Full Text Available Characterizing the genetic determinants of complex diseases can be further augmented by incorporating knowledge of underlying structure or classifications of the genome, such as newly developed mappings of protein-coding genes, epigenetic marks, enhancer elements and non-coding RNAs.We apply a simple class-level testing framework, termed Genetic Class Association Testing (GenCAT, to identify protein-coding gene association with 14 cardiometabolic (CMD related traits across 6 publicly available genome wide association (GWA meta-analysis data resources. GenCAT uses SNP-level meta-analysis test statistics across all SNPs within a class of elements, as well as the size of the class and its unique correlation structure, to determine if the class is statistically meaningful. The novelty of findings is evaluated through investigation of regional signals. A subset of findings are validated using recently updated, larger meta-analysis resources. A simulation study is presented to characterize overall performance with respect to power, control of family-wise error and computational efficiency. All analysis is performed using the GenCAT package, R version 3.2.1.We demonstrate that class-level testing complements the common first stage minP approach that involves individual SNP-level testing followed by post-hoc ascribing of statistically significant SNPs to genes and loci. GenCAT suggests 54 protein-coding genes at 41 distinct loci for the 13 CMD traits investigated in the discovery analysis, that are beyond the discoveries of minP alone. An additional application to biological pathways demonstrates flexibility in defining genetic classes.We conclude that it would be prudent to include class-level testing as standard practice in GWA analysis. GenCAT, for example, can be used as a simple, complementary and efficient strategy for class-level testing that leverages existing data resources, requires only summary level data in the form of test statistics, and
Lunt David H
Full Text Available Abstract Background The existence of "ancient asexuals", taxa that have persisted for long periods of evolutionary history without sexual recombination, is both controversial and important for our understanding of the evolution and maintenance of sexual reproduction. A lack of sex has consequences not only for the ecology of the asexual organism but also for its genome. Several genetic signatures are predicted from long-term asexual (apomictic reproduction including (i large "allelic" sequence divergence (ii lack of phylogenetic clustering of "alleles" within morphological species and (iii decay and loss of genes specific to meiosis and sexual reproduction. These genetic signatures can be hard to assess since it is difficult to demonstrate the allelic nature of very divergent sequences, divergence levels may be complicated by processes such as inter-specific hybridization, and genes may have secondary roles unrelated to sexual reproduction. Apomictic species of Meloidogyne root knot nematodes have been suggested previously to be ancient asexuals. Their relatives reproduce by meiotic parthenogenesis or facultative sexuality, which in combination with the abundance of nematode genomic sequence data, makes them a powerful system in which to study the consequences of reproductive mode on genomic divergence. Results Here, sequences from nuclear protein-coding genes are used to demonstrate that the first two predictions of ancient asexuality are found within the apomictic root knot nematodes. Alleles are more divergent in the apomictic taxa than in those species exhibiting recombination and do not group phylogenetically according to recognized species. In contrast some nuclear alleles, and mtDNA, are almost identical across species. Sequencing of Major Sperm Protein, a gamete-specific gene, from both meiotic and ameiotic species reveals no increase in evolutionary rate nor change in substitution pattern in the apomictic taxa, indicating that the locus
... Staying Safe Videos for Educators Search English Español Genetic Testing KidsHealth / For Parents / Genetic Testing What's in ... blood, skin, bone, or other tissue is needed. Genetic Testing During Pregnancy For genetic testing before birth, ...
... is responding to gluten. Unlike antibody testing, the HLA gene testing for celiac disease measures the presence or ... found on the surface of some cells. The HLA gene test for celiac disease can be performed at ...
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... Involved Donate Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing By Deborah Hartzfeld, MS, CGC, Certified Genetic ... guarantee a person will develop symptoms of ALS. Genetic Counseling If there is more than one person ...
... Testing What is genetic ancestry testing? What is genetic ancestry testing? Genetic ancestry testing, or genetic genealogy, ... mixed with other groups. For more information about genetic ancestry testing: The University of Utah provides video ...
... Advocacy For Patients About ACOG Prenatal Genetic Testing Chart (Infographic) Home For Patients Search FAQs Prenatal Genetic Testing Chart (Infographic) PFSI010 ››› Weeks 1–4 Weeks 5–8 ...
Ashida, Sato; Koehly, Laura M; Roberts, J Scott; Chen, Clara A; Hiraki, Susan; Green, Robert C
This study evaluates the extent to which psychological adaptation (validated measures of depressive symptoms, anxiety, and test-specific distress) after genetic susceptibility testing is influenced by changes in beliefs about Alzheimer's disease (AD) and sharing of test results with others. Adult children of AD patients (N=269) from a randomized clinical trial involving genetic testing for apolipoprotein E (APOE) provided information before, as well as 6 weeks and 12 months after results disclosure. The levels of adaptation varied highly among participants at 12-month assessment. Participants who learned that they were ε4 negative (lower risk) had a reduction in perceived risk and concern about developing AD compared with those who learned that they were ε4 positive. Those who received results through an extended educational protocol (three in-person visits) had a larger decline in AD concern than those in a condensed protocol (educational brochure and two in-person visits). Increase in AD concern 6 weeks after disclosure was associated with increase in depression scores (b=0.20, Ppsychological adaptation.
... Testing How is genetic testing done? How is genetic testing done? Once a person decides to proceed ... is called informed consent . For more information about genetic testing procedures: The National Society of Genetic Counselors ...
Skip to main content Regulation of Genetic Tests Enter Search Term(s): Español Research Funding An Overview Bioinformatics Current Grants Education and Training Funding Extramural Research News Features Funding Divisions ...
Bilen, Ozlem; Pokharel, Yashashwi; Ballantyne, Christie M
Hereditary dyslipidemias are often underdiagnosed and undertreated, yet with significant health implications, most importantly causing preventable premature cardiovascular diseases. The commonly used clinical criteria to diagnose hereditary lipid disorders are specific but are not very sensitive. Genetic testing may be of value in making accurate diagnosis and improving cascade screening of family members, and potentially, in risk assessment and choice of therapy. This review focuses on using genetic testing in the clinical setting for lipid disorders, particularly familial hypercholesterolemia. Copyright © 2015 Elsevier Inc. All rights reserved.
Djémié, Tania; Weckhuysen, Sarah; von Spiczak, Sarah
BACKGROUND: Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying...
[Zhang L., Lu S., Sun D., and Peng J. 2015 Genetic variation and geographical differentiation revealed using ISSR markers in tung tree,. Vernicia fordii. J. Genet. 94, e5–e9. Online only: http://www.ias.ac.in/jgenet/OnlineResources/94/e5.pdf]. Introduction. Tung tree, Vernicia fordii is an oil-bearing woody plant species of ...
Genetic relationship among Musa genotypes revealed by microsatellite markers. NAP Abdullah, GB Saleh, ETS Putra, ZB Wahab. Abstract. A banana germplasm was established containing 44 Musa genotypes collected from various locations in Malaysia. To detect their genetic variation and to rule out duplicates among ...
Haugaa, Kristina Hermann; Leren, Trond P.; Amlie, Jan Peder
An increasing number of genetic tests for cardiomyopathies are becoming available for clinical use. This commentary will give a short overview of indications and challenges concerning genetic testing for these conditions.
... pair-wise comparisons of 16 populations. An assignment test conformed to known population histories and provided additional support for the hypothesis of low differentiation between populations. There was no evidence of loss of genetic diversity in any individual population. Parentage analysis confirmed the utility of the ...
Verma, Ishwar Chander; Paliwal, Preeti; Singh, Kanika
The authors review the utility of genetic testing in ophthalmic disorders - precise diagnosis, accurate prognosis, genetic counseling, prenatal diagnosis, and entry into gene-specific therapeutic trials. The prerequisites for a successful outcome of a genetic test are an accurate clinical diagnosis, a careful family history that guides which genes to study, and genetic counseling (both pre-test and post-test). The common eye disorders for which genetic testing is commonly requested are briefly discussed - anophthalmia, microphthalmia, coloboma, anterior segment dysgenesis, corneal dystrophies, cataracts, optic atrophy, congenital glaucoma, congenital amaurosis, retinitis pigmentosa, color blindness, juvenile retinoshisis, retinoblastoma etc. A protocol for genetic testing is presented. If specific mutations in a gene are common, they should form the first tier test, as the mutations in Leber hereditary optic neuropathy. If mutations in one gene are likely, sequencing of that gene should be carried out, e.g. GALT gene in galactosemia, RS1 gene in retinoshisis. Disorders with genetic heterogeneity require multi-gene panel tests, and if these show no abnormality, then deletion / duplication or microarray studies are recommended, followed in sequence by clinical exome (5000 to 6000 genes), full exome (about 20,000 genes or whole genome studies (includes all introns). It is fortunate that most genetic tests in ophthalmology are available in India, including gene panel and whole exome/genome sequencing tests.
Shearer, A Eliot; Smith, Richard J H
To provide an update on recently discovered human deafness genes and to describe advances in comprehensive genetic testing platforms for deafness, both of which have been enabled by new massively parallel sequencing technologies. Over the review period, three syndromic and six nonsyndromic deafness genes have been discovered, bringing the total number of nonsyndromic deafness genes to 64. Four studies have shown the utility of massively parallel sequencing for comprehensive genetic testing for deafness. Three of these platforms have been released on a clinical or commercial basis. Deafness is the most common sensory deficit in humans. Genetic diagnosis has traditionally been difficult due to extreme genetic heterogeneity and a lack of phenotypic variability. For these reasons, comprehensive genetic screening platforms have been developed with the use of massively parallel sequencing. These technologies are also accelerating the pace of gene discovery for deafness. Because genetic diagnosis is the basis for molecular therapies, these advances lay the foundation for the clinical care of deaf and hard-of-hearing persons in the future.
... GEO) Profiles Genome Workbench HomoloGene Map Viewer Online Mendelian Inheritance in Man (OMIM) RefSeqGene UniGene All Genes & Expression Resources... Genetics & Medicine Bookshelf Database of Genotypes and Phenotypes (dbGaP) ...
Arndt, Anne-Karin; MacRae, Calum A
The review is designed to outline the major developments in genetic testing in the cardiovascular arena in the past year or so. This is an exciting time in genetic testing as whole exome and whole genome approaches finally reach the clinic. These new approaches offer insight into disease causation in families in which this might previously have been inaccessible, and also bring a wide range of interpretative challenges. Among the most significant recent findings has been the extent of physiologic rare coding variation in the human genome. New disease genes have been identified through whole exome studies in neonatal arrhythmia, congenital heart disease and coronary artery disease that were simply inaccessible with other techniques. This has not only shed light on the challenges of genetic testing at this scale, but has also sharply defined the limits of prior gene-panel focused testing. As novel therapies targeting specific genetic subsets of disease become available, genetic testing will become a part of routine clinical care. The pace of change in sequencing technologies has begun to transform clinical medicine, and cardiovascular disease is no exception. The complexity of such studies emphasizes the importance of real-time communication between the genetics laboratory and genetically informed clinicians. New efforts in data and knowledge management will be central to the continued advancement of genetic testing.
Hofman, Nynke; van Langen, Irene; Wilde, Arthur A. M.
To review the current state and different aspects, including the yield, of genetic counseling and genetic testing in inherited heart disease. The number of counselees is growing rapidly all over the world, and the first studies about patients' perspectives and follow-up have been published. Progress
Full Text Available Genetic screening for BRCA1 and BRCA2 gives women the opportunity for early detection, surveillance, and intervention. One key feature of genetic testing and counseling is the provision of personal lifetime risk. However, little attention has been paid to how women interpret lifetime risk information, despite the fact that they base screening, treatment and family planning decisions on such information. To study this vital issue, we set out to test the ability of women to choose the most appropriate interpretation of National Cancer Institute's (NCI message about lifetime risk of developing cancer for a woman with altered BRCA1 and BRCA2 genes. Participants included 277 women who had not undergone genetic testing or had cancer and 207 women who had undergone genetic testing or had cancer. Over 50\\% of the women who had not undergone genetic testing or had cancer and 40\\% of those who had undergone genetic testing or had cancer misunderstood NCI's information. Furthermore, in line with a growing body of research, we found that high numeracy level (objective or subjective is positively associated with a woman's ability to correctly interpret NCI's message.
José Alexandre F. Diniz-Filho
Full Text Available The comparison of genetic divergence or genetic distances, estimated by pairwise F ST and related statistics, with geographical distances by Mantel test is one of the most popular approaches to evaluate spatial processes driving population structure. There have been, however, recent criticisms and discussions on the statistical performance of the Mantel test. Simultaneously, alternative frameworks for data analyses are being proposed. Here, we review the Mantel test and its variations, including Mantel correlograms and partial correlations and regressions. For illustrative purposes, we studied spatial genetic divergence among 25 populations of Dipteryx alata ("Baru", a tree species endemic to the Cerrado, the Brazilian savannas, based on 8 microsatellite loci. We also applied alternative methods to analyze spatial patterns in this dataset, especially a multivariate generalization of Spatial Eigenfunction Analysis based on redundancy analysis. The different approaches resulted in similar estimates of the magnitude of spatial structure in the genetic data. Furthermore, the results were expected based on previous knowledge of the ecological and evolutionary processes underlying genetic variation in this species. Our review shows that a careful application and interpretation of Mantel tests, especially Mantel correlograms, can overcome some potential statistical problems and provide a simple and useful tool for multivariate analysis of spatial patterns of genetic divergence.
Jallinoja, P; Hakonen, A; Aro, A R
A survey study was conducted among 1169 people to evaluate attitudes towards genetic testing in Finland. Here we present an analysis of the contradictions detected in people's attitudes towards genetic testing. This analysis focuses on the approval of genetic testing as an individual choice...... and on the confidence in control of the process of genetic testing and its implications. Our analysis indicated that some of the respondents have contradictory attitudes towards genetic testing. It is proposed that contradictory attitudes towards genetic testing should be given greater significance both in scientific...... studies on attitudes towards genetic testing as well as in the health care context, e.g. in genetic counselling....
Keers, Robert; Coleman, Jonathan R. I.; Lester, Kathryn J.; Roberts, Susanna; Breen, Gerome; Thastum, Mikael; Bogels, Susan; Schneider, Silvia; Heiervang, Einar; Meiser-Stedman, Richard; Nauta, Maaike; Creswell, Cathy; Thirlwall, Kerstin; Rapee, Ronald M.; Hudson, Jennifer L.; Lewis, Cathryn; Plomin, Robert; Eley, Thalia C.
Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such
... of the American Heart Association Cardiology Patient Page Genetic Testing for Inherited Heart Disease Allison L. Cirino , ... for developing the family’s heart condition. What Is Genetic Testing and What Can it Tell Me? Genetic ...
Mar 29, 2012 ... by microsatellite markers. Nur Ashikin Psyquay Abdullah, Ghizan Bin Saleh*, Eka Tarwaca ... Two new wild banana species, Musa bauensis. Hākkinen and Meekiong (Hakkinen, 2004) and Musa ... powerful genetic markers for genetic mapping and evolutionary studies (Yue et al., 2009). During the esta-.
Ingles, Jodie; Semsarian, Christopher
Genetic testing is an important and necessary aspect of the management of families with cardiac genetic conditions. Commercial genetic tests are available for most cardiac genetic diseases, and increasing uptake amongst patients has contributed to a vastly improved knowledge of the genetic basis of these diseases. The incredible advances in genetic technologies have translated to faster, more comprehensive, and inexpensive commercial genetic tests and has completely changed the landscape of commercial genetic testing in recent years. While there are enormous challenges, mostly relating to interpretation of variants, the value of a genetic diagnosis should not be underestimated. In almost all cases, the single greatest utility is for the predictive genetic testing of family members. This review will describe the value of cardiac genetic testing in the current climate of rapid genetic advancements. Copyright © 2014 Elsevier Inc. All rights reserved.
Camelus dromedarius) populations. Results from questionnaires on demography indicated that approximately 476 camels were extant in South Africa, Namibia and Botswana in 2003. We have sampled 234 camels for genetic analysis using a ...
... sell their tests online and through multi-level marketing networks. The Federal Trade Commission (FTC) wants you to know the facts about the DTC marketing of genetic tests. Genes and Genetic Tests Interpreting ...
... page: https://medlineplus.gov/news/fullstory_167507.html Genetic Testing Can Help Pinpoint Epilepsy Earlier Faster diagnosis ... 2017 (HealthDay News) -- A new study supports routine genetic testing for epilepsy in young children with seizures. " ...
Secundo, Lavi; Snitz, Kobi; Weissler, Kineret; Pinchover, Liron; Shoenfeld, Yehuda; Loewenthal, Ron; Agmon-Levin, Nancy; Frumin, Idan; Bar-Zvi, Dana; Shushan, Sagit; Sobel, Noam
Each person expresses a potentially unique subset of ∼ 400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10(-4)), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10(-6)). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.
Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress. Indrajeet Ghodke and K Muniyappa. Supplementary Material. Supplementary table 1. Plasmids used in this study ...
Cherchye, L.J.H.; de Rock, B.; Vermeulen, F.M.P.; Verriest, E.; Molina, J.A.
This chapter contains a state of the art of revealed preference tests for consistency of observed household behavior with Pareto efficiency. These tests are entirely nonparametric, since they do not require any assumptions regarding the parametric form of individual preferences or the intrahousehold
Genetic diversity of taraxacum germplasm revealed by sequence-related amplified polymorphism (SRAP) analysis. ... African Journal of Biotechnology ... The genetic relationships analyzed with un-weighed pairgroup method with arithmetic mean (UPMGA) showed that 11 population of taraxacum were grouped into three ...
Genetic relationships revealed by simple sequence repeat (SSR) markers among Ghanaian cassava cultivars released by different research groups. ... Genetic diversity was observed within populations (HS = 0.552) and, therefore, suggesting a low rate of inter-population gene flow among the individuals constituting the ...
Oct 5, 2011 ... (Lande,1988; Packer et al., 1991; Pimm and Raven,. 2000). It is very difficult for small isolated populations to maintain long-term survival even though excellent habitat or few human disturbances occur (Pimm and Raven,. 2000; Loucks et .... The Wilcoxon signed-rank test was used to determine significance.
Jiandong YANG, Zhihe ZHANG, Fujun SHEN, Xuyu YANG, Liang ZHANG, Limin CHEN, Wenping ZHANG, Qing ZHU, Rong HOU
Full Text Available Understanding present patterns of genetic diversity is critical in order to design effective conservation and management strategies for endangered species. Tangjiahe Nature Reserve (NR is one of the most important national reserves for giant pandas Ailuropoda melanoleuca in China. Previous studies have shown that giant pandas in Tangjiahe NR may be threatened by population decline and fragmentation. Here we used 10 microsatellite DNA markers to assess the genetic variability in the Tangjiahe population. The results indicate a low level of genetic differentiation between the Hongshihe and Motianling subpopulations in the reserve. Assignment tests using the Bayesian clustering method in STRUCTURE identified one genetic cluster from 42 individuals of the two subpopulations. All individuals from the same subpopulation were assigned to one cluster. This indicates high gene flow between subpopulations. F statistic analyses revealed a low FIS-value of 0.024 in the total population and implies a randomly mating population in Tangjiahe NR. Additionally, our data show a high level of genetic diversity for the Tangjiahe population. Mean allele number (A, Allelic richness (AR and mean expected heterozygosity (HE for the Tangjiahe population was 5.9, 5.173 and 0.703, respectively. This wild giant panda population can be restored through concerted effort [Current Zoology 57 (6: 717–724, 2011].
Zallen, Doris T.
Considers the opportunities and ethical issues involved in genetic testing. Reviews the history of genetics from the first discoveries of Gregor Mendel, through the spurious pseudo-science of eugenics, and up to the discovery of DNA by James Watson and Francis Crick. Explains how genetic tests are done. (MJP)
Advances in technical developments of genetic diagnostics for more than 50 years, as well as the fact that human genetic testing is usually performed only once in a lifetime, with additional impact for blood relatives, are determining the extraordinary importance of quality assurance in human genetic testing. Abidance of laws, directives, and guidelines plays a major role. This article aims to present the major laws, directives, and guidelines with respect to quality assurance of human genetic testing, paying careful attention to internal and external quality assurance. The information on quality assurance of human genetic testing was obtained through a web-based search of the web pages that are referred to in this article. Further information was retrieved from publications in the German Society of Human Genetics and through a PubMed-search using term quality + assurance + genetic + diagnostics. The most important laws, directives, and guidelines for quality assurance of human genetic testing are the gene diagnostics law (GenDG), the directive of the Federal Medical Council for quality control of clinical laboratory analysis (RiliBÄK), and the S2K guideline for human genetic diagnostics and counselling. In addition, voluntary accreditation under DIN EN ISO 15189:2013 offers a most recommended contribution towards quality assurance of human genetic testing. Legal restraints on quality assurance of human genetic testing as mentioned in § 5 GenDG are fulfilled once RiliBÄK requirements are followed.
Yichuanxue Zazhi = Chinese Journal of Medical Genetics 27(5): 501–505. Wu, Y. R., H. Y. Lin, C. M. Chen, et al. 2004 Genetic Testing in Spinocerebellar Ataxia in Taiwan: Expansions of Trinucleotide Repeats in SCA8 and SCA17 Are Associated with Typical Parkinson's Disease. Clinical Genetics 65(3): 209–214.
Lalani, Seema R
With the growing understanding of the magnitude of genetic diseases in newborns and equally rapid advancement of tools used for genetic diagnoses, healthcare providers must have a sufficient knowledge base to both recognize and evaluate genetic diseases in the neonatal period. Genetic assessment has become an essential aspect of medicine, and professionals need to know when genetic evaluation is indispensable. Much progress has been made in recent years in utilizing massively parallel sequencing for rapid diagnosis of genetic conditions in neonates. Next-generation sequencing is increasingly being used for noninvasive prenatal diagnosis, and it may become an essential component of newborn screening. This review will define some basic genetic terms and concepts, explain the gamut of genetic testing available for early diagnosis of genetic diseases, and describe some common chromosomal abnormalities, genomic disorders, and single-gene diseases relevant to neonatal medicine. Copyright © 2016. Published by Elsevier B.V.
Seema R. Lalani
Full Text Available With the growing understanding of the magnitude of genetic diseases in newborns and equally rapid advancement of tools used for genetic diagnoses, healthcare providers must have a sufficient knowledge base to both recognize and evaluate genetic diseases in the neonatal period. Genetic assessment has become an essential aspect of medicine, and professionals need to know when genetic evaluation is indispensable. Much progress has been made in recent years in utilizing massively parallel sequencing for rapid diagnosis of genetic conditions in neonates. Next-generation sequencing is increasingly being used for noninvasive prenatal diagnosis, and it may become an essential component of newborn screening. This review will define some basic genetic terms and concepts, explain the gamut of genetic testing available for early diagnosis of genetic diseases, and describe some common chromosomal abnormalities, genomic disorders, and single-gene diseases relevant to neonatal medicine.
[7-10] Genetic counseling increases the accuracy of risk perception, decreases intention for mutation testing among women who are unlikely carriers, and decreases cancer-related worry, anxiety, and depression.. Genetic testing has the potential to provide information about cancer risk, thereby significantly contributing to ...
Taylor, Ann; Sajan, Samin
The polymerase chain reaction (PCR) is a Nobel Prize-winning technique that amplifies a specific segment of DNA and is commonly used to test for the presence of genetic modifications. Students use PCR to test corn meal and corn-muffin mixes for the presence of a promoter commonly used in genetically modified foods, the cauliflower mosaic virus 35S…
Home; Journals; Journal of Biosciences; Volume 41; Issue 4. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress. INDRAJEET GHODKE K MUNIYAPPA. ARTICLE Volume 41 Issue 4 December 2016 pp ...
Full Text Available BACKGROUND: The availability of direct-to-consumer personalized genetic testing has enabled the public to access and interpret their own genetic information. Various genetic traits can be determined including resistance to norovirus through a nonsense mutation (G428A in the FUT2 gene. Although this trait is believed to confer resistance to the most dominant norovirus genotype (GII.4, the spectrum of resistance to other norovirus strains is unknown. The present report describes a cluster of symptomatic norovirus GI.6 infection in a family identified to have norovirus resistance through personalized genetic testing.
Marneros, Alexander G
The molecular mechanisms that control skin morphogenesis are complex and only incompletely understood. Aplasia cutis manifests with localized skin defects at birth and is a feature in various syndromes. Identifying the genes that cause these genetic skin conditions provides the opportunity to define novel regulators of skin morphogenesis. Recently, human genetic approaches have led to the identification of aplasia cutis-causing mutations in genes that have previously not been implicated to have an important role in skin biology. These findings reveal novel molecular mechanisms that are involved in skin formation during development.
There are many risks and concerns accompanied with the benefits of big data in genomics science. In a recent poll conducted by the Huntington Post and YouGov organization on the DNA breakthroughs, the majority of Americans (38%) is excited about the main scientific breakthroughs on human, plant and animal DNA (YouGov, 2014). However, many of them are concerned about the privacy and ethics of genetic research. 34% of the surveyors strongly disapproved of scientists using DNA and cloning techno...
Mariat, D; Robert, L
We are studying the genetic polymorphism associated with Variable Number of Tandem Repeat (VNTR) loci in 13 breeds of dogs, namely: Alaskan Malamute, Barzoi, Beagle, Belgian Shepherd, Fox Terrier, Griffon, Labrador, Irish Setter, Spaniel, Dachshund, Irish Terrier, Shar Pei and Poodle. Our approach is based upon synthetic tandem repeats (STRs). Using a panel of these arbitrary unit polymers to detect minisatellites, we are attempting to develop paternity testing systems on pure bred dog pedigrees. We are evaluating the potential importance of STRs as a tool for the isolation of minisatellites in dogs, as well as for the characterization of dog genetic markers.
Bauer, Sarah C; Msall, Michael E
Children with autism spectrum disorders (ASD) have unique developmental and behavioral phenotypes, and they have specific challenges with communication, social skills, and repetitive behaviors. At this time, no single etiology for ASD has been identified. However, evidence from family studies and linkage analyses suggests that genetic factors play a pivotal role in the etiology of ASD. However, ASD appear to be influenced by complex genetic and environmental factors, and evidence suggests that this is not a single gene disorder. In particular, ASD has a complex behavioral phenotype, and this variation reflects complex genotypes under the influence of external factors. With these considerations in mind, it is important to recognize that genetic testing is a vital component of the diagnostic evaluation of children with ASD. For example, children with ASD who have definitive etiologies may be able to access more specific resources, they may be spared long, emotionally and financially exhausting diagnostic journeys, and associated medical conditions and comorbidities can be managed proactively. Most importantly, children with disabilities of unknown origin should have an ongoing evaluation of potential etiologies for their symptoms (Crocker, 1987). Our purpose is to describe current trends in genetic testing for ASD, potential genetic etiologies of ASD, known genetic disorders associated with ASD, and recommendations for genetic testing in ASD. We will also emphasize the importance of access to informed health professionals, especially in the contexts of stigma and community supports. Copyright © 2012 Wiley Periodicals, Inc.
Markowitz, Dina G.; DuPre, Michael J.; Holt, Susan; Chen, Shaw-Ree; Wischnowski, Michael
This article discusses "Family Secrets," a problem-based learning (PBL) curriculum module that focuses on the bioethical implications of genetic testing. In high school biology classrooms throughout New York State, students are using "Family Secrets" to learn about DNA testing; Huntington's disease (HD); and the ethical, legal,…
Perry, George H.; Melsted, Páll; Marioni, John C.; Wang, Ying; Bainer, Russell; Pickrell, Joseph K.; Michelini, Katelyn; Zehr, Sarah; Yoder, Anne D.; Stephens, Matthew; Pritchard, Jonathan K.; Gilad, Yoav
Comparative genomic studies in primates have yielded important insights into the evolutionary forces that shape genetic diversity and revealed the likely genetic basis for certain species-specific adaptations. To date, however, these studies have focused on only a small number of species. For the majority of nonhuman primates, including some of the most critically endangered, genome-level data are not yet available. In this study, we have taken the first steps toward addressing this gap by sequencing RNA from the livers of multiple individuals from each of 16 mammalian species, including humans and 11 nonhuman primates. Of the nonhuman primate species, five are lemurs and two are lorisoids, for which little or no genomic data were previously available. To analyze these data, we developed a method for de novo assembly and alignment of orthologous gene sequences across species. We assembled an average of 5721 gene sequences per species and characterized diversity and divergence of both gene sequences and gene expression levels. We identified patterns of variation that are consistent with the action of positive or directional selection, including an 18-fold enrichment of peroxisomal genes among genes whose regulation likely evolved under directional selection in the ancestral primate lineage. Importantly, we found no relationship between genetic diversity and endangered status, with the two most endangered species in our study, the black and white ruffed lemur and the Coquerel's sifaka, having the highest genetic diversity among all primates. Our observations imply that many endangered lemur populations still harbor considerable genetic variation. Timely efforts to conserve these species alongside their habitats have, therefore, strong potential to achieve long-term success. PMID:22207615
Alburaki, Mohamed; Bertrand, Bénédicte; Legout, Hélène; Moulin, Sibyle; Alburaki, Ali; Sheppard, Walter Steven; Garnery, Lionel
Apiculture has been practiced in North Africa and the Middle-East from antiquity. Several thousand years of selective breeding have left a mosaic of Apis mellifera subspecies in the Middle-East, many uniquely adapted and survived to local environmental conditions. In this study we explore the genetic diversity of A. mellifera from Syria (n = 1258), Lebanon (n = 169) and Iraq (n = 35) based on 14 short tandem repeat (STR) loci in the context of reference populations from throughout the Old World (n = 732). Our data suggest that the Syrian honeybee Apis mellifera syriaca occurs in both Syrian and Lebanese territories, with no significant genetic variability between respective populations from Syria and Lebanon. All studied populations clustered within a new fifth independent nuclear cluster, congruent with an mtDNA Z haplotype identified in a previous study. Syrian honeybee populations are not associated with Oriental lineage O, except for sporadic introgression into some populations close to the Turkish and Iraqi borders. Southern Syrian and Lebanese populations demonstrated high levels of genetic diversity compared to the northern populations. This study revealed the effects of foreign queen importations on Syrian bee populations, especially for the region of Tartus, where extensive introgression of A. m. anatolica and/or A. m. caucasica alleles were identified. The policy of creating genetic conservation centers for the Syrian subspecies should take into consideration the influence of the oriental lineage O from the northern Syrian border and the large population of genetically divergent indigenous honeybees located in southern Syria.
McNamee, Michael John; Müller, Arno; van Hilvoorde, Ivo; Holm, Søren
Sports medicine ethics is neither a well established branch of sports medicine nor of medical ethics. It is therefore important to raise to more general awareness some of the significant ethical implications of sports medicine practices. The field of genetics in sports is likewise in its infancy and raises significant ethical concerns. It is not yet clear how genetics will alter our understanding of human potential and performance in sports. While a number of professional medical bodies accept genetic interventions of a therapeutic nature, we argue that the use of genetic technologies to predict sports potential may well breach both the European bioethics convention and North American anti-discrimination legislation, which are designed to support important ethical ideals and the ongoing commitment of the physician to the welfare of their patient. We highlight further ethical problems associated with confidentiality and consent that may arise in genetic testing as opposed to more conventional methods of testing in sports medicine. We conclude that genetic testing in sport that is not strictly limited to the protection of the athlete against harm, should be viewed in a very sceptical light by sports medicine professionals.
... to more than a thousand dollars. The growing market for direct-to-consumer genetic testing may promote ... to-consumer genetic testing (PDF) (2015). The American Society of Human Genetics, a professional membership organization for ...
Olwi, Duaa; Merdad, Leena; Ramadan, Eman
Genetic testing has been gradually permeating the practice of medicine. Health-care providers may be confronted with new genetic approaches that require genetically informed decisions which will be influenced by patients' knowledge of genetics and their attitudes toward genetic testing. This study assesses the knowledge of genetics and attitudes toward genetic testing among college students. A cross-sectional study was conducted using a multistage stratified sample of 920 senior college students enrolled at King Abdulaziz University, Saudi Arabia. Information regarding knowledge of genetics, attitudes toward genetic testing, and sociodemographic data were collected using a self-administered questionnaire. In general, students had a good knowledge of genetics but lacked some fundamentals of genetics. The majority of students showed positive attitudes toward genetic testing, but some students showed negative attitudes toward certain aspects of genetic testing such as resorting to abortion in the case of an untreatable major genetic defect in an unborn fetus. The main significant predictors of knowledge were faculty, gender, academic year, and some prior awareness of 'genetic testing'. The main significant predictors of attitudes were gender, academic year, grade point average, and some prior awareness of 'genetic testing'. The knowledge of genetics among college students was higher than has been reported in other studies, and the attitudes toward genetic testing were fairly positive. Genetics educational programs that target youths may improve knowledge of genetics and create a public perception that further supports genetic testing. © 2016 S. Karger AG, Basel.
Claustres, Mireille; Kozich, Viktor; Dequeker, Els; Fowler, Brain; Hehir-Kwa, Jayne Y.; Miller, Konstantin; Oosterwijk, Cor; Peterlin, Borut; van Ravenswaaij-Arts, Conny; Zimmermann, Uwe; Zuffardi, Orsetta; Hastings, Ros J.; Barton, David E.
Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report
Pilarski, Robert; Nagy, Rebecca
Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.
Gates, Elena A
Prenatal testing for Down syndrome and neural tube defects has become routine, and testing for other genetic conditions is becoming commonplace. Counseling about these tests involves a discussion of risk information, so pregnant women and their partners can use the information effectively when they make choices about testing. Discussing risk can be challenging, as many individuals, particularly those of lower literacy, have a poor understanding of the numerical concept of risk. Furthermore, whether risk is comprehended accurately or not, it is interpreted by patients in light of their existing knowledge and past experiences. Strategies available to optimize understanding of risk include communication of risk figures as frequencies rather than as probabilities or percentages and explicit discussion of a woman's preconceptions about her risk and about the condition being tested for.
Jombart, T; Devillard, S; Dufour, A-B; Pontier, D
Increasing attention is being devoted to taking landscape information into account in genetic studies. Among landscape variables, space is often considered as one of the most important. To reveal spatial patterns, a statistical method should be spatially explicit, that is, it should directly take spatial information into account as a component of the adjusted model or of the optimized criterion. In this paper we propose a new spatially explicit multivariate method, spatial principal component analysis (sPCA), to investigate the spatial pattern of genetic variability using allelic frequency data of individuals or populations. This analysis does not require data to meet Hardy-Weinberg expectations or linkage equilibrium to exist between loci. The sPCA yields scores summarizing both the genetic variability and the spatial structure among individuals (or populations). Global structures (patches, clines and intermediates) are disentangled from local ones (strong genetic differences between neighbors) and from random noise. Two statistical tests are proposed to detect the existence of both types of patterns. As an illustration, the results of principal component analysis (PCA) and sPCA are compared using simulated datasets and real georeferenced microsatellite data of Scandinavian brown bear individuals (Ursus arctos). sPCA performed better than PCA to reveal spatial genetic patterns. The proposed methodology is implemented in the adegenet package of the free software R.
Houshang NOSRATI; Mohammad Ali Hosseinpour FEIZI; Sona Seyed TARRAH; Ahmad Razban HAGHIGHI
Studies on plants show that populations growing on the stressful environments indicate higher levels of genetic diversity, and that in outcrossing species majority of total genetic variation allocated to within population rather than between populations. We compared the level of genetic variation between populations growing in stressful and normal environments, and measured levels of within- and between population genetic variations in Onobrychis viciifolia L. (Sainfoin, Fabaceae) based on RA...
Stephen R Proulx
Full Text Available Evolutionary theory predicts that organisms should evolve the ability to produce high fitness phenotypes in the face of environmental disturbances (environmental robustness or genetic mutations (genetic robustness. While several studies have uncovered mechanisms that lead to both environmental and genetic robustness, we have yet to understand why some components of the genome are more robust than others. According to evolutionary theory, environmental and genetic robustness will have different responses to selective forces. Selection on environmental robustness for a trait is expected to be strong and related to the fitness costs of altering that trait. In contrast to environmental robustness, selection on genetic robustness for a trait is expected to be largely independent of the fitness cost of altering the trait and instead should correlate with the standing genetic variation for the trait that can potentially be buffered. Several mechanisms that provide both environmental and genetic robustness have been described, and this correlation could be explained by direct selection on both forms of robustness (direct selection hypothesis, or through selection on environmental robustness and a correlated response in genetic robustness (congruence hypothesis.Using both published and novel data on gene expression in the yeast Saccharomyces cerevisiae, we find that genetic robustness is correlated with environmental robustness across the yeast genome as predicted by the congruence hypothesis. However, we also show that environmental robustness, but not genetic robustness, is related to per-gene fitness effects. In contrast, genetic robustness is significantly correlated with network position, suggesting that genetic robustness has been under direct selection.We observed a significant correlation between our measures of genetic and environmental robustness, in agreement with the congruence hypothesis. However, this correlation alone cannot explain the co
Full Text Available As the interface between a microbe and its environment, the bacterial cell envelope has broad biological and clinical significance. While numerous biosynthesis genes and pathways have been identified and studied in isolation, how these intersect functionally to ensure envelope integrity during adaptive responses to environmental challenge remains unclear. To this end, we performed high-density synthetic genetic screens to generate quantitative functional association maps encompassing virtually the entire cell envelope biosynthetic machinery of Escherichia coli under both auxotrophic (rich medium and prototrophic (minimal medium culture conditions. The differential patterns of genetic interactions detected among > 235,000 digenic mutant combinations tested reveal unexpected condition-specific functional crosstalk and genetic backup mechanisms that ensure stress-resistant envelope assembly and maintenance. These networks also provide insights into the global systems connectivity and dynamic functional reorganization of a universal bacterial structure that is both broadly conserved among eubacteria (including pathogens and an important target.
Gaitán-Espitia, Juan Diego; Marshall, Dustin; Dupont, Sam; Bacigalupe, Leonardo D; Bodrossy, Levente; Hobday, Alistair J
Geographical gradients in selection can shape different genetic architectures in natural populations, reflecting potential genetic constraints for adaptive evolution under climate change. Investigation of natural pH/pCO2 variation in upwelling regions reveals different spatio-temporal patterns of natural selection, generating genetic and phenotypic clines in populations, and potentially leading to local adaptation, relevant to understanding effects of ocean acidification (OA). Strong directional selection, associated with intense and continuous upwellings, may have depleted genetic variation in populations within these upwelling regions, favouring increased tolerances to low pH but with an associated cost in other traits. In contrast, diversifying or weak directional selection in populations with seasonal upwellings or outside major upwelling regions may have resulted in higher genetic variances and the lack of genetic correlations among traits. Testing this hypothesis in geographical regions with similar environmental conditions to those predicted under climate change will build insights into how selection may act in the future and how populations may respond to stressors such as OA. © 2017 The Author(s).
Hellenthal, Nicole; Gaertner-Rommel, Anna; Klauke, Bärbel; Paluszkiewicz, Lech; Stuhr, Markus; Kerner, Thoralf; Farr, Martin; Püschel, Klaus; Milting, Hendrik
Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (forensic department. We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice.
Sandford, Erin; Burmeister, Margit
Ataxia is a neurological cerebellar disorder characterized by loss of coordination during muscle movements affecting walking, vision, and speech. Genetic ataxias are very heterogeneous, with causative variants reported in over 50 genes, which can be inherited in classical dominant, recessive, X-linked, or mitochondrial fashion. A common mechanism of dominant ataxias is repeat expansions, where increasing lengths of repeated DNA sequences result in non-functional proteins that accumulate in the body causing disease. Greater understanding of all ataxia genes has helped identify several different pathways, such as DNA repair, ubiquitination, and ion transport, which can be used to help further identify new genes and potential treatments. Testing for the most common mutations in these genes is now clinically routine to help with prognosis and treatment decisions, but next generation sequencing will revolutionize how genetic testing will be done. Despite the large number of known ataxia causing genes, however, many individuals with ataxia are unable to obtain a genetic diagnosis, suggesting that more genes need to be discovered. Utilization of next generation sequencing technologies, expression studies, and increased knowledge of ataxia pathways will aid in the identification of new ataxia genes.
Angelone-Alasaad, Samer; Biebach, Iris; Pérez, Jesús M; Soriguer, Ramón C; Granados, José E
Genetic differentiation in historically connected populations could be the result of genetic drift or adaptation, two processes that imply a need for differing strategies in population management. The aim of our study was to use neutral genetic markers to characterize C. pyrenaica populations genetically and examine results in terms of (i) demographic history, (ii) subspecific classification and (iii) the implications for the management of Iberian ibex. We used 30 neutral microsatellite markers from 333 Iberian ibex to explore genetic diversity in the three main Iberian ibex populations in Spain corresponding to the two persisting subspecies (victoria and hispanica). Our molecular analyses detected recent genetic bottlenecks in all the studied populations, a finding that coincides with the documented demographic decline in C. pyrenaica in recent decades. Genetic divergence between the two C. pyrenaica subspecies (hispanica and victoriae) was substantial (FST between 0.39 and 0.47). Unexpectedly, we found similarly high genetic differentiation between two populations (Sierra Nevada and Maestrazgo) belonging to the subspecies hispanica. The genetic pattern identified in our study could be the result of strong genetic drift due to the severe genetic bottlenecks in the studied populations, caused in turn by the progressive destruction of natural habitat, disease epidemics and/or uncontrolled hunting. Previous Capra pyrenaica conservation decision-making was based on the clear distinction between the two subspecies (victoriae and hispanica); yet our paper raises questions about the usefulness for conservation plans of the distinction between these subspecies.
Full Text Available Enhancing water use efficiency of coriander (Coriandrum sativum L. is a major focus for coriander breeding to cope with drought stress. The purpose of this study was; (a to identify the predominant mechanism(s of drought resistance in coriander and (b to evaluate the genetic control mechanism(s of traits associated with drought resistance and higher fruit yield. To reach this purpose, 15 half-diallel hybrids of coriander and their six parents were evaluated under well-watered and water deficit stressed (WDS in both glasshouse lysimetric and field conditions. The parents were selected for their different response to water deficit stress following preliminary experiments. Results revealed that the genetic control mechanism of fruit yield is complex, variable and highly affected by environment. The mode of inheritance and nature of gene action for percent assimilate partitioned to fruits were similar to those for flowering time in both well-watered and WDS conditions. A significant negative genetic linkage was found between fruit yield and percent assimilate partitioned to root, percent assimilate partitioned to shoot, root number, root diameter, root dry mass, root volume, and early flowering. Thus, to improve fruit yield under water deficit stress, selection of low values of these traits could be used. In contrast, a significant positive genetic linkage between fruit yield and percent assimilate partitioned to fruits, leaf relative water content and chlorophyll content indicate selection for high values of these traits. These secondary or surrogate traits could be selected during early segregating generations. The early ripening parent (P1; TN-59-230 contained effective genes involved in preferred percent assimilate partitioning to fruit and drought stress resistance. In conclusion, genetic improvement of fruit yield and drought resistance could be simultaneously gained in coriander when breeding for drought resistance.
Kim, M S; Moore, P H; Zee, F; Fitch, M M M; Steiger, D L; Manshardt, R M; Paull, R E; Drew, R A; Sekioka, T; Ming, R
Genetic relationships among Carica papaya cultivars, breeding lines, unimproved germplasm, and related species were established using amplified fragment length polymorphism (AFLP) markers. Seventy-one papaya accessions and related species were analyzed with nine EcoRI-MseI primer combinations. A total of 186 informative AFLP markers was generated and analyzed. Cluster analysis suggested limited genetic variation in papaya, with an average genetic similarity among 63 papaya accessions of 0.880. Genetic diversity among cultivars derived from the same or similar gene pools was smaller, such as Hawaiian Solo hermaphrodite cultivars and Australian dioecious cultivars with genetic similarity at 0.921 and 0.912, respectively. The results indicated that self-pollinated hermaphrodite cultivars were as variable as open-pollinated dioecious cultivars. Genetic diversity between C. papaya and six other Carica species was also evaluated. Carica papaya shared the least genetic similarity with these species, with an average genetic similarity of 0.432; the average genetic similarity among the six other species was 0.729. The results from AFLP markers provided detailed estimates of the genetic variation within and among papaya cultivars, and supported the notion that C. papaya diverged from the rest of Carica species early in the evolution of this genus.
Lynch syndrome is the most common cause of inherited colorectal and endometrial cancers. Individuals with Lynch syndrome have a 10-80 % lifetime risk for colorectal cancer and a 15-60 % lifetime risk for endometrial cancer. Both cancers are preventable through chemoprevention, intensive cancer surveillance, and risk-reducing surgery options. Efforts to identify as many individuals with Lynch syndrome as possible will prevent cancers and save lives. This includes the traditional cancer genetic counseling model whereby individuals with and without cancer are evaluated for a possible Lynch syndrome diagnosis based on their personal and family history of colon polyps and cancers. It also includes universal tumor screening for Lynch syndrome whereby all individuals with colorectal or endometrial cancer are screened for tumor features of Lynch syndrome at the time of diagnosis. Those with tumors suspicious for Lynch syndrome are referred for cancer genetic counseling regardless of their family history of cancer. This two approaches must be maximized to attain high patient reach. Finally, and perhaps most importantly, cascade testing among the at-risk relatives of those diagnosed with Lynch syndrome is critically important to maximize the diagnosis of individuals with Lynch syndrome. In fact, the cost-effectiveness of universal tumor screening for Lynch syndrome relies entirely on counseling and testing as many at-risk individuals as possible since young unaffected individuals stand to benefit the most from an early diagnosis of Lynch syndrome. This approach must be optimized to achieve high family reach. It will take a concerted effort from patients, clinicians and public health officials to improve current approaches to the diagnosis of Lynch syndrome and the prevention and treatment of Lynch syndrome-associated cancer but these lessons can be applied to other conditions as the ultimate example of personalized medicine.
Does quantum dynamics play a role in DNA replication? What type of tests would reveal that? Some statistical checks that distinguish classical and quantum dynamics in DNA replication are proposed. Author Affiliations. Apoorva Patel1. Centre for Theoretical Studies, and Supercomputer Education and Research Centre, ...
Given the increasing availability and complexity of genetic testing, it is imperative that the practicing obstetrician-gynecologist or other health care provider has a firm comprehension of the benefits, limitations, and risks of offering a specific genetic test, as well as the importance of appropriate pretest and posttest counseling. The purpose of this Committee Opinion is to provide an outline of how obstetrician-gynecologists and other health care providers can best incorporate these tests into their current practices and provide appropriate pretest and posttest counseling to patients. Obstetrician-gynecologists and other health care providers should determine which tests will be offered as the standard in their practices so that similar testing strategies are made available to all patients. Practices should have procedures in place that ensure timely disclosure of test results to patients. As with any medical test, expectations regarding the performance of a genetic test should be discussed with the patient before the test is ordered. After counseling, patients should have the option to decline any or all testing. Pretest and posttest counseling should be done in a clear, objective, and nondirective fashion, which allows patients sufficient time to understand information and make informed decisions regarding testing and further evaluation or treatment. In addition to counseling each patient about her own personal risk, obstetrician-gynecologists and other health care providers should counsel patients regarding the risk for family members, including their potential to have affected offspring.
Given the increasing availability and complexity of genetic testing, it is imperative that the practicing obstetrician-gynecologist or other health care provider has a firm comprehension of the benefits, limitations, and risks of offering a specific genetic test, as well as the importance of appropriate pretest and posttest counseling. The purpose of this Committee Opinion is to provide an outline of how obstetrician-gynecologists and other health care providers can best incorporate these tests into their current practices and provide appropriate pretest and posttest counseling to patients. Obstetrician-gynecologists and other health care providers should determine which tests will be offered as the standard in their practices so that similar testing strategies are made available to all patients. Practices should have procedures in place that ensure timely disclosure of test results to patients. As with any medical test, expectations regarding the performance of a genetic test should be discussed with the patient before the test is ordered. After counseling, patients should have the option to decline any or all testing. Pretest and posttest counseling should be done in a clear, objective, and nondirective fashion, which allows patients sufficient time to understand information and make informed decisions regarding testing and further evaluation or treatment. In addition to counseling each patient about her own personal risk, obstetrician-gynecologists and other health care providers should counsel patients regarding the risk for family members, including their potential to have affected offspring.
Full Text Available Studies on plants show that populations growing on the stressful environments indicate higher levels of genetic diversity, and that in outcrossing species majority of total genetic variation allocated to within population rather than between populations. We compared the level of genetic variation between populations growing in stressful and normal environments, and measured levels of within- and between population genetic variations in Onobrychis viciifolia L. (Sainfoin, Fabaceae based on RAPDs. Our results show that populations growing on he stressful environment i.e. saline soils indicated either the lowest 0.2466 or highest (0.3186 within-population genetic variation based on Nei’s diversity. That disagrees with Niche-Width Variation Theory, which expects highest genetic diversity within stressful populations. Partitioning the total genetic variation by analysis of molecular variance (AMOVA showed that 89.03% of total genetic diversity allocated to within populations while 10.97% of this variation dedicated to among populations, indicating predominantly outcrossing mode of pollination in sainfoin. The two population pairs growing under similar environmental stresses (cold climate and saline soil showed higher genetic similarity. This may suggest that RAPDs patterns reflex selection rather than random drift.
3Section on Statistical Genomics, State Key Laboratory of Crop Genetics and Germplasm Enhancement/Chinese National ... that the dominance, overdominance and epistatic effect were important in conditioning the genetic basis of heterosis of the two elite hybrids. ...... basis of inbreeding depression and heterosis in rice.
Nov 28, 2011 ... gram using wild relatives. Key words: Genetic diversity, green gram, Vigna radiata, STMS. INTRODUCTION. Among Vigna group, in economic terms, green gram is the most ... Molecular markers employed for the analysis of genetic diversity in green ..... and is critical to their conservation and management.
A total of seventeen caprine microsatellite markers were used on 169 goats to investigate genetic diversity of eight Cameroon native goats and to assess genetic differentiation with the east African small goat. All microsatellites showed a high polymorphic content (PIC) of more than 0.5 in almost all ecotypes.
Home; Journals; Journal of Genetics; Volume 94; Issue 2. Genomewide ... heterosis; empirical bayes; NCIII design; recombinant inbred line; quantitative trait locus. Abstract. North Carolina design III (NCIII) is one of the most powerful and widely used mating designs for understanding the genetic basis of heterosis. However ...
cassava genotypes at 0.93 similarity coefficient. These five primers clustered the 36 cassavas into 16 groups at 0.70 similarity coefficient. Application of this few SSR primers would ultimately reduce the cost and time of research for genetic diversity and genotype identification studies for the genetic improvement program of ...
Hadzsiev, Kinga; Balikó, László; Komlósi, Katalin; Lőcsei-Fekete, Anett; Csábi, Györgyi; Bene, Judit; Kisfali, Péter; Melegh, Béla
Hereditary spastic paraplegia is the overall term for clinically and genetically diverse disorders characterized with progressive and variable severe lower extremity spasticity. The most common causes of autosomal dominantly inherited hereditary spastic paraplegias are different mutations of the spastin gene with variable incidence in different ethnic groups, ranging between 15-40%. Mutations in the spastin gene lead to loss of spastins function, causing progressive neuronal failure, which results in axon degeneration finally. The molecular testing of spastin gene is available in the institution of the authors since January, 2014. The experience gained with the examination of the first eleven patients is described in this article. After polymerase chain reaction, Sanger sequencing was performed to examine the 17 exons of the spastin gene. Multiplex ligation-dependent probe amplification was performed to detect greater rearrangements in the spastin gene. Eight of the patients were examined in the genetic counseling clinic of the authors and after detailed phenotype assessment spastin gene testing was obtained. The other three patients were referred to the laboratory from different outpatient clinics. Out of the 11 examined patients, four different pathogenic mutations were found in 5 patients. The first Hungarian data, gained with the examination of spastin gene are presented in this article. The five patients, in whom mutations were detected, represent 45.5% of all tested patients with hereditary spastic paraplegia, which is similar to those published in the international literature. Molecular testing and subsequent detailed genotype-phenotype correlations of the Hungarian patients may serve valuable new information about the disease, which later on may influence our therapeutic possibilities and decisions.
Francesco Paolo Casale
Full Text Available Joint genetic models for multiple traits have helped to enhance association analyses. Most existing multi-trait models have been designed to increase power for detecting associations, whereas the analysis of interactions has received considerably less attention. Here, we propose iSet, a method based on linear mixed models to test for interactions between sets of variants and environmental states or other contexts. Our model generalizes previous interaction tests and in particular provides a test for local differences in the genetic architecture between contexts. We first use simulations to validate iSet before applying the model to the analysis of genotype-environment interactions in an eQTL study. Our model retrieves a larger number of interactions than alternative methods and reveals that up to 20% of cases show context-specific configurations of causal variants. Finally, we apply iSet to test for sub-group specific genetic effects in human lipid levels in a large human cohort, where we identify a gene-sex interaction for C-reactive protein that is missed by alternative methods.
group method with arithmetic averages (UPGMA) clustering analysis. These results will be useful for the exploitation of grape germplasm in basic and applied research. Key words: Vitis vinifera L., simple sequence repeat (SSR), genetic diversity, ...
van der Zande, Paul; Waarlo, Arend Jan; Brekelmans, Mieke; Akkerman, Sanne F.; Vermunt, Jan D.
Recent developments in the field of genomics will impact the daily practice of biology teachers who teach genetics in secondary education. This study reports on the first results of a research project aimed at enhancing biology teacher knowledge for teaching genetics in the context of genetic testing. The increasing body of scientific knowledge concerning genetic testing and the related consequences for decision-making indicate the societal relevance of such a situated learning approach. What content knowledge do biology teachers need for teaching genetics in the personal health context of genetic testing? This study describes the required content knowledge by exploring the educational practice and clinical genetic practices. Nine experienced teachers and 12 respondents representing the clinical genetic practices (clients, medical professionals, and medical ethicists) were interviewed about the biological concepts and ethical, legal, and social aspects (ELSA) of testing they considered relevant to empowering students as future health care clients. The ELSA suggested by the respondents were complemented by suggestions found in the literature on genetic counselling. The findings revealed that the required teacher knowledge consists of multiple layers that are embedded in specific genetic test situations: on the one hand, the knowledge of concepts represented by the curricular framework and some additional concepts (e.g. multifactorial and polygenic disorder) and, on the other hand, more knowledge of ELSA and generic characteristics of genetic test practice (uncertainty, complexity, probability, and morality). Suggestions regarding how to translate these characteristics, concepts, and ELSA into context-based genetics education are discussed.
Lalani, Seema R.
With the growing understanding of the magnitude of genetic diseases in newborns and equally rapid advancement of tools used for genetic diagnoses, healthcare providers must have a sufficient knowledge base to both recognize and evaluate genetic diseases in the neonatal period. Genetic assessment has become an essential aspect of medicine, and professionals need to know when genetic evaluation is indispensable. Much progress has been made in recent years in utilizing massively parallel sequenc...
Hawkins, Alice K; Ho, Anita
Over the last several years, direct to consumer(DTC) genetic testing has received increasing attention in the public, healthcare and academic realms. DTC genetic testing companies face considerable criticism and scepticism,particularly from the medical and genetic counseling community. This raises the question of what specific aspects of DTC genetic testing provoke concerns, and conversely,promises, for genetic counselors. This paper addresses this question by exploring DTC genetic testing through an ethic allens. By considering the fundamental ethical approaches influencing genetic counseling (the ethic of care and principle-based ethics) we highlight the specific ethical concerns raised by DTC genetic testing companies. Ultimately,when considering the ethics of DTC testing in a genetic counseling context, we should think of it as a balancing act. We need careful and detailed consideration of the risks and troubling aspects of such testing, as well as the potentially beneficial direct and indirect impacts of the increased availability of DTC genetic testing. As a result it is essential that genetic counselors stay informed and involved in the ongoing debate about DTC genetic testing and DTC companies. Doing so will ensure that the ethical theories and principles fundamental to the profession of genetic counseling are promoted not just in traditional counseling sessions,but also on a broader level. Ultimately this will help ensure that the public enjoys the benefits of an increasingly genetic based healthcare system.
Harris, A.; Kelly, S.; Wyatt, S.
Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing
Vella, Noel; Vella, Adriana
Hexanchus griseus is a globally distributed deep-water shark species. It inhabits tropical and temperate waters throughout the world, including the Mediterranean Sea where it is by-caught by small-scale fisheries in the region. In this study, we analysed the genetic variation of H. griseus specimens collected from different areas within and outside the Mediterranean region, to assess its genetic connectivity. The mitochondrial DNA (mtDNA) sequence analysed in this study ranged from cytochrome b to 16S rRNA genes including the control region, the 12S rRNA gene and the interspersed tRNA genes in the region, covering a total of 3731 to 3914 nucleotides. Results have shown that this species exhibits geographically distinct maternal lineages, indicating population structure along geographical ranges. These findings reveal population subdivisions not only between the Pacific Ocean and the Atlantic Ocean, but also within the oceans and on a smaller scale within the Mediterranean Sea. This highlights the need to consider each population subdivision separately when designing management plans for the conservation of this species. Copyright © 2017 Elsevier B.V. All rights reserved.
Rose, Abigail L; Peters, Nikki; Shea, Judy A; Armstrong, Katrina
To describe awareness, knowledge, and attitudes about genetic testing for cancer risk among the general public. Thirty-eight adults participated in focus groups in West Philadelphia, Pennsylvania. Participants' beliefs about what genetic testing is ranged from 'dianetics' to an accurate description of DNA analysis. Themes included misconceptions about genetic tests, the ability to gain control of one's life through genetic testing, anxiety that might be caused by testing, risk of insurance and employment discrimination, use of genetic information for racial or ethnic discrimination, concerns about medical information confidentiality and lack of informed consent. Although there was some accurate understanding of what genetic testing is and how the results could be used, there also exist significant misconceptions. In many cases, misconceptions may be barriers to uptake of genetic testing. Dispelling these misconceptions is an important step in the translation of advances in human genomics into improvements in health.
Since 1990's, a business condition that company sells genetic testing services directly to consumers without through medical facility, so called "direct-to-consumers (DTC) genetic testing", has risen. They provide genetic testing for obesity, disease susceptibility or paternity, etc. There are serious problems in this kind of business. Most of the providers do not make sales with face-to-face selling, and do through internet instead. They do not provide genetic counseling by certified genetic counselor or clinical geneticist. Most DTC genetic testing services for disease susceptibility or predispositions including obesity, lack scientific validity, clinical validity and clinical utility. And also including paternity genetic testing, they all have risks of ethical legal and social issues (ELSI) in genetic discrimination and/or eugenics. The specific problem in Japan is that the healthcare section of the government still has not paid attention and not taken seriously the requirement to deploy safety net.
Full Text Available We used the phenomenon of prenatal genetic testing to learn more about how siblings of disabled people understand prenatal genetic testing and social meanings of disability. By interweaving data on siblings' conscious and unconscious disability attitudes and prenatal testing with siblings' explanations of their views of prenatal testing we explored siblings' unique relationships with disability, a particular set of perspectives on prenatal genetic testing, and examined how siblings' decision-making processes reveal their attitudes about disability more generally. In doing so we found siblings have both personal and broad stakes regarding their experiences with disability that impact their views.
... such as nurses, psychologists, or social workers). Genetic counseling can help people consider the risks, benefits, and limitations of ... other health care professional trained in genetics can help an individual ... counseling may include discussing recommendations for preventive care and ...
... Disease Control and Prevention) Glossary (National Center for Biotechnology Information) Talking Glossary of Genetic Terms (National Human Genome Research Institute) Also in Spanish Find an Expert Cancer Genetics Services Directory (National Cancer Institute) Centers for ...
Harris, Anna; Kelly, Susan E; Wyatt, Sally
Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing companies offer genetic counseling. There has been no examination to date of this service provision, whether it meets critics' concerns and implications it may have for the genetic counseling profession. Considering the increasing relevance of genetics in healthcare, the complexity of genetic information provided by DTC GT, the mediating role of the internet in counseling, and potential conflicts of interest, this is a topic which deserves further attention. In this paper we offer a discourse analysis of ways in which genetic counseling is represented on DTC GT websites, blogs and other online material. This analysis identified four types of genetic counseling represented on the websites: the integrated counseling product; discretionary counseling; independent counseling; and product advice. Genetic counselors are represented as having the following roles: genetics educator; mediator; lifestyle advisor; risk interpreter; and entrepreneur. We conclude that genetic counseling as represented on DTC GT websites demonstrates shifting professional roles and forms of expertise in genetic counseling. Genetic counselors are also playing an important part in how the genetic testing market is taking shape. Our analysis offers important and timely insights into recent developments in the genetic counseling profession, which have relevance for practitioners, researchers and policy makers concerned with the evolving field of personal genomics.
Mar 12, 2015 ... ethnic, linguistic and geographic diversity of India. In the present study we aimed to find out whether the. Indian populations differ in risk allele frequencies (RAFs) at. NAFLD-associated candidate SNPs, and also to predict the genetic risk score of NAFLD in different Indian populations, as well as to compare ...
Nov 28, 2011 ... by STMS markers. Avinash Pandey1*, Amit Kumar1 and Ramya P2. 1ICAR RC for NEH Region, Umiam, Meghalaya-793103, India. 2Division of Genetics, IARI, New Delhi-12, India. Accepted 17 June, 2011. Molecular characterization of green gram (Vigna radiata (L.) Wilczek) germplasm is essential for.
Mar 16, 2016 ... Genetic diversity and structure of goats within an early ... due to their recognized features and characteristics. The ... Genomic DNA was extracted from whole blood using. DNeasy® Blood and Tissue Kit (Qiagen GmbH, Germany). DNA concentration and purity were assessed using the BioPhotometer.
There was low variation among the highland Zengada landraces, but these landraces were quite strongly differentiated and fell into one population cluster. The low to moderate genetic differentiation between landraces from various geographic origins could be attributed to gene flow across the region as a consequence of ...
The present study evaluated genetic variability of superior bael genotypes collected from different parts of Andaman Islands, India using fruit characters and random amplified polymorphic DNA (RAPD) markers. Genomic DNA extracted from leaf material using cetyl trimethyl ammonium bromide (CTAB) method was ...
another wheat T. intermedium translocation line, P961341, varied with different genetic backgrounds. ... mitted normally in Thatcher and China Spring wheat back- grounds (McIntosh et al. 1976). However, high ..... transferred to common wheat with rust resistance from Aegilops speltoides. Euphytica 171, 71–85. McIntosh ...
c Indian Academy of Sciences. ONLINE RESOURCES. Genetic relationship of a ... cultivated vegetables, ranked fourth after tomato, onion and cabbage (Pitrat et al. 1999). It originates from India, and. China is .... Biosoft International, California, USA), primers were de- signed flanking the SSRs and allowed to generate PCR ...
Dec 3, 2007 ... passport data for various end uses. This may also go a long way to developing a core collection (from the germ- plasm) that is easier to manage and utilize for development of better varieties for genetic improvement program of cassava in Nigeria. Traditional characterization of local varieties in Nigeria.
The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.
Technological advances in genomics are shifting the genetic testing paradigm, from testing targeted mutations in selected genes to testing whole genes and even whole genomes. These exciting developments raise numerous practical pitfalls and ethical issues. Two articles in this issue of the SAMJ address genetic testing ...
Marosi, Krisztina; Horváth, Endre; Nagy, Péter; Köles, Bernadett; Nagy, Zsolt B
There is compelling evidence for a genetic contribution to physical performance. In addition, there is an advanced scientific knowledge on the predisposition to sports-related diseases and injuries. Genetic testing of performance related polymorphisms can serve as a new opportunity for developing the process of talent selection. Sport-related genetic information may also allow for individualization of the training and improve performance. Genetic testing may also play an important role in the pre-participation screening for injuries and disease risks.
Full Text Available The amplified fragment length polymorphism (AFLP technique with three EcoRI/TaqI primer combinations was used in 185 unrelated individuals, representative of 6 local goat breeds of Albania, and 107 markers were generated. The mean Nei’s expected heterozygosity value for the whole population was 0.199 and the mean Shannon index was 0.249, indicating a high level of within-breed diversity. Wright’s FST index, Nei’s unbiased genetic distance and Reynolds’ genetic distance were calculated. Pairwise Fst values among the populations ranged from 0.019 to 0.047. A highly significant average FST of 0.031 was estimated, showing a low level of breed subdivision. Most of the variation is accounted for by differences among individuals. Cluster analysis based on Reynolds’ genetic distance between breeds and PCA were performed. An individual UPGMA tree based on Jaccard’s similarity index showed clusters with individuals from all goat breeds. Analysis of population structure points to a high level of admixture among breeds.
Zhao, Huiying; Nyholt, Dale R
Studies using genome-wide association (GWA) single nucleotide polymorphism (SNP) level data have indicated genetic overlap across the five major disorders in the Psychiatric Genomics Consortium (PGC): attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), and schizophrenia (SCZ). However, such SNP-level analyses reveal little about the underlying biology and are reliant on correlated SNP effects across disorders. In contrast to SNPs, genes are more closely related to biology and gene-based tests can incorporate allelic heterogeneity. This study aimed to extend genetic overlap analysis across the five disorders from SNP level to gene level using a novel gene-based approach. Gene-based tests for association were performed using PGC GWA summary results for the five disorders in samples including 33,332 cases and 27,888 controls of European ancestry. After accounting for non-independence of gene-based test results, we determined whether the proportion of genes with association across multiple disorders was more than expected by chance. Similar to previous SNP-level analyses, we observed significant pairwise genetic overlap between ASD, BPD, MDD and SCZ. However, our approach also produced evidence for genetic overlap between ADHD and ASD, ADHD and BPD, and ADHD and MDD. Combining gene-based association results across disorders, 36 genes produced genome-wide significant P values (<3.2 × 10-6). Pathway analysis of genes with P values <1.0 × 10-3 highlighted magnesium ion binding and transport, as well as signal peptide processing, and provide insight into the biological mechanisms underlying these major psychiatric disorders.
Varga, Orsolya; Soini, Sirpa; Kääriäinen, Helena; Cassiman, Jean-Jacques; Nippert, Irmgard; Rogowski, Wolf; Nys, Herman; Kristoffersson, Ulf; Schmidtke, Jörg; Sequeiros, Jorge
The definition of "genetic testing" is not a simple matter, and the term is often used with different meanings. The purpose of this work was the collection and analysis of European (and other) legislation and policy instruments regarding genetic testing, to scrutinise the definitions of genetic testing therewith contained the following: 60 legal documents were identified and examined-55 national and five international ones. Documents were analysed for the type (context) of testing and the material tested and compared by legal fields (privacy and confidentiality, data protection, biobanks, insurance and labour law, forensic medicine); some instruments are very complex and deal with various legal fields at the same time. There was no standard for the definitions used, and different approaches were identified (from wide general, to some very specific and technically based). Often, legal documents did not contain any definitions, and many did not distinguish between genetic testing and genetic information. Genetic testing was more often defined in non-binding legal documents than in binding ones. Definitions are core elements of legal documents, and their accuracy and harmonisation (particularly within a particular legal field) is critical, not to compromise their enforcement. We believe to have gathered now the evidence for adopting the much needed differentiation between (a) "clinical genetics testing", (b) "genetics laboratory-based genetic testing" and (c) "genetic information", as proposed before.
Cirino, Allison L; Harris, Stephanie; Lakdawala, Neal K; Michels, Michelle; Olivotto, Iacopo; Day, Sharlene M; Abrams, Dominic J; Charron, Philippe; Caleshu, Colleen; Semsarian, Christopher; Ingles, Jodie; Rakowski, Harry; Judge, Daniel P; Ho, Carolyn Y
Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics. Clinicians and patients must have accurate and realistic expectations about the yield of genetic testing and its role in management. Familiarity with the rationale, implications, benefits, and limitations of genetic testing is essential to achieve the best possible outcomes. Successfully incorporating genetic testing into clinical practice requires (1) recognizing when inherited cardiovascular disease may be present, (2) identifying appropriate individuals in the family for testing, (3) selecting the appropriate genetic test, (4) understanding the complexities of result interpretation, and (5) effectively communicating the results and implications to the patient and family. Obtaining a detailed family history is critical to identify families who will benefit from genetic testing, determine the best strategy, and interpret results. Instead of focusing on an individual patient, genetic testing requires consideration of the family as a unit. Consolidation of care in centers with a high level of expertise is recommended. Clinicians without expertise in genetic testing will benefit from establishing referral or consultative networks with experienced clinicans in specialized multidisciplinary clinics. Genetic testing provides a foundation for transitioning to more precise and individualized management. By distinguishing phenotypic subgroups, identifying disease mechanisms, and focusing family care, gene-based diagnosis can improve management. Successful integration of
Best, Sunayna; Rosser, Elisabeth; Bajaj, Monika
To evaluate genetic disease among children referred to a community paediatric clinic. Retrospective cohort study. Community paediatric clinic, Tower Hamlets, London. All patients seen for first time in the Child Development Team (CDT) clinic between 1999 and 2013. Clinical notes were reviewed. Genetic test results were obtained. Exploratory Excel analysis was performed. Patients without an identified genetic disorder were labelled 'more likely genetic cause' if they had at least two out of three risk factors: developmental delay, congenital abnormality or parental consanguinity, and 'unlikely genetic cause' if they had one or no risk factors, or an obvious alternative cause. Prevalence of genetic diagnoses and parental consanguinity, undertaking of genetic tests, predicted likelihood of a genetic cause among unsolved patients. 749 patients were included. 404 (53.9%) had undergone genetic testing and 158 of those tested (39.1%) had a confirmed genetic diagnosis. Parental relatedness was documented in 461 patients, of which 128 (27.8%) had first-cousin parents. The number of patients undergoing genetic testing increased over time. Aneuploidies and syndromic/Mendelian disorders were most common. Of the 591 patients without a genetic diagnosis, 29.9% were classified 'more likely genetic cause'. Patients with consanguineous parents were significantly more likely to have a diagnosed genetic disorder than those with non-consanguineous parents (43/128 vs 72/333), particularly an autosomal recessive condition (27/43 vs 6/72). Genetic disease was common and genetic testing is important in evaluating children in this clinic. Consanguinity increases the likelihood of autosomal recessive disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Understanding Task Force Recommendations Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-related Cancer in Women The U.S. Preventive Services Task Force (Task Force) has issued a final ...
sequencing (NGS) featured with high throughput and low cost of sequencing capacity develops fast, especially with the improvement of its read length, read accuracy and the immergence of small-sized machines, making it a powerful genetic testing tool. In this study, we applied NGS to develop novel genetic...... developed a targeted sequencing based preimplantation genetic diagnosis (PGD) method for monogenic diseases and tested it in a family suffering from β-thalassaemia major undergoing PGD. Moreover, we developed a method which can achieve detection of point mutation and copy number variation simultaneously......The discovery of genetic factors behind increasing number of human diseases and the growth of education of genetic knowledge to the public make demands for genetic testing increase rapidly. However, traditional genetic testing methods cannot meet all kinds of the requirements. Next generation...
Beltrao, Pedro; Cagney, Gerard; Krogan, Nevan J.
In the past, biomedical research has embraced a reductionist approach, primarily focused on characterizing the individual components that comprise a system of interest. Recent technical developments have significantly increased the size and scope of data describing biological systems. At the same time, advances in the field of systems biology have evoked a broader view of how the underlying components are interconnected. In this essay, we discuss how quantitative genetic interaction mapping has enhanced our view of biological systems, allowing a deeper functional interrogation at different biological scales. PMID:20510918
Paul Rupa, Anamika; Singh, Sweta; Zhu, Qian
Accelerated by the Human Genome Project, genetic testing has become an increasingly integral component in diagnosis, treatment, management, and prevention of numerous diseases and conditions. More than 480 laboratories perform genetic tests for more than 4,600 rare and common medical conditions. These tests can effectively help health professionals to determine or predict the genetic conditions of their patients. However, physicians have not actively incorporated such innovative genetic technology into their clinical practices according to two national wide surveys commissioned by UnitedHealth Group. To fill the gap of insufficient use of a large number of genetic tests, we generated a single Resource Description Framework (RDF) resource, called GT2RDF (Genetic Testing data to RDF) by integrating information about disease, gene, phenotype, genetic test, and drug from multiple sources including Genetic Testing Registry (GTR), Online Mendelian Inheritance in Man (OMIM), MedGen, Human Phenotype Ontology (HPO), ClinVar, National Drug File Reference Terminology (NDF-RT). Meanwhile, we manually annotated and extracted information from 200 randomly selected GeneReviews chapters, and integrated into the GT2RDF. We performed two case studies to demonstrate the usability of the GT2RDF. GT2RDF will serve as a data foundation to support the design of a genetic testing recommendation system, called iGenetics, which will ultimately facilitate the pace of precision medicine by means of actively and effectively incorporating innovative genetic technology in clinical settings. Abbreviations: GT2RDF: Genetic Testing data to RDF; SWT: Semantic web technology; OWL: Ontology Web Language; RDF: Resource Description Framework; SPARQL: SPARQL Protocol and RDF Query Language; GTR: Genetic Testing Registry; OMIM: Online Mendelian Inheritance in Man; HPO: Human Phenotype Ontology; NDF-RT: National Drug File Reference Terminology; UMLS: Unified Medical Language System.
Sui, Suli; Sleeboom-Faulkner, Margaret
This paper provides an empirical account of commercial genetic testing in China. Commercial predictive genetic testing has emerged and is developing rapidly in China, but there is no strict and effective governance. This raises a number of serious social and ethical issues as a consequence of the enormous potential market for such tests. The paper…
Youssef, Muhammad; James, Andrew C; Rivera-Madrid, Renata; Ortiz, Rodomiro; Escobedo-GraciaMedrano, Rosa María
The sequence-related amplified polymorphism (SRAP) technique, aimed for the amplification of open reading frames (ORFs), vis-â-vis that of the amplified fragment length polymorphisms (AFLP) were used to analyze the genetic variation and relationships among forty Musa accessions; which include commercial cultivars and wild species of interest for the genetic enhancement of Musa. A total of 403 SRAP and 837 AFLP amplicons were generated by 10 SRAP and 15 AFLP primer combinations, of which 353 and 787 bands were polymorphic, respectively. Both cluster analysis of unweighted pair-grouping method with arithmetic averages (UPGMA) and principal coordinate (PCO) analysis separated the forty accessions into their recognized sections (Eumusa, Australimusa, Callimusa and Rhodochlamys) and species. The percentage of polymorphism amongst sections and species and the relationships within Eumusa species and subspecies varied between the two marker systems. In addition to its practical simplicity, SRAP exhibited approximately threefold more specific and unique bands than AFLP, 37 and 13%, respectively. SRAP markers are demonstrated here to be proficient tools for discriminating amongst M. acuminata, M. balbisiana and M. schizocarpa in the Eumusa section, as well as between plantains and cooking bananas within triploid cultivars.
Genetic linkage analysis involves estimating parameters in a genetic model in which a genetic trait is regressed on some factors such as polygenic values and environmental effects. Since only phenotypes are observed, hypothesis testing in such cases needs calculation of likelihood function in which one needs to consider ...
Michael J. Hall; Olufunmilayo I. Olopade
.... Nonetheless, differential access to and utilization of genetic counseling and cancer predisposition testing among underserved racial and ethnic minorities compared with the white population has led...
Five SSR primers that have PIC values between 0.50 and 0.67 were selected and further assessed using simple arithmetic progression combination method. The results obtained revealed a combination of these 5 primers from SSR primers collection at IITA that could readily distinguish the 36 cassava genotypes at 0.93 ...
Stoffel, Elena M; Boland, C Richard
Colorectal cancer (CRC) remains the third most common cancer affecting men and women in the United States. Approximately one-third of CRCs are diagnosed in individuals who have family members also affected with the disease. Although the vast majority of colorectal neoplasms develop as a consequence of somatic genomic alterations arising in individual cells, approximately 5% of all CRCs arise in the setting of germline mutations in genes involved in key cellular processes. To date, multiple genes have been implicated in single-gene hereditary cancer syndromes, many of which are associated with increased risk for CRC, as well as other tumor types. This review outlines the clinical, pathologic, and genetic features of the hereditary cancer syndromes known to be associated with increased risk for CRC and delineates strategies for implementing genetic risk assessments in clinical settings. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Borry, Pascal; Evers-Kiebooms, Gerry; Cornel, Martina C
Although various guidelines and position papers have discussed, in the past, the ethical aspects of genetic testing in asymptomatic minors, the European Society of Human Genetics had not earlier endorsed any set of guidelines exclusively focused on this issue. This paper has served as a background...... of best interests, participation of minors in health-care decisions, parents' responsibilities to share genetic information, the role of clinical genetics and the health-care system in communication within the family. Second, it discusses, respectively, the presymptomatic and predictive genetic testing...
Lukowski, Samuel W; Lloyd-Jones, Luke R; Holloway, Alexander; Kirsten, Holger; Hemani, Gibran; Yang, Jian; Small, Kerrin; Zhao, Jing; Metspalu, Andres; Dermitzakis, Emmanouil T; Gibson, Greg; Spector, Timothy D; Thiery, Joachim; Scholz, Markus; Montgomery, Grant W; Esko, Tonu; Visscher, Peter M; Powell, Joseph E
Transcript co-expression is regulated by a combination of shared genetic and environmental factors. Here, we estimate the proportion of co-expression that is due to shared genetic variance. To do so, we estimated the genetic correlations between each pairwise combination of 2469 transcripts that are highly heritable and expressed in whole blood in 1748 unrelated individuals of European ancestry. We identify 556 pairs with a significant genetic correlation of which 77% are located on different chromosomes, and report 934 expression quantitative trait loci, identified in an independent cohort, with significant effects on both transcripts in a genetically correlated pair. We show significant enrichment for transcription factor control and physical proximity through chromatin interactions as possible mechanisms of shared genetic control. Finally, we construct networks of interconnected transcripts and identify their underlying biological functions. Using genetic correlations to investigate transcriptional co-regulation provides valuable insight into the nature of the underlying genetic architecture of gene regulation.Covariance of gene expression pairs is due to a combination of shared genetic and environmental factors. Here the authors estimate the genetic correlation between highly heritable pairs and identify transcription factor control and chromatin interactions as possible mechanisms of correlation.
Full Text Available Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders.
Göl, Şurhan; Göktay, Mehmet; Allmer, Jens; Doğanlar, Sami; Frary, Anne
Spinach is a popular leafy green vegetable due to its nutritional composition. It contains high concentrations of vitamins A, E, C, and K, and folic acid. Development of genetic markers for spinach is important for diversity and breeding studies. In this work, Next Generation Sequencing (NGS) technology was used to develop genomic simple sequence repeat (SSR) markers. After cleaning and contig assembly, the sequence encompassed 2.5% of the 980 Mb spinach genome. The contigs were mined for SSRs. A total of 3852 SSRs were detected. Of these, 100 primer pairs were tested and 85% were found to yield clear, reproducible amplicons. These 85 markers were then applied to 48 spinach accessions from worldwide origins, resulting in 389 alleles with 89% polymorphism. The average gene diversity (GD) value of the markers (based on a GD calculation that ranges from 0 to 0.5) was 0.25. Our results demonstrated that the newly developed SSR markers are suitable for assessing genetic diversity and population structure of spinach germplasm. The markers also revealed clustering of the accessions based on geographical origin with clear separation of Far Eastern accessions which had the overall highest genetic diversity when compared with accessions from Persia, Turkey, Europe, and the USA. Thus, the SSR markers have good potential to provide valuable information for spinach breeding and germplasm management. Also they will be helpful for genome mapping and core collection establishment.
Zhang, Jie; Yao, Jian-Ting; Sun, Zhong-Min; Fu, Gang; Galanin, Dmitry A; Nagasato, Chikako; Motomura, Taizo; Hu, Zi-Min; Duan, De-Lin
Population structure and genetic diversity of marine organisms in the Northwestern Pacific Ocean exhibited complex patterns. Saccharina japonica is a commercially and ecologically important kelp species widely distributed along the coast of Japan Sea. However, it is still poorly known about population genetics and phylogeographic patterns of wild S. japonica populations on a large geographic scale, which is an important contribution to breeding and conservation of this marine crop. We collected 612 mitochondrial COI and trnW-trnL sequences. Diversity indices suggested that S. japonica populations along the coast of Hokkaido exhibited the highest genetic diversity. Bayesian Analysis of Population Structure (BAPS) revealed four clusters in the kelp species (cluster 1: Hokkaido and South Korea; cluster 2: northwestern Hokkaido; cluster 3: Far Eastern Russia; cluster 4: China). The network inferred from concatenated data exhibited two shallow genealogies corresponding to two BAPS groups (cluster 2 and cluster 3). We did not detect gene flow between the two shallow genealogies, but populations within genealogy have asymmetric gene exchange. Bayesian skyline plots and neutrality tests suggested that S. japonica experienced postglacial expansion around 10.45 ka. The coast of Hokkaido might be the origin and diversification center of S. japonica. Gene exchange among S. japonica populations could be caused by anthropogenic interference and oceanographic regimes. Postglacial expansions and gene exchange apparently led to more shared haplotypes and less differentiation that in turn led to the present shallow phylogeographical patterns in S. japonica.
Sanna, Daria; Cossu, Piero; Dedola, Gian Luca; Scarpa, Fabio; Maltagliati, Ferruccio; Castelli, Alberto; Franzoi, Piero; Lai, Tiziana; Cristo, Benedetto; Curini-Galletti, Marco; Francalacci, Paolo; Casu, Marco
Pinna nobilis is the largest endemic Mediterranean marine bivalve. During past centuries, various human activities have promoted the regression of its populations. As a consequence of stringent standards of protection, demographic expansions are currently reported in many sites. The aim of this study was to provide the first large broad-scale insight into the genetic variability of P. nobilis in the area that encompasses the western Mediterranean, Ionian Sea, and Adriatic Sea marine ecoregions. To accomplish this objective twenty-five populations from this area were surveyed using two mitochondrial DNA markers (COI and 16S). Our dataset was then merged with those obtained in other studies for the Aegean and Tunisian populations (eastern Mediterranean), and statistical analyses (Bayesian model-based clustering, median-joining network, AMOVA, mismatch distribution, Tajima's and Fu's neutrality tests and Bayesian skyline plots) were performed. The results revealed genetic divergence among three distinguishable areas: (1) western Mediterranean and Ionian Sea; (2) Adriatic Sea; and (3) Aegean Sea and Tunisian coastal areas. From a conservational point of view, populations from the three genetically divergent groups found may be considered as different management units.
Full Text Available Pinna nobilis is the largest endemic Mediterranean marine bivalve. During past centuries, various human activities have promoted the regression of its populations. As a consequence of stringent standards of protection, demographic expansions are currently reported in many sites. The aim of this study was to provide the first large broad-scale insight into the genetic variability of P. nobilis in the area that encompasses the western Mediterranean, Ionian Sea, and Adriatic Sea marine ecoregions. To accomplish this objective twenty-five populations from this area were surveyed using two mitochondrial DNA markers (COI and 16S. Our dataset was then merged with those obtained in other studies for the Aegean and Tunisian populations (eastern Mediterranean, and statistical analyses (Bayesian model-based clustering, median-joining network, AMOVA, mismatch distribution, Tajima's and Fu's neutrality tests and Bayesian skyline plots were performed. The results revealed genetic divergence among three distinguishable areas: (1 western Mediterranean and Ionian Sea; (2 Adriatic Sea; and (3 Aegean Sea and Tunisian coastal areas. From a conservational point of view, populations from the three genetically divergent groups found may be considered as different management units.
Full Text Available The genetic differentiation of many marine fish species is low. Yet local adaptation may be common in marine fish species as the vast and changing marine environment provides more chances for natural selection. Here, we used anonymous as well as known protein gene linked microsatellites and mitochondrial DNA to detect the population structure of the small yellow croaker (Larimichthys polyactis in the Northwest Pacific marginal seas. Among these loci, we detected at least two microsatellites, anonymous H16 and HSP27 to be clearly under diversifying selection in outlier tests. Sequence cloning and analysis revealed that H16 was located in the intron of BAHCC1 gene. Landscape genetic analysis showed that H16 mutations were significantly associated with temperature, which further supported the diversifying selection at this locus. These marker types presented different patterns of population structure: (i mitochondrial DNA phylogeny showed no evidence of genetic divergence and demonstrated only one glacial linage; (ii population differentiation using putatively neutral microsatellites presented a pattern of high gene flow in the L. polyactis. In addition, several genetic barriers were identified; (iii the population differentiation pattern revealed by loci under diversifying selection was rather different from that revealed by putatively neutral loci. The results above suggest local adaptation in the small yellow croaker. In summary, population genetic studies based on different marker types disentangle the effects of demographic history, migration, genetic drift and local adaptation on population structure and also provide valuable new insights for the design of management strategies in L. polyactis.
Lu, Mengfei; Lewis, Cathryn M.; Traylor, Matthew
Abstract Background Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests repor...
McConkie-Rosell, Allyn; Spiridigliozzi, Gail A
Genetic testing in minor children presents a complex ethical and social problem. Current guidelines state that genetic testing of children is recommended only under circumstances where a clear medical or psychosocial benefit to the child can be demonstrated. Because of the difficulty in determining a psychosocial benefit, the discussion about genetic testing of minors ultimately tends to focus on who has the right to make the decision and whose right to autonomy is jeopardized, the parent's or the child's, when there is no identified medical benefit. Historically, a western bioethics paradigm, Principlism, has been used to guide genetic counseling sessions and genetic-testing guidelines for minors. This bioethics paradigm is guided by the principles: respect for autonomy, beneficence, nonmaleficence, and justice. Genetic testing in children, when viewed through a traditional bioethics filter is limited by its focus on the individual because children are not only individuals, they are also integral parts of a larger social context, that of their family. Because this bioethics paradigm places a strong emphasis on individual autonomy, the family's beliefs and values and the parents' concern for their children may be overshadowed by the medical community's attempt to preserve the child's "right" to an autonomous decision about genetic testing. The purpose of this paper is to first discuss the circumstances in which genetic testing of minors occurs and then present a theoretical and ethics-based conceptual framework that may be useful in the development of genetic counseling interventions.
The largest and most comprehensive genomic analysis of individuals with Ewing sarcoma performed to date reveals that some patients are genetically predisposed to developing the cancer. Learn more...
Verschuere, B.; Kleinberg, B.
The Internet has already changed people's lives considerably and is likely to drastically change forensic research. We developed a web-based test to reveal concealed autobiographical information. Initial studies identified a number of conditions that affect diagnostic efficiency. By combining these
... they require a sample of amniotic fluid or tissue from around the fetus. Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People ...
Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.
OBJECTIVE: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,
Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.
Objective: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,
Crozier, S; Robertson, N; Dale, M
Huntington's disease (HD) is a neurodegenerative genetic condition for which a predictive genetic test by mutation analysis has been available since 1993. However, whilst revealing the future presence of the disease, testing may have an adverse psychological impact given that the disease is progressive, incurable and ultimately fatal. This review seeks to systematically explore the psychological impact of genetic testing for individuals undergoing pre-symptomatic mutation analysis. Three databases (Medline, PsycInfo and Scopus) were interrogated for studies utilising standardised measures to assess psychological impact following predictive genetic testing for HD. From 100 papers initially identified, eight articles were eligible for inclusion. Psychological impact of predictive genetic testing was not found to be associated with test result. No detrimental effect of predictive genetic testing on non-carriers was found, although the process was not found to be psychologically neutral. Fluctuation in levels of distress was found over time for carriers and non-carriers alike. Methodological weaknesses of published literature were identified, notably the needs of individuals not requesting genetic testing, as well as inadequate support for individuals registering elevated distress and declining post-test follow-up. Further assessment of these vulnerable individuals is warranted to establish the extent and type of future psychological support.
Full Text Available Genetic testing is a medical tool employed to screen changes in genes linked to cancer and other genetic diseases. Genetic tests are available for breast, ovarian, colon, thyroid, and some other cancers and they represent the main tool for early identification of the “risk” subjects. The choice to undergo genetic testing by a healthy or affected cancer patient with family history of the cancer has to be the fruit of a careful and prudent assessment of the advantages and disadvantages discussed during oncogenetic counselling. The latter, in turn, in the case of a patient's positive and informed choice, must constantly affiliate the genetic testing, in order to preserve the prediction and information role of the test as much as possible.
Mariela Yaneva – Deliverska
Full Text Available Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. The main difference between direct-to-consumer genetic testing and the standard genetic testing is the way informational support is provided in internet offers of testing. Counselling may be offered as an additional special service at extra costs and at the customer's request. It may also be that a recommendation or at least an offer is given for the customer to contact a doctor or health practitioner from the company via phone for counselling.In a liberal society the fundamental individual rights can be considered to include access to medical treatment and diagnostics that may be helpful for improving one's health condition or that can help an individual make decisions regarding life style and health. At the European level, there are no binding legal regulations that specifically apply for genetic testing. In some European counties, national laws, require a responsible medical person to be involved before a genetic test is provided. The Convention on Human Rights and Biomedicine was adopted by the Committee of Ministers on 19 November 1996, while an Additional Protocol to the Convention, concerning Genetic Testing for Health Purposes, was adopted by the Committee of Ministers on 7 May 2008.Direct-to-consumer genetic testing is closely watched by the community of medical genetics and counsellors, and the EU funded Eurogentest Network of Excellence.In 2010, the European Society of Human Genetics has releaseda statement on direct-to-consumer gene testing for health-related purposes. The European Society of Human Genetics is concerned about the way in which commercial companies are
Macaron, Carole; Leach, Brandie H; Burke, Carol A
Colorectal cancer (CRC) is a leading cause of cancer and cancer deaths in the Western world. Approximately 5-10% of CRC are hereditary, due to a defined genetic cause. Individuals and families affected with a hereditary CRC syndrome exhibit benign and malignant extra-intestinal tumors, require aggressive cancer screening and benefit from management by a multi-disciplinary team of professionals. The clinical manifestations, genetic causes and current management of patients with hereditary colon cancer syndrome is provided. © 2014 Wiley Periodicals, Inc.
King, Elisabeth; Mahon, Suzanne M
The practice of genetic testing for hereditary cancer syndromes has changed dramatically in recent years, and patients often approach oncology nurses requesting information about genetic testing. . This article aims to explore changes in cancer genetics, the role of genetics professionals in providing comprehensive genetic care, and the implications of these new developments in genetics for oncology nurses. . A literature review was conducted and focused on articles about the updating of genetic tests with panel testing, insurance changes, alternative genetic counseling strategies, and direct-to-consumer genetic testing. . Oncology nurses play an important role in identifying and referring patients, including those who have tested negative for hereditary susceptibility genes, to genetics professionals. Genetics professionals can assist with insurance issues, interpretation of test results, clarification when a variant of unknown clinical significance is detected, and recommendations for care based on personal and family history and testing results. Oncology nurses can assist families with understanding the limitations of direct-to-consumer genetic testing.
Aro, A R; Hakonen, A; Hietala, M
The aim of the study was to analyze effects of age, education and gender on acceptance of genetic testing. Subjects, n = 1967 aged 15-69, were a stratified random sample of the Finnish population. One thousand, one hundred and sixty nine subjects, 530 men and 639 women, returned the questionnaire....... The majority of the respondents approved of the availability of genetic testing. Young, aged 15-24, were more favourable towards testing and more willing to undergo suggested tests, but they were also more worried than others about the misuse of test results. Men aged 45-69 with only basic education were more...... in favour of mandatory genetic testing than other respondents. Respondents with university education were more critical towards genetic testing and expressed their worry about eugenics more often than other education groups. In conclusion, there are age, education and gender related differences...
Warren, Narelle; Gardner, John
Online personalized genetic testing services offer accessible and convenient options for satisfying personal curiosity about health and obtaining answers about one's genetic provenance. They are especially attractive to healthy people who wish to learn about their future risk of disease, as Paul Mason's (2017) case study of "Jordan" illustrates. In this response, we consider how online genetic testing services are used by people diagnosed with a common neurodegenerative disease, Parkinson's disease, to gain a sense of certainty regarding the future.
... a genetic test is valid and useful? How can consumers be sure a genetic test is valid ... particular gene or genetic change. In other words, can the test accurately detect whether a specific genetic ...
Li, Chuang; Gong, Wenbing; Zhang, Lin; Yang, Zhiquan; Nong, Wenyan; Bian, Yinbing; Kwan, Hoi-Shan; Cheung, Man-Kit; Xiao, Yang
Association mapping is a robust approach for the detection of quantitative trait loci (QTLs). Here, by genotyping 297 genome-wide molecular markers of 89 Lentinula edodes cultivars in China, the genetic diversity, population structure and genetic loci associated with 11 agronomic traits were examined. A total of 873 alleles were detected in the tested strains with a mean of 2.939 alleles per locus, and the Shannon's information index was 0.734. Population structure analysis revealed two robustly differentiated groups among the Chinese L. edodes cultivars (FST = 0.247). Using the mixed linear model, a total of 43 markers were detected to be significantly associated with four traits. The number of markers associated with traits ranged from 9 to 26, and the phenotypic variations explained by each marker varied from 12.07% to 31.32%. Apart from five previously reported markers, the remaining 38 markers were newly reported here. Twenty-one markers were identified as simultaneously linked to two to four traits, and five markers were associated with the same traits in cultivation tests performed in two consecutive years. The 43 traits-associated markers were related to 97 genes, and 24 of them were related to 10 traits-associated markers detected in both years or identified previously, 13 of which had a >2-fold expression change between the mycelium and primordium stages. Our study has provided candidate markers for marker-assisted selection (MAS) and useful clues for understanding the genetic architecture of agronomic traits in the shiitake mushroom.
... about medical care. Forensic testing Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or ...
Sun, Rongxi; Lin, Furong; Huang, Ping; Zheng, Yongqi
Chinese sweetgum (Liquidambar formosana) is a relatively fast-growing ecological pioneer species. It is widely used for multiple purposes. To assess the genetic diversity and genetic differentiation of the species, genic SSR markers were mined from transcriptome data for subsequent analysis of the genetic diversity and population structure of natural populations. A total of 10645 potential genic SSR loci were identified in 80482 unigenes. The average frequency was one SSR per 5.12 kb, and the dinucleotide unit was the most abundant motif. A total of 67 alleles were found, with a mean of 6.091 alleles per locus and a mean polymorphism information content of 0.390. Moreover, the species exhibited a relatively moderate level of genetic diversity (He = 0.399), with the highest was found in population XY (He = 0.469). At the regional level, the southwestern region displayed the highest genetic diversity (He = 0.435) and the largest number of private alleles (n = 5), which indicated that the Southwestern region may be the diversity hot spot of L. formosana. The AMOVA results showed that variation within populations (94.02%) was significantly higher than among populations (5.98%), which was in agreement with the coefficient of genetic differentiation (Fst = 0.076). According to the UPGMA analysis and principal coordinate analysis and confirmed by the assignment test, 25 populations could be divided into three groups, and there were different degrees of introgression among populations. No correlation was found between genetic distance and geographic distance (P > 0.05). These results provided further evidence that geographic isolation was not the primary factor leading to the moderate genetic differentiation of L. formosana. As most of the genetic diversity of L. formosana exists among individuals within a population, individual plant selection would be an effective way to use natural variation in genetic improvement programs. This would be helpful to not only protect the
McNamee, M.J.; Muller, A.J.; van Hilvoorde, I.M.; Holm, S.
Sports medicine ethics is neither a well established branch of sports medicine nor of medical ethics. It is therefore important to raise to more general awareness some of the significant ethical implications of sports medicine practices. The field of genetics in sports is likewise in its infancy and
The genetic relationships among ten types of endod (Phytolacca dodecandra) cultivated by the Institute of Pathobiology of the Addis Ababa University to combat the disease bilharzia in Ethiopia were studied using morphology and molecular markers. A total of 18 morphological characters, 194 amplified fragment length polymorphism (AFLP) and 42 random amplified polymorphic DNA (RAPD) markers were used to determine genetic proximity between types. Genetic distance and cluster analysis of the AFLP data revealed the lack of genetic difference between E47 and E48 but relatively wider genetic difference among the other endod types. Cluster and principal component analyses performed on the AFLP and RAPD markers demonstrated the presence of distinct separation of E56 but not that of E44 from the others. The AFLP and RAPD data, thcrefore, did not support the hypothesis that the superiority of E44 in agronomic traits and molluscicidal potency is linked to its distinct genetic difference from the other endod types. Matrices correspondence tests demonstrated the presence of greater correspondence between AFLP and RAPD data (r = 0.842) but not between the morphology and that of AFLP and RAPD. This indicates the correspondence more between the two DNA markers systems than either of them with morphological traits. The cophenetic correlation coefficients also revealed poor fit for morphology (r = 0.716), good fit for RAPD (r = 0.872) and very good fit for AFLP (r = 0.975), reflecting the hyper-variability and higher resolving power of AFLP.
Full Text Available Thuja sutchuenensis Franch. is a critically endangered plant endemic to the North-East Chongqing, China. Genetic variation was studied to assess the distribution of genetic diversity within and among seven populations from the single remnant locations, using inter-simple sequence repeat (ISSR markers. A total of 15 primers generated 310 well defined bands, with an average of 20.7 bands per primer. The seven populations revealed a relatively high level of genetic diversity in the species. The percentage of polymorphic bands, Nei’s gene diversity and Shannon’s information index at the population and species level were 76.1%, 0.155, 0.252 and 100%, 0.165, 0.295, respectively. A low level of genetic differentiation among populations (GST = 0.102, in line with the results of Analyses of Molecular Variance (AMOVA, and a high level of gene flow (Nm = 4.407 were observed. Both the Unweighted Pair Group Method with Arithmatic Mean (UPGMA cluster analysis and Principal Coordinates Analysis (PCoA supported the grouping of all seven populations into two groups. In addition, Mantel test revealed no significant correlation between genetic and geographical distances (r = 0.329, p = 0.100. The low genetic differentiation among populations implies that the conservation efforts should aim to preserve all the extant populations of this endangered species.
Ottman, Ruth; Hirose, Shinichi; Jain, Satish; Lerche, Holger; Lopes-Cendes, Iscia; Noebels, Jeffrey L.; Serratosa, José; Zara, Federico; Scheffer, Ingrid E.
SUMMARY In this report, the International League Against Epilepsy (ILAE) Genetics Commission discusses essential issues to be considered with regard to clinical genetic testing in the epilepsies. Genetic research on the epilepsies has led to the identification of more than 20 genes with a major effect on susceptibility to idiopathic epilepsies. The most important potential clinical application of these discoveries is genetic testing: the use of genetic information, either to clarify the diagnosis in people already known or suspected to have epilepsy (diagnostic testing), or to predict onset of epilepsy in people at risk because of a family history (predictive testing). Although genetic testing has many potential benefits, it also has potential harms, and assessment of these potential benefits and harms in particular situations is complex. Moreover, many treating clinicians are unfamiliar with the types of tests available, how to access them, how to decide whether they should be offered, and what measures should be used to maximize benefit and minimize harm to their patients. Because the field is moving rapidly, with new information emerging practically every day, we present a framework for considering the clinical utility of genetic testing that can be applied to many different syndromes and clinical contexts. Given the current state of knowledge, genetic testing has high0020clinical utility in few clinical contexts, but in some of these it carries implications for daily clinical practice. PMID:20100225
Nautiyal, Katherine M; Wall, Melanie M; Wang, Shuai; Magalong, Valerie M; Ahmari, Susanne E; Balsam, Peter D; Blanco, Carlos; Hen, René
Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity.
Lu, Mengfei; Lewis, Cathryn M; Traylor, Matthew
.... Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals...
To discuss the factors to consider when evaluating patients with a suspected genetic endocrine disorder, so as to guide practicing endocrinologists through the process of genetic testing and result interpretation. The author's experience and review of appropriate literature have been used to give a personal perspective on the role of genetic testing in hereditary endocrine disorders. Recent advances in our understanding of genetics and genomics have uncovered that they have a far more important role in the pathogenesis of endocrine disease than previously appreciated. Not only are we expanding our understanding of rare mendelian disorders such as multiple endocrine neoplasia type 1 and 2, but we are also beginning to understand the clinical significance of genetic factors in the pathogenesis of common disorders such as obesity and dyslipidemia. It can be difficult to appreciate the clinical significance and utility of genetic testing that is currently available, and the interpretation of genetic test results can be challenging. Decisions on whether genetic testing is needed should be made on a case-by-case basis, with the endocrinologist and geneticist working together from the outset.
Ahram, Mamoun; Soubani, Majd; Abu Salem, Lana; Saker, Haneen; Ahmad, Muayyad
Genetic testing has a potential in the prevention of genetic diseases, particularly in communities with high rates of consanguineous marriage. Therefore, knowledge, practice, and attitudes of the public in Jordan regarding genetic testing were investigated. Individuals (N = 3,196) were questioned about the concepts of genetic testing and genetic counselors, if they underwent any genetic tests, the type of test, the method of consenting to the test, as well as their level of satisfaction with the privacy of the genetic testing service. The likelihood of pursuing predictive genetic testing for cancer was also investigated. Although almost 70 % of respondents knew the term "genetic testing," only 18 % had undergone genetic testing, primarily the mandatory premarital test. In addition, there was a lack of general knowledge about genetic counselors. Many of those who had genetic testing (45 %) indicated they did not go through a consent process, and a lack of consent was significantly related to dissatisfaction with the privacy of the service. Approximately 55 % of respondents indicated they would potentially pursue predictive genetic testing for cancer. Going for routine health checkups was not significantly correlated with either actual or potential uptake of genetic testing, suggesting health care providers do not play an influential role in patients' testing decisions. Our results show a gap between the knowledge and uptake of genetic testing and may help to guide the design of effective strategies to initiate successful genetic counseling and testing services.
The thesis checks the validity of the efficient markets hypothesis focusing on stock markets. Technical trading rules are generated by using an evolutionary optimization algorithm (Genetic Programming) based on training samples. The trading rules are subsequently applied to data samples unknown to the algorithm beforehand. The benchmark strategy consists of a classic buy-and-hold strategy in the DAX and the Hang Seng. The trading rules generally fail at consistently beating the benchmark thu...
Full Text Available Abstract Diffuse parenchymal lung diseases (DPLD represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases, the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood. Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice. This review focuses on idiopathic pulmonary fibrosis (IPF and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF.
Brøndum-Nielsen, Karen; Jensen, Hanne; Timshel, Susanne
Advances in genetics have made genetic testing in patients with inherited eye disease increasingly accessible, and the initiation of clinical intervention trials makes it increasingly clinically relevant. Based on a multidisciplinary collaboration between ophthalmologists and clinical geneticists......, the extensive register of families with monogenic inherited eye diseases at the National Eye Clinic of the Kennedy Center in Denmark provides a valuable asset waiting to be exploited in the global effort to reduce blindness caused by genetic defects....
Lu, Mengfei; Lewis, Cathryn M.; Traylor, Matthew
Background Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. Methods The research papers listed under each 23a...
Lu, Mengfei; Lewis, Cathryn M.; Traylor, Matthew
BackgroundRapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests.MethodsThe research papers listed under each 23andM...
Progress in the genetics of dementing disorders and the availability of clinical tests for practicing physicians increase the need for a better understanding of multifaceted issues associated with genetic testing. The genetics of dementia is complex, and genetic testing is fraught with many ethical concerns. Genetic testing can be considered for patients with a family history suggestive of a single gene disorder as a cause of dementia. Testing of affected patients should be accompanied by competent genetic counseling that focuses on probabilistic implications for at-risk first-degree relatives. Predictive testing of at-risk asymptomatic patients should be modeled after presymptomatic testing for Huntington's disease. Testing using susceptibility genes has only a limited diagnostic value at present because potential improvement in diagnostic accuracy does not justify potentially negative consequences for first-degree relatives. Predictive testing of unaffected subjects using susceptibility genes is currently not recommended because individual risk cannot be quantified and there are no therapeutic interventions for dementia in presymptomatic patients.
Linda J. Herbert
Full Text Available It has been well-established that some adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD are at increased risk for cigarette smoking. Current research on the genetic basis of this association could ultimately translate into genetic tests capable of identifying smoking-prone adolescents with ADHD. In this study we examined 81 ADHD affected adolescents’ (age 13–21 interest in genetic testing for nicotine addiction susceptibility. Fifty-seven percent of adolescents indicated a fair amount of interest or more in testing. Most adolescents indicated that the personal information revealed from testing would be either useful (29% or interesting (37%. Implications for genetically-informed smoking prevention and cessation interventions in high risk adolescents with ADHD are discussed.
Full Text Available BACKGROUND: The geometrid moths of Europe are one of the best investigated insect groups in traditional taxonomy making them an ideal model group to test the accuracy of the Barcode Index Number (BIN system of BOLD (Barcode of Life Datasystems, a method that supports automated, rapid species delineation and identification. METHODOLOGY/PRINCIPAL FINDINGS: This study provides a DNA barcode library for 219 of the 249 European geometrid moth species (88% in five selected subfamilies. The data set includes COI sequences for 2130 specimens. Most species (93% were found to possess diagnostic barcode sequences at the European level while only three species pairs (3% were genetically indistinguishable in areas of sympatry. As a consequence, 97% of the European species we examined were unequivocally discriminated by barcodes within their natural areas of distribution. We found a 1:1 correspondence between BINs and traditionally recognized species for 67% of these species. Another 17% of the species (15 pairs, three triads shared BINs, while specimens from the remaining species (18% were divided among two or more BINs. Five of these species are mixtures, both sharing and splitting BINs. For 82% of the species with two or more BINs, the genetic splits involved allopatric populations, many of which have previously been hypothesized to represent distinct species or subspecies. CONCLUSIONS/SIGNIFICANCE: This study confirms the effectiveness of DNA barcoding as a tool for species identification and illustrates the potential of the BIN system to characterize formal genetic units independently of an existing classification. This suggests the system can be used to efficiently assess the biodiversity of large, poorly known assemblages of organisms. For the moths examined in this study, cases of discordance between traditionally recognized species and BINs arose from several causes including overlooked species, synonymy, and cases where DNA barcodes revealed
Schiffman, Jason; Lawrence, Ryan E; Demro, Caroline; Appelbaum, Paul S; Dixon, Lisa B
Within schizophrenia, genetic factors contribute greatly to risk, yet genetic testing for the disorder is not available. For some individuals with specific genotypes, cannabis use may increase risk of schizophrenia. It is possible that genetic tests could be offered in the future to inform individuals of the risk of schizophrenia if they use cannabis. Previous research, however, provides little guidance on how young adults might respond to such tests. We assessed a group of young adults (n = 83) to determine how the perceived magnitude of increased risk for schizophrenia in the presence of cannabis use influences decisions to undergo genetic testing, as well as subsequent attitudes and intentions towards cannabis use. Participants were significantly more likely to indicate willingness to get tested if the results identified a 10% risk versus a 2% risk of schizophrenia. Participants also indicated that if the results of their test reflected increased risk due to cannabis use, it would be more important to avoid cannabis in the 10% risk scenario as compared to the 2% risk scenario. These findings remained consistent among a subset of participants who indicated cannabis use. Results suggest that cannabis users and non-users were positively influenced in terms of intentions to change behaviour based on the magnitude of risk conveyed by genetic testing. These findings provide an initial step towards understanding young people's attitudes towards genetic testing and may help prepare interventions specifically tailored around cannabis use reduction for people at risk for schizophrenia. © 2014 Wiley Publishing Asia Pty Ltd.
Brurberg, May Bente; Elameen, Abdelhameed; Le, Ving Hong
Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). The pathogen is highly adaptable and to get an overview of the genetic variation in the Nordic countries, Denmark, Finland, Norway and Sweden we have analyzed 200 isolates from...
Diehl, Scott R; Kuo, Fengshen; Hart, Thomas C
It has been proposed that the PST and PerioPredict genetic tests that are based on polymorphisms in interleukin 1 (IL-1) genes identify a subset of patients who experience fewer tooth extractions if provided with 2 annual preventive visits. Economic analyses indicate rationing preventive care to only "high-risk" genotypes, smokers, patients with diabetes, or combinations of these risk factors would reduce the cost of dental care by $4.8 billion annually in the United States. Data presented in the study that claimed clinical utility for the PST and PerioPredict tests were obtained for reanalysis using logistic regression to assess whether the PST genetic test, smoking, diabetes, or number of preventive visits were risk factors for tooth extraction during a span of 16 years. Consistency of risk classification by the PST (version 1) and PerioPredict (version 2) genetic tests was evaluated in different ethnic groups from the 1000 Genomes database. Multivariate analyses revealed association of tooth extraction with diabetes (P preventive visits (P = .004), but no support for the PST genetic test (P = .96) nor indication that the benefit of 2 preventive visits was affected by this genetic test (P = .58). Classification of risk was highly inconsistent between the PST (version 1) and PerioPredict (version 2) genetic tests. Two annual preventive visits were supported as beneficial for all patients, and there was no evidence that the IL-1 PST genetic test has any effect on tooth extraction risk or influences the benefits of 2 annual preventive visits. Neither IL-1 PST nor PerioPredict genetic tests are useful for rationing preventive dental care. Further research is needed to identify genetic biomarkers with robust clinical validity and clinical utility to effectively personalize the practice of dentistry. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.
Wei Tong; Qiang He; Yong-Jin Park
Mitochondrial genome variations have been detected despite the overall conservation of this gene content, which has been valuable for plant population genetics and evolutionary studies. Here, we describe mitochondrial variation architecture and our performance of a phylogenetic dissection of Korean landrace and weedy rice. A total of 4,717 variations across the mitochondrial genome were identified adjunct with 10 wild rice. Genetic diversity assessment revealed that wild rice has higher nucle...
... certain other cancers or cancer in both breasts, ancestry, and family health history of breast, ovarian, and ... mutations, so genetic testing will not help most women with a family health history of breast and ...
Jie, He; Hao, Zhang; Lili, Zhang
Based on the present situation and the development of experiment tests in universities, we introduced a reform in tests of genetics experiments. According to the teaching goals and course contents of genetics experiment, the tests of genetics experiments contain four aspects on the performance of students: the adherence to the experimental procedures, the depth of participation in experiment, the quality of experiment report, and the mastery of experiment principles and skills, which account for 10 %, 20 %, 40 % and 30 % in the total scores, respectively. All four aspects were graded quantitatively. This evaluation system has been tested in our experiment teaching. The results suggest that it has an effect on the promotion of teaching in genetics experiments.
Paul R. Brezina MD, MBA
Full Text Available The past hundred years have given birth to arguably the most profound changes in society, medicine, and technology the world has ever witnessed. Genetics is one such field that has enjoyed a meteoric rise during this time. Progressing from Mendelian genetics to the discovery of DNA to the ability to sequence the human genome, perhaps no other discipline holds more promise to affect future change than genetics. Technology currently exists to evaluate some of the genetic information held by developing embryos in the context of an in vitro fertilization (IVF cycle. This information is then used to determine which embryos are selected for uterine transfer. Many societies have enacted legislation to protect against possible abuses utilizing this technology. However, it is incumbent upon society to continue ensuring that preimplantation genetic diagnosis (PGD–-and genetic testing in general–-is applied in a way that utilizes its potential in a responsible manner to improve health care.
Brezina, Paul R
The past hundred years have given birth to arguably the most profound changes in society, medicine, and technology the world has ever witnessed. Genetics is one such field that has enjoyed a meteoric rise during this time. Progressing from Mendelian genetics to the discovery of DNA to the ability to sequence the human genome, perhaps no other discipline holds more promise to affect future change than genetics. Technology currently exists to evaluate some of the genetic information held by developing embryos in the context of an in vitro fertilization (IVF) cycle. This information is then used to determine which embryos are selected for uterine transfer. Many societies have enacted legislation to protect against possible abuses utilizing this technology. However, it is incumbent upon society to continue ensuring that preimplantation genetic diagnosis (PGD)-and genetic testing in general-is applied in a way that utilizes its potential in a responsible manner to improve health care.
Mills Shaw, Kenna R.; Van Horne, Katie; Zhang, Hubert; Boughman, Joann
National educational organizations have called upon scientists to become involved in K–12 education reform. From sporadic interaction with students to more sustained partnerships with teachers, the engagement of scientists takes many forms. In this case, scientists from the American Society of Human Genetics (ASHG), the Genetics Society of America (GSA), and the National Society of Genetic Counselors (NSGC) have partnered to organize an essay contest for high school students as part of the activities surrounding National DNA Day. We describe a systematic analysis of 500 of 2443 total essays submitted in response to this contest over 2 years. Our analysis reveals the nature of student misconceptions in genetics, the possible sources of these misconceptions, and potential ways to galvanize genetics education. PMID:18245328
Mills Shaw, Kenna R; Van Horne, Katie; Zhang, Hubert; Boughman, Joann
National educational organizations have called upon scientists to become involved in K-12 education reform. From sporadic interaction with students to more sustained partnerships with teachers, the engagement of scientists takes many forms. In this case, scientists from the American Society of Human Genetics (ASHG), the Genetics Society of America (GSA), and the National Society of Genetic Counselors (NSGC) have partnered to organize an essay contest for high school students as part of the activities surrounding National DNA Day. We describe a systematic analysis of 500 of 2443 total essays submitted in response to this contest over 2 years. Our analysis reveals the nature of student misconceptions in genetics, the possible sources of these misconceptions, and potential ways to galvanize genetics education.
Smart, Andrew; Bolnick, Deborah A; Tutton, Richard
It is becoming increasingly difficult to keep information about genetic ancestry separate from information about health, and consumers of genetic ancestry tests are becoming more aware of the potential health risks associated with particular ancestral lineages. Because some of the proposed associations have received little attention from oversight agencies and professional genetic associations, scientific developments are currently outpacing governance regimes for consumer genetic testing. We highlight the recent and unremarked upon emergence of biomedical studies linking markers of genetic ancestry to disease risks, and show that this body of scientific research is becoming part of public discourse connecting ancestry and health. For instance, data on genome-wide ancestry informative markers are being used to assess health risks, and we document over 100 biomedical research articles that propose associations between mitochondrial DNA and Y chromosome markers of genetic ancestry and a wide variety of disease risks. Taking as an example an association between coronary heart disease and British men belonging to Y chromosome haplogroup I, we show how this science was translated into mainstream and online media, and how it circulates among consumers of genetic tests for ancestry. We find wide variations in how the science is interpreted, which suggests the potential for confusion or misunderstanding. We recommend that stakeholders involved in creating and using estimates of genetic ancestry reconsider their policies for communicating with each other and with the public about the health implications of ancestry information.
Lawrence, Ryan E; Appelbaum, Paul S.
The advent of genetic testing for psychiatric conditions raises difficult questions about when and how the tests should be used. Development of policies regarding these issues may be informed in a variety of ways by the views of key stakeholders: patients, family members, healthcare professionals, and the general public. Here we review empirical studies of attitudes towards genetic testing among these groups. Patients and family members show strong interest in diagnostic and predictive genetic testing, and to a considerable extent psychiatrists share their enthusiasm. Prenatal test utilization seems likely to depend both on parental views on abortion and the seriousness of the disorder. Parents show a surprising degree of interest in predictive testing of children, even when there are no preventive interventions available. Many persons report themselves ready to alter their lifestyles and plans for marriage and family in response to test results. Respondents also fear negative consequences, from discrimination to being unable to cope with knowledge of their “genetic fate.” Empirical studies of beliefs about genetic testing suggest tests are likely to be embraced widely, but the studies have methodologic limitations, reducing the certainty of their conclusions, and indicating a need for further research with more representative samples. PMID:22168293
Wood, Sarah G.; Hart, Sara A.; Little, Callie W.; Phillips, Beth M.
Past research suggests that reading comprehension test performance does not rely solely on targeted cognitive processes such as word reading, but also on other nontarget aspects such as test anxiety. Using a genetically sensitive design, we sought to understand the genetic and environmental etiology of the association between test anxiety and…
Schubert, Mikkel; Jáónsson, Hákon; Chang, Dan
Significance The domestication of the horse revolutionized warfare, trade, and the exchange of people and ideas. This at least 5,500-y-long process, which ultimately transformed wild horses into the hundreds of breeds living today, is difficult to reconstruct from archeological data and modern...... genetics alone. We therefore sequenced two complete horse genomes, predating domestication by thousands of years, to characterize the genetic footprint of domestication. These ancient genomes reveal predomestic population structure and a significant fraction of genetic variation shared with the domestic...
Khimoun, Aurélie; Peterman, William; Eraud, Cyril; Faivre, Bruno; Navarro, Nicolas; Garnier, Stéphane
Within the framework of landscape genetics, resistance surface modelling is particularly relevant to explicitly test competing hypotheses about landscape effects on gene flow. To investigate how fragmentation of tropical forest affects population connectivity in a forest specialist bird species, we optimized resistance surfaces without a priori specification, using least-cost (LCP) or resistance (IBR) distances. We implemented a two-step procedure in order (i) to objectively define the landscape thematic resolution (level of detail in classification scheme to describe landscape variables) and spatial extent (area within the landscape boundaries) and then (ii) to test the relative role of several landscape features (elevation, roads, land cover) in genetic differentiation in the Plumbeous Warbler (Setophaga plumbea). We detected a small-scale reduction of gene flow mainly driven by land cover, with a negative impact of the nonforest matrix on landscape functional connectivity. However, matrix components did not equally constrain gene flow, as their conductivity increased with increasing structural similarity with forest habitat: urban areas and meadows had the highest resistance values whereas agricultural areas had intermediate resistance values. Our results revealed a higher performance of IBR compared to LCP in explaining gene flow, reflecting suboptimal movements across this human-modified landscape, challenging the common use of LCP to design habitat corridors and advocating for a broader use of circuit theory modelling. Finally, our results emphasize the need for an objective definition of landscape scales (landscape extent and thematic resolution) and highlight potential pitfalls associated with parameterization of resistance surfaces. © 2017 John Wiley & Sons Ltd.
Li, Shao-Tzu; Yuen, Jeanette; Zhou, Ke; Binte Ishak, Nur Diana; Chen, Yanni; Met-Domestici, Marie; Chan, Sock Hoai; Tan, Yee Pin; Allen, John Carson; Lim, Soon Thye; Soo, Khee Chee; Ngeow, Joanne
Previous reports cite high costs of clinical cancer genetic testing as main barriers to patient's willingness to test. We report findings of a pilot study that evaluates how different subsidy schemes impact genetic testing uptake and total cost of cancer management. We included all patients who attended the Cancer Genetics Service at the National Cancer Centre Singapore (January 2014-May 2016). Two subsidy schemes, the blanket scheme (100% subsidy to all eligible patients), and the varied scheme (patients received 50%-100% subsidy dependent on financial status) were compared. We estimated total spending on cancer management from government's perspective using a decision model. 445 patients were included. Contrasting against the blanket scheme, the varied scheme observed a higher attendance of patients (34 vs 8 patients per month), of which a higher proportion underwent genetic testing (5% vs 38%), while lowering subsidy spending per person (S$1098 vs S$1161). The varied scheme may potentially save cost by reducing unnecessary cancer surveillance when first-degree relatives uptake rate is above 36%. Provision of subsidy leads to a considerable increase in genetic testing uptake rate. From the government's perspective, subsidising genetic testing may potentially reduce total costs on cancer management. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Powell-Young, Yolanda M; Spruill, Ida J
To describe views and beliefs that Black nurses hold regarding several conceptual areas of genetic research and testing. Data were generated using a descriptive, cross-sectional design. The sample consisted of 384 Black nurses attending the 2009 annual conference of the National Black Nurses Association in Las Vegas, Nevada. The chi-squared test was used to evaluate group differences by education level, functional area, age, and gender. One half of the Black nurses surveyed believed the potential for the discriminative misuse of genetic information against minority populations exists. However, 84% of these nurses believed the possibility of information misuse should not be used as a barrier to participation in genetic research and testing by the Black populace. Black nurses expressed concerns about the potential for discriminatory use of genetic information gleaned from research and testing. Yet, Black nurses recognize the importance of racial-ethnic minority participation in genetic research and testing. Participation in genetic research and testing by diverse populations will provide opportunities to improve the healthcare delivery system and aid the eradication of health disparities. More research is needed to clarify factors that contribute to the bifurcation of importance for participation, reluctance to participate, and what interventions might reduce reluctance. © 2013 Sigma Theta Tau International.
Jiménez, Ares; Holderegger, Rolf; Csencsics, Daniela; Quintanilla, Luis G
A previous study detected no allozyme diversity in Iberian populations of the buckler-fern Dryopteris aemula. The use of a more sensitive marker, such as microsatellites, was thus needed to reveal the genetic diversity, breeding system and spatial genetic structure of this species in natural populations. Eight microsatellite loci for D. aemula were developed and their cross-amplification with other ferns was tested. Five polymorphic loci were used to characterize the amount and distribution of genetic diversity of D. aemula in three populations from the Iberian Peninsula and one population from the Azores. Most microsatellite markers developed were transferable to taxa close to D. aemula. Overall genetic variation was low (H(T) = 0.447), but was higher in the Azorean population than in the Iberian populations of this species. Among-population genetic differentiation was high (F(ST) = 0.520). All loci strongly departed from Hardy-Weinberg equilibrium. In the population where genetic structure was studied, no spatial autocorrelation was found in any distance class. The higher genetic diversity observed in the Azorean population studied suggested a possible refugium in this region from which mainland Europe has been recolonized after the Pleistocene glaciations. High among-population genetic differentiation indicated restricted gene flow (i.e. lack of spore exchange) across the highly fragmented area occupied by D. aemula. The deviations from Hardy-Weinberg equilibrium reflected strong inbreeding in D. aemula, a trait rarely observed in homosporous ferns. The absence of spatial genetic structure indicated effective spore dispersal over short distances. Additionally, the cross-amplification of some D. aemula microsatellites makes them suitable for use in other Dryopteris taxa.
Burns, Charlotte; McGaughran, Julie; Davis, Andrew; Semsarian, Christopher; Ingles, Jodie
Ongoing challenges of clinical assessment of long QT syndrome (LQTS) highlight the importance of genetic testing in the diagnosis of asymptomatic at-risk family members. Effective access, uptake, and communication of genetic testing are critical for comprehensive cascade family screening and prevention of disease complications such as sudden cardiac death. The aim of this study was to describe factors influencing uptake of LQTS genetic testing, including those relating to access and family communication. We show those who access genetic testing are overrepresented by the socioeconomically advantaged, and that although overall family communication is good, there are some important barriers to be addressed. There were 75 participants (aged 18 years or more, with a clinical and/or genetic diagnosis of LQTS; response rate 71%) who completed a survey including a number of validated scales; demographics; and questions about access, uptake, and communication. Mean age of participants was 46 ± 16 years, 20 (27%) were males and 60 (80%) had genetic testing with a causative gene mutation in 42 (70%). Overall uptake of cascade testing within families was 60% after 4 years from proband genetic diagnosis. All participants reported at least one first-degree relative had been informed of their risk, whereas six (10%) reported at least one first-degree relative had not been informed. Those who were anxious or depressed were more likely to perceive barriers to communicating. Genetic testing is a key aspect of care in LQTS families and intervention strategies that aim to improve equity in access and facilitate effective family communication are needed. © 2015 Wiley Periodicals, Inc.
Murphy, Sinead M
Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.
Fulda, K G; Lykens, K
As a result of the increase in genetic testing and the fear of discrimination by insurance companies, employers, and society as a result of genetic testing, the disciplines of ethics, public health, and genetics have converged. Whether relatives of someone with a positive predictive genetic test should be notified of the results and risks is a matter urgently in need of debate. Such a debate must encompass the moral and ethical obligations of the diagnosing physician and the patient. The decision to inform or not will vary depending on what moral theory is used. Utilising the utilitarian and libertarian theories produces different outcomes. The principles of justice and non-maleficence will also play an important role in the decision.
Rong xi Sun
Full Text Available Chinese sweetgum (Liquidambar formosana is a relatively fast-growing ecological pioneer species. It is widely used for multiple purposes. To assess the genetic diversity and genetic differentiation of the species, genic SSR markers were mined from transcriptome data for subsequent analysis of the genetic diversity and population structure of natural populations. A total of 10645 potential genic SSR loci were identified in 80482 unigenes. The average frequency was one SSR per 5.12 kb, and the dinucleotide unit was the most abundant motif. A total of 67 alleles were found, with a mean of 6.091 alleles per locus and a mean polymorphism information content of 0.390. Moreover, the species exhibited a relatively moderate level of genetic diversity (He=0.399, with the highest was found in population XY (He=0.469. At the regional level, the southwestern region displayed the highest genetic diversity (He=0.435 and the largest number of private alleles (n=5, which indicated that the Southwestern region may be the diversity hot spot of L. formosana. The AMOVA results showed that variation within populations (94.02% was significantly higher than among populations (5.98%, which was in agreement with the coefficient of genetic differentiation (Fst = 0.076. According to the UPGMA analysis and principal coordinate analysis and confirmed by the assignment test, 25 populations could be divided into three groups, and there were different degrees of introgression among populations. No correlation was found between genetic distance and geographic distance (P>0.05. These results provided further evidence that geographic isolation was not the primary factor leading to the moderate genetic differentiation of L. formosana. As most of the genetic diversity of L. formosana exists among individuals within a population, individual plant selection would be an effective way to use natural variation in genetic improvement programs. This would be helpful to not only protect the
Luis David Castiel
Full Text Available The author analyzes the underlying theoretical aspects in the construction of the molecular watershed of epidemiology and the concept of genetic risk, focusing on issues raised by contemporary reality: new technologies, globalization, proliferation of communications strategies, and the dilution of identity matrices. He discusses problems pertaining to the establishment of such new interdisciplinary fields as molecular epidemiology and molecular genetics. Finally, he analyzes the repercussions of the social communication of genetic content, especially as related to predictive genetic tests and cloning of animals, based on triumphal, deterministic metaphors sustaining beliefs relating to the existence and supremacy of concepts such as 'purity', 'essence', and 'unification' of rational, integrated 'I's/egos'.
Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul
Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213
Chen, Na; Tanaka, Kanji; Watanabe, Katsumi
Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow). Makin and Wuerger tested the theory using the Implicit Association Test (IAT) and did not find clear evidence for Kandinsky's color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky's theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow) in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people's color-shape associations (circle-red, square-blue, triangle-yellow) can be observed by both direct and indirect experimental methods.
Full Text Available Kandinsky proposed a correspondence theory that suggests associations between specific colors and shapes (i.e., circle-blue, square-red, triangle-yellow. Makin and Wuerger tested the theory using the Implicit Association Test (IAT and did not find clear evidence for Kandinsky's color-shape associations among British participants. In the present study, we first replicated the previous study among Japanese participants and found similar results to those of Makin and Wuerger, showing little support for Kandinsky's theory. In the subsequent experiment, we tested another set of color-shape associations that had been revealed by using an explicit matching method (circle-red, square-blue, triangle-yellow in Japanese participants. The IAT tests showed that response times were significantly faster when circle-red, square-blue, and triangle-yellow combinations were mapped onto the same response key, rather than different key combinations, indicating that these color-shape combinations were encoded. These results provide the first empirical evidence that color-shape associations can be measured by indirect behavioral methods, and in particular, Japanese people's color-shape associations (circle-red, square-blue, triangle-yellow can be observed by both direct and indirect experimental methods.
Crook, Ashley; Williams, Kelly; Adams, Lorel; Blair, Ian; Rowe, Dominic B
Once a gene mutation that is causal of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) is identified in a family, relatives may decide to undergo predictive genetic testing to determine whether they are at risk of developing disease. Recent advances in gene discovery have led to a pressing need to better understand the implications of predictive genetic testing. Here we review the uptake of genetic counselling, predictive and reproductive testing, and the factors that impact the decision to undergo testing, for consideration in clinical practice. The literature suggests that the factors impacting the decision to undergo testing are complex due to the nature of these diseases, absence of available preventative medical treatment and variable age of onset in mutation carriers. Gaining further insight into the decision-making process and the impact of testing is critical as we seek to develop best-practice guidelines for predictive testing for familial ALS and FTD.
Wade, Christopher H.; Shiloh, Shoshana; Woolford, Samuel W.; Roberts, J. Scott; Alford, Sharon Hensley; Marteau, Theresa M.; Biesecker, Barbara B.
New genetic tests reveal risks for multiple conditions simultaneously, although little is understood about the psychological factors that affect testing uptake. We assessed a conceptual model called the Multiplex Genetic Testing Model (MGTM) using structural equation modeling (SEM). The MGTM delineates worry, perceived severity, perceived risk, response efficacy and attitudes toward testing as predictors of intentions and behavior. Participants were 270 healthy insured adults age 25–40 from t...
Full Text Available Abstract Background The Cochran-Armitage trend test (CATT is powerful in detecting association between a susceptible marker and a disease. This test, however, may suffer from a substantial loss of power when the underlying genetic model is unknown and incorrectly specified. Thus, it is useful to derive tests obtaining the plausible power against all common genetic models. For this purpose, the genetic model selection (GMS and genetic model exclusion (GME methods were proposed recently. Simulation results showed that GMS and GME can obtain the plausible power against three common genetic models while the overall type I error is well controlled. Results Although GMS and GME are powerful statistically, they could be seriously affected by known confounding factors such as gender, age and race. Therefore, in this paper, via comparing the difference of Hardy-Weinberg disequilibrium coefficients between the cases and the controls within each sub-population, we propose the stratified genetic model selection (SGMS and exclusion (SGME methods which could eliminate the effect of confounding factors by adopting a matching framework. Our goal in this paper is to investigate the robustness of the proposed statistics and compare them with other commonly used efficiency robust tests such as MAX3 and χ2 with 2 degrees of freedom (df test in matched case-control association designs through simulation studies. Conclusion Simulation results showed that if the mean genetic effect of the heterozygous genotype is between those of the two homozygous genotypes, then the proposed tests and MAX3 are preferred. Otherwise, χ2 with 2 df test may be used. To illustrate the robust procedures, the proposed tests are applied to a real matched pair case-control etiologic study of sarcoidosis.
Ingles, Jodie; Zodgekar, Poonam R; Yeates, Laura; Macciocca, Ivan; Semsarian, Christopher; Fatkin, Diane
Inherited gene variants have been implicated increasingly in cardiac disorders but the clinical impact of these discoveries has been variable. For some disorders, such as familial hypertrophic cardiomyopathy, long QT syndrome, and familial hypercholesterolaemia, genetic testing has a high yield and has become an integral part of family management. For other disorders, including dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and atrial fibrillation, relatively less is known about the genes involved and genetic testing has a lower yield. Recent advances in sequencing and array-based technologies promise to change the landscape of our understanding of the genetic basis of human disease and will dramatically increase the rate of detection of genomic variants. Since every individual is expected to harbour thousands of variants, many of which may be novel, interpretation of the functional significance of any single variant is critical, and should be undertaken by experienced personnel. Genotype results can have a wide range of medical and psychosocial implications for affected and unaffected individuals and hence, genetic testing should be performed in a specialised cardiac genetic clinic or clinical genetics service where appropriate family management and genetic counselling can be offered. Copyright © 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.
Hensley Alford, Sharon; McBride, Colleen M; Reid, Robert J; Larson, Eric B; Baxevanis, Andreas D; Brody, Lawrence C
Advances in technology have made individual access to personal genetic information foreseeable in the near future. Policy makers and the media forecast that the ready availability of personal genetic profiles would benefit both the individual and the health care system by improving outcomes and decreasing cost. However, there is a significant gap between having access to genetic data and either wanting or understanding the information it provides. Our primary aim was to evaluate, using a population-based sample of healthy adults, whether gender, race and education status influences interest and participation in a multiplex genetic susceptibility test. Healthy, insured individuals, 25-40 years of age, were approached via a large, integrated health system in which primary and specialty care is available. Study participants were offered personalized genetic risk information on 8 common chronic health conditions. Social groups historically known not to participate in genetic research (men, African Americans and those from lower education neighborhoods) were oversampled. We describe the recruitment outcomes and testing decisions of these social groups. We found that even among those with access to health care, African Americans were less likely to participate in the multiplex genetic susceptibility test, while those from higher education neighborhoods were more likely to participate. Our results suggest that large social groups will likely be underrepresented in research in personalized genomics even when robust population-based recruitment strategies are employed. Copyright © 2010 S. Karger AG, Basel.
Yazidi, Rihab; Bettaieb, Jihene; Ghawar, Wissem; Jaouadi, Kaouther; Châabane, Sana; Zaatour, Amor; Ben Salah, Afif
Zoonotic cutaneous leishmaniasis caused by Leishmania (L.) major is endemoepidemic in the Center and South of Tunisia. The clinical course of the disease varies widely among different patients and geographic regions. Although genetic diversity in L. major parasites has been suggested as a potential factor influencing their pathogenic variability, little information on genetic polymorphism among L. major strains is available in the literature. This work aimed to estimate the genetic variability within different isolates of L. major. Our sample comprised 39 isolates (confirmed as L. major by restriction fragment length polymorphism typing) from patients experiencing the same clinical manifestations but living in different regions of Tunisia where L. major is endemic. Random amplified polymorphic DNA (RAPD) PCR marker polymorphism was estimated by calculating Nei and Li's genetic distances and by an analysis of molecular variance (AMOVA). Analysis of the genetic diversity among the isolates revealed a high level of polymorphism (43 %) among them. AMOVA indicated that the highest variability (99 %) existed within the study regions. Our results revealed a heterogeneous genetic profile for L. major with similar clinical manifestations occurring within the different geographical regions. Additional L. major isolates from patients, insect vectors, and reservoir hosts from different endemic foci should be collected for further analysis.
Taylor, Ann T S; Rogers, Jill Cellars
The development of classroom experiments where students examine their own DNA is frequently described as an innovative teaching practice. Often these experiences involve students analyzing their genes for various polymorphisms associated with disease states, like an increased risk for developing cancer. Such experiments can muddy the distinction between classroom investigation and medical testing. Although the goals and issues surrounding classroom genotyping do not directly align with those of clinical testing, instructors can use the guidelines and standards established by the medical genetics community when evaluating the ethics of human genotyping. We developed a laboratory investigation and discussion which allowed undergraduate science students to explore current DNA manipulation techniques to isolate their p53 gene, followed by a dialogue probing the ethical implications of examining their sample for various polymorphisms. Students never conducted genotyping on their samples because of the ethical concerns presented in this paper, so the discussion replaced the actual genetic testing in the class. A science faculty member led the laboratory portion, while a genetic counselor facilitated the discussion of the ethical concepts underlying genetic counseling: autonomy, beneficence, confidentiality, and justice. In their final papers, students demonstrated an understanding of the practice guidelines established by the genetics community and acknowledged the ethical considerations inherent in p53 genotyping. Given the burgeoning market for personalized medicine, teaching undergraduates about the psychosocial and ethical dimensions of human genetic testing is important and timely. Moreover, incorporating a genetic counselor in the classroom discussion provided a rich and dynamic discussion of human genetic testing. Copyright © 2011 Wiley Periodicals, Inc.
As knowledge increases about the human genome, prenatal genetic testing will become cheaper, safer and more comprehensive. It is likely that there will be a great deal of support for making prenatal testing for a wide range of genetic disorders a routine part of antenatal care. Such routine testing is necessarily coercive in nature and does not involve the same standard of consent as is required in other health care settings. This paper asks whether this level of coercion is ethically justifiable in this case, or whether pregnant women have a right to remain in ignorance of the genetic make-up of the fetus they are carrying. While information gained by genetic testing may be useful for pregnant women when making decisions about their pregnancy, it does not prevent harm to future children. It is argued that as this kind of testing provides information in the interests of the pregnant women and not in the interests of any future child, the same standards of consent that are normally required for genetic testing should be required in this instance.
Full Text Available Abstract Background Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM in 705 individuals from 47 localities. Results A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P Conclusions The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and postglacial recolonization. Our study is a typical case of the significance of the uplift of the Qinghai-Tibet Plateau and the Quaternary Glacial in spatial genetic structure of eastern Asian plants, and sheds new light on the evolution of biodiversity in the Qinghai-Tibet Plateau at the intraspecies level.
Kappe, A.L.; van de Zande, L.; Vedder, E.J.; Bijlsma, R.; van Delden, Wilke
Genetic variation in two harbour seal (Phoca vitulina) populations from the Dutch Wadden Sea and Scotland was examined by RAPD analysis and DNA fingerprinting. For comparison a population of grey seals (Halichoerus grypus) was studied. The RAPD method revealed a very low number of polymorphic bands.
Kumar, Vikas; Kutschera, Verena E; Nilsson, Maria A; Janke, Axel
The genus Vulpes (true foxes) comprises numerous species that inhabit a wide range of habitats and climatic conditions, including one species, the Arctic fox (Vulpes lagopus) which is adapted to the arctic region. A close relative to the Arctic fox, the red fox (Vulpes vulpes), occurs in subarctic to subtropical habitats. To study the genetic basis of their adaptations to different environments, transcriptome sequences from two Arctic foxes and one red fox individual were generated and analyzed for signatures of positive selection. In addition, the data allowed for a phylogenetic analysis and divergence time estimate between the two fox species. The de novo assembly of reads resulted in more than 160,000 contigs/transcripts per individual. Approximately 17,000 homologous genes were identified using human and the non-redundant databases. Positive selection analyses revealed several genes involved in various metabolic and molecular processes such as energy metabolism, cardiac gene regulation, apoptosis and blood coagulation to be under positive selection in foxes. Branch site tests identified four genes to be under positive selection in the Arctic fox transcriptome, two of which are fat metabolism genes. In the red fox transcriptome eight genes are under positive selection, including molecular process genes, notably genes involved in ATP metabolism. Analysis of the three transcriptomes and five Sanger re-sequenced genes in additional individuals identified a lower genetic variability within Arctic foxes compared to red foxes, which is consistent with distribution range differences and demographic responses to past climatic fluctuations. A phylogenomic analysis estimated that the Arctic and red fox lineages diverged about three million years ago. Transcriptome data are an economic way to generate genomic resources for evolutionary studies. Despite not representing an entire genome, this transcriptome analysis identified numerous genes that are relevant to arctic
Full Text Available Turning Turing's logic on its head, we used widespread letter-based Turing Tests found on the internet (CAPTCHAs to shed light on human cognition. We examined the basis of the human ability to solve CAPTCHAs, where machines fail. We asked whether this is due to our use of slow-acting inferential processes that would not be available to machines, or whether fast-acting automatic orthographic processing in humans has superior robustness to shape variations. A masked priming lexical decision experiment revealed efficient processing of CAPTCHA words in conditions that rule out the use of slow inferential processing. This shows that the human superiority in solving CAPTCHAs builds on a high degree of invariance to location and continuous transforms, which is achieved during the very early stages of visual word recognition in skilled readers.
Calvin F. Bey; E. Bayne Snyder
A progeny test of 226 superior tree selections from nine geographic sources across the South confirmed earlier results that showed the Gulf Coast source superior in survival and growth. Family variation within a region was large and provided additional genetic gain. Control-pollinated tests of elite x elite trees yielded even more gains. Progeny of the elite x elite...
the brain and testes. FMRP has been shown to down-regulate the translation of specific target messenger RNAs and plays a vital role in synaptic plasticity.. Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: A 20-year review. F B Essop ...
Metcalf, Mary P; Tanner, T Bradley; Buchanan, Amanda
It is increasingly important that physicians have a thorough understanding of the basic science of human genetics and the ethical, legal and social implications (ELSI) associated with genetic testing and counseling. The authors developed a series of web-based courses for medical students on these topics. The course modules are interactive, emphasize clinical case studies, and can easily be incorporated into existing medical school curricula. Results of a 'real world' effectiveness trial indicate that the courses have a statistically significant effect on knowledge, attitude, intended behavior and self-efficacy related to genetic testing (pmedical students on the ELSI associated with genetic testing and for promoting positive changes in students' confidence, counseling attitudes and behaviors.
Vajda, Alice; McLaughlin, Russell L; Heverin, Mark; Thorpe, Owen; Abrahams, Sharon; Al-Chalabi, Ammar; Hardiman, Orla
To determine the degree of consensus among clinicians on the clinical use of genetic testing in amyotrophic lateral sclerosis (ALS) and the factors that determine decision-making. ALS researchers worldwide were invited to participate in a detailed online survey to determine their attitudes and practices relating to genetic testing. Responses from 167 clinicians from 21 different countries were analyzed. The majority of respondents (73.3%) do not consider that there is a consensus definition of familial ALS (FALS). Fifty-seven percent consider a family history of frontotemporal dementia and 48.5% the presence of a known ALS genetic mutation as sufficient for a diagnosis of FALS. Most respondents (90.2%) offer genetic testing to patients they define as having FALS and 49.4% to patients with sporadic ALS. Four main genes (SOD1, C9orf72, TARDBP, and FUS) are commonly tested. A total of 55.2% of respondents would seek genetic testing if they had personally received a diagnosis of ALS. Forty-two percent never offer presymptomatic testing to family members of patients with FALS. Responses varied between ALS specialists and nonspecialists and based on the number of new patients seen per year. There is a lack of consensus among clinicians as to the definition of FALS. Substantial variation exists in attitude and practices related to genetic testing of patients and presymptomatic testing of their relatives across geographic regions and between experienced specialists in ALS and nonspecialists. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Several genetic disorders are specific to Jewish heritage; one of the most devastating is Tay-Sachs disease.Tay-Sachs is a fatal hereditary disease, causing progressive neurological problems for which there is no cure. Ethical issues surrounding genetic testing for Tay-Sachs within the Jewish community continue to be complex and multifaceted. A perspective of Tay-Sachs, using rights-based ethics and virtue ethics as a theoretical framework, is explored.
Arribas-Ayllon, M.; Sarangi, Srikant; Clarke, Angus
Advances in molecular genetics have led to the increasing availability of genetic testing for a variety of inherited disorders. While this new knowledge presents many obvious health benefits to prospective individuals and their families it also raises complex ethical and moral dilemmas for families......, the assessment of competence and maturity, the ability to engage in shared decision-making through acts of disclosure and choice, are just some of the issues that are examined in detail....
Zhang, D; Ding, Ge; Ge, B; Zhang, H; Tang, B
Genetic diversity, population genetic structure and molecular phylogeographic pattern of mantis shrimp Oratosquilla oratoria in Bohai Sea and South China Sea were analyzed by mitochondrial DNA sequences. Nucleotide and haplotype diversities were 0.00409-0.00669 and 0.894-0.953 respectively. Neighbor-Joining phylogenetic tree clustered two distinct lineages. Both phylogenetic tree and median-joining network showed the consistent genetic structure corresponding to geographical distribution. Mismatch distributions, negative neutral test and "star-like" network supported a sudden population expansion event. And the time was estimated about 44000 and 50000 years ago.
October M Sessions
Full Text Available 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.
Selkoe, Kimberly A; Watson, James R; White, Crow; Horin, Tal Ben; Iacchei, Matthew; Mitarai, Satoshi; Siegel, David A; Gaines, Steven D; Toonen, Robert J
Marine species frequently show weak and/or complex genetic structuring that is commonly dismissed as 'chaotic' genetic patchiness and ecologically uninformative. Here, using three datasets that individually feature weak chaotic patchiness, we demonstrate that combining inferences across species and incorporating environmental data can greatly improve the predictive value of marine population genetics studies on small spatial scales. Significant correlations in genetic patterns of microsatellite markers among three species, kelp bass Paralabrax clathratus, Kellet's whelk Kelletia kelletii and California spiny lobster Panulirus interruptus, in the Southern California Bight suggest that slight differences in diversity and pairwise differentiation across sampling sites are not simply noise or chaotic patchiness, but are ecologically meaningful. To test whether interspecies correlations potentially result from shared environmental drivers of genetic patterns, we assembled data on kelp bed size, sea surface temperature and estimates of site-to-site migration probability derived from a high resolution multi-year ocean circulation model. These data served as predictor variables in linear models of genetic diversity and linear mixed models of genetic differentiation that were assessed with information-theoretic model selection. Kelp was the most informative predictor of genetics for all three species, but ocean circulation also played a minor role for kelp bass. The shared patterns suggest a single spatial marine management strategy may effectively protect genetic diversity of multiple species. This study demonstrates the power of environmental and ecological data to shed light on weak genetic patterns and highlights the need for future focus on a mechanistic understanding of the links between oceanography, ecology and genetic structure.
Qian, Meng; Shao, Yongzhao
Summary Most existing association tests for genome-wide association studies (GWAS) fail to account for genetic heterogeneity. Zhou and Pan proposed a binomial mixture model based association test to account for the possible genetic heterogeneity in case-control studies. The idea is elegant, however, the proposed test requires an EM-type iterative algorithm to identify the penalized maximum likelihood estimates and a permutation method to assess p-values. The intensive computational burden induced by the EM-algorithm and the permutation becomes prohibitive for direct applications to genome-wide association studies. This paper develops a likelihood ratio test (LRT) for genome-wide association studies under genetic heterogeneity based on a more general alternative mixture model. In particular, a closed-form formula for the likelihood ratio test statistic is derived to avoid the EM-type iterative numerical evaluation. Moreover, an explicit asymptotic null distribution is also obtained which avoids using the permutation to obtain p-values. Thus, the proposed LRT is easy to implement for genome-wide association studies (GWAS). Furthermore, numerical studies demonstrate that the LRT has power advantages over the commonly used Armitage trend test and other existing association tests under genetic heterogeneity. A breast cancer GWAS data set is used to illustrate the newly proposed LRT. PMID:23362943
The past year has been marked by the emergence of several companies, such as 23andMe, deCODEME, Navigenics and Knome, offering tests using genome-wide technology direct to consumers over the internet. On the basis of the published research findings of GWAS and other studies, these companies will calculate an individual's risk to a number of common diseases, without the necessity of going through a medical practitioner. One of the significant challenges of direct-to-consumer testing is that it shifts the control of genetic testing from the clinical domain and medical professionals into the hands of consumers. No longer is genetic testing being carried out solely for medical reasons, by specialists in clinical genetics. Testing is now being used to empower consumers and can be used 'to shed new light on your distant ancestors, your close family and most of all, yourself' (23andMe). Such information can be shared with family and friends for 'fun', as part of the new 'recreational genomics'. Direct-to-consumer testing challenges many of the assumptions that underpin current practice surrounding genetic tests while at the same time exposing the deficiencies in the current regulatory frameworks to regulate this area. The purpose of this paper is to explore some of these issues, at a time when the science and the law are changing rapidly.
Higgs, Jenny; Gambhir, Nikki; Ramsden, Simon C; Poulton, Kay; Newman, William G
For certain drugs, pharmacogenetic tests can reduce adverse drug reactions and improve treatment efficacy. However, the adoption of pharmacogenetics into clinical practice has been relatively slow. One potential barrier is the capacity of laboratories to meet the demands of a clinical pharmacogenetic service. We aimed to establish the range, capacity to deliver, and demand for germline pharmacogenetic testing in the United Kingdom and Ireland, through an e-survey of 34 molecular genetics and 28 histocompatibility and immunogenetics (H&I) laboratories. Thirty-five percent of molecular genetics laboratories and 54% of H&I laboratories responded to the survey. The majority of H&I laboratories (93%) offered pharmacogenetic testing, whereas only one molecular genetics laboratory provided a pharmacogenetic service. HLA-B*5701 was most commonly tested to identify those at risk of abacavir hypersensitivity among patients with HIV. A number of barriers to testing were identified, including lack of clinician knowledge and a lack of scientific evidence. All molecular genetics laboratories believed that national coordination of clinical pharmacogenetic services was required, whereas only 50% of H&I laboratories supported this view. In the United Kingdom, pharmacogenetic testing is currently being predominantly provided through H&I laboratories for a limited number of indications. The number of laboratories offering pharmacogenetic tests is increasing and is likely to continue to increase over the coming years.
Corcoran, Martin M.; Phad, Ganesh E.; Bernat, Néstor Vázquez; Stahl-Hennig, Christiane; Sumida, Noriyuki; Persson, Mats A. A.; Martin, Marcel; Hedestam, Gunilla B. Karlsson
Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.
Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland
Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.
Garg, Rahul; Vogelgesang, Joseph; Kelly, Kimberly
Despite the importance of altruism in an individual’s participation in genetic counseling and testing, little research has explored the change in altruistic motivations to test over time. This study analyzed altruistic motivations to test and change in altruistic motivations after genetic counseling and testing among individuals (N=120) at elevated risk for BRCA1/2 mutations. The perceived benefits of genetic testing were assessed and utilized in a mixed-methods, repeated measures design at three time points: pre-counseling, counseling and post-genetic testing, along with transcripts of genetic counseling sessions. Qualitative analysis using an immersion/crystallization method resulted in six common perceived benefits of testing: cancer prevention, awareness, family’s survival, relief from anxiety, for science, and future planning. Perceived benefits were then coded into three categories according to Hamilton’s kin selection theory: altruistic motivation, personal motivation, and motivation for mutual benefit. At pre-counseling, those with a personal cancer history (p=0.003) and those with one or more children (p=.013), were significantly more likely to cite altruistic motivations to test. Altruistic motivations significantly increased post-counseling (p=0.01) but declined post-testing (paltruistic and personal motivations. The possibility of a positive test result might have led those with personal history of cancer to have altruistic motivations for testing. Genetic counseling may have increased altruistic motivations to help family and may be a prime opportunity to discuss other forms of altruism. PMID:26578231
Lee, Omay; Porteous, Mary
Genetic testing is increasingly important for investigating suspected inherited neurological conditions. A genetic diagnosis can have a huge impact on patients and also their families. It is important for neurologists to appreciate the presymptomatic and prenatal testing options available to patients and their at-risk relatives once a genetic disorder is diagnosed. Asymptomatic family members can experience considerable psychological distress from the knowledge that they might have inherited a neurodegenerative condition. They may also be concerned about the risk of their children inheriting the condition. Information on reproductive options can provide hope and reassurance. This paper reviews the principles of genetic testing in neurological practice, and how they can be applied in prenatal and preimplantation genetic diagnosis. We explain the basis for direct and exclusion testing, use case examples to illustrate the process by which families are counselled and discuss the ethical implications of reproductive technologies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Hafertepen, Laura; Pastorino, Alyssa; Morman, Nichole; Snow, Jennifer; Halaharvi, Deepa; Byrne, Lindsey; Cripe, Mark
Genetic testing results influence treatment recommendations in newly diagnosed breast cancer patients. However, at-risk patients do not uniformly undergo genetic testing. The goal of this study was to identify barriers to genetic testing in newly diagnosed breast cancer patients. A prospective database of newly diagnosed breast cancer patients meeting specific criteria over an 18-month period was created and retrospectively reviewed. A total of 532 patients were identified at risk for genetic mutation. Of these 313 (59%) patients completed a genetic counseling appointment and 292 (55%) underwent genetic testing. One hundred seven (24%) were never referred to genetic counselors and 89 (17%) were referred but did not complete an appointment. Patients referred to genetics were younger than the nonreferred patients (50.9 vs 60.6 years, P testing was lack of physician referral; therefore, provider education must be improved. Appointments should be convenient and providers should proactively discuss the significant implications of testing results. Copyright © 2016 Elsevier Inc. All rights reserved.
Baker, Robert L; Leong, Wen Fung; Brock, Marcus T; Markelz, R J Cody; Covington, Michael F; Devisetty, Upendra K; Edwards, Christine E; Maloof, Julin; Welch, Stephen; Weinig, Cynthia
Improved predictions of fitness and yield may be obtained by characterizing the genetic controls and environmental dependencies of organismal ontogeny. Elucidating the shape of growth curves may reveal novel genetic controls that single-time-point (STP) analyses do not because, in theory, infinite numbers of growth curves can result in the same final measurement. We measured leaf lengths and widths in Brassica rapa recombinant inbred lines (RILs) throughout ontogeny. We modeled leaf growth and allometry as function valued traits (FVT), and examined genetic correlations between these traits and aspects of phenology, physiology, circadian rhythms and fitness. We used RNA-seq to construct a SNP linkage map and mapped trait quantitative trait loci (QTL). We found genetic trade-offs between leaf size and growth rate FVT and uncovered differences in genotypic and QTL correlations involving FVT vs STPs. We identified leaf shape (allometry) as a genetic module independent of length and width and identified selection on FVT parameters of development. Leaf shape is associated with venation features that affect desiccation resistance. The genetic independence of leaf shape from other leaf traits may therefore enable crop optimization in leaf shape without negative effects on traits such as size, growth rate, duration or gas exchange. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
Full Text Available ABSTRACT It has been argued that genetic diversity in crop varieties has been on the decline in recent times due to plant breeding. This can have serious consequences for both the genetic vulnerability of crops and their plasticity when responding to changes in production environments. It is, therefore, vital for plant breeding programs to maintain sufficient diversity in the cultivars deployed for multi-period cultivation. In this study, to understand the temporal genetic diversity in durum wheat, 21 improved durum wheat cultivars released in Morocco, since 1956 and five exotic cultivars currently used in crossing programs were analyzed using 13 microsatellite markers. The analysis revealed a total of 44 alleles and average genetic diversity of 0.485 with genetic distances ranging from 0.077 to 0.846 at 13 microsatellite loci in Moroccan durum wheat cultivars. All the durum cultivars of Morocco could be distinguished using the 13 microsatellite markers. The total number of alleles and unique alleles were highest in cultivars developed before 1990, decreasing in cultivars developed during the 1990s and 2000s, indicating that recent durum breeding efforts have reduced allelic richness in recent cultivars. Thus, deployment of exotic durum wheat lines in breeding programs could enhance genetic diversity in durum wheat cultivars.
Tindano, K; Moula, N; Leroy, P; Traoré, A; Antoine-Moussiaux, N
Farm animal genetic resources are threatened worldwide. Participation in markets, while representing a crucial way out of poverty for many smallholders, affects genetic management choices with associated sustainability concerns. This paper proposes a contextualized study of the interactions between markets and animal genetic resources management, in the case of sheep markets in Ouagadougou, Burkina Faso. It focusses on the organization of marketing chains and the valuation of genetic characteristics by value chain actors. Marketing chain characterization was tackled through semi-structured interviews with 25 exporters and 15 butchers, both specialized in sheep. Moreover, revealed preference methods were applied to analyse the impact of animals' attributes on market pricing. Data were collected from 338 transactions during three different periods: Eid al-Adha, Christmas and New Year period, and a neutral period. The neutral period is understood as a period not close to any event likely to influence the demand for sheep. The results show that physical characteristics such as live weight, height at withers and coat colour have a strong influence on the animals' prices. Live weight has also had an increasing marginal impact on price. The different markets (local butcher, feasts, export market, sacrifices) represent distinct demands for genetic characteristics, entailing interesting consequences for animal genetic resource management. Any breeding programme should therefore take this diversity into account to allow this sector to contribute better to a sustainable development of the country.
Avitia, Morena; Escalante, Ana E; Rebollar, Eria A; Moreno-Letelier, Alejandra; Eguiarte, Luis E; Souza, Valeria
Comparative population studies can help elucidate the influence of historical events upon current patterns of biodiversity among taxa that coexist in a given geographic area. In particular, comparative assessments derived from population genetics and coalescent theory have been used to investigate population dynamics of bacterial pathogens in order to understand disease epidemics. In contrast, and despite the ecological relevance of non-host associated and naturally occurring bacteria, there is little understanding of the processes determining their diversity. Here we analyzed the patterns of genetic diversity in coexisting populations of three genera of bacteria (Bacillus, Exiguobacterium, and Pseudomonas) that are abundant in the aquatic systems of the Cuatro Cienegas Basin, Mexico. We tested the hypothesis that a common habitat leaves a signature upon the genetic variation present in bacterial populations, independent of phylogenetic relationships. We used multilocus markers to assess genetic diversity and (1) performed comparative phylogenetic analyses, (2) described the genetic structure of bacterial populations, (3) calculated descriptive parameters of genetic diversity, (4) performed neutrality tests, and (5) conducted coalescent-based historical reconstructions. Our results show a trend of synchronic expansions across most populations independent of both lineage and sampling site. Thus, we provide empirical evidence supporting the analysis of coexisting bacterial lineages in natural environments to advance our understanding of bacterial evolution beyond medical or health-related microbes.
Li, Ke; Kohn, Michael H; Zhang, Songmei; Wan, Xinrong; Shi, Dazhao; Wang, Deng
The colonial habit of Brandt's vole (Lasiopodomys brandtii) differs from that of most other species of the genus Microtus. The demographic history of this species and the patterns shaping its current genetic structure remain unknown. Here, we explored patterns of genetic differentiation and infered the demographic history of Brandt's vole populations through analyses of nuclear microsatellite and D-loop sequences. Phylogenetic analyses divided the sampled populations into three main clusters, which represent the southeastern, northeastern and western parts of the total range in Mongolia and China. Molecular data revealed an ancestral area located in the southeast of the extant range, in the Xilinguole District, Inner Mongolia, China, from where Brandt's vole populations began expanding. A gene flow analysis suggested that the most likely colonization route was from the ancestral area and was followed by subsequent northeastward and westward range expansions. We identified decreases in genetic diversity with increasing distance from the founder population within the newly occupied regions (northeastern and western regions), clinal patterns in the allele frequencies, alleles that were rare in the original area that have become common in the newly occupied regions, and higher genetic differentiation in the expanded range compared with the original one. Our results indicate that L. brandtii most likely originated from the southeastern part of its current geographic range, and subsequently colonized into the northeastern and western parts by expansion. The genetic patterns among the derived populations and with respect to the original population are consistent with that expected under genetic surfing models, which indicated that genetic drift, rather than gene flow, is the predominant factor underlying the genetic structure of expanding Brandt's vole populations.
Bao, Xiaoan; Xiong, Zijian; Zhang, Na; Qian, Junyan; Wu, Biao; Zhang, Wei
The automatic generation of test cases oriented paths in an effective manner is a challenging problem for structural testing of software. The use of search-based optimization methods, such as genetic algorithms (GAs), has been proposed to handle this problem. This paper proposes an improved adaptive genetic algorithm (IAGA) for test cases generation by maintaining population diversity. It uses adaptive crossover rate and mutation rate in dynamic adjustment according to the differences between individual similarity and fitness values, which enhances the exploitation of searching global optimum. This novel approach is experimented and tested on a benchmark and six industrial programs. The experimental results confirm that the proposed method is efficient in generating test cases for path coverage.
Chen, Laura P; Beck, Anita E; Tsuchiya, Karen D; Chow, Penny M; Mirzaa, Ghayda M; Wiester, Rebecca T; Feldman, Kenneth W
Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. Copyright © 2015 by the American Academy of Pediatrics.
Kutscher, Eric J; Joshi, Sucheta M; Patel, Anup D; Hafeez, Baria; Grinspan, Zachary M
Children with public insurance (Medicaid) have increased barriers to specialty care in the United States. For children with epilepsy, the relationship between public insurance and barriers to genetic testing is understudied. We surveyed a sample of US child neurology clinicians. We performed quantitative and qualitative analysis of responses. There were 302 responses (of 1982 surveyed; response rate 15%) from clinicians from 46 states, the District of Columbia, and Puerto Rico, including board-certified child neurologists (82%), resident physicians (6%), nurses (3%), and nurse practitioners (3%). Clinicians felt it was more difficult to get genetic testing for patients with Medicaid insurance compared with commercial insurance, (43% vs 12%, P testing was associated with less complex testing (P testing (P testing, compared with children with commercial insurance, particularly for more advanced testing. Potential strategies to improve access include broader coverage, lower co-pays, increased capacity for testing outside of specialty laboratories, fewer preauthorization requirements, improved clinician education, ongoing development and dissemination of guidelines, improved availability of clinical genetics services, and continued assistance programs from commercial laboratories. Copyright © 2017 Elsevier Inc. All rights reserved.
Shearer, A Eliot; Black-Ziegelbein, E Ann; Hildebrand, Michael S; Eppsteiner, Robert W; Ravi, Harini; Joshi, Swati; Guiffre, Angelica C; Sloan, Christina M; Happe, Scott; Howard, Susanna D; Novak, Barbara; Deluca, Adam P; Taylor, Kyle R; Scheetz, Todd E; Braun, Terry A; Casavant, Thomas L; Kimberling, William J; Leproust, Emily M; Smith, Richard J H
Non-syndromic hearing loss (NSHL) is the most common sensory impairment in humans. Until recently its extreme genetic heterogeneity precluded comprehensive genetic testing. Using a platform that couples targeted genomic enrichment (TGE) and massively parallel sequencing (MPS) to sequence all exons of all genes implicated in NSHL, we tested 100 persons with presumed genetic NSHL and in so doing established sequencing requirements for maximum sensitivity and defined MPS quality score metrics that obviate Sanger validation of variants. We examined DNA from 100 sequentially collected probands with presumed genetic NSHL without exclusions due to inheritance, previous genetic testing, or type of hearing loss. We performed TGE using post-capture multiplexing in variable pool sizes followed by Illumina sequencing. We developed a local Galaxy installation on a high performance computing cluster for bioinformatics analysis. To obtain maximum variant sensitivity with this platform 3.2-6.3 million total mapped sequencing reads per sample were required. Quality score analysis showed that Sanger validation was not required for 95% of variants. Our overall diagnostic rate was 42%, but this varied by clinical features from 0% for persons with asymmetric hearing loss to 56% for persons with bilateral autosomal recessive NSHL. These findings will direct the use of TGE and MPS strategies for genetic diagnosis for NSHL. Our diagnostic rate highlights the need for further research on genetic deafness focused on novel gene identification and an improved understanding of the role of non-exonic mutations. The unsolved families we have identified provide a valuable resource to address these areas.
Full Text Available Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP, the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease.
Nantoume, Aminata Dolo; Andersen, Sven Bode; Jensen, Brita Dahl
This study describes the genetic differentiation of a collection of 134 watermelon landrace accessions from Mali, representing red fleshed dessert and white fleshed seed and cooking type watermelons from five regions, plus three commercial dessert type cultivars with red flesh. The material...... the accessions into use groups (dessert, cooking, seed processing) explained 25 % of the variation. When categorising the accessions further into 10 landrace types, differentiated on the basis of use groups, local accession name, flesh colour and seed phenotype, these landrace types explained 26...... % of the variation. Analysis with the software Structure revealed that the accessions with confidence could be separated into two major genetic groups, related to flesh colour (red and white) of the watermelon fruits. The same analysis further indicated that the material may be differentiated into eight genetic sub...
Wangsomnuk, P P; Khampa, S; Wangsomnuk, P; Jogloy, S; Mornkham, T; Ruttawat, B; Patanothai, A; Fu, Y B
Jerusalem artichoke (Helianthus tuberosus) is a wild relative of the cultivated sunflower (H. annuus); it is an old tuber crop that has recently received renewed interest. We used RAPD markers to characterize 147 Jerusalem artichoke accessions from nine countries. Thirty RAPD primers were screened; 13 of them detected 357 reproducible RAPD bands, of which 337 were polymorphic. Various diversity analyses revealed several different patterns of RAPD variation. More than 93% of the RAPD variation was found within accessions of a country. Weak genetic differentiation was observed between wild and cultivated accessions. Six groups were detected in this germplasm set. Four ancestral groups were found for the Canadian germplasm. The most genetically distinct accessions were identified. These findings provide useful diversity information for understanding the Jerusalem artichoke gene pool, for conserving Jerusalem artichoke germplasm, and for choosing germplasm for genetic improvement.
Chen, Shaotian; Xing, Yaowu; Su, Tao; Zhou, Zhekun; Dilcher, Emeritus David L; Soltis, Douglas E
Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM) in 705 individuals from 47 localities. A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P northern lineage in the region outside the Qinghai-Tibet Plateau. The divergence between these two lineages was estimated at 4.4 MYA. A correlation between the genetic and the geographic distances indicates that genetic drift was more influential than gene flow in the northern clade with lower diversity and divergence. However, a scenario of regional equilibrium between gene flow and drift was shown for the southern clade. The feature of spatial distribution of the genetic diversity of the southern lineage possibly indicated that allopatric fragmentation was dominant in the collections from the eastern Qinghai-Tibet Plateau. The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and postglacial recolonization. Our study is a typical case of the significance of the uplift of the Qinghai-Tibet Plateau and the Quaternary Glacial in spatial genetic structure of eastern Asian plants, and sheds new light on the evolution of biodiversity in the Qinghai
Steven E. Massey
Full Text Available The standard genetic code (SGC is central to molecular biology and its origin and evolution is a fundamental problem in evolutionary biology, the elucidation of which promises to reveal much about the origins of life. In addition, we propose that study of its origin can also reveal some fundamental and generalizable insights into mechanisms of molecular evolution, utilizing concepts from complexity theory. The first is that beneficial traits may arise by non-adaptive processes, via a process of “neutral emergence”. The structure of the SGC is optimized for the property of error minimization, which reduces the deleterious impact of point mutations. Via simulation, it can be shown that genetic codes with error minimization superior to the SGC can emerge in a neutral fashion simply by a process of genetic code expansion via tRNA and aminoacyl-tRNA synthetase duplication, whereby similar amino acids are added to codons related to that of the parent amino acid. This process of neutral emergence has implications beyond that of the genetic code, as it suggests that not all beneficial traits have arisen by the direct action of natural selection; we term these “pseudaptations”, and discuss a range of potential examples. Secondly, consideration of genetic code deviations (codon reassignments reveals that these are mostly associated with a reduction in proteome size. This code malleability implies the existence of a proteomic constraint on the genetic code, proportional to the size of the proteome (P, and that its reduction in size leads to an “unfreezing” of the codon – amino acid mapping that defines the genetic code, consistent with Crick’s Frozen Accident theory. The concept of a proteomic constraint may be extended to propose a general informational constraint on genetic fidelity, which may be used to explain variously, differences in mutation rates in genomes with differing proteome sizes, differences in DNA repair capacity and genome
Van den Veyver, Ignatia B.
The introduction of new technologies has dramatically changed the current practice of prenatal screening and testing for genetic abnormalities in the fetus. Expanded carrier screening panels and non-invasive cell-free fetal DNA-based screening for aneuploidy and single-gene disorders, and more recently for subchromosomal abnormalities, have been introduced into prenatal care. More recently introduced technologies such as chromosomal microarray analysis and whole-exome sequencing can diagnose more genetic conditions on samples obtained through amniocentesis or chorionic villus sampling, including many disorders that cannot be screened for non-invasively. All of these options have benefits and limitations, and genetic counseling has become increasingly complex for providers who are responsible for guiding patients in their decisions about screening and testing before and during pregnancy. PMID:27853526
Edea, Zewdu; Dessie, Tadelle; Dadi, Hailu; Do, Kyoung-Tag; Kim, Kwan-Suk
Sheep in Ethiopia are adapted to a wide range of environments, including extreme habitats. Elucidating their genetic diversity is critical for improving breeding strategies and mapping quantitative trait loci associated with productivity. To this end, the present study investigated the genetic diversity and population structure of five Ethiopian sheep populations exhibiting distinct phenotypes and sampled from distinct production environments, including arid lowlands and highlands. To investigate the genetic relationships in greater detail and infer population structure of Ethiopian sheep breeds at the continental and global levels, we analyzed genotypic data of selected sheep breeds from the Ovine SNP50K HapMap dataset. All Ethiopian sheep samples were genotyped with Ovine Infinium HD SNP BeadChip (600K). Mean genetic diversity ranged from 0.29 in Arsi-Bale to 0.32 in Menz sheep, while estimates of genetic differentiation among populations ranged from 0.02 to 0.07, indicating low to moderate differentiation. An analysis of molecular variance revealed that 94.62 and 5.38% of the genetic variation was attributable to differences within and among populations, respectively. Our population structure analysis revealed clustering of five Ethiopian sheep populations according to tail phenotype and geographic origin-i.e., short fat-tailed (very cool high-altitude), long fat-tailed (mid to high-altitude), and fat-rumped (arid low-altitude), with clear evidence of admixture between long fat-tailed populations. North African sheep breeds showed higher levels of within-breed diversity, but were less differentiated than breeds from Eastern and Southern Africa. When African breeds were grouped according to geographic origin (North, South, and East), statistically significant differences were detected among groups (regions). A comparison of population structure between Ethiopian and global sheep breeds showed that fat-tailed breeds from Eastern and Southern Africa clustered
Full Text Available Insulin is a major regulator of metabolism in metazoans, including the fruit fly Drosophila melanogaster. Genome-wide association studies (GWAS suggest a genetic basis for reductions of both insulin sensitivity and insulin secretion, phenotypes commonly observed in humans with type 2 diabetes mellitus (T2DM. To identify molecular functions of genes linked to T2DM risk, we developed a genetic tool to measure insulin-like peptide 2 (Ilp2 levels in Drosophila, a model organism with superb experimental genetics. Our system permitted sensitive quantification of circulating Ilp2, including measures of Ilp2 dynamics during fasting and re-feeding, and demonstration of adaptive Ilp2 secretion in response to insulin receptor haploinsufficiency. Tissue specific dissection of this reduced insulin signaling phenotype revealed a critical role for insulin signaling in specific peripheral tissues. Knockdown of the Drosophila orthologues of human T2DM risk genes, including GLIS3 and BCL11A, revealed roles of these Drosophila genes in Ilp2 production or secretion. Discovery of Drosophila mechanisms and regulators controlling in vivo insulin dynamics should accelerate functional dissection of diabetes genetics.
... If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out ...
Laporte, Martin; Rogers, Sean M; Dion-Côté, Anne-Marie; Normandeau, Eric; Gagnaire, Pierre-Alexandre; Dalziel, Anne C; Chebib, Jobran; Bernatchez, Louis
Parallel changes in body shape may evolve in response to similar environmental conditions, but whether such parallel phenotypic changes share a common genetic basis is still debated. The goal of this study was to assess whether parallel phenotypic changes could be explained by genetic parallelism, multiple genetic routes, or both. We first provide evidence for parallelism in fish shape by using geometric morphometrics among 300 fish representing five species pairs of Lake Whitefish. Using a genetic map comprising 3438 restriction site-associated DNA sequencing single-nucleotide polymorphisms, we then identified quantitative trait loci underlying body shape traits in a backcross family reared in the laboratory. A total of 138 body shape quantitative trait loci were identified in this cross, thus revealing a highly polygenic architecture of body shape in Lake Whitefish. Third, we tested for evidence of genetic parallelism among independent wild populations using both a single-locus method (outlier analysis) and a polygenic approach (analysis of covariation among markers). The single-locus approach provided limited evidence for genetic parallelism. However, the polygenic analysis revealed genetic parallelism for three of the five lakes, which differed from the two other lakes. These results provide evidence for both genetic parallelism and multiple genetic routes underlying parallel phenotypic evolution in fish shape among populations occupying similar ecological niches. Copyright © 2015 Laporte et al.
Full Text Available Calypogeia azurea, a widespread, subboreal-montane liverwort species, is one of a few representatives of the Calypogeia genus that are characterized by the occurrence of blue oil bodies. The aim of the study was to investigate the genetic variation and population structure of C. azurea originating from different parts of its distribution range (Europe and North America. Plants of C. azurea were compared with C. peruviana, another Calypogeia species with blue oil bodies. In general, 339 gametophytes from 15 populations of C. azurea were examined. Total gene diversity (HT estimated on the basis of nine isozyme loci of C. azurea at the species level was 0.201. The mean Nei’s genetic distance between European populations was equal to 0.083, whereas the mean genetic distance between populations originating from Europe and North America was 0.413. The analysis of molecular variance (AMOVA showed that 69% of C. azurea genetic variation was distributed among regions (Europe and North America, 15% - among populations within regions, and 16% - within populations. Our study revealed that C. azurea showed genetic diversity within its geographic distribution. All examined samples classified as C. azurea differed in respect of isozyme patterns from C. peruviana.
Hodoğlugil, Uğur; Mahley, Robert W
Turkey has experienced major population movements. Population structure and genetic relatedness of samples from three regions of Turkey, using over 500,000 SNP genotypes, were compared together with Human Genome Diversity Panel (HGDP) data. To obtain a more representative sampling from Central Asia, Kyrgyz samples (Bishkek, Kyrgyzstan) were genotyped and analysed. Principal component (PC) analysis reveals a significant overlap between Turks and Middle Easterners and a relationship with Europeans and South and Central Asians; however, the Turkish genetic structure is unique. FRAPPE, STRUCTURE, and phylogenetic analyses support the PC analysis depending upon the number of parental ancestry components chosen. For example, supervised STRUCTURE (K=3) illustrates a genetic ancestry for the Turks of 45% Middle Eastern (95% CI, 42-49), 40% European (95% CI, 36-44) and 15% Central Asian (95% CI, 13-16), whereas at K=4 the genetic ancestry of the Turks was 38% European (95% CI, 35-42), 35% Middle Eastern (95% CI, 33-38), 18% South Asian (95% CI, 16-19) and 9% Central Asian (95% CI, 7-11). PC analysis and FRAPPE/STRUCTURE results from three regions in Turkey (Aydin, Istanbul and Kayseri) were superimposed, without clear subpopulation structure, suggesting sample homogeneity. Thus, this study demonstrates admixture of Turkish people reflecting the population migration patterns. © 2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing Ltd/University College London.
Barth, Dana; Krenek, Sascha; Fokin, Sergei I; Berendonk, Thomas U
Studies of intraspecific genetic diversity of ciliates, such as population genetics and biogeography, are particularly hampered by the lack of suitable DNA markers. For example, sequences of the non-coding ribosomal internal transcribed spacer (ITS) regions are often too conserved for intraspecific analyses. We have therefore identified primers for the mitochondrial cytochrome c oxidase I (COI) gene and applied them for intraspecific investigations in Paramecium caudatum and Paramecium multimicronucleatum. Furthermore, we obtained sequences of the ITS regions from the same strains and carried out comparative sequence analyses of both data sets. The mitochondrial sequences revealed substantially higher variation in both Paramecium species, with intraspecific divergences up to 7% in P. caudatum and 9.5% in P. multimicronucleatum. Moreover, an initial survey of the population structure discovered different mitochondrial haplotypes of P. caudatum in one pond, thereby demonstrating the potential of this genetic marker for population genetic analyses. Our primers successfully amplified the COI gene of other Paramecium. This is the first report of intraspecific variation in free-living protozoans based on mitochondrial sequence data. Our results show that the high variation in mitochondrial DNA makes it a suitable marker for intraspecific and population genetic studies.
Hannen, E.J. van; Agterveld, M.P. van; Gons, H.J.; Laanbroek, H.J.
A new Eucarya-specific 18S rDNA primer set was constructed and tested using denaturing gradient gel electrophoresis to analyze the genetic diversity of eukaryotic microorganisms in aquatic environments. All eukaryal lines of descent exhibited four or fewer nucleotide mismatches in the forward
Van Hannen, E.J.; Van Agterveld, M.P.; Gons, H.J.; Laanbroek, H.J.
A new Eucarya-specific 18S rDNA primer set was constructed and tested using denaturing gradient gel electrophoresis to analyze the genetic diversity of eukaryotic microorganisms in aquatic environments. All eukaryal lines of descent exhibited four or fewer nucleotide mismatches in the forward primer
Nicol, Dianne; Liddicoat, John
Health policy and law reform agencies lack a sound evidence base of the impacts of patents on innovation and access to healthcare to assist them in their deliberations. This paper reports the results of a survey of managers of Australian genetic testing laboratories that asked a series of questions relating to the tests they perform, whether they pay to access patented inventions and whether they have received notifications from patent holders about patents associated with particular tests. Some diagnostics facilities are exposed to patent costs, but they are all located in the private sector. No public hospitals reported paying licence fees or royalties beyond those included in the price of commercial test kits. Some respondents reported having received enforcement notices from patent holders, but almost all related to the widely known breast cancer-associated patents. Respondents were also asked for their views on the most effective mechanisms to protect their ability to provide genetic tests now and in the future. Going to the media, paying licence fees, ignoring patent rights and relying on the government to take action were widely seen as most effective. Litigation and applications for compulsory licences were seen as some of the least effective mechanisms. These results provide an evidence base for development of health policy and law reform. What is known about the topic? The impact of patents on the delivery of genetic testing services remains unclear in Australia. What does this paper add? The survey reported in this paper suggests that, aside from well-known enforcement actions relating to the breast cancer associated patents, there is little evidence that providers of genetic testing services are being exposed to aggressive patent-enforcement practices. What are the implications for practitioners? Although patent-enforcement actions may increase in the future, a range of strategies are available to providers of testing services to protect them against
Full Text Available This paper uses the developed parallel version of Michalewicz's Genocop III Genetic Algorithm (GA searching technique to optimize the coil geometry of an eddy current non-destructive testing probe (ECTP. The electromagnetic field is computed using FEMM 2D finite element code. The aim of this optimization was to determine coil dimensions and positions that improve ECTP sensitivity to physical properties of the tested devices.
Arribas-Ayllon, Michael; Sarangi, Srikant; Clarke, Angus
Childhood genetic testing raises complex ethical and moral dilemmas for both families and professionals. In the family sphere, the role of communication is a key aspect in the transmission of 'genetic responsibility' between adults and children. In the professional sphere, genetic responsibility is an interactional accomplishment emerging from the sometimes competing views over what constitutes the 'best interests' of the child in relation to parental preferences on the one hand, and professional judgements on the other. In the present paper we extend our previous research into parental accounts of childhood genetic testing and explore the ethical accounts of professionals in research interviews. Interviews (n = 20) were conducted with professional practitioners involved in the genetic diagnosis and management of children and their families. We first identify four inter-related themes-juxtaposition of parental rights vis-à-vis child's autonomy, elicitation of the child's autonomy, avoidance of parental responsibility and recognition of professional uncertainty. Then, using Rhetorical Discourse Analysis, we examine the range of discourse devices through which ethical accounts are situationally illustrated: contrast, reported speech, constructed dialogue, character and event work. An overarching device in these ethical accounts is the use of extreme case scenarios, which reconstruct dilemmas as justifications of professional conduct. While acknowledging ambivalence, our analysis suggests that professional judgement is not a simple matter of implementing ethical principles but rather of managing the practical conditions and consequences of interactions with parents and children. We conclude that more attention is needed to understand the way professional practitioners formulate judgements about ethical practice.
Ingles, Jodie; Sarina, Tanya; Yeates, Laura; Hunt, Lauren; Macciocca, Ivan; McCormack, Louise; Winship, Ingrid; McGaughran, Julie; Atherton, John; Semsarian, Christopher
Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified. Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002-2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected. A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012). Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.
Iacocca, Michael A; Hegele, Robert A
Familial hypercholesterolemia (FH) is a common genetic cause of premature coronary heart disease that is widely underdiagnosed and undertreated. To improve the identification of FH and initiate timely and appropriate treatment strategies, genetic testing is becoming increasingly offered worldwide as a central part of diagnosis. Areas covered: Recent advances have been propelled by an improved understanding of the genetic determinants of FH together with substantially reduced costs of appropriate screening strategies. Here we review the various methods available for obtaining a molecular diagnosis of FH, and highlight the particular advantages of targeted next-generation sequencing (NGS) platforms as the most robust approach. Furthermore, we note the importance of screening for copy number variants and common polymorphisms to aid in molecularly defining suspected FH cases. Expert commentary: The need for genetic analysis of FH will increase, both for diagnosis and reimbursement of new therapies. An effective molecular diagnostic method must detect: 1) molecular and gene locus heterogeneity; 2) a wide range of mutation types; and 3) the polygenic component of FH. As availability of genetic testing for FH expands, standardization of variant curation, maintenance of clinical databases and registries, and wider health care provider education all assume greater importance.
Full Text Available Amyotrophic lateral sclerosis (ALS is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs. We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have shown that G4C2-repeat RNA sequesters RNA-binding proteins. A logical consequence of this is that loss-of-function mutations in G4C2-binding partners might contribute to ALS pathogenesis independently of and/or synergistically with C9ORF72 expansions. Targeted sequencing of genomic DNA encoding either RNA-binding proteins or known ALS genes (n = 274 genes was performed in ALS patients to identify rare deleterious genetic variants and explore genotype-phenotype relationships. Genomic DNA was extracted from 103 ALS patients including 42 familial ALS patients and 61 young-onset (average age of onset 41 years sporadic ALS patients; patients were chosen to maximize the probability of identifying genetic causes of ALS. Thirteen patients carried a G4C2-repeat expansion of C9ORF72. We identified 42 patients with rare deleterious variants; 6 patients carried more than one variant. Twelve mutations were discovered in known ALS genes which served as a validation of our strategy. Rare deleterious variants in RNA-binding proteins were significantly enriched in ALS patients compared to control frequencies (p = 5.31E-18. Nineteen patients featured at least one variant in a RNA-binding protein containing a PrLD. The number of variants per patient correlated with rate of disease progression (t-test, p = 0.033. We identified eighteen patients with a single variant in a G4C2-repeat binding protein. Patients with a G4C2-binding protein variant in combination with a C9ORF72 expansion had a significantly faster disease course (t-test, p = 0.025. Our data are
Coustasse, Alberto; Pekar, Alicia; Sikula, Andrew; Lurie, Sue
The aim of this literature review was to determine if there is adequate ethical justification for presymptomatic genetic testing on potential Huntington's disease patients. Huntington's disease is a neurological genetic disorder characterized by midlife onset which consists of cognitive, physical, and emotional deterioration. Although genetic testing has traditionally been guided by the principle of autonomy, severe psychological consequences such as depression, anxiety, survival guilt, and suicide have complicated the ethical issue of providing a presymptomatic yet definitive diagnosis for an incurable disease. An analysis of available articles yielded inconclusive findings, namely due to insufficient evidence, self-selection bias of test participants, or lack of a longitudinal design. Additional results indicated psychological distress is not solely associated with test result, but rather with individual characteristics including, but not limited to, psychological history, test motivation, level of preparation, social support, and age. In the interest of upholding the principles of autonomy, beneficence, nonmaleficence, and justice, it is recommended that medical professionals follow strict protocol, provide extensive counseling, and employ vigilance when assessing at-risk individuals for HD presymptomatic test eligibility to ensure psychological well-being.
Shen, Yiping; Dies, Kira A; Holm, Ingrid A; Bridgemohan, Carolyn; Sobeih, Magdi M; Caronna, Elizabeth B; Miller, Karen J; Frazier, Jean A; Silverstein, Iris; Picker, Jonathan; Weissman, Laura; Raffalli, Peter; Jeste, Shafali; Demmer, Laurie A; Peters, Heather K; Brewster, Stephanie J; Kowalczyk, Sara J; Rosen-Sheidley, Beth; McGowan, Caroline; Duda, Andrew W; Lincoln, Sharyn A; Lowe, Kathryn R; Schonwald, Alison; Robbins, Michael; Hisama, Fuki; Wolff, Robert; Becker, Ronald; Nasir, Ramzi; Urion, David K; Milunsky, Jeff M; Rappaport, Leonard; Gusella, James F; Walsh, Christopher A; Wu, Bai-Lin; Miller, David T
Multiple lines of evidence indicate a strong genetic contribution to autism spectrum disorders (ASDs). Current guidelines for clinical genetic testing recommend a G-banded karyotype to detect chromosomal abnormalities and fragile X DNA testing, but guidelines for chromosomal microarray analysis have not been established. A cohort of 933 patients received clinical genetic testing for a diagnosis of ASD between January 2006 and December 2008. Clinical genetic testing included G-banded karyotype, fragile X testing, and chromosomal microarray (CMA) to test for submicroscopic genomic deletions and duplications. Diagnostic yield of clinically significant genetic changes was compared. Karyotype yielded abnormal results in 19 of 852 patients (2.23% [95% confidence interval (CI): 1.73%-2.73%]), fragile X testing was abnormal in 4 of 861 (0.46% [95% CI: 0.36%-0.56%]), and CMA identified deletions or duplications in 154 of 848 patients (18.2% [95% CI: 14.76%-21.64%]). CMA results for 59 of 848 patients (7.0% [95% CI: 5.5%-8.5%]) were considered abnormal, which includes variants associated with known genomic disorders or variants of possible significance. CMA results were normal in 10 of 852 patients (1.2%) with abnormal karyotype due to balanced rearrangements or unidentified marker chromosome. CMA with whole-genome coverage and CMA with targeted genomic regions detected clinically relevant copy-number changes in 7.3% (51 of 697) and 5.3% (8 of 151) of patients, respectively, both higher than karyotype. With the exception of recurrent deletion and duplication of chromosome 16p11.2 and 15q13.2q13.3, most copy-number changes were unique or identified in only a small subset of patients. CMA had the highest detection rate among clinically available genetic tests for patients with ASD. Interpretation of microarray data is complicated by the presence of both novel and recurrent copy-number variants of unknown significance. Despite these limitations, CMA should be considered as part
Antoñanzas, Fernando; Rodríguez-Ibeas, R; Hutter, M F; Lorente, R; Juárez, C; Pinillos, M
We review the published economic evaluation studies applied to genetic technologies in the EU to know the main diseases addressed by these studies, the ways the studies were conducted and to assess the efficiency of these new technologies. The final aim of this review was to understand the possibilities of the economic evaluations performed up to date as a tool to contribute to decision making in this area. We have reviewed a set of articles found in several databases until March 2010. Literature searches were made in the following databases: PubMed; Euronheed; Centre for Reviews and Dissemination of the University of York-Health Technology Assessment, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database; and Scopus. The algorithm was "(screening or diagnosis) and genetic and (cost or economic) and (country EU27)". We included studies if they met the following criteria: (1) a genetic technology was analysed; (2) human DNA must be tested for; (3) the analysis was a real economic evaluation or a cost study, and (4) the articles had to be related to any EU Member State. We initially found 3,559 papers on genetic testing but only 92 articles of economic analysis referred to a wide range of genetic diseases matched the inclusion criteria. The most studied diseases were as follows: cystic fibrosis (12), breast and ovarian cancer (8), hereditary hemochromatosis (6), Down's syndrome (7), colorectal cancer (5), familial hypercholesterolaemia (5), prostate cancer (4), and thrombophilia (4). Genetic tests were mostly used for screening purposes, and cost-effectiveness analysis is the most common type of economic study. The analysed gene technologies are deemed to be efficient for some specific population groups and screening algorithms according to the values of their cost-effectiveness ratios that were below the commonly accepted threshold of 30,000€. Economic evaluation of genetic technologies matters but the number of published studies is still
Ayling Roger D
Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.
Leahy, Laura G
Genetic testing in psychiatric practice may be a beneficial adjunct to the nursing toolbox of considerations used to improve patient outcomes. Since 2004, the psychiatric community has used genotyping to personalize medication options for their patients. Although not a definitive or exact science, pharmacogenetic testing for psychopharmacological treatment options offers nurses and their patients insights into potential treatments that will reduce the current trial-and-error prescribing practices and more quickly improve patients' quality of life. The current article guides nurses through the process of conducting genetic testing, interpreting the results, and applying the results in clinical practice using a fictitious case example. [Journal of Psychosocial Nursing and Mental Health Services, 55(3), 19-23.]. Copyright 2017, SLACK Incorporated.
Kampuansai, Jatupol; Völgyi, Antónia; Kutanan, Wibhu; Kangwanpong, Daoroong; Pamjav, Horolma
Since prehistoric times, Mon-Khmer speaking people have been recognized as indigenous ethnic groups living in northern Thailand. After the period of Tai colonization in the thirteenth century CE, the Mon-Khmer inhabitants were fragmented; some were expelled to rural areas while some were integrated into the mainstream of Tai society. Autosomal STR variations revealed that the present-day Mon-Khmer people could be genetically divided into two clusters. This finding appears to be consistent with the level of historical contact with the Tai majority ethnic groups. The cluster consisting of the Khamu, Lua, Paluang and Htin people, indicate that they have lived in remote areas and have had little historical contact with the Tai people. In this way, they appeared to have maintained aspects of their Mon-Khmer ancestral genetic bloodline but have genetically diverged from the Tai people. The cluster comprised of the Mon and Lawa people had an exclusively close relationship with the Tai people during the establishment of the prosperous Lan Na Kingdom. A fraction of the Tai genetic component investigated among the Mon people and some Lawa populations reflected the evidence of genetic admixture. However, some Lawa people, who have lived in the mountainous area of Mae Hong Son Province have exhibited a unique gene pool, which might have been shaped by the founder effect that occurred during their historical fragmentation. The rise of the genetic assimilation of the hill-tribe Karen people into the Mon-Khmer and the Tai gene pools indicated that different languages, cultures, and geographical distances have lost their power as barriers of inter-ethnic marriages in the present day. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Geddes, Gabrielle C; Basel, Donald; Frommelt, Peter; Kinney, Aaron; Earing, Michael
Genetic testing is routinely performed on infants with critical congenital heart disease (CHD). This project reviewed the effect of implementing a genetic testing protocol in this population. Charts of infants with critical CHD were reviewed for genetic testing and results across two time periods: the time before implementation of a genetic testing protocol (pre-protocol) and the time after implementation (post-protocol). The use of karyotype, 22q11.2 Deletion testing, and chromosomal microarray were compared across these two time periods. Records of 891 infants were reviewed. 562 (63%) had at least one of the target genetic tests completed. During the pre-protocol time period, 66% of patients who had genetic testing underwent multiple tests versus 24% during the post-protocol time period (p testing increased from 60% in the pre-protocol time period to 77% in the post-protocol time period (p tests and more likely to have a diagnosis of genetic disease. In addition there was a significant reduction in cost per diagnosis during the post-protocol time period. Genetic testing protocols for infants with critical CHD promoted more efficient use of genetic testing and increased the rate of diagnosis of genetic conditions in this population.
Patrick-Miller, Linda J; Egleston, Brian L; Fetzer, Dominique; Forman, Andrea; Bealin, Lisa; Rybak, Christina; Peterson, Candace; Corbman, Melanie; Albarracin, Julio; Stevens, Evelyn; Daly, Mary B; Bradbury, Angela R
Dissemination of genetic testing for disease susceptibility, one application of "personalized medicine", holds the potential to empower patients and providers through informed risk reduction and prevention recommendations. Genetic testing has become a standard practice in cancer prevention for high-risk populations. Heightened consumer awareness of "cancer genes" and genes for other diseases (eg, cardiovascular and Alzheimer's disease), as well as the burgeoning availability of increasingly complex genomic tests (ie, multi-gene, whole-exome and -genome sequencing), has escalated interest in and demand for genetic risk assessment and the specialists who provide it. Increasing demand is expected to surpass access to genetic specialists. Thus, there is urgent need to develop effective and efficient models of delivery of genetic information that comparably balance the risks and benefits to the current standard of in-person communication. The aim of this pilot study was to develop and evaluate a theoretically grounded and rigorously developed protocol for telephone communication of BRCA1/2 (breast cancer) test results that might be generalizable to genetic testing for other hereditary cancer and noncancer syndromes. Stakeholder data, health communication literature, and our theoretical model grounded in Self-Regulation Theory of Health Behavior were used to develop a telephone communication protocol for the communication of BRCA1/2 genetic test results. Framework analysis of selected audiotapes of disclosure sessions and stakeholders' feedback were utilized to evaluate the efficacy and inform refinements to this protocol. Stakeholder feedback (n=86) and audiotapes (38%, 33/86) of telephone disclosures revealed perceived disadvantages and challenges including environmental factors (eg, non-private environment), patient-related factors (eg, low health literacy), testing-related factors (eg, additional testing needed), and communication factors (eg, no visual cues
Christiansen, Camilla Worm; Gerdes, Anne-Marie Axø
Direct-to-consumer genetic tests are sold over the internet to consumers all over the world - including Denmark. No regulation of these tests has been introduced neither in Denmark nor in Europe, even though they have been on the market since 2007. Such tests have several advantages, but indeed also a long list of potential disadvantages, which are most often ignored, and among these is insufficient training of general practitioners in performing the necessary counselling but also the risk of increased expenses to unnecessary follow-up consultations.
Gong, Jie; Wu, Weiwei; Ran, MengLong; Wang, Xiaowen; Liu, Wei; Wan, Zhe; Yao, Limin; Li, Ruoyu
Little is known regarding the population information of Trichophyton rubrum due to a lack of strains with clear sampling information and molecular markers with high discriminatory power. In the present study, we developed a set of microsatellite markers that have a cumulative discriminatory power was 0.993. Using these microsatellites loci, 243 strains T. rubrum that had clear sampling information were analysed. Three genetic diversity indices (Shannon's Information Index, Nei's unbiased gene diversity and allelic richness) were shown to be related to the human population size of the sampling city rather than mean annual temperature or humidity. Population structure analyses revealed that T. rubrum can be separated into two clusters. AMOVA results indicated that genetic variation was more significant between these two clusters than among geographical populations. Our work is the first to reveal population information of T. rubrum using highly discriminatory molecular markers, and suggest that T. rubrum populations in cities with larger population size might have better adaptability due to higher genetic diversity under selective pressures (such as antifungal agents). Copyright © 2016 Elsevier Inc. All rights reserved.
Marra, Nicholas J; Romero, Andrea; DeWoody, J Andrew
One adaptation of ecological and evolutionary interest is the extraordinary ability of desert rodents to retain water during waste production. Much is known regarding the unique kidney physiology of kangaroo rats (Dipodomys spp.) and their ability to retain water during waste production, yet the genetic basis of these physiological adaptations is relatively unknown. Herein, we utilized RNA-seq data to conduct a comparative study to identify osmoregulatory genes expressed in heteromyid rodents. We sequenced kidney tissue from two temperate desert species (Dipodomys spectabilis and Chaetodipus baileyi) from two separate subfamilies of the Heteromyidae and compared these transcriptomes to a tropical mesic species (Heteromys desmarestianus) from a third subfamily. The evolutionary history of these subfamilies provided a robust phylogenetic control that allowed us to separate shared evolutionary history from convergence. Using two methods to detect differential expression (DE), we identified 1890 genes that showed consistent patterns of DE between the arid and mesic species. A three-species reciprocal BLAST analysis revealed 3511 sets of putative orthologues that, upon comparison to known Mus musculus sequences, revealed 323 annotated and full-length genic regions. Selection tests displayed evidence of positive selection (dn/ds > 1) on six genes in the two desert species and remained significant for one of these genes after correction for multiple testing. Thus, our data suggest that both the coding sequence and expression of genes have been shaped by natural selection to provide the genetic architecture for efficient osmoregulation in desert-adapted heteromyid rodents. © 2014 John Wiley & Sons Ltd.
Lyons, Leslie A; Grahn, Robert A; Genova, Francesca; Beccaglia, Michela; Hopwood, John J; Longeri, Maria
The release of new DNA-based diagnostic tools has increased tremendously in companion animals. Over 70 different DNA variants are now known for the cat, including DNA variants in disease-associated genes and genes causing aesthetically interesting traits. The impact genetic tests have on animal breeding and health management is significant because of the ability to control the breeding of domestic cats, especially breed cats. If used properly, genetic testing can prevent the production of diseased animals, causing the reduction of the frequency of the causal variant in the population, and, potentially, the eventual eradication of the disease. However, testing of some identified DNA variants may be unwarranted and cause undo strife within the cat breeding community and unnecessary reduction of gene pools and availability of breeding animals. Testing for mucopolysaccharidosis Type VI (MPS VI) in cats, specifically the genetic testing of the L476P (c.1427T>C) and the D520N (c.1558G>A) variants in arylsulfatase B (ARSB), has come under scrutiny. No health problems are associated with the D520N (c.1558G>A) variant, however, breeders that obtain positive results for this variant are speculating as to possible correlation with health concerns. Birman cats already have a markedly reduced gene pool and have a high frequency of the MPS VI D520N variant. Further reduction of the gene pool by eliminating cats that are heterozygous or homozygous for only the MPS VI D520N variant could lead to more inbreeding depression effects on the breed population. Herein is debated the genetic testing of the MPS VI D520N variant in cats. Surveys from different laboratories suggest the L476P (c.1427T>C) disease-associated variant should be monitored in the cat breed populations, particularly breeds with Siamese derivations and outcrosses. However, the D520N has no evidence of association with disease in cats and testing is not recommended in the absence of L476P genotyping. Selection
Wang, Wei; Litchy, William J; Mandrekar, Jay; Dyck, Peter J; Klein, Christopher J
In severely affected inherited polyneuropathy patients, primary demyelination can be difficult to determine by routine extremity limb nerve conduction studies (NCS). Blink reflexes may help classify severe polyneuropathies as either axonal or demyelinating. However, blink reflex studies have not been studied systematically in any genetically confirmed cohort. Patients with a genetic diagnosis who had undergone blink reflex testing and extremity NCS were identified retrospectively. Blink reflex R1 latency, extremity NCS, and severity were compared. We identified 26 demyelinating and 23 axonal, genetically confirmed cases, including 20 with PMP22 duplications. In 12 (25%), the ulnar CMAP amplitude was ≤0.5 mV making electrophysiological classification difficult. However, the R1-latency cutoff of >13 ms (demyelinating) robustly classified all patients regardless of severity. We show that blink reflex studies are reliable for identification of inherited demyelinating polyneuropathy regardless of severity and can facilitate algorithmic decisions in genetic testing. Muscle Nerve 55: 316-322, 2017. © 2016 Wiley Periodicals, Inc.
Successful software depends as much on scrupulous testing as it does on solid architecture or elegant code. But testing is not a routine process, it's a constant exploration of methods and an evolution of good ideas. Beautiful Testing offers 23 essays from 27 leading testers and developers that illustrate the qualities and techniques that make testing an art. Through personal anecdotes, you'll learn how each of these professionals developed beautiful ways of testing a wide range of products -- valuable knowledge that you can apply to your own projects. Here's a sample of what you'll find i
Hao, Chenyang; Wang, Lanfen; Ge, Hongmei; Dong, Yuchen; Zhang, Xueyong
Two hundred and fifty bread wheat lines, mainly Chinese mini core accessions, were assayed for polymorphism and linkage disequilibrium (LD) based on 512 whole-genome microsatellite loci representing a mean marker density of 5.1 cM. A total of 6,724 alleles ranging from 1 to 49 per locus were identified in all collections. The mean PIC value was 0.650, ranging from 0 to 0.965. Population structure and principal coordinate analysis revealed that landraces and modern varieties were two relatively independent genetic sub-groups. Landraces had a higher allelic diversity than modern varieties with respect to both genomes and chromosomes in terms of total number of alleles and allelic richness. 3,833 (57.0%) and 2,788 (41.5%) rare alleles with frequencies of whole genome for locus pairs with r(2)>0.05 (Pwhole genome level was wheat genetic resources.
Petersen, L.; Østergård, H.; Giese, H.
Genetic variability of cultivated and wild barley, Hordeum vulgare ssp. vulgare and spontaneum, respectively, was assessed by RFLP analysis. The material consisted of 13 European varietes, single-plant offspring lines of eight land races from Ethiopia and Nepal, and five accessions of ssp....... spontaneum from Israel, Iran and Turkey. Seventeen out of twenty-one studied cDNA and gDNA probes distributed across all seven barley chromosomes revealed polymorphism when DNA was digested with one of four restriction enzymes. A tree based on genetic distances using frequencies of RFLP banding patterns...... an intermediate level. The proportion of gene diversity residing among,geographical groups (F-ST) varied from 0.19 to 0.94 (average 0.54) per RFLP pattern, indicating large diversification between geographical groups....
Alagrund, Katariina; Orpana, Arto K
The rising role of nucleic acid testing in clinical decision making is creating a need for efficient and automated diagnostic nucleic acid test platforms. Clinical use of nucleic acid testing sets demands for shorter turnaround times (TATs), lower production costs and robust, reliable methods that can easily adopt new test panels and is able to run rare tests in random access principle. Here we present a novel home-brew laboratory automation platform for diagnostic mutation testing. This platform is based on the cyclic minisequecing (cMS) and two color near-infrared (NIR) detection. Pipetting is automated using Tecan Freedom EVO pipetting robots and all assays are performed in 384-well micro plate format. The automation platform includes a data processing system, controlling all procedures, and automated patient result reporting to the hospital information system. We have found automated cMS a reliable, inexpensive and robust method for nucleic acid testing for a wide variety of diagnostic tests. The platform is currently in clinical use for over 80 mutations or polymorphisms. Additionally to tests performed from blood samples, the system performs also epigenetic test for the methylation of the MGMT gene promoter, and companion diagnostic tests for analysis of KRAS and BRAF gene mutations from formalin fixed and paraffin embedded tumor samples. Automation of genetic test reporting is found reliable and efficient decreasing the work load of academic personnel.
Mason, Matthew; Levenson, James; Quillin, John
Since the introduction of the Orphan Drug Act (ODA) in 1983, orphan drug approvals in the United States have jumped from consumer (DTC) genetic testing companies. This emerging trend is the subject of this article, which begins by considering how rare-disease drugs are regulated and the rising interest in nonclinical genetic testing. It then outlines how DTC companies analyze DNA and how their techniques benefit researchers and drug developers. Then, after an overview of the current partnerships between DTCs and drug developers, it examines concerns about privacy and cost brought up by these partnerships. The article concludes by contrasting the enormous positive potential of DTC-pharma relationships and their concomitant dangers, especially to consumer privacy and cost to the healthcare system.
Bandelt, Hans-Jürgen; Yao, Yong-Gang; Richards, Martin B; Salas, Antonio
The commercialization of 'big science' is in full swing, leading to situations in which the ethical principles of academia are beginning to be compromised. This is exemplified by the profitable business of genetic ancestry testing. The goals of this sort of 'big science' are not necessarily in any way novel, however. In particular, large genotyping projects have a certain start-up time when their design is frozen in, so that the projects often lag behind the development of genetic knowledge. On the other hand, extremely provisional knowledge about potential disease markