetic algorithm. Shuffling message's bits-order provides us with a new way to improve the performance of steganography. Experimental results show that our method outperforms classical steganographic methods in image quality, while preserving characteristics of histogram and providing high capacity.

  8. Manipulator Neural Network Control Based on Fuzzy Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The three-layer forward neural networks are used to establish the inverse kinem a tics models of robot manipulators. The fuzzy genetic algorithm based on the line ar scaling of the fitness value is presented to update the weights of neural net works. To increase the search speed of the algorithm, the crossover probability and the mutation probability are adjusted through fuzzy control and the fitness is modified by the linear scaling method in FGA. Simulations show that the propo sed method improves considerably the precision of the inverse kinematics solutio ns for robot manipulators and guarantees a rapid global convergence and overcome s the drawbacks of SGA and the BP algorithm.

  9. Genetic adaptation of the antibacterial human innate immunity network

    Directory of Open Access Journals (Sweden)

    Lazarus Ross

    2011-07-01

    Full Text Available Abstract Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  10. Feature Selection for Image Retrieval based on Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Preeti Kushwaha

    2016-12-01

    Full Text Available This paper describes the development and implementation of feature selection for content based image retrieval. We are working on CBIR system with new efficient technique. In this system, we use multi feature extraction such as colour, texture and shape. The three techniques are used for feature extraction such as colour moment, gray level co- occurrence matrix and edge histogram descriptor. To reduce curse of dimensionality and find best optimal features from feature set using feature selection based on genetic algorithm. These features are divided into similar image classes using clustering for fast retrieval and improve the execution time. Clustering technique is done by k-means algorithm. The experimental result shows feature selection using GA reduces the time for retrieval and also increases the retrieval precision, thus it gives better and faster results as compared to normal image retrieval system. The result also shows precision and recall of proposed approach compared to previous approach for each image class. The CBIR system is more efficient and better performs using feature selection based on Genetic Algorithm.

  11. Genetic based optimization for multicast routing algorithm for MANET

    Indian Academy of Sciences (India)

    C Rajan; N Shanthi

    2015-12-01

    Mobile Ad hoc Network (MANET) is established for a limited period, for special extemporaneous services related to mobile applications. This ad hoc network is set up for a limited period, in environments that change with the application. While in Internet the TCP/IP protocol suite supports a wide range of application, in MANETs protocols are tuned to specific customer/application. Multicasting is emerging as a popular communication format where the same packet is sent to multiple nodes in a network. Routing in multicasting involves maintaining routes and finding new node locations in a group and is NP-complete due to the dynamic nature of the network. In this paper, a Hybrid Genetic Based Optimization for Multicast Routing algorithm is proposed. The proposed algorithm uses the best features of Genetic Algorithm (GA) and particle swarm optimization (PSO) to improve the solution. Simulations were conducted by varying number of mobile nodes and results compared with Multicast AODV (MAODV) protocol, PSO based and GA based solution. The proposed optimization improves jitter, end to end delay and Packet Delivery Ratio (PDR) with faster convergence.

  12. Estimating genetic correlations based on phenotypic data: a simulation-based method

    Indian Academy of Sciences (India)

    Elias Zintzaras

    2011-04-01

    Knowledge of genetic correlations is essential to understand the joint evolution of traits through correlated responses to selection, a difficult and seldom, very precise task even with easy-to-breed species. Here, a simulation-based method to estimate genetic correlations and genetic covariances that relies only on phenotypic measurements is proposed. The method does not require any degree of relatedness in the sampled individuals. Extensive numerical results suggest that the propose method may provide relatively efficient estimates regardless of sample sizes and contributions from common environmental effects.

  13. [Teaching design and practice of human blood type traits in genetics comprehensive laboratory course].

    Science.gov (United States)

    Zhao, Jian; Hu, Dongmei; Yu, Dade; Dong, Mingliang; Li, Yun; Fan, Yingming; Wang, Yanwei; Zhang, Jinfeng

    2016-05-01

    Comprehensive laboratory courses, which enable students to aptly apply theoretic knowledge and master experiment skills, play an important role in the present educational reform of laboratory courses. We utilized human ABO blood type as the experimental subject, and designed the experiment--"Molecular Genotyping of Human ABO Blood Type and Analysis of Population Genetic Equilibrium". In the experiment, DNA in mucosal cells is extracted from students' saliva, and each student's genotype is identified using a series of molecular genetics technologies, including PCR amplification of target fragments, enzymatic digestion, and electrophoretic separation. Then, taking the whole class as an analogous Mendel population, a survey of genotype frequency of ABO blood type is conducted, followed with analyses of various population genetic parameters using Popgene. Through the open laboratory course, students can not only master molecular genetic experimental skills, but also improve their understanding of theoretic knowledge through independent design and optimization of molecular techniques. After five years of research and practice, a stable experimental system of molecular genetics has been established to identify six genotypes of ABO blood types, namely I(A)I(A), I(A)i, I(B)I(B), I(B)i, I(A)I(B) and ii. Laboratory courses of molecular and population genetics have been integrated by calculating the frequencies of the six genotypes and three multiple alleles and testing population genetic equilibrium. The goal of the open laboratory course with independent design and implementation by the students has been achieved. This laboratory course has proved effective and received good reviews from the students. It could be applied as a genetics laboratory course for the biology majors directly, and its ideas and methods could be promoted and applied to other biological laboratory courses.

  14. The genome of a Mongolian individual reveals the genetic imprints of Mongolians on modern human populations.

    Science.gov (United States)

    Bai, Haihua; Guo, Xiaosen; Zhang, Dong; Narisu, Narisu; Bu, Junjie; Jirimutu, Jirimutu; Liang, Fan; Zhao, Xiang; Xing, Yanping; Wang, Dingzhu; Li, Tongda; Zhang, Yanru; Guan, Baozhu; Yang, Xukui; Yang, Zili; Shuangshan, Shuangshan; Su, Zhe; Wu, Huiguang; Li, Wenjing; Chen, Ming; Zhu, Shilin; Bayinnamula, Bayinnamula; Chang, Yuqi; Gao, Ying; Lan, Tianming; Suyalatu, Suyalatu; Huang, Hui; Su, Yan; Chen, Yujie; Li, Wenqi; Yang, Xu; Feng, Qiang; Wang, Jian; Yang, Huanming; Wang, Jun; Wu, Qizhu; Yin, Ye; Zhou, Huanmin

    2014-11-05

    Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians.

  15. Teachers' Conceptions about the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    Science.gov (United States)

    Castéra, Jérémy; Clément, Pierre

    2014-01-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed…

  16. Human-competitive evolution of quantum computing artefacts by Genetic Programming.

    Science.gov (United States)

    Massey, Paul; Clark, John A; Stepney, Susan

    2006-01-01

    We show how Genetic Programming (GP) can be used to evolve useful quantum computing artefacts of increasing sophistication and usefulness: firstly specific quantum circuits, then quantum programs, and finally system-independent quantum algorithms. We conclude the paper by presenting a human-competitive Quantum Fourier Transform (QFT) algorithm evolved by GP.

  17. Genetics and human rights: Two histories: restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil

    Directory of Open Access Journals (Sweden)

    Victor B. Penchaszadeh

    2014-01-01

    Full Text Available Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.

  18. Genetics and human rights. Two histories: Restoring genetic identity after forced disappearance and identity suppression in Argentina and after compulsory isolation for leprosy in Brazil.

    Science.gov (United States)

    Penchaszadeh, Victor B; Schuler-Faccini, Lavinia

    2014-03-01

    Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.

  19. The Genetic Effects of Aging on Human Mesenchymal Stem Cells through Consecutive Subcultures

    Directory of Open Access Journals (Sweden)

    H. Pourjafari

    2013-04-01

    Full Text Available Introduction & Objective: Stem cells are determined by their unique features. One of them is high proliferation ability and the other is potency of differentiation to various tissues. The results of new works in various countries around the world including Iran show the growing momentum of works on stem cell therapy. Working with stem cells from different origins including the cells originated from fetal and adult origin (such as bone marrow, dental root, cord , etcis in progress. The goal of this work was to clear the maintenance and stability of genetic materials of human mesenchymal stem cells through consecutive subcultures in our lab conditions in Hamadan Uni-versity of Medical Sciences. Materials & Methods: In an experimental work, human umbilical cord was used as a rich source of stem cells. Isolated stem cells, after proliferation phase, increased and filled the bottom of the flasks in consecutive passages. After some successive consecutive subcultures, stem cells aged and this may cause damages to genetic material that is evaluated in primary passages (passages number 1-5, middle passages (passages number 8-12 and late passages (passages number 15-18 by the single cell gel electrophoresis assay (comet assay. Also their karyotypes were ex-amined; Solid technique and G-banding staining for chromosome analysis in the stem cells were employed. Several microscopic slides from each passage were prepared. Then 20 cells were ran-domly selected from the slides related to each group. In all selected cells, damages were exam-ined and their degree of damages were scored based on the standard patterns, from 0 to 4. The averages were compared by Kruskal–Wallis test in different groups. Results: Average scores related to three studied cell groups, primary, middle and late passages, were 0.4, 2.8 and 3.6, respectively. Prepared karyotypes from the cells belonging to passages 1-5 were normal but in the aged passages they were abnormal numerically and

  20. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    Adriana eBarman

    2014-04-01

    Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

  1. Integration of the cytogenetic, genetic, and physical maps of the human genome by FISH mapping of CEPH YAC clones

    Energy Technology Data Exchange (ETDEWEB)

    Bray-Ward, P.; Menninger, J.; Lieman, J. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

    1996-02-15

    This article discusses the genetic mapping of over 950 yeast artificial chromosome (YAC) clones on human chromosomes. This integration of the cytogenetic, genetic and physical maps of the human genome was accomplished using fluorescence in situ hybridization (FISH) mapping and the CEPH library of YAC clones. 27 refs., 2 figs., 1 tab.

  2. Genetic alteration of poly(ADP-ribose) polymerase-1 in human germ cell tumors.

    Science.gov (United States)

    Shiokawa, Motoko; Masutani, Mitsuko; Fujihara, Hisako; Ueki, Keisuke; Nishikawa, Ryo; Sugimura, Takashi; Kubo, Harumi; Nakagama, Hitoshi

    2005-02-01

    Accumulated evidence suggests that poly(ADP-ribose) polymerase-1 (PARP-1) is involved in DNA repair, cell-death induction, differentiation and tumorigenesis. Parp-1 deficiency also induces trophoblast differentiation from mouse embryonic stem cells during teratocarcinoma-like tumor formation. To understand the relationship of PARP-1 dysfunction and development of germ cell tumors, we conducted a genetic analysis of the PARP-1 gene in human germ cell tumors. Sixteen surgical specimens of germ cell tumors that developed in the brain and testes were used. Two known single nucleotide polymorphisms (SNPs) (Val762Ala and Lys940Arg), which are listed in the SNP database of the NCBI (National Center for Biotechnology Information), were detected. In both cases, cSNPs encoded amino acids located within peptide stretches in the catalytic domain, which are highly conserved among various animal species. Furthermore, another novel sequence alteration, a base change of ATG to ACG, was identified in a tumor specimen, which would result in the amino acid substitution, Met129Thr. This base change was observed in one allele of both tumor and normal tissues, suggesting that it is either a rare SNP or a germline mutation of the PARP-1 gene. Notably, the amino acid Met129 is located within the second zinc finger domain, which is essential for DNA binding and is conserved among animal species. One SNP in intron 2 and one in the upstream 5'-UTR (untranslated region) were also detected.

  3. A new automatic alignment technology for single mode fiber-waveguide based on improved genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yu; CHEN Zhuang-zhuang; LI Ya-juan; DUAN Jian

    2009-01-01

    A novel automatic alignment algorithm of single mode fiber-waveguide based on improved genetic algorithm is proposed. The genetic searching is based on the dynamic crossover operator and the adaptive mutation operator to solve the premature convergence of simple genetic algorithm The improved genetic algorithm combines with hill-climbing method and pattern searching algorithm, to solve low precision of simple genetic algorithm in later searching. The simulation results indicate that the improved genetic algorithm can rise the alignment precision and reach the coupling loss of 0.01 dB when platform moves near 207 space points averagely.

  4. Optimal approximation of head-related transfer function's pole-zero model based on genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jie; MA Hao; WU Zhen-yang

    2006-01-01

    In the research on spatial hearing and virtual auditory space,it is important to effectively model the head-related transfer functions (HRTFs).Based on the analysis of the HRTFs' spectrum and some perspectives of psychoacoustics,this paper applied multiple demes' parallel and real-valued coding genetic algorithm (GA) to approximate the HRTFs' zero-pole model.Using the logarithmic magnitude's error criterion for the human auditory sense,the results show that the performance of the GA is on the average 39% better than that of the traditional Prony method,and 46% better than that of the Yule-Walker algorithm.

  5. Family genetic algorithms based on gene exchange and its application

    Institute of Scientific and Technical Information of China (English)

    Li Jianhua; Ding Xiangqian; Wang Sunan; Yu Qing

    2006-01-01

    Genetic Algorithms (GA) are a search techniques based on mechanics of nature selection and have already been successfully applied in many diverse areas. However, increasing samples show that GA's performance is not as good as it was expected to be. Criticism of this algorithm includes the slow speed and premature result during convergence procedure. In order to improve the performance, the population size and individuals' space is emphatically described. The influence of individuals' space and population size on the operators is analyzed. And a novel family genetic algorithm (FGA) is put forward based on this analysis. In this novel algorithm, the optimum solution families closed to quality individuals is constructed, which is exchanged found by a search in the world space. Search will be done in this microspace. The family that can search better genes in a limited period of time would win a new life. At the same time, the best gene of this micro space with the basic population in the world space is exchanged. Finally, the FGA is applied to the function optimization and image matching through several experiments. The results show that the FGA possessed high performance.

  6. Cognitive heterogeneity in genetically based prosopagnosia: a family study.

    Science.gov (United States)

    Schmalzl, Laura; Palermo, Romina; Coltheart, Max

    2008-03-01

    Congenital prosopagnosia (CP) is a selective difficulty in recognizing familiar faces that is present from birth. There is mounting evidence for a familial factor in CP, possibly due to a simple autosomal inheritance pattern. However, potential candidate genes remain to be established, and the question whether genetically based CP is a single trait, or a cluster of related subtypes differing in the pattern of impairments to specific components of the face-processing system, remains unanswered. In addition, since the great majority of so far described cases with CP were adult at the time of investigation, it remains unknown which specific aspects of face processing are impaired in small children with CP. Here we present the first study that specifically addresses these questions by elucidating the specific mechanisms underlying face-recognition impairments in seven individuals with CP (aged 4-87 years) belonging to four generations of the same family. Our results indicate that genetically based CP is not a single trait but a cluster of related subtypes, since the pattern of impairments to specific components of the face-processing system varies in individuals belonging to the same family. In addition, we show that the heterogeneity of the cognitive profile in CP with respect to specific aspects of face processing is apparent from early childhood.

  7. Application of genetic algorithm to hexagon-based motion estimation.

    Science.gov (United States)

    Kung, Chih-Ming; Cheng, Wan-Shu; Jeng, Jyh-Horng

    2014-01-01

    With the improvement of science and technology, the development of the network, and the exploitation of the HDTV, the demands of audio and video become more and more important. Depending on the video coding technology would be the solution for achieving these requirements. Motion estimation, which removes the redundancy in video frames, plays an important role in the video coding. Therefore, many experts devote themselves to the issues. The existing fast algorithms rely on the assumption that the matching error decreases monotonically as the searched point moves closer to the global optimum. However, genetic algorithm is not fundamentally limited to this restriction. The character would help the proposed scheme to search the mean square error closer to the algorithm of full search than those fast algorithms. The aim of this paper is to propose a new technique which focuses on combing the hexagon-based search algorithm, which is faster than diamond search, and genetic algorithm. Experiments are performed to demonstrate the encoding speed and accuracy of hexagon-based search pattern method and proposed method.

  8. Population and clinical genetics of human transposable elements in the (post) genomic era

    Science.gov (United States)

    Rishishwar, Lavanya; Wang, Lu; Clayton, Evan A.; Mariño-Ramírez, Leonardo; McDonald, John F.; Jordan, I. King

    2017-01-01

    ABSTRACT Recent technological developments—in genomics, bioinformatics and high-throughput experimental techniques—are providing opportunities to study ongoing human transposable element (TE) activity at an unprecedented level of detail. It is now possible to characterize genome-wide collections of TE insertion sites for multiple human individuals, within and between populations, and for a variety of tissue types. Comparison of TE insertion site profiles between individuals captures the germline activity of TEs and reveals insertion site variants that segregate as polymorphisms among human populations, whereas comparison among tissue types ascertains somatic TE activity that generates cellular heterogeneity. In this review, we provide an overview of these new technologies and explore their implications for population and clinical genetic studies of human TEs. We cover both recent published results on human TE insertion activity as well as the prospects for future TE studies related to human evolution and health.

  9. Fostering students' knowledge and argumentation skills through dilemmas in human genetics

    Science.gov (United States)

    Zohar, Anat; Nemet, Flora

    2002-01-01

    This study examined the outcomes of a unit that integrates explicit teaching of general reasoning patterns into the teaching of a specific science content. Specifically, this article examined the teaching of argumentation skills in the context of dilemmas in human genetics. Before instruction only a minority (16.2%) of the students referred to correct, specific biological knowledge in constructing arguments in the context of dilemmas in genetics. Approximately 90% of the students were successful in formulating simple arguments. An assessment that took place following instruction supported the conclusion that integrating explicit teaching of argumentation into the teaching of dilemmas in human genetics enhances performance in both biological knowledge and argumentation. An increase was found in the frequency of students who referred to correct, specific biological knowledge in constructing arguments. Students in the experimental group scored significantly higher than students in the comparison group in a test of genetics knowledge. An increase was also found in the quality of students' argumentation. Students were able to transfer the reasoning abilities taught in the context of genetics to the context of dilemmas taken from everyday life. The effects of metacognitive thinking and of changing students' thinking dispositions by modifying what is considered valuable in the class culture are discussed.

  10. Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells.

    Science.gov (United States)

    Chen, Lu; Ge, Bing; Casale, Francesco Paolo; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yan, Ying; Kundu, Kousik; Ecker, Simone; Datta, Avik; Richardson, David; Burden, Frances; Mead, Daniel; Mann, Alice L; Fernandez, Jose Maria; Rowlston, Sophia; Wilder, Steven P; Farrow, Samantha; Shao, Xiaojian; Lambourne, John J; Redensek, Adriana; Albers, Cornelis A; Amstislavskiy, Vyacheslav; Ashford, Sofie; Berentsen, Kim; Bomba, Lorenzo; Bourque, Guillaume; Bujold, David; Busche, Stephan; Caron, Maxime; Chen, Shu-Huang; Cheung, Warren; Delaneau, Oliver; Dermitzakis, Emmanouil T; Elding, Heather; Colgiu, Irina; Bagger, Frederik O; Flicek, Paul; Habibi, Ehsan; Iotchkova, Valentina; Janssen-Megens, Eva; Kim, Bowon; Lehrach, Hans; Lowy, Ernesto; Mandoli, Amit; Matarese, Filomena; Maurano, Matthew T; Morris, John A; Pancaldi, Vera; Pourfarzad, Farzin; Rehnstrom, Karola; Rendon, Augusto; Risch, Thomas; Sharifi, Nilofar; Simon, Marie-Michelle; Sultan, Marc; Valencia, Alfonso; Walter, Klaudia; Wang, Shuang-Yin; Frontini, Mattia; Antonarakis, Stylianos E; Clarke, Laura; Yaspo, Marie-Laure; Beck, Stephan; Guigo, Roderic; Rico, Daniel; Martens, Joost H A; Ouwehand, Willem H; Kuijpers, Taco W; Paul, Dirk S; Stunnenberg, Hendrik G; Stegle, Oliver; Downes, Kate; Pastinen, Tomi; Soranzo, Nicole

    2016-11-17

    Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14(+) monocytes, CD16(+) neutrophils, and naive CD4(+) T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.

  11. Meganucleases Revolutionize the Production of Genetically Engineered Pigs for the Study of Human Diseases.

    Science.gov (United States)

    Redel, Bethany K; Prather, Randall S

    2016-04-01

    Animal models of human diseases are critically necessary for developing an in-depth knowledge of disease development and progression. In addition, animal models are vital to the development of potential treatments or even cures for human diseases. Pigs are exceptional models as their size, physiology, and genetics are closer to that of humans than rodents. In this review, we discuss the use of pigs in human translational research and the evolving technology that has increased the efficiency of genetically engineering pigs. With the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein 9 system technology, the cost and time it takes to genetically engineer pigs has markedly decreased. We will also discuss the use of another meganuclease, the transcription activator-like effector nucleases , to produce pigs with severe combined immunodeficiency by developing targeted modifications of the recombination activating gene 2 (RAG2).RAG2mutant pigs may become excellent animals to facilitate the development of xenotransplantation, regenerative medicine, and tumor biology. The use of pig biomedical models is vital for furthering the knowledge of, and for treating human, diseases.

  12. Genetic Risk for Recurrent Urinary Tract Infections in Humans: A Systematic Review

    Directory of Open Access Journals (Sweden)

    M. Zaffanello

    2010-01-01

    Full Text Available Urinary tract infections (UTIs are a frequent cause of morbidity in children and adults and affect up to 10% of children; its recurrence rate is estimated at 30–40%. UTI may occur in up to 50% of all women in their lifetimes and frequently require medication. Recent advances have suggested that a deregulation of candidate genes in humans may predispose patients to recurrent UTI. The identification of a genetic component of UTI recurrences will make it possible to diagnose at-risk adults and to predict genetic recurrences in their offspring. Six out of 14 genes investigated in humans may be associated with susceptibility to recurrent UTI in humans. In particular, the HSPA1B, CXCR1 & 2, TLR2, TLR4, TGF-1 genes seem to be associated with an alteration of the host response to UTIs at various levels.

  13. Genetic risk for recurrent urinary tract infections in humans: a systematic review.

    Science.gov (United States)

    Zaffanello, M; Malerba, G; Cataldi, L; Antoniazzi, F; Franchini, M; Monti, E; Fanos, V

    2010-01-01

    Urinary tract infections (UTIs) are a frequent cause of morbidity in children and adults and affect up to 10% of children; its recurrence rate is estimated at 30-40%. UTI may occur in up to 50% of all women in their lifetimes and frequently require medication. Recent advances have suggested that a deregulation of candidate genes in humans may predispose patients to recurrent UTI. The identification of a genetic component of UTI recurrences will make it possible to diagnose at-risk adults and to predict genetic recurrences in their offspring. Six out of 14 genes investigated in humans may be associated with susceptibility to recurrent UTI in humans. In particular, the HSPA1B, CXCR1 & 2, TLR2, TLR4, TGF-beta1 genes seem to be associated with an alteration of the host response to UTIs at various levels.

  14. Insects feeding on cadavers as an alternative source of human genetic material

    Directory of Open Access Journals (Sweden)

    Rafał Skowronek

    2015-03-01

    Full Text Available In some criminal cases, the use of classical sources of human genetic material is difficult or even impossible. One solution may be the use of insects, especially blowfly larvae which feed on corpses. A recent review of case reports and experimental studies available in biomedical databases has shown that insects can be a valuable source of human mitochondrial and genomic deoxyribonucleic acid (DNA, allowing for an effective analysis of hypervariable region (HVR sequences and short tandem repeat (STR profiles, respectively. The optimal source of human DNA is the crop (a part of the gut of active third-instar blowfly larvae. Pupae and insect faeces can be also used in forensic genetic practice instead of the contents of the alimentary tract.

  15. Attitudes of young adults to prenatal screening and genetic correction for human attributes and psychiatric conditions.

    Science.gov (United States)

    Milner, K K; Collins, E E; Connors, G R; Petty, E M

    1998-03-05

    With recent advances in DNA technology, questions have arisen as to how this technology should be appropriately used. In this article, results obtained from a survey designed to elicit attitudes of college students to prenatal testing and gene therapy for human attributes and psychiatric conditions are reported. The eleven hypothetical disease phenotypes included schizophrenia, alcoholism, tendency toward violent behavior, attention deficit/hyperactivity disorder, depression requiring medical treatment, obesity, involvement in "dangerous" sports activities, homosexuality, borderline normal IQ (80-100), proportional short stature, and inability to detect perfect pitch. Most students supported prenatal genetic testing for psychiatric disorders and behavior that might result in harm to others (i.e., tendency towards violent behavior) and found prenatal genetic testing for human attributes less desirable. However, the lack of unilateral agreement or disagreement toward any one condition or attribute suggests the potential difficulties ahead in the quest for guidelines for the application of new technologies available to manipulate the human genome.

  16. The Nazi symbiosis: politics and human genetics at the Kaiser Wilhelm Institute.

    Science.gov (United States)

    Berez, Thomas M; Weiss, Sheila Faith

    2004-12-01

    The case of the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics (KWIA), from its inception in Weimar Republic Germany to its apogee under the rule of the Third Reich, is an example of how politics and human heredity can function as mutually beneficial resources. Whether it was a result of the Nazi bureaucrats' desire to legitimize their racial policy through science, or the KWIA personnel's desire to secure more funding for their research, the symbiotic relationship that developed between human genetics and Nazi politics could help explain why many scientists in the Third Reich undertook research projects that wholly transgressed the boundaries of morally acceptable science.

  17. The Effective Clustering Partition Algorithm Based on the Genetic Evolution

    Institute of Scientific and Technical Information of China (English)

    LIAO Qin; LI Xi-wen

    2006-01-01

    To the problem that it is hard to determine the clustering number and the abnormal points by using the clustering validity function, an effective clustering partition model based on the genetic algorithm is built in this paper. The solution to the problem is formed by the combination of the clustering partition and the encoding samples, and the fitness function is defined by the distances among and within clusters. The clustering number and the samples in each cluster are determined and the abnormal points are distinguished by implementing the triple random crossover operator and the mutation. Based on the known sample data, the results of the novel method and the clustering validity function are compared. Numerical experiments are given and the results show that the novel method is more effective.

  18. Human genetics in rheumatoid arthritis guides a high-throughput drug screen of the CD40 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Gang Li

    2013-05-01

    Full Text Available Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA, there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10(-9. Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10(-9, a finding corroborated by expression quantitative trait loci (eQTL analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2 and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65, a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L and conduct an HTS of 1,982 chemical compounds and FDA-approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel

  19. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    Science.gov (United States)

    Li, Gang; Diogo, Dorothée; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10−9). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10−9), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA–approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in

  20. Human amniotic fluid stem cells as a model for functional studies of genes involved in human genetic diseases or oncogenesis.

    Science.gov (United States)

    Rosner, Margit; Dolznig, Helmut; Schipany, Katharina; Mikula, Mario; Brandau, Oliver; Hengstschläger, Markus

    2011-09-01

    Besides their putative usage for therapies, stem cells are a promising tool for functional studies of genes involved in human genetic diseases or oncogenesis. For this purpose induced pluripotent stem (iPS) cells can be derived from patients harbouring specific mutations. In contrast to adult stem cells, iPS cells are pluripotent and can efficiently be grown in culture. However, iPS cells are modulated due to the ectopic induction of pluripotency, harbour other somatic mutations accumulated during the life span of the source cells, exhibit only imperfectly cleared epigenetic memory of the source cell, and are often genomically instable. In addition, iPS cells from patients only allow the investigation of mutations, which are not prenatally lethal. Embryonic stem (ES) cells have a high proliferation and differentiation potential, but raise ethical issues. Human embryos, which are not transferred in the course of in vitro fertilization, because of preimplantation genetic diagnosis of a genetic defect, are still rarely donated for the establishment of ES cell lines. In addition, their usage for studies on gene functions for oncogenesis is hampered by the fact the ES cells are already tumorigenic per se. In 2003 amniotic fluid stem (AFS) cells have been discovered, which meanwhile have been demonstrated to harbour the potential to differentiate into cells of all three germ layers. Monoclonal human AFS cell lines derived from amniocenteses have a high proliferative potential, are genomically stable and are not associated with ethical controversies. Worldwide amniocenteses are performed for routine human genetic diagnosis. We here discuss how generation and banking of monoclonal human AFS cell lines with specific chromosomal aberrations or monogenic disease mutations would allow to study the functional consequences of disease causing mutations. In addition, recently a protocol for efficient and highly reproducible siRNA-mediated long-term knockdown of endogenous gene

  1. [MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

    Science.gov (United States)

    Liu, Ren-Hu; Meng, Jin-Ling

    2003-05-01

    MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

  2. The population genomic landscape of human genetic structure, admixture history and local adaptation in Peninsular Malaysia.

    Science.gov (United States)

    Deng, Lian; Hoh, Boon Peng; Lu, Dongsheng; Fu, Ruiqing; Phipps, Maude E; Li, Shilin; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Ismail, Endom; Mokhtar, Siti Shuhada; Jin, Li; Zilfalil, Bin Alwi; Marshall, Christian R; Scherer, Stephen W; Al-Mulla, Fahd; Xu, Shuhua

    2014-09-01

    Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration

  3. Genetic and linguistic affinities between human populations in Eurasia and West Africa.

    Science.gov (United States)

    Nettle, Daniel; Harriss, Louise

    2003-06-01

    This study examines the relationship between genetic distance and linguistic affiliation for five regional sets of populations from Eurasia and West Africa. Human genetic and linguistic diversity have been proposed to be generally correlated, either through a direct link, whereby linguistic and genetic affiliations reflect the same past population processes, or an indirect one, where the evolution of the two types of diversity is independent but conditioned by the same geographical factors. By controlling for proximity, indirect correlations due to common geography are eliminated, and any residual relationships found are likely to reflect common linguistic-genetic processes. Clear relationships between genetic distances and linguistic relatedness are detectable in Europe and East and Central Asia, but not in the Middle East, Southeast Asia, or West Africa. We suggest that linguistic and genetic affiliations will only be correlated under specific conditions, such as where there have been large-scale demic diffusions in the last few thousand years, and relative sedentism in the subsequent period.

  4. Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD).

    Science.gov (United States)

    Pogue, A I; Lukiw, W J

    2016-06-01

    The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer's disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of "human biochemical individuality" and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity.

  5. Glacial Refugia of Ginkgo biloba and Human Impact on Its Genetic Diversity: Evidence from Chloroplast DNA

    Institute of Scientific and Technical Information of China (English)

    Wei Gong; Zhen Zeng; Ye-Ye Chen; Chuan Chen; Ying-Xiong Qiu; Cheng-Xin Fu

    2008-01-01

    Variations in the trnK region of chloroplast DNA were investigated in the present study using polymerase chain reaction-restriction fragment length polymorphism to detect the genetic structure and to infer the possible glacial refugia of Ginkgo biloba L. in China. In total, 220 individuals from 12 populations in China and three populations outside China were analyzed, representing the largest number of populations studied by molecular markers to date. Nineteen haplotypes were produced and haplotype A was found in all populations. Populations in south-western China, including WC, JF, PX, and SP, contained 14 of the 19 haplotypes and their genetic diversity ranged from 0.771 4 to 0.867 6. The TM population from China also showed a high genetic diversity (H=0.848 5). Most of the genetic variation existed within populations and the differentiation among populations was low (GST>=0.2). According to haplotype distribution and the historical record, we suggest that populations of G. biloba have been subjected to extensive human impact, which has compounded our attempt to infer glacial refugia for Ginkgo. Nevertheless, the present results suggest that the center of genetic diversity of Ginkgo is mainly in south-western China and in situ conservation is needed to protect and preserve the genetic resources.

  6. Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Ivana Antonucci

    2016-04-01

    Full Text Available In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

  7. Performance Optimization of Discrete Wavelets Transform Based Image Watermarking Using Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    A. Al-Haj

    2008-01-01

    Full Text Available The excellent spatial localization, frequency spread and multi-resolution characteristics of the Discrete Wavelets Transform (DWT, which were similar to the theoretical models of the human visual system, facilitated the development of many imperceptible and robust DWT-based watermarking algorithms. There had been extremely few proposed algorithms on optimized DWT-based image watermarking that can simultaneously provide perceptual transparency and robustness since these two watermarking requirements are conflicting, in this study we treat the DWT-based image watermarking problem as an optimization problem and solve it using genetic algorithms. We demonstrate through the experimental results we obtained that optimal DWT-based image watermarking can be achieved only if watermarking has been applied at specific wavelet sub-bands and by using specific watermark-amplification values.

  8. X-ray sensitivity of fifty-three human diploid fibroblast cell strains from patients with characterized genetic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1980-03-01

    The in vitro response of 53 human diploid fibroblast strains to x-irradiation was studied using a clonogenic survival assay. The strains, derived from patients with a variety of characterized clinical conditions, most with a genetic component, ranged in Do (a measure of the slope of the survival curve) from 43 to 168 rads. The mean Do's of six strains from normal individuals was 140 to 152 rads, with an overall range, based on the extremes of their standard errors, of 128 to 164 rads. Three-quarters of the strains studied fell within this range. Strains identified as sensitive came from patients with ataxia telangiectasia, progeria, the two genetic forms of retinoblastoma, and partial trisomy of chromosome 13. No marked radiosensitivity was found among strains derived from patients with a number of other conditions associated with a predisposition to malignancy.

  9. Improving human forensics through advances in genetics, genomics and molecular biology.

    Science.gov (United States)

    Kayser, Manfred; de Knijff, Peter

    2011-03-01

    Forensic DNA profiling currently allows the identification of persons already known to investigating authorities. Recent advances have produced new types of genetic markers with the potential to overcome some important limitations of current DNA profiling methods. Moreover, other developments are enabling completely new kinds of forensically relevant information to be extracted from biological samples. These include new molecular approaches for finding individuals previously unknown to investigators, and new molecular methods to support links between forensic sample donors and criminal acts. Such advances in genetics, genomics and molecular biology are likely to improve human forensic case work in the near future.

  10. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  11. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.

    Science.gov (United States)

    Amberger, Joanna S; Bocchini, Carol A; Schiettecatte, François; Scott, Alan F; Hamosh, Ada

    2015-01-01

    Online Mendelian Inheritance in Man, OMIM(®), is a comprehensive, authoritative and timely research resource of curated descriptions of human genes and phenotypes and the relationships between them. The new official website for OMIM, OMIM.org (http://omim.org), was launched in January 2011. OMIM is based on the published peer-reviewed biomedical literature and is used by overlapping and diverse communities of clinicians, molecular biologists and genome scientists, as well as by students and teachers of these disciplines. Genes and phenotypes are described in separate entries and are given unique, stable six-digit identifiers (MIM numbers). OMIM entries have a structured free-text format that provides the flexibility necessary to describe the complex and nuanced relationships between genes and genetic phenotypes in an efficient manner. OMIM also has a derivative table of genes and genetic phenotypes, the Morbid Map. OMIM.org has enhanced search capabilities such as genome coordinate searching and thesaurus-enhanced search term options. Phenotypic series have been created to facilitate viewing genetic heterogeneity of phenotypes. Clinical synopsis features are enhanced with UMLS, Human Phenotype Ontology and Elements of Morphology terms and image links. All OMIM data are available for FTP download and through an API. MIMmatch is a novel outreach feature to disseminate updates and encourage collaboration.

  12. A New Genetic Algorithm Methodology for Design Optimization of Truss Structures: Bipopulation-Based Genetic Algorithm with Enhanced Interval Search

    Directory of Open Access Journals (Sweden)

    Tugrul Talaslioglu

    2009-01-01

    Full Text Available A new genetic algorithm (GA methodology, Bipopulation-Based Genetic Algorithm with Enhanced Interval Search (BGAwEIS, is introduced and used to optimize the design of truss structures with various complexities. The results of BGAwEIS are compared with those obtained by the sequential genetic algorithm (SGA utilizing a single population, a multipopulation-based genetic algorithm (MPGA proposed for this study and other existing approaches presented in literature. This study has two goals: outlining BGAwEIS's fundamentals and evaluating the performances of BGAwEIS and MPGA. Consequently, it is demonstrated that MPGA shows a better performance than SGA taking advantage of multiple populations, but BGAwEIS explores promising solution regions more efficiently than MPGA by exploiting the feasible solutions. The performance of BGAwEIS is confirmed by better quality degree of its optimal designations compared to algorithms proposed here and described in literature.

  13. Improved Cost-Base Design of Water Distribution Networks using Genetic Algorithm

    Science.gov (United States)

    Moradzadeh Azar, Foad; Abghari, Hirad; Taghi Alami, Mohammad; Weijs, Steven

    2010-05-01

    Population growth and progressive extension of urbanization in different places of Iran cause an increasing demand for primary needs. The water, this vital liquid is the most important natural need for human life. Providing this natural need is requires the design and construction of water distribution networks, that incur enormous costs on the country's budget. Any reduction in these costs enable more people from society to access extreme profit least cost. Therefore, investment of Municipal councils need to maximize benefits or minimize expenditures. To achieve this purpose, the engineering design depends on the cost optimization techniques. This paper, presents optimization models based on genetic algorithm(GA) to find out the minimum design cost Mahabad City's (North West, Iran) water distribution network. By designing two models and comparing the resulting costs, the abilities of GA were determined. the GA based model could find optimum pipe diameters to reduce the design costs of network. Results show that the water distribution network design using Genetic Algorithm could lead to reduction of at least 7% in project costs in comparison to the classic model. Keywords: Genetic Algorithm, Optimum Design of Water Distribution Network, Mahabad City, Iran.

  14. Catalog of genetic progression of human cancers: breast cancer.

    Science.gov (United States)

    Desmedt, Christine; Yates, Lucy; Kulka, Janina

    2016-03-01

    With the rapid development of next-generation sequencing, deeper insights are being gained into the molecular evolution that underlies the development and clinical progression of breast cancer. It is apparent that during evolution, breast cancers acquire thousands of mutations including single base pair substitutions, insertions, deletions, copy number aberrations, and structural rearrangements. As a consequence, at the whole genome level, no two cancers are identical and few cancers even share the same complement of "driver" mutations. Indeed, two samples from the same cancer may also exhibit extensive differences due to constant remodeling of the genome over time. In this review, we summarize recent studies that extend our understanding of the genomic basis of cancer progression. Key biological insights include the following: subclonal diversification begins early in cancer evolution, being detectable even in in situ lesions; geographical stratification of subclonal structure is frequent in primary tumors and can include therapeutically targetable alterations; multiple distant metastases typically arise from a common metastatic ancestor following a "metastatic cascade" model; systemic therapy can unmask preexisting resistant subclones or influence further treatment sensitivity and disease progression. We conclude the review by describing novel approaches such as the analysis of circulating DNA and patient-derived xenografts that promise to further our understanding of the genomic changes occurring during cancer evolution and guide treatment decision making.

  15. Identification of Hammerstein Model Based on Quantum Genetic Algorithm

    OpenAIRE

    Zhang Hai Li

    2013-01-01

    Nonlinear system identification is a main topic of modern identification. A new method for nonlinear system identification is presented by using Quantum Genetic Algorithm(QGA).The problems of nonlinear system identification are cast as function optimization overprameter space,and the Quantum Genetic Algorithm is adopted to solve the optimization problem. Simulation experiments show that: compared with the genetic algorithm, quantum genetic algorithm is an effective swarm intelligence algorith...

  16. The X chromosome Alu insertions as a tool for human population genetics: data from European and African human groups.

    Science.gov (United States)

    Athanasiadis, Georgios; Esteban, Esther; Via, Marc; Dugoujon, Jean-Michel; Moschonas, Nicholas; Chaabani, Hassen; Moral, Pedro

    2007-05-01

    Alu elements are the most abundant mobile elements in the human genome (approximately 1,100,000 copies). Polymorphic Alu elements have been proved to be useful in studies of human origins and relationships owing to two important advantages: identity by descent and absence of the Alu element known to be the ancestral state. Alu variation in the X chromosome has been described previously in human populations but, as far as we know, these elements have not been used in population relationship studies. Here, we describe the allele frequencies of 13 'young' Alu elements of the X chromosome (Ya5DP62, Ya5DP57, Yb8DP49, Ya5a2DP1, Yb8DP2, Ya5DP3, Ya5NBC37, Yd3JX437, Ya5DP77, Ya5NBC491, Yb8NBC578, Ya5DP4 and Ya5DP13) in six human populations from sub-Saharan Africa (the Ivory Coast), North Africa (Moroccan High Atlas, Siwa oasis in Egypt, Tunisia), Greece (Crete Island) and Spain (Basque Country). Eight out of 13 Alu elements have shown remarkably high gene diversity values in all groups (average heterozygosities: 0.342 in the Ivory Coast, 0.250 in North Africa, 0.209 in Europe). Genetic relationships agree with a geographical pattern of differentiation among populations, with some peculiar features observed in North Africans. Crete Island and the Basque Country show the lowest genetic distance (0.0163) meanwhile Tunisia, in spite of its geographical location, lies far from the other two North African samples. The results of our work demonstrate that X chromosome Alu elements comprise a reliable set of genetic markers useful to describe human population relationships for fine-scale geographical studies.

  17. Optimization of unit commitment based on genetic algorithms

    Institute of Scientific and Technical Information of China (English)

    蔡兴国; 初壮

    2002-01-01

    How to solve unit commitment and load dispatch of power system by genetic algorithms is discussed in this paper. A combination encoding scheme of binary encoding and floating number encoding and corresponding genetic operators are developed. Meanwhile a contract mapping genetic algorithm is used to enhance traditional GA' s convergence. The result of a practical example shows that this algorithm is effective.

  18. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Science.gov (United States)

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  19. Similarity in recombination rate estimates highly correlates with genetic differentiation in humans.

    Directory of Open Access Journals (Sweden)

    Hafid Laayouni

    Full Text Available Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans. We calculated the recombination rates between adjacent pairs of 636,933 common single-nucleotide polymorphism loci in 28 worldwide human populations and analyzed them in relation to genetic distances between populations. We found a strong and highly significant correlation between similarity in the recombination rates corrected for effective population size and genetic differentiation between populations. This correlation is observed at the genome-wide level, but also for each chromosome and when genetic distances and recombination similarities are calculated independently from different parts of the genome. Moreover, and more relevant, this relationship is robustly maintained when considering presence/absence of recombination hotspots. Simulations show that this correlation cannot be explained by biases in the inference of recombination rates caused by haplotype sharing among similar populations. This result indicates a rapid pace of evolution of recombination, within the time span of differentiation of modern humans.

  20. New frontiers in the study of human cultural and genetic evolution.

    Science.gov (United States)

    Ross, Cody T; Richerson, Peter J

    2014-12-01

    In this review, we discuss the dynamic linkages between culture and the genetic evolution of the human species. We begin by briefly describing the framework of gene-culture coevolutionary (or dual-inheritance) models for human evolutionary change. Until recently, the literature on gene-culture coevolution was composed primarily of mathematical models and formalized theory describing the complex dynamics underlying human behavior, adaptation, and technological evolution, but had little empirical support concerning genetics. The rapid progress in the fields of molecular genetics and genomics, however, is now providing the kinds of data needed to produce rich empirical support for gene-culture coevolutionary models. We briefly outline how theoretical and methodological progress in genome sciences has provided ways for the strength of selection on genes to be evaluated, and then outline how evidence of selection on several key genes can be directly linked to human cultural practices. We then describe some exciting new directions in the empirical study of gene-culture coevolution, and conclude with a discussion of the role of gene-culture evolutionary models in the future integration of medical, biological, and social sciences.

  1. Genetic identification of missing persons: DNA analysis of human remains and compromised samples.

    Science.gov (United States)

    Alvarez-Cubero, M J; Saiz, M; Martinez-Gonzalez, L J; Alvarez, J C; Eisenberg, A J; Budowle, B; Lorente, J A

    2012-01-01

    Human identification has made great strides over the past 2 decades due to the advent of DNA typing. Forensic DNA typing provides genetic data from a variety of materials and individuals, and is applied to many important issues that confront society. Part of the success of DNA typing is the generation of DNA databases to help identify missing persons and to develop investigative leads to assist law enforcement. DNA databases house DNA profiles from convicted felons (and in some jurisdictions arrestees), forensic evidence, human remains, and direct and family reference samples of missing persons. These databases are essential tools, which are becoming quite large (for example the US Database contains 10 million profiles). The scientific, governmental and private communities continue to work together to standardize genetic markers for more effective worldwide data sharing, to develop and validate robust DNA typing kits that contain the reagents necessary to type core identity genetic markers, to develop technologies that facilitate a number of analytical processes and to develop policies to make human identity testing more effective. Indeed, DNA typing is integral to resolving a number of serious criminal and civil concerns, such as solving missing person cases and identifying victims of mass disasters and children who may have been victims of human trafficking, and provides information for historical studies. As more refined capabilities are still required, novel approaches are being sought, such as genetic testing by next-generation sequencing, mass spectrometry, chip arrays and pyrosequencing. Single nucleotide polymorphisms offer the potential to analyze severely compromised biological samples, to determine the facial phenotype of decomposed human remains and to predict the bioancestry of individuals, a new focus in analyzing this type of markers.

  2. Genetic diversity and disease susceptibility.

    OpenAIRE

    Bodmer, W F

    1997-01-01

    The range of genetic diversity within human populations is enormous. Genetic susceptibility to common chronic disease is a significant part of this genetic diversity, which also includes a variety of rare clear-cut inherited diseases. Modern DNA-based genomic analysis can now routinely lead to the identification of genes involved in disease susceptibility, provides the basis for genetic counselling in affected families, and more widely for a genetically targeted approach to disease prevention...

  3. Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry.

    Science.gov (United States)

    Tadayon, Sayed H; Vaziri-Pashkam, Maryam; Kahali, Pegah; Ansari Dezfouli, Mitra; Abbassian, Abdolhossein

    2016-01-01

    Brain asymmetry varies across individuals. However, genetic factors contributing to this normal variation are largely unknown. Here we studied variation of cortical surface area asymmetry in a large sample of subjects. We performed principal component analysis (PCA) to capture correlated asymmetry variation across cortical regions. We found that caudal and rostral anterior cingulate together account for a substantial part of asymmetry variation among individuals. To find SNPs associated with this subset of brain asymmetry variation we performed a genome-wide association study followed by replication in an independent cohort. We identified one SNP (rs11691187) that had genome-wide significant association (P Combined = 2.40e-08). The rs11691187 is in the first intron of VIT. In a follow-up analysis, we found that VIT gene expression is associated with brain asymmetry in six donors of the Allen Human Brain Atlas. Based on these findings we suggest that VIT contributes to normal brain asymmetry variation. Our results can shed light on disorders associated with altered brain asymmetry.

  4. Mycobacterium bovis in Burkina Faso: epidemiologic and genetic links between human and cattle isolates.

    Directory of Open Access Journals (Sweden)

    Adama Sanou

    2014-10-01

    Full Text Available In sub-Saharan Africa, bovine tuberculosis (bTB is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations.Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5 or humans (1 or from both (1. Moreover, these data (genetic analyses and phenetic tree showed that the M. bovis isolates belonged to the African 1 (Af1 clonal complex (81.8% and the putative African 5 (Af5 clonal complex (18.2%, in agreement with the results of RDAf1 deletion typing.This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso.

  5. Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

    Science.gov (United States)

    Hodgkinson, Conrad P; Gomez, José A; Mirotsou, Maria; Dzau, Victor J

    2010-11-01

    The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

  6. The Genetic Influences on Oxycodone Response Characteristics in Human Experimental Pain

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia Møller

    2015-01-01

    PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P ...Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response...... to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral...

  7. Familial Alzheimer's disease: genetic analysis related to disease heterogeneity, Down syndrome and human brain evolution.

    Science.gov (United States)

    Schapiro, M B; Rapoport, S I

    1989-01-01

    Etiologically heterogeneous subgroups of patients with Alzheimer's disease (AD) exist and need to be distinguished so as to better identify genetic causes of familial cases. Furthermore, the presence of AD neuropathology in Down syndrome (trisomy 21) subjects older than 35 years suggests that AD in some cases is caused by dysregulation of expression of genes on chromosome 21. Cerebral metabolic abnormalities in life, and the distribution of AD neuropathology in the post-mortem brain, indicate that AD involves the association neocortices and subcortical regions with which they evolved during evolution of the human brain. Accordingly, understanding the molecular basis of this evolution should elucidate the genetic basis of AD, whereas knowing the genetics of AD should be informative about the genomic changes which promoted brain evolution.

  8. Practice-based competencies for accreditation of and training in graduate programs in genetic counseling.

    Science.gov (United States)

    Fine, B A; Baker, D L; Fiddler, M B

    1996-09-01

    In January 1996, the American Board of Genetic Counseling (ABGC) adopted 27 practice-based competencies as a standard for assessing the training of graduate students in genetic counseling. These competencies were identified and refined through a collective, narrative process that took place from January through November 1994, and included directors of graduate programs in genetic counseling, ABGC board members and expert consultants. These competencies now form the basis of the document "Requirements for Graduate Programs in Genetic Counseling Seeking Accreditation by the American Board of Genetic Counseling" (American Board of Genetic Counseling, 1996). The competencies are organized into four domains and are presented and discussed in this article.

  9. Ontogeny and phylogeny of femoro-tibial characters in humans and hominid fossils: functional influence and genetic determinism.

    Science.gov (United States)

    Tardieu, C

    1999-11-01

    prominence of the lateral lip of the trochlea arises before any use, and thus appears to be genetically determined. However, the postnatal development of this joint shows that this feature is also modified epigenetically by use. It is argued that the hominid femoro-patellar joint would have been reshaped following the process of genetic assimilation (Waddington [1942] Nature 3811:563-565). The prominence of the lateral lip of the femoral trochlea was probably selected following a two-staged process-first epigenetic, then genetic. Far from being a Lamarckian explanation, this concept applies precisely to adaptive characters that are induced by an external stimulus during a single lifetime and are replaced through natural selection by genetically based equivalent characters. The nature of the structures involved in the studied features is shown to be an important parameter determining their mode of development and selection.

  10. Extended Range Guided Munition Parameter Optimization Based on Genetic Algorithms

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Many factors influencing range of extended range guided munition (ERGM) are analyzed. The definition domain of the most important three parameters are ascertained by preparatory mathematical simulation, the optimized mathematical model of ERGM maximum range with boundary conditions is created, and parameter optimization based on genetic algorithm (GA) is adopted. In the GA design, three-point crossover is used and the best chromosome is kept so that the convergence speed becomes rapid. Simulation result shows that GA is feasible, the result is good and it can be easy to attain global optimization solution, especially when the objective function is not the convex one for independent variables and it is a multi-parameter problem.

  11. Fuzzy Genetic Algorithm Based on Principal Operation and Inequity Degree

    Science.gov (United States)

    Li, Fachao; Jin, Chenxia

    In this paper, starting from the structure of fuzzy information, by distinguishing principal indexes and assistant indexes, give comparison of fuzzy information on synthesizing effect and operation of fuzzy optimization on principal indexes transformation, further, propose axiom system of fuzzy inequity degree from essence of constraint, and give an instructive metric method; Then, combining genetic algorithm, give fuzzy optimization methods based on principal operation and inequity degree (denoted by BPO&ID-FGA, for short); Finally, consider its convergence using Markov chain theory and analyze its performance through an example. All these indicate, BPO&ID-FGA can not only effectively merge decision consciousness into the optimization process, but possess better global convergence, so it can be applied to many fuzzy optimization problems.

  12. GENETIC ALGORITHM BASED CONCEPT DESIGN TO OPTIMIZE NETWORK LOAD BALANCE

    Directory of Open Access Journals (Sweden)

    Ashish Jain

    2012-07-01

    Full Text Available Multiconstraints optimal network load balancing is an NP-hard problem and it is an important part of traffic engineering. In this research we balance the network load using classical method (brute force approach and dynamic programming is used but result shows the limitation of this method but at a certain level we recognized that the optimization of balanced network load with increased number of nodes and demands is intractable using the classical method because the solution set increases exponentially. In such case the optimization techniques like evolutionary techniques can employ for optimizing network load balance. In this paper we analyzed proposed classical algorithm and evolutionary based genetic approach is devise as well as proposed in this paper for optimizing the balance network load.

  13. Optimization of transmission system design based on genetic algorithm

    Directory of Open Access Journals (Sweden)

    Xianbing Chen

    2016-05-01

    Full Text Available Transmission system is a crucial precision mechanism for twin-screw chemi-mechanical pulping equipment. The structure of the system designed by traditional method is not optimal because the structure designed by the traditional methods is easy to fall into the local optimum. To achieve the global optimum, this article applies the genetic algorithm which has grown in recent years in the field of structure optimization. The article uses the volume of transmission system as the objective function to optimize the structure designed by traditional method. Compared to the simulation results, the original structure is not optimal, and the optimized structure is tighter and more reasonable. Based on the optimized results, the transmission shafts in the transmission system are designed and checked, and the parameters of the twin screw are selected and calculated. The article provided an effective method to design the structure of transmission system.

  14. Voidage measurement based on genetic algorithm and electrical capacitance tomography

    Institute of Scientific and Technical Information of China (English)

    WANG Wei-wei; WANG Bao-liang; HUANG Zhi-yao; LI Hai-qing

    2005-01-01

    A new voidage measurement method based on electrical capacitance tomography (ECT) technique, Genetic Algorithm (GA) and Partial Least Square (PLS) method was proposed. The voidage measurement model, linear capacitance combination, was developed to measure on-line voidage. GA and PLS method were used to determine the coefficients of the voidage measurement model. GA was used to explore the optimal capacitance combination which gave significant contribution to the voidage measurement. PLS method was applied to determine the weight coefficient of the contribution of each capacitance to the voidage measurement. Flow pattern identification result was introduced to improve the voidage measurement accuracy. Experimental results showed that the proposed voidage measurement method is effective and that the measurement accuracy is satisfactory.

  15. FRACTIONAL ORDER SYSTEM IDENTIFICATION BASED ON GENETIC ALGORITHMS

    Directory of Open Access Journals (Sweden)

    MAZIN Z. OTHMAN

    2013-12-01

    Full Text Available System identification deals with estimating the plant parameters under control using input-output measuring data. Most of practical plants have fractional order dynamic properties which are based on integration and differentiation of noninteger order. In this work the structure and the parameters of fractional order unknown transfer function are estimated using input-output data. Integer order Least Squares identification is used first to confirm the structure (order of the unknown transfer function. Then, Genetic Algorithms (GAs is followed to find the most accurate fractional order estimate that represents the system. Illustrative examples are presented in which fractional order transfer functions are identified in a way that faithfully estimates the dynamics of the unknown plants.

  16. Haplotyping a single triploid individual based on genetic algorithm.

    Science.gov (United States)

    Wu, Jingli; Chen, Xixi; Li, Xianchen

    2014-01-01

    The minimum error correction model is an important combinatorial model for haplotyping a single individual. In this article, triploid individual haplotype reconstruction problem is studied by using the model. A genetic algorithm based method GTIHR is presented for reconstructing the triploid individual haplotype. A novel coding method and an effectual hill-climbing operator are introduced for the GTIHR algorithm. This relatively short chromosome code can lead to a smaller solution space, which plays a positive role in speeding up the convergence process. The hill-climbing operator ensures algorithm GTIHR converge at a good solution quickly, and prevents premature convergence simultaneously. The experimental results prove that algorithm GTIHR can be implemented efficiently, and can get higher reconstruction rate than previous algorithms.

  17. Resizing Technique-Based Hybrid Genetic Algorithm for Optimal Drift Design of Multistory Steel Frame Buildings

    Directory of Open Access Journals (Sweden)

    Hyo Seon Park

    2014-01-01

    Full Text Available Since genetic algorithm-based optimization methods are computationally expensive for practical use in the field of structural optimization, a resizing technique-based hybrid genetic algorithm for the drift design of multistory steel frame buildings is proposed to increase the convergence speed of genetic algorithms. To reduce the number of structural analyses required for the convergence, a genetic algorithm is combined with a resizing technique that is an efficient optimal technique to control the drift of buildings without the repetitive structural analysis. The resizing technique-based hybrid genetic algorithm proposed in this paper is applied to the minimum weight design of three steel frame buildings. To evaluate the performance of the algorithm, optimum weights, computational times, and generation numbers from the proposed algorithm are compared with those from a genetic algorithm. Based on the comparisons, it is concluded that the hybrid genetic algorithm shows clear improvements in convergence properties.

  18. Discovery and resolve: the Human Genetics Society of Australasia Oration 2011.

    Science.gov (United States)

    Pearn, John

    2011-10-01

    Human genetics spans every facet of biology from molecular science, through laboratory and clinical practice, to psychology and anthropology. In each of these areas, the history of human genetics has been punctuated by paradigm shifts in knowledge. Each such new concept has been received with skepticism, often with perplexity, and sometimes with frank incredulity. Such comprise the datum milestones along the path leading to our present corpus of genetic knowledge. In parallel to the personal threats to Copernicus and Galileo in the field of astronomy in the 17th century, almost all genetic discoveries of the 19th and 20th centuries were seen as challenges to the received wisdom, and sometimes the social order, of their time and place. Researchers, scientists and clinicians encountering such new and often-heretical paradigm shifts have required considerable resolve to promote and publish their work. Just as in the field of astronomy, new directions in genetics have threatened not only the reputations and sometimes the careers of scientists, but also have been challenges to fundamental religious and sociological beliefs in society more broadly. Examples followed the discovery of biological sexual dimorphism (in plants as well as animals) by Nehemiah Grew (1641-1712). Darwinian evolution, Mendel's First and Second Laws, the existence of mitochondrial genes, apoptosis and its genetic basis, and uniparental disomy are more recent examples. Many of these new revelations, which today have led to the current understanding of fundamental biology, were discovered by individuals working in relative isolation. To promote and publish findings that fundamentally challenge received wisdom continues to require considerable resolve, if not courage. Herein lies a message for all clinicians and researchers.

  19. Family-Based Genetic Association for Molar-Incisor Hypomineralization.

    Science.gov (United States)

    Jeremias, Fabiano; Pierri, Ricardo A G; Souza, Juliana F; Fragelli, Camila Maria B; Restrepo, Manuel; Finoti, Livia S; Bussaneli, Diego G; Cordeiro, Rita C L; Secolin, Rodrigo; Maurer-Morelli, Claudia V; Scarel-Caminaga, Raquel M; Santos-Pinto, Lourdes

    2016-01-01

    Despite some evidence of genetic and environmental factors on molar-incisor hypomineralization (MIH), its aetiology remains unclear. This family-based genetic association study aimed more comprehensively to investigate the genetic carriage potentially involved in MIH development. DNA was obtained from buccal cells of 391 individuals who were birth family members of 101 Brazilian nuclear families. Sixty-three single nucleotide polymorphisms (SNPs) were investigated in 21 candidate genes related to amelogenesis using the TaqMan™ OpenArray™ Genotyping platform. All SNPs were genotyped in 165 birth family members unaffected by MIH, 96 with unknown MIH status and 130 affected individuals (50.7% with severe MIH). Association analysis was performed by the transmission/disequilibrium test (TDT), and statistical results were corrected using the false discovery rate. Significant results were obtained for SNPs rs7821494 (FAM83H gene, OR = 3.7; 95% CI = 1.75-7.78), rs34367704 (AMBN gene, OR = 2.7; 95% CI = 1.16-6.58), rs3789334 (BMP2 gene, OR = 2.9; 95% CI = 1.34-6.35), rs6099486 (BMP7 gene, OR = 2.2; 95% CI = 1.14-4.38), rs762642 (BMP4 gene, OR = 2.3; 95% CI = 1.38-3.65), rs7664896 (ENAM gene, OR = 2.1; 95% CI = 1.19-3.51), rs1711399 (MMP20 gene, OR = 0.4; 95% CI = 0.20-0.72), rs1711423 (MMP20 gene, OR = 2.1; 95% CI = 1.18-3.61), rs2278163 (DLX3 gene, OR = 2.8; 95% CI = 1.26-6.41), rs6996321 (FGFR1 gene, OR = 2.7; 95% CI = 1.20-5.88), and rs5979395 (AMELX gene, OR = 11.7; 95% CI = 1.63-84.74). Through this family-based association study, we concluded that variations in genes related to amelogenesis were associated with the susceptibility to develop MIH. This result is in agreement with the multifactorial idea of the MIH aetiology, but further studies are necessary to investigate more thoroughly the factors that could influence MIH.

  20. Human Genome Project discoveries: Dialectics and rhetoric in the science of genetics

    Science.gov (United States)

    Robidoux, Charlotte A.

    The Human Genome Project (HGP), a $437 million effort that began in 1990 to chart the chemical sequence of our three billion base pairs of DNA, was completed in 2003, marking the 50th anniversary that proved the definitive structure of the molecule. This study considered how dialectical and rhetorical arguments functioned in the science, political, and public forums over a 20-year period, from 1980 to 2000, to advance human genome research and to establish the official project. I argue that Aristotle's continuum of knowledge--which ranges from the probable on one end to certified or demonstrated knowledge on the other--provides useful distinctions for analyzing scientific reasoning. While contemporary scientific research seeks to discover certified knowledge, investigators generally employ the hypothetico-deductive or scientific method, which often yields probable rather than certain findings, making these dialectical in nature. Analysis of the discourse describing human genome research revealed the use of numerous rhetorical figures and topics. Persuasive and probable reasoning were necessary for scientists to characterize unknown genetic phenomena, to secure interest in and funding for large-scale human genome research, to solve scientific problems, to issue probable findings, to convince colleagues and government officials that the findings were sound and to disseminate information to the public. Both government and private venture scientists drew on these tools of reasoning to promote their methods of mapping and sequencing the genome. The debate over how to carry out sequencing was rooted in conflicting values. Scientists representing the academic tradition valued a more conservative method that would establish high quality results, and those supporting private industry valued an unconventional approach that would yield products and profits more quickly. Values in turn influenced political and public forum arguments. Agency representatives and investors sided

  1. Trypanosoma brucei gambiense Type 1 populations from human patients are clonal and display geographical genetic differentiation.

    Science.gov (United States)

    Morrison, Liam J; Tait, Andy; McCormack, Gillian; Sweeney, Lindsay; Black, Alana; Truc, Philippe; Likeufack, Anne C L; Turner, C Michael; MacLeod, Annette

    2008-12-01

    We have rigorously tested the hypothesis that Trypanosoma brucei gambiense Type 1 is composed of genetically homogenous populations by examining the parasite population present in Human African Trypanosomiasis (HAT) patients from the Democratic Republic of Congo (DRC) and Cameroon (CAM). We amplified eight microsatellite markers by PCR directly from blood spots on FTA filters, thereby avoiding the significant parasite selection inherent in the traditional isolation techniques of rodent inoculation or in vitro culture. All microsatellite markers were polymorphic, although for four markers there was only polymorphism between the DRC and CAM populations, not within populations, suggesting very limited genetic exchange. Within the largest population from the DRC, Hardy-Weinberg equilibrium is not evident at any loci. This evidence suggests a clonal population. However, there was significant sub-structuring between the DRC and CAM samples (F(ST) = 0.32), indicating that Trypanosoma brucei gambiense Type 1 has genetically distinct clades. The data combine to indicate that genetic exchange plays a very limited role. The finding of distinct clades in different places suggests the possibility that samples from humans with clinical signs represent clonal expansions from an underlying population that requires identifying and characterising.

  2. Problems of genetic diagnosis: serological markers in the prognosis of the development of human speed abilities

    Directory of Open Access Journals (Sweden)

    Serhiyenko Leonid Prokopovich

    2011-10-01

    Full Text Available The article deals with the study of correlation between blood groups system AB0 and Rh with the peculiarities of the development of human speed abilities. Complex of genetic markers is defined. It is possible to use this complex in the individual prognosis of the development of human motor abilities. With 0(I and A(II blood groups and Rh+ have a high inclination to the physical development. Better identify trends in the phenotypic expression of high-speed abilities in people with 0(I and A(II blood groups in comparison with people with the AB(IV and B(III blood group. The pattern of decreasing susceptibility to the development of high-speed abilities as follows: 0(I>A(II>B(III>AB (IV. It is established that a complex system of genetic markers AB0 and Rh blood has no gender differences.

  3. Antimicrobial Functions of Lactoferrin Promote Genetic Conflicts in Ancient Primates and Modern Humans.

    Directory of Open Access Journals (Sweden)

    Matthew F Barber

    2016-05-01

    Full Text Available Lactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Additionally, lactoferrin possesses cationic protein domains that directly bind and inhibit diverse microbes. The implications for these dual functions on lactoferrin evolution and genetic conflicts with microbes remain unclear. Here we show that lactoferrin has been subject to recurrent episodes of positive selection during primate divergence predominately at antimicrobial peptide surfaces consistent with long-term antagonism by bacteria. An abundant lactoferrin polymorphism in human populations and Neanderthals also exhibits signatures of positive selection across primates, linking ancient host-microbe conflicts to modern human genetic variation. Rapidly evolving sites in lactoferrin further correspond to molecular interfaces with opportunistic bacterial pathogens causing meningitis, pneumonia, and sepsis. Because microbes actively target lactoferrin to acquire iron, we propose that the emergence of antimicrobial activity provided a pivotal mechanism of adaptation sparking evolutionary conflicts via acquisition of new protein functions.

  4. Antimicrobial Functions of Lactoferrin Promote Genetic Conflicts in Ancient Primates and Modern Humans

    Science.gov (United States)

    Kronenberg, Zev; Yandell, Mark; Elde, Nels C.

    2016-01-01

    Lactoferrin is a multifunctional mammalian immunity protein that limits microbial growth through sequestration of nutrient iron. Additionally, lactoferrin possesses cationic protein domains that directly bind and inhibit diverse microbes. The implications for these dual functions on lactoferrin evolution and genetic conflicts with microbes remain unclear. Here we show that lactoferrin has been subject to recurrent episodes of positive selection during primate divergence predominately at antimicrobial peptide surfaces consistent with long-term antagonism by bacteria. An abundant lactoferrin polymorphism in human populations and Neanderthals also exhibits signatures of positive selection across primates, linking ancient host-microbe conflicts to modern human genetic variation. Rapidly evolving sites in lactoferrin further correspond to molecular interfaces with opportunistic bacterial pathogens causing meningitis, pneumonia, and sepsis. Because microbes actively target lactoferrin to acquire iron, we propose that the emergence of antimicrobial activity provided a pivotal mechanism of adaptation sparking evolutionary conflicts via acquisition of new protein functions. PMID:27203426

  5. Blue eyes in lemurs and humans: same phenotype, different genetic mechanism

    DEFF Research Database (Denmark)

    Bradley, Brenda J; Pedersen, Anja; Mundy, Nicholas I

    2009-01-01

    Almost all mammals have brown or darkly-pigmented eyes (irises), but among primates, there are some prominent blue-eyed exceptions. The blue eyes of some humans and lemurs are a striking example of convergent evolution of a rare phenotype on distant branches of the primate tree. Recent work...... on humans indicates that blue eye color is associated with, and likely caused by, a single nucleotide polymorphism (rs12913832) in an intron of the gene HERC2, which likely regulates expression of the neighboring pigmentation gene OCA2. This raises the immediate question of whether blue eyes in lemurs might...... have a similar genetic basis. We addressed this by sequencing the homologous genetic region in the blue-eyed black lemur (Eulemur macaco flavifrons; N = 4) and the closely-related black lemur (Eulemur macaco macaco; N = 4), which has brown eyes. We then compared a 166-bp segment corresponding...

  6. Genetic counselors' current use of personal health records-based family histories in genetic clinics and considerations for their future adoption.

    Science.gov (United States)

    Widmer, Chaney; Deshazo, Jonathan P; Bodurtha, Joann; Quillin, John; Creswick, Heather

    2013-06-01

    Given the widespread adoption of electronic medical records and recent emergence of electronic family history tools, we examined genetic counselors' perspectives on the emerging technology of the personal health record (PHR)-based family history tool that links to an electronic medical record (EMR). Two-hundred thirty-three genetic counselors responded to an on-line survey eliciting current use of electronic family history (EFH) tools and familiarity with PHR-based family history tools. Additionally, after being shown a series of screen shots of a newly developed PHR-based family history tool based on the U.S. Surgeon General's My Family Health Portrait (United States Department of Health and Human Services 2009), participants were surveyed about the perceived usefulness, ease of use, and impact on current workflow that this kind of tool would have in their practices. Eighty-three percent reported that their institution has an EMR, yet only 35 % have a dedicated space for family history. Eighty-two percent reported that less than 5 % of their patients have a PHR, and only 16 % have worked with patients who have a PHR. Seventy-two percent or more agreed that a PHR-based family history tool would facilitate communication, increase accuracy of information, ensure consistency in recording information, increase focus on actual counseling, reduce repetitive questions, improve efficiency, and increase the legibility and clarity. Our findings suggest that participants were familiar with existing EFH tools, but that the majority did not use them in practice. Genetic counselors' adoption of such tools is limited due to non-existence of this kind of technology or inability to integrate it into their clinics. They are also strongly in favor of adopting a PHR-based family history tool in genetics clinics, but have practical concerns that must be addressed before the tool can be implemented.

  7. Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    OpenAIRE

    Castéra, Jérémy; Clément, Pierre

    2014-01-01

    International audience; This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. gene...

  8. Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs.

    Directory of Open Access Journals (Sweden)

    David López Herráez

    Full Text Available BACKGROUND: Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world. METHODOLOGY: We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations from the Human Genome Diversity Panel (HGDP-CEPH. When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental level. CONCLUSIONS: Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.

  9. Role of phenylthiocarbamide as a genetic marker in predicting the predisposition of disease traits in humans

    OpenAIRE

    Shivaprasad, H. S.; Chaithra, P. T.; Kavitha, P; Malini, Suttur S.

    2012-01-01

    The main objective of this study is to find out the genetic variation and predisposition of overweight/obese, smoking/alcoholism and thyroid disease traits among tasters and non-tasters in Mysore population, South India. Bitter-taste perception for phenylthiocarbamide (PTC) is a classically variable trait both within and between human populations. Many studies have reported that in world population, approximately 30% of them are PTC non-tasters and 70% are tasters. This investigation was cond...

  10. Genetic studies of two inherited human phenotypes : Hearing loss and monoamine oxidase activity

    OpenAIRE

    Balciuniene, Jorune

    2001-01-01

    This thesis focuses on the identification of genetic factors underlying two inherited human phenotypes: hearing loss and monoamine oxidase activity. Non-syndromic hearing loss segregating in a Swedish family was tested for linkage to 13 previously reported candidate loci for hearing disabilities. Linkage was found to two loci: DFNA12 (llq22-q24) and DFNA2 (lp32). A detailed analysis of the phenotypes and haplotypes shared by the affected individuals supported the hypothesis of digenic inheri...

  11. Comparative genetic approaches to the evolution of human brain and behavior.

    Science.gov (United States)

    Vallender, Eric J

    2011-01-01

    With advances in genomic technologies, the amount of genetic data available to scientists today is vast. Genomes are now available or planned for 14 different primate species and complete resequencing of numerous human individuals from numerous populations is underway. Moreover, high-throughput deep sequencing is quickly making whole genome efforts within the reach of single laboratories allowing for unprecedented studies. Comparative genetic approaches to the identification of the underlying basis of human brain, behavior, and cognitive ability are moving to the forefront. Two approaches predominate: inter-species divergence comparisons and intra-species polymorphism studies. These methodological differences are useful for different time scales of evolution and necessarily focus on different evolutionary events in the history of primate and hominin evolution. Inter-species divergence is more useful in studying large scale primate, or hominoid, evolution whereas intra-species polymorphism can be more illuminating of recent hominin evolution. These differences in methodological utility also extend to studies of differing genetic substrates; current divergence studies focus primarily on protein evolution whereas polymorphism studies are substrate ambivalent. Some of the issues inherent in these studies can be ameliorated by current sequencing capabilities whereas others remain intractable. New avenues are also being opened that allow for the incorporation of novel substrates and approaches. In the post-genomic era, the study of human evolution, specifically as it relates to the brain, is becoming more complete focusing increasingly on the totality of the system and better conceptualizing the entirety of the genetic changes that have lead to the human phenotype today.

  12. Genetic and epigenetic changes of genes on chromosome 3 in human urogenital tumors

    Directory of Open Access Journals (Sweden)

    Gordiyuk V. V.

    2011-02-01

    Full Text Available Numerous disorders of genes and alterations of their expression are observed on a short arm of human chromosome 3, particularly in 3p14, 3p21, 3p24 compact regions in epithelial tumors. These aberrations affect the key biological processes specific for cancerogenesis. Such genes or their products could be used for diagnostics and prognosis of cancer. Genetical and epigenetical changes of a number of genes on chromosome 3 in human urogenital cancer, their role in cellular processes and signal pathways and perspectives as molecular markers of cancer diseases are analyzed in the review

  13. What Mendel did not discover: exceptions in Mendelian genetics and their role in inherited human disease.

    Science.gov (United States)

    Hern, Laura M; Bidichandani, Sanjay I

    2004-01-01

    It has been one hundred and thirty-eight years after the initial publication of Mendel's laws of inheritance. Following a couple of decades of unprecedented progress in deciphering the molecular basis of human genetic disease, we have the luxury of hindsight to revisit Mendel's original discoveries in order to recognize variations in the themes that have otherwise endured the test of time. In this article we focus on diseases inherited in a Mendelian (or near Mendelian) fashion and describe deviations from the laws of Mendelian inheritance. We discuss relevant examples of inherited human disease and the underlying molecular mechanisms for the observed variations in Mendelian laws of inheritance.

  14. The humankind genome: from genetic diversity to the origin of human diseases.

    Science.gov (United States)

    Belizário, Jose E

    2013-12-01

    Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.

  15. Does elevated C-reactive protein cause human atherothrombosis? Novel insights from genetics, intervention trials, and elsewhere

    DEFF Research Database (Denmark)

    Nordestgaard, Børge

    2009-01-01

    PURPOSE OF REVIEW: To evaluate evidence from human epidemiology, mechanistic studies, animal studies, human genetics, and human intervention trials to address whether elevated C-reactive protein (CRP) causes human atherothrombotic cardiovascular disease. RECENT FINDINGS: Human epidemiology...... demonstrates that elevated CRP levels are associated with increased risk of atherothrombosis. Mechanistic and animal studies provide evidence both for and against a causal relationship of CRP with atherothrombosis. Human genetics demonstrate that genetic variation in the CRP gene is associated with lifelong...... increased CRP levels, but not with increased risk of atherothrombosis. A human intervention trial in healthy people with low LDL cholesterol and elevated CRP demonstrated that aggressive statin treatment caused reductions of 50% in LDL cholesterol, 37% in CRP, 50% in atherothrombotic cardiovascular events...

  16. Structural and functional characterization of pathogenic non- synonymous genetic mutations of human insulin-degrading enzyme by in silico methods.

    Science.gov (United States)

    Shaik, Noor A; Kaleemuddin, Mohammed; Banaganapalli, Babajan; Khan, Fazal; Shaik, Nazia S; Ajabnoor, Ghada; Al-Harthi, Sameer E; Bondagji, Nabeel; Al-Aama, Jumana Y; Elango, Ramu

    2014-04-01

    Insulin-degrading enzyme (IDE) is a key protease involved in degrading insulin and amyloid peptides in human body. Several non-synonymous genetic mutations of IDE gene have been recently associated with susceptibility to both diabetes and Alzheimer's diseases. However, the consequence of these mutations on the structure of IDE protein and its substrate binding characteristics is not well elucidated. The computational investigation of genetic mutation consequences on structural level of protein is recently found to be an effective alternate to traditional in vivo and in vitro approaches. Hence, by using a combination of empirical rule and support vector machine based in silico algorithms, this study was able to identify that the pathogenic nonsynonymous genetic mutations corresponding to p.I54F, p.P122T, p.T533R, p.P581A and p.Y609A have more potential role in structural and functional deviations of IDE activity. Moreover, molecular modeling and secondary structure analysis have also confirmed their impact on the stability and secondary properties of IDE protein. The molecular docking analysis of IDE with combinational substrates has revealed that peptide inhibitors compared to small non-peptide inhibitor molecules possess good inhibitory activity towards mutant IDE. This finding may pave a way to design novel potential small peptide inhibitors for mutant IDE. Additionally by un-translated region (UTR) scanning analysis, two regulatory pathogenic genetic mutations i.e., rs5786997 (3' UTR) and rs4646954 (5' UTR), which can influence the translation pattern of IDE gene through sequence alteration of upstream-Open Reading Frame and Internal Ribosome Entry Site elements were identified. Our findings are expected to help in narrowing down the number of IDE genetic variants to be screened for disease association studies and also to select better competitive inhibitors for IDE related diseases.

  17. Distribution of trinucleotide microsatellites in different categories of mammalian genomic sequence: Implications for human genetic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L. (Univ. of Pittsburgh, PA (United States))

    1994-05-01

    The distribution of all trinucleotide microsatellite sequences in the GenBank database was surveyed to provide insight into human genetic disease syndromes that result from expansion of microsatellites. The microsatellite motif (CAG)[sub n] is one of the most abundant microsatellite motifs in human GenBank DNA sequences and is the most abundant microsatellite found in exons. This fact may explain why (CAG)[sub n] repeats are thus far the predominant microsatellites expanded in human genetic diseases. Surprisingly, (CAG)[sub n] microsatellites are excluded from intronic regions in a strand-specific fashion, possibly because of similarity to the 3[prime] consensus splice site, CAGG. A comparison of the positions of microsatellites in human vs rodent homologous sequences indicates that some arrays are not extensively conserved for long periods of time, even when they form parts of protein coding sequences. The general lack of conservation of trinucleotide repeat loci in diverse mammals indicates that animal models for some human microsatellite expansion syndromes may be difficult to find. 20 refs., 5 tabs.

  18. Genetics of human longevity with emphasis on the relevance of HSP70 as candidate genes.

    Science.gov (United States)

    Singh, Ripudaman; Kolvraa, Steen; Rattan, Suresh I S

    2007-05-01

    Human longevity is determined to a certain extent by genetic factors. Several candidate genes have been studied for their association with human longevity, but the data collected so far are inconclusive. One of the reasons is the choice of the candidate genes in addition to the choice of an appropriate study design and methodology. Since aging is characterized by a progressive accumulation of molecular damage and an attenuation of the cellular defense mechanisms, the focus of studies on human longevity association with genes has now shifted to the pathways of cellular maintenance and repair mechanisms. One such pathway includes the battery of stress response genes, especially the heat shock protein HSP70 genes. Three such genes, HSPA1A, HSPA1B and HSPA1L, are present within the MHC-III region on the short arm of chromosome 6. We and others have found alleles, genotypes and haplotypes which have been significantly associated with human longevity and survival. We have also provided some functional evidence for these genetic associations by showing that isolated peripheral blood cells from those genotypes which are negatively associated with human longevity also have less ability to respond to heat shock. Stress response genes, particularly HSP70, are now the major candidates in the gene-longevity association studies.

  19. On recent advances in human engineering Provocative trends in embryology, genetics, and regenerative medicine.

    Science.gov (United States)

    Anton, Roman

    2016-01-01

    Advances in embryology, genetics, and regenerative medicine regularly attract attention from scientists, scholars, journalists, and policymakers, yet implications of these advances may be broader than commonly supposed. Laboratories culturing human embryos, editing human genes, and creating human-animal chimeras have been working along lines that are now becoming intertwined. Embryogenic methods are weaving traditional in vivo and in vitro distinctions into a new "in vivitro" (in life in glass) fabric. These and other methods known to be in use or thought to be in development promise soon to bring society to startling choices and discomfiting predicaments, all in a global effort to supply reliably rejuvenating stem cells, to grow immunologically non-provocative replacement organs, and to prevent, treat, cure, or even someday eradicate diseases having genetic or epigenetic mechanisms. With humanity's human-engineering era now begun, procedural prohibitions, funding restrictions, institutional controls, and transparency rules are proving ineffective, and business incentives are migrating into the most basic life-sciences inquiries, wherein lie huge biomedical potentials and bioethical risks. Rights, health, and heritage are coming into play with bioethical presumptions and formal protections urgently needing reassessment.

  20. Comparison of LAIR-1 genetic pathways in murine vs human internal organs.

    Science.gov (United States)

    Sun, Shuqiu; Jiao, Yan; Wei, Wei; Postlethwaite, Arnold E; Gu, Weikuan; Sun, Dianjun

    2014-11-15

    Growing evidence suggests that defective expression or dysfunction of LAIR-1, a novel immunoinhibitory receptor for collagen, is closely associated with some autoimmune diseases, cancers, as well as viral infections. We analyzed the variation of LAIR-1 genetic pathways in murine versus human internal organs, including the lung and brain. The results showed that, under physiological conditions, LAIR-1 links more closely to the common genes in mouse than in human, which poses tissue specificity. It means that mice experimental data in relation to the role of LAIR-1 immune regulation may be overestimated when applied to assess human conditions. Moreover, we found that the in vivo interaction of LAIR-1 with LAIR-2 rarely occurs, implying that the species difference in LAIR-1 genetic pathways could not be primarily attributed to the existence of human LAIR-2. In summary, this study opens the door for insight into LAIR-1 functions inside the human body, and raises concern as to extrapolative credibility of the murine model in biomedical research.

  1. Manteia, a predictive data mining system for vertebrate genes and its applications to human genetic diseases.

    Science.gov (United States)

    Tassy, Olivier; Pourquié, Olivier

    2014-01-01

    The function of genes is often evolutionarily conserved, and comparing the annotation of ortholog genes in different model organisms has proved to be a powerful predictive tool to identify the function of human genes. Here, we describe Manteia, a resource available online at http://manteia.igbmc.fr. Manteia allows the comparison of embryological, expression, molecular and etiological data from human, mouse, chicken and zebrafish simultaneously to identify new functional and structural correlations and gene-disease associations. Manteia is particularly useful for the analysis of gene lists produced by high-throughput techniques such as microarrays or proteomics. Data can be easily analyzed statistically to characterize the function of groups of genes and to correlate the different aspects of their annotation. Sophisticated querying tools provide unlimited ways to merge the information contained in Manteia along with the possibility of introducing custom user-designed biological questions into the system. This allows for example to connect all the animal experimental results and annotations to the human genome, and take advantage of data not available for human to look for candidate genes responsible for genetic disorders. Here, we demonstrate the predictive and analytical power of the system to predict candidate genes responsible for human genetic diseases.

  2. Femtosecond optical transfection as a tool for genetic manipulation of human embryonic stem cells

    Science.gov (United States)

    Torres-Mapa, M. L.; Gardner, J.; Bradburn, H.; King, J.; Dholakia, K.; Gunn-Moore, F.

    2013-03-01

    We demonstrate the use of femtosecond optical transfection for the genetic manipulation of human embryonic stem cells. Using a system with an SLM combined with a scanning mirror allows poration of both single-cell and colony-formed human embryonic stem cells in a rapid and targeted manner. In this work, we show successful transfection of plasmid DNA tagged with fluorescent reporters into human embryonic stem cells using three doses of focused femtosecond laser. A significant number of transfected cells retained their undifferentiated morphological feature of large nucleus with high nucleus to cytoplasmic ratio, 48h after photoporation. Furthermore, DNA constructs driven by different types of promoters were also successfully transfected into human embryonic stem cells using this technique.

  3. The Role of Genetic Drift in Shaping Modern Human Cranial Evolution: A Test Using Microevolutionary Modeling

    Directory of Open Access Journals (Sweden)

    Heather F. Smith

    2011-01-01

    Full Text Available The means by which various microevolutionary processes have acted in the past to produce patterns of cranial variation that characterize modern humans is not thoroughly understood. Applying a microevolutionary framework, within- and among-population variance/covariance (V/CV structure was compared for several functional and developmental modules of the skull across a worldwide sample of modern humans. V/CV patterns in the basicranium, temporal bone, and face are proportional within and among groups, which is consistent with a hypothesis of neutral evolution; however, mandibular morphology deviated from this pattern. Degree of intergroup similarity in facial, temporal bone, and mandibular morphology is significantly correlated with geographic distance; however, much of the variance remains unexplained. These findings provide insight into the evolutionary history of modern human cranial variation by identifying signatures of genetic drift, gene flow, and migration and set the stage for inferences regarding selective pressures that early humans encountered since their initial migrations around the world.

  4. Optimizing Fuzzy Rule Base for Illumination Compensation in Face Recognition using Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Bima Sena Bayu Dewantara

    2014-12-01

    Full Text Available Fuzzy rule optimization is a challenging step in the development of a fuzzy model. A simple two inputs fuzzy model may have thousands of combination of fuzzy rules when it deals with large number of input variations. Intuitively and trial‐error determination of fuzzy rule is very difficult. This paper addresses the problem of optimizing Fuzzy rule using Genetic Algorithm to compensate illumination effect in face recognition. Since uneven illumination contributes negative effects to the performance of face recognition, those effects must be compensated. We have developed a novel algorithmbased on a reflectance model to compensate the effect of illumination for human face recognition. We build a pair of model from a single image and reason those modelsusing Fuzzy.Fuzzy rule, then, is optimized using Genetic Algorithm. This approachspendsless computation cost by still keepinga high performance. Based on the experimental result, we can show that our algorithm is feasiblefor recognizing desired person under variable lighting conditions with faster computation time. Keywords: Face recognition, harsh illumination, reflectance model, fuzzy, genetic algorithm

  5. CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish.

    Science.gov (United States)

    González, Federico

    2016-07-01

    Because of their extraordinary differentiation potential, human pluripotent stem cells (hPSCs) can differentiate into virtually any cell type of the human body, providing a powerful platform not only for generating relevant cell types useful for cell replacement therapies, but also for modeling human development and disease. Expanding this potential, structures resembling human organs, termed organoids, have been recently obtained from hPSCs through tissue engineering. Organoids exhibit multiple cell types self-organizing into structures recapitulating in part the physiology and the cellular interactions observed in the organ in vivo, offering unprecedented opportunities for human disease modeling. To fulfill this promise, tissue engineering in hPSCs needs to be supported by robust and scalable genome editing technologies. With the advent of the CRISPR/Cas9 technology, manipulating the genome of hPSCs has now become an easy task, allowing modifying their genome with superior precision, speed, and throughput. Here we review current and potential applications of the CRISPR/Cas9 technology in hPSCs and how they contribute to establish hPSCs as a model of choice for studying human genetics. Developmental Dynamics 245:788-806, 2016. © 2016 Wiley Periodicals, Inc.

  6. Average Gait Differential Image Based Human Recognition

    Directory of Open Access Journals (Sweden)

    Jinyan Chen

    2014-01-01

    Full Text Available The difference between adjacent frames of human walking contains useful information for human gait identification. Based on the previous idea a silhouettes difference based human gait recognition method named as average gait differential image (AGDI is proposed in this paper. The AGDI is generated by the accumulation of the silhouettes difference between adjacent frames. The advantage of this method lies in that as a feature image it can preserve both the kinetic and static information of walking. Comparing to gait energy image (GEI, AGDI is more fit to representation the variation of silhouettes during walking. Two-dimensional principal component analysis (2DPCA is used to extract features from the AGDI. Experiments on CASIA dataset show that AGDI has better identification and verification performance than GEI. Comparing to PCA, 2DPCA is a more efficient and less memory storage consumption feature extraction method in gait based recognition.

  7. Genetic Reassortment Among the Influenza Viruses (Avian Influenza, Human Influenza and Swine Influenza in Pigs

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2012-12-01

    Full Text Available Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries for 80 years. In 1998, triple reassortant H3N2 swine influenza viruses that contains genes of human influenza A virus (H3N2, swine influenza virus (H1N1 and avian influenza are reported as cause an outbreaks in pigs in North America. Furthermore, the circulation of triple reassortant H3N2 swine influenza virus resulting reassortant H1N1 swine influenza and reassortant H1N2 swine influenza viruses cause infection in humans. Humans who were infected by triple reassortant swine influenza A virus (H1N1 usually made direct contact with pigs. Although without any clinical symptoms, pigs that are infected by triple reassortant swine influenza A (H1N1 can transmit infection to the humans around them. In June 2009, WHO declared that pandemic influenza of reassortant H1N1 influenza A virus (novel H1N1 has reached phase 6. In Indonesia until 2009, there were 1005 people were infected by H1N1 influenza A and 5 of them died. Novel H1N1 and H5N1 viruses have been circulated in humans and pigs in Indonesia. H5N1 reassortant and H1N1 viruses or the seasonal flu may could arise because of genetic reassortment between avian influenza and humans influenza viruses that infect pigs together.

  8. Research on Modeling of Genetic Networks Based on Information Measurement

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guo-wei; SHAO Shi-huang; ZHANG Ying; LI Hai-ying

    2006-01-01

    As the basis of network of biology organism, the genetic network is concerned by many researchers.Current modeling methods to genetic network, especially the Boolean networks modeling method are analyzed. For modeling the genetic network, the information theory is proposed to mining the relations between elements in network. Through calculating the values of information entropy and mutual entropy in a case, the effectiveness of the method is verified.

  9. Key Frames Extraction Based on the Improved Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    ZHOU Dong-sheng; JIANG Wei; YI Peng-fei; LIURui

    2014-01-01

    In order toovercomethe poor local search ability of genetic algorithm, resulting in the basic genetic algorithm is time-consuming, and low search abilityin the late evolutionary, we use thegray coding instead ofbinary codingatthebeginning of the coding;we use multi-point crossoverto replace the originalsingle-point crossoveroperation.Finally, theexperimentshows that the improved genetic algorithmnot only has a strong search capability, but also thestability has been effectively improved.

  10. Genetic Mapping

    Science.gov (United States)

    ... Fact Sheets Fact Sheets En Español: Mapeo Genético Genetic Mapping What is genetic mapping? How do researchers create ... genetic map? What are genetic markers? What is genetic mapping? Among the main goals of the Human Genome ...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Evert Thomas

    Full Text Available 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

  13. NOVEL QUANTUM-INSPIRED GENETIC ALGORITHM BASED ON IMMUNITY

    Institute of Scientific and Technical Information of China (English)

    Li Ying; Zhao Rongchun; Zhang Yanning; Jiao Licheng

    2005-01-01

    A novel algorithm, the Immune Quantum-inspired Genetic Algorithm (IQGA), is proposed by introducing immune concepts and methods into Quantum-inspired Genetic Algorithm (QGA). With the condition of preserving QGA's advantages, IQGA utilizes the characteristics and knowledge in the pending problems for restraining the repeated and ineffective operations during evolution, so as to improve the algorithm efficiency. The experimental results of the knapsack problem show that the performance of IQGA is superior to the Conventional Genetic Algorithm (CGA), the Immune Genetic Algorithm (IGA) and QGA.

  14. Identification of Hammerstein Model Based on Quantum Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Zhang Hai Li

    2013-07-01

    Full Text Available Nonlinear system identification is a main topic of modern identification. A new method for nonlinear system identification is presented by using Quantum Genetic Algorithm(QGA.The problems of nonlinear system identification are cast as function optimization overprameter space,and the Quantum Genetic Algorithm is adopted to solve the optimization problem. Simulation experiments show that: compared with the genetic algorithm, quantum genetic algorithm is an effective swarm intelligence algorithm, its salient features of the algorithm parameters, small population size, and the use of Quantum gate update populations, greatly improving the recognition in the optimization of speed and accuracy. Simulation results show the effectiveness of the proposed method.

  15. Efficient Satellite Scheduling Based on Improved Vector Evaluated Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Tengyue Mao

    2012-03-01

    Full Text Available Satellite scheduling is a typical multi-peak, many-valley, nonlinear multi-objective optimization problem. How to effectively implement the satellite scheduling is a crucial research in space areas.This paper mainly discusses the performance of VEGA (Vector Evaluated Genetic Algorithm based on the study of basic principles of VEGA algorithm, algorithm realization and test function, and then improves VEGA algorithm through introducing vector coding, new crossover and mutation operators, new methods to assign fitness and hold good individuals. As a result, the diversity and convergence of improved VEGA algorithm of improved VEGA algorithm have been significantly enhanced and will be applied to Earth-Mars orbit optimization. At the same time, this paper analyzes the results of the improved VEGA, whose results of performance analysis and evaluation show that although VEGA has a profound impact upon multi-objective evolutionary research,  multi-objective evolutionary algorithm on the basis of Pareto seems to be a more effective method to get the non-dominated solutions from the perspective of diversity and convergence of experimental result. Finally, based on Visual C + + integrated development environment, we have implemented improved vector evaluation algorithm in the satellite scheduling.

  16. A Gene-Pool Based Genetic Algorithm for TSP

    Institute of Scientific and Technical Information of China (English)

    Yang Hui; Kang Li-shan; Chen Yu-ping

    2003-01-01

    Based on the analysis of previous genetic algo rithms (GAs) for TSP, a novel method called Ge GA is proposed. It combines gene pool and GA so as to direct the evo lution of the whole population. The core of Ge GA is the construction of gene pool and how to apply it to GA. Different from standard GAs, Ge-GA aims to enhance the ability of exploration and exploitation by incorporating global search with local search. On one hand a local search called Ge LocalSearch operator is proposed to improve the solution quality, on the other hand the modified Inver-Over operator called Ge InverOver is considered as a global search mechanism to expand solution space of local minimal. Both of these operators are based on the gene pool. Our algorithm is applied to 11 well-known traveling salesman problems whose numbers of cities are from 70 to 1577 cities. The experiments results indicate that Ge GA has great robustness for TSP. For each test instance, the average value of solution quality, found in accepted time, stays within 0. 001 % from the optimum.

  17. Nanotechnology Based Treatments for Neurological Disorders from Genetics Perspective

    Directory of Open Access Journals (Sweden)

    Nicholas S. Kurek

    2013-02-01

    Full Text Available Nanotechology involves the application, analysis and manipulation of nanomaterials. These materials have unique and medically useful properties due to their nanoscale parameters. Nanotechnology based treatments and diagnostics might eventually bring great relief to people suffering from neurological disorders including autism spectrum disorders, Alzheimer’s disease and Parkinson’s disorders. A large variety of nonmaterials such as viruses, carbon nanotubes, gold and silica nanoparticles, nanoshells, quantum dots, genetic material and proteins as well as hordes of other forms of nanotechnology have been researched in order to determine their potential in enhancing disease treatments and diagnostics. Nanotechnology has shown countless applications and might eventually be used in every biotech/health industry. Nevertheless, many nanomaterials may pose some safety risks and whether their benefits overweigh the risk is still being debated. Once the proper ethical and safety protocols are established and enough research is completed, nanotechnology is expected to benefit the mankind enormously. In this article, we will discuss and analyze many ways in which, nanotechnology based treatments and diagnostics will be used to help people with neurological disorders through the methods that we currently have at our disposal. [Archives Medical Review Journal 2013; 22(1.000: 12-32

  18. The Australian joint inquiry into the Protection of Human Genetic Information.

    Science.gov (United States)

    Weisbrot, David

    2003-04-01

    The Australian Law Reform Commission (ALRC) and the Australian Health Ethics Committee are currently engaged in an inquiry into the Protection of Human Genetic Information. In particular, the Attorney-General and the Minister for Health and Ageing have asked us to focus, in relation to human genetic information and tissue samples, on how best to ensure world's best practice in relation to: privacy protection; protection against unlawful discrimination; and the maintenance of high ethical standards in medical research and clinical practice. While initial concerns and controversies have related mainly to aspects of medical research (e.g. consent; re-use of samples) and access to private insurance coverage, relevant issues arise in a wide variety of contexts, including: employment; medical practice; tissue banks and genetic databases; health administration; superannuation; access to government services (e.g. schools, nursing homes); law enforcement; and use by government authorities (e.g. for immigration purposes) or other bodies (e.g. by sports associations). Under the Australian federal system, it is also the case that laws and practices may vary across states and territories. For example, neonatal genetic testing is standard, but storage and retention policies for the resulting 'Guthrie cards' differ markedly. Similarly, some states have developed highly linked health information systems (e.g. incorporating hospitals, doctors' offices and public records), while others discourage such linkages owing to concerns about privacy. The challenge for Australia is to develop policies, standards and practices that promote the intelligent use of genetic information, while providing a level of security with which the community feels comfortable. The inquiry is presently reviewing the adequacy of existing laws and regulatory mechanisms, but recognizes that it will be even more important to develop a broad mix of strategies, such as community and professional education, and the

  19. Genetics algorithm optimization of DWT-DCT based image Watermarking

    Science.gov (United States)

    Budiman, Gelar; Novamizanti, Ledya; Iwut, Iwan

    2017-01-01

    Data hiding in an image content is mandatory for setting the ownership of the image. Two dimensions discrete wavelet transform (DWT) and discrete cosine transform (DCT) are proposed as transform method in this paper. First, the host image in RGB color space is converted to selected color space. We also can select the layer where the watermark is embedded. Next, 2D-DWT transforms the selected layer obtaining 4 subband. We select only one subband. And then block-based 2D-DCT transforms the selected subband. Binary-based watermark is embedded on the AC coefficients of each block after zigzag movement and range based pixel selection. Delta parameter replacing pixels in each range represents embedded bit. +Delta represents bit “1” and –delta represents bit “0”. Several parameters to be optimized by Genetics Algorithm (GA) are selected color space, layer, selected subband of DWT decomposition, block size, embedding range, and delta. The result of simulation performs that GA is able to determine the exact parameters obtaining optimum imperceptibility and robustness, in any watermarked image condition, either it is not attacked or attacked. DWT process in DCT based image watermarking optimized by GA has improved the performance of image watermarking. By five attacks: JPEG 50%, resize 50%, histogram equalization, salt-pepper and additive noise with variance 0.01, robustness in the proposed method has reached perfect watermark quality with BER=0. And the watermarked image quality by PSNR parameter is also increased about 5 dB than the watermarked image quality from previous method.

  20. The possibility of aromorphosis in further development of closed human life support systems using genetically modified organisms

    Science.gov (United States)

    Gitelson, Josef

    evolution of the CES, the use of the advantages offered by genetically modified organisms produced by modern biotechnology can be regarded as aromorphosis. If the genetic program of biosyntheses performed by plants in-cludes the new genes that will program the synthesis of all molecules necessary for humans, the plants, both unicellular and higher, will produce the whole range of food substances perfectly corresponding to the requirements of the human body. This is a long way, but the investment of resources and time will be justified not only by the creation of an LSS for long-distance space missions and colonization of planets that will contain as many closed loops as possible and be energy efficient. This will also be a convenient and safest instrument to study and justify the wide use of products of genetically modified plants on Earth. Today, humanity is extremely wary of this idea because of its novelty. As experimental human life support ecosystems are closed systems, they provide the most reliable and safest instrument for studying issues related to GMO and preparing scientifically based suggestions for their practical use. The report will contain data on the spectra of mismatches between vegetable foods produced in BIOS-3 and human requirements, and the objectives of correcting the biosynthesis programs in the CES.

  1. Psychiatrists' views of the genetic bases of mental disorders and behavioral traits and their use of genetic tests.

    Science.gov (United States)

    Klitzman, Robert; Abbate, Kristopher J; Chung, Wendy K; Marder, Karen; Ottman, Ruth; Taber, Katherine Johansen; Leu, Cheng-Shiun; Appelbaum, Paul S

    2014-07-01

    We examined how 372 psychiatrists view genetic aspects of mental disorders and behaviors and use genetic tests (GTs). Most thought that the genetic contribution was moderate/high for bipolar disorder, schizophrenia, depression, Alzheimer's, intelligence, creativity, anxiety, and suicidality. In the past 6 months, 14.1% ordered GTs, 18.3% discussed prenatal testing with patients, 36.0% initiated discussions about other GTs, 41.6% had patients ask about GTs, and 5.3% excluded GT results from patient records. Many thought that GTs; were available for schizophrenia (24.3%) and major depression (19.6%). Women were more likely to report that patients asked about GTs; and were less certain about the degree of genetic contribution to several disorders. Psychiatrists perceive strong genetic bases for numerous disorders and traits, and many have discussed and ordered tests for GTs, but have relatively limited knowledge about available tests. These data suggest possible sex differences in psychiatrists' beliefs about genetic contributions to disorders and have implications for future research, education, policy, and care.

  2. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policyEuropean Society of Human Genetics and European Society of Human Reproduction and Embryology

    OpenAIRE

    Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C.; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather

    2013-01-01

    In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogent...

  3. Genetic Diversity on the Human X Chromosome Does Not Support a Strict Pseudoautosomal Boundary.

    Science.gov (United States)

    Cotter, Daniel J; Brotman, Sarah M; Wilson Sayres, Melissa A

    2016-05-01

    Unlike the autosomes, recombination between the X chromosome and the Y chromosome is often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, whereas the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to PAR1 and PAR2, there is a human-specific X-transposed region that was duplicated from the X to the Y chromosome. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in nonrecombining regions because recombination reduces the effect of linked selection. In this study, we investigated patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We found that genetic diversity in PAR1 is significantly greater than in the nonrecombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the nonrecombining regions, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. A consequence of recombination spanning this boundary potentially includes increasing the rate of sex-linked disorders (e.g., de la Chapelle) and sex chromosome aneuploidies. In contrast, diversity in PAR2 is not significantly elevated compared to the nonPARs, suggesting that recombination is not obligatory in PAR2. Finally, diversity in the X-transposed region is higher than in the surrounding nonPARs, providing evidence that recombination may occur with some frequency between the X and Y chromosomes in the X-transposed region.

  4. [Search problems of human radiation protection in the world of genetics of aging].

    Science.gov (United States)

    Koterov, A N

    2013-01-01

    Currently, the urgency for protection from negative effects of radiation in the range of low and medium dose where classic radioprotectors are ineffective is increased. In this respect it seems promising to study the molecular pathways that increase, on the one hand, the stability of the genome against radiation damage (inducers of carcinogenesis), and, on the other hand, elevate the radiation sensitivity of cell populations in order to eliminate potentially carcinogenic cells. This approach requires modification of cascade mechanisms of signal transduction to apoptosis and responses to DNA damage. Research plan is similar to the Genetics of Aging, where a number of hypotheses about the mechanism of aging have been proposed, including a decrease in the stability of the genome to external influences. Proceedings of the 2nd International Conference "The genetics of aging and longevity" (Moscow, April 2012) demonstrated, however, that patterns of aging mechanisms identified in model animals (nematodes, drosophila and mice) are far from the possibility of their practical application. Discovered genes that may be responsible for life expectancy (stress-inducible protein and other components of the signal transduction cascade, as well as suppressors and inducers) rarely find significance in the study of the genomes of centenarian cohorts. This may be due to the difficulty in transferring molecular genetic patterns from model objects to large mammals, including humans, with respect to systems of signal transduction. This point must be taken into account during the search for a new generation of radioprotective agents that promote anti-carcinogenic potential of human cells exposed to radiation at low and moderate doses. It may be necessary to search for such tools in large laboratory animals and in human tissue cultures obtained through genetic engineering or cloning.

  5. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  6. Web-based, participant-driven studies yield novel genetic associations for common traits.

    Directory of Open Access Journals (Sweden)

    Nicholas Eriksson

    2010-06-01

    Full Text Available Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here we report initial results from a participant-driven study of 22 traits. Replications of associations (in the genes OCA2, HERC2, SLC45A2, SLC24A4, IRF4, TYR, TYRP1, ASIP, and MC1R for hair color, eye color, and freckling validate the Web-based, self-reporting paradigm. The identification of novel associations for hair morphology (rs17646946, near TCHH; rs7349332, near WNT10A; and rs1556547, near OFCC1, freckling (rs2153271, in BNC2, the ability to smell the methanethiol produced after eating asparagus (rs4481887, near OR2M7, and photic sneeze reflex (rs10427255, near ZEB2, and rs11856995, near NR2F2 illustrates the power of the approach.

  7. Web-based, participant-driven studies yield novel genetic associations for common traits.

    Science.gov (United States)

    Eriksson, Nicholas; Macpherson, J Michael; Tung, Joyce Y; Hon, Lawrence S; Naughton, Brian; Saxonov, Serge; Avey, Linda; Wojcicki, Anne; Pe'er, Itsik; Mountain, Joanna

    2010-06-24

    Despite the recent rapid growth in genome-wide data, much of human variation remains entirely unexplained. A significant challenge in the pursuit of the genetic basis for variation in common human traits is the efficient, coordinated collection of genotype and phenotype data. We have developed a novel research framework that facilitates the parallel study of a wide assortment of traits within a single cohort. The approach takes advantage of the interactivity of the Web both to gather data and to present genetic information to research participants, while taking care to correct for the population structure inherent to this study design. Here we report initial results from a participant-driven study of 22 traits. Replications of associations (in the genes OCA2, HERC2, SLC45A2, SLC24A4, IRF4, TYR, TYRP1, ASIP, and MC1R) for hair color, eye color, and freckling validate the Web-based, self-reporting paradigm. The identification of novel associations for hair morphology (rs17646946, near TCHH; rs7349332, near WNT10A; and rs1556547, near OFCC1), freckling (rs2153271, in BNC2), the ability to smell the methanethiol produced after eating asparagus (rs4481887, near OR2M7), and photic sneeze reflex (rs10427255, near ZEB2, and rs11856995, near NR2F2) illustrates the power of the approach.

  8. Research on the fully fuzzy time-cost trade-off based on genetic algorithms

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    It is very difficult to estimate exact values of time and cost of an activity in project scheduling process because many uncertain factors, such as weather, productivity level, human factors etc. , dynamically affect them during project implementation process. A GAs-based fully fuzzy optimal time-cost trade-off model is presented based on fuzzy sets and genetic algorithms (GAs). In tihs model all parameters and variables are characteristics by fuzzy numbers. And then GAs is adopted to search for the optimal solution to this model. The method solves the time-cost trade-off problems under an uncertain environment and is proved practicable through a giving example in ship building scheduling.

  9. Genetic algorithm to estimate the input parameters of Klatt and HLSyn formant-based speech synthesizers.

    Science.gov (United States)

    Araújo, Fabíola; Filho, José; Klautau, Aldebaro

    2016-12-01

    Voice imitation basically consists in estimating a synthesizer's input parameters to mimic a target speech signal. This is a difficult inverse problem because the mapping is time-varying, non-linear and from many to one. It typically requires considerable amount of time to be done manually. This work presents the evolution of a system based on a genetic algorithm (GA) to automatically estimate the input parameters of the Klatt and HLSyn formant synthesizers using an analysis-by-synthesis process. Results are presented for natural (human-generated) speech for three male speakers. The results obtained with the GA-based system outperform those obtained with the baseline Winsnoori with respect to four objective figures of merit and a subjective test. The GA with Klatt synthesizer generated similar voices to the target and the subjective tests indicate an improvement in the quality of the synthetic voices when compared to the ones produced by the baseline.

  10. Robotics-based synthesis of human motion

    KAUST Repository

    Khatib, O.

    2009-05-01

    The synthesis of human motion is a complex procedure that involves accurate reconstruction of movement sequences, modeling of musculoskeletal kinematics, dynamics and actuation, and characterization of reliable performance criteria. Many of these processes have much in common with the problems found in robotics research. Task-based methods used in robotics may be leveraged to provide novel musculoskeletal modeling methods and physiologically accurate performance predictions. In this paper, we present (i) a new method for the real-time reconstruction of human motion trajectories using direct marker tracking, (ii) a task-driven muscular effort minimization criterion and (iii) new human performance metrics for dynamic characterization of athletic skills. Dynamic motion reconstruction is achieved through the control of a simulated human model to follow the captured marker trajectories in real-time. The operational space control and real-time simulation provide human dynamics at any configuration of the performance. A new criteria of muscular effort minimization has been introduced to analyze human static postures. Extensive motion capture experiments were conducted to validate the new minimization criterion. Finally, new human performance metrics were introduced to study in details an athletic skill. These metrics include the effort expenditure and the feasible set of operational space accelerations during the performance of the skill. The dynamic characterization takes into account skeletal kinematics as well as muscle routing kinematics and force generating capacities. The developments draw upon an advanced musculoskeletal modeling platform and a task-oriented framework for the effective integration of biomechanics and robotics methods.

  11. Asymmetry in scientific method and limits to cross-disciplinary dialogue: toward a shared language and science policy in pharmacogenomics and human disease genetics.

    Science.gov (United States)

    Ozdemir, Vural; Williams-Jones, Bryn; Graham, Janice E; Preskorn, Sheldon H; Gripeos, Dimitrios; Glatt, Stephen J; Friis, Robert H; Reist, Christopher; Szabo, Sandor; Lohr, James B; Someya, Toshiyuki

    2007-04-01

    Pharmacogenomics is a hybrid field of experimental science at the intersection of human disease genetics and clinical pharmacology sharing applications of the new genomic technologies. But this hybrid field is not yet stable or fully integrated, nor is science policy in pharmacogenomics fully equipped to resolve the challenges of this emerging hybrid field. The disciplines of human disease genetics and clinical pharmacology contain significant differences in their scientific practices. Whereas clinical pharmacology originates as an experimental science, human disease genetics is primarily observational in nature. The result is a significant asymmetry in scientific method that can differentially impact the degree to which gene-environment interactions are discerned and, by extension, the study sample size required in each discipline. Because the number of subjects enrolled in observational genetic studies of diseases is characteristically viewed as an important criterion of scientific validity and reliability, failure to recognize discipline-specific requirements for sample size may lead to inappropriate dismissal or silencing of meritorious, although smaller-scale, craft-based pharmacogenomic investigations using an experimental study design. Importantly, the recognition that pharmacogenomics is an experimental science creates an avenue for systematic policy response to the ethical imperative to prospectively pursue genetically customized therapies before regulatory approval of pharmaceuticals. To this end, we discuss the critical role of interdisciplinary engagement between medical sciences, policy, and social science. We emphasize the need for development of shared standards across scientific, methodologic, and socioethical epistemologic divides in the hybrid field of pharmacogenomics to best serve the interests of public health.

  12. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    NARCIS (Netherlands)

    Li, Gang; Diogo, Dorothee; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant

  13. Multiple Query Evaluation Based on an Enhanced Genetic Algorithm.

    Science.gov (United States)

    Tamine, Lynda; Chrisment, Claude; Boughanem, Mohand

    2003-01-01

    Explains the use of genetic algorithms to combine results from multiple query evaluations to improve relevance in information retrieval. Discusses niching techniques, relevance feedback techniques, and evolution heuristics, and compares retrieval results obtained by both genetic multiple query evaluation and classical single query evaluation…

  14. Simulation based virtual learning environment in medical genetics counseling

    DEFF Research Database (Denmark)

    Makransky, Guido; Bonde, Mads T; Wulff, Julie S G;

    2016-01-01

    understanding of medical genetics, 82 % thought that medical genetics was more interesting, 93 % indicated that they were more interested and motivated, and had gained confidence by having experienced working on a case story that resembled the real working situation of a doctor, and 78 % indicated...

  15. Catalog of genetic progression of human cancers: non-Hodgkin lymphoma.

    Science.gov (United States)

    Bödör, Csaba; Reiniger, Lilla

    2016-03-01

    The recent application of next-generation sequencing technologies lead to significant improvements in our understanding of genetic underpinnings of non-Hodgkin lymphomas with identification of an unexpectedly high number of novel mutation targets across the different B-cell lymphoma entities. These recently discovered molecular lesions are expected to have a major impact on development of novel biomarkers and targeted therapies as well as patient stratification based on the underlying genetic profile. This review will cover the major discoveries in B-cell lymphomas using next-generation sequencing technologies over the last few years, highlighting alterations associated with relapse and progression of these diseases.

  16. Genetic Algorithm Based Proportional Integral Controller Design for Induction Motor

    Directory of Open Access Journals (Sweden)

    Mohanasundaram Kuppusamy

    2011-01-01

    Full Text Available Problem statement: This study has expounded the application of evolutionary computation method namely Genetic Algorithm (GA for estimation of feedback controller parameters for induction motor. GA offers certain advantages such as simple computational steps, derivative free optimization, reduced number of iterations and assured near global optima. The development of the method is well documented and computed and measured results are presented. Approach: The design of PI controller parameter for three phase induction motor drives was done using Genetic Algorithm. The objective function of motor current reduction, using PI controller, at starting is formulated as an optimization problem and solved with Genetic Algorithm. Results: The results showed the selected values of PI controller parameter using genetic algorithm approach, with objective of induction motor starting current reduction. Conclusions/Recommendation: The results proved the robustness and easy implementation of genetic algorithm selection of PI parameters for induction motor starting.

  17. Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development

    Science.gov (United States)

    Klar, Amar J. S.

    2016-01-01

    Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of the DLX5 (distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating the DLX5 gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells. Accordingly, one daughter cell inherits both expressed DLX5 copies while the other daughter inherits both epigenetically silenced ones from a single deterministic cell of the developing limb. Thus, differentiated daughter cells after further proliferation will correspondingly produce proximal/distal-limb tissues. Published results of a Chr. 7 translocation with a centromere-proximal breakpoint situated over 41 million bases away from the DLX locus, centromeric and DLX5-region inversions have satisfied key genetic and developmental biology predictions of the mechanism. Further genetic tests of the mechanism are proposed. We propose that the DNA double helical structure itself causes the development of sister cells' gene regulation asymmetry. We also argue against the conventionally invoked morphogen model of development. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821526

  18. [Application of case-based method in genetics and eugenics teaching].

    Science.gov (United States)

    Li, Ya-Xuan; Zhao, Xin; Zhang, Fei-Xiong; Hu, Ying-Kao; Yan, Yue-Ming; Cai, Min-Hua; Li, Xiao-Hui

    2012-05-01

    Genetics and Eugenics is a cross-discipline between genetics and eugenics. It is a common curriculum in many Chinese universities. In order to increase the learning interest, we introduced case teaching method and got a better teaching effect. Based on our teaching practices, we summarized some experiences about this subject. In this article, the main problem of case-based method applied in Genetics and Eugenics teaching was discussed.

  19. The application of genetics approaches to the study of exceptional longevity in humans: potential and limitations

    Directory of Open Access Journals (Sweden)

    Ferrario Anna

    2012-04-01

    Full Text Available Abstract The average life-span of the population of industrialized countries has improved enormously over the last decades. Despite evidence pointing to the role of food intake in modulating life-span, exceptional longevity is still considered primarily an inheritable trait, as pointed out by the description of families with centenarian clusters and by the elevated relative probability of siblings of centenarians to become centenarians themselves. However, rather than being two separate concepts, the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants and environmentally modulated mechanisms (caloric restriction, specific nutrients. In support of this hypothesis, polymorphisms selected for in the centenarian population as a consequence of demographic pressure have been found to modulate cellular signals controlled also by caloric restriction. Here, we give an overview of the recent findings in the field of the genetics of human exceptional longevity, of how some of the identified polymorphisms modulate signals also influenced by food intake and caloric restriction, of what in our view have been the limitations of the approaches used over the past years to study genetics (sib-pair-, candidate gene association-, and genome-wide association-studies, and briefly of the limitations and the potential of the new, high-throughput, next-generation sequencing techniques applied to exceptional longevity.

  20. Genetic variants influencing effectiveness of exercise training programmes in obesity - an overview of human studies.

    Science.gov (United States)

    Leońska-Duniec, A; Ahmetov, I I; Zmijewski, P

    2016-09-01

    Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary.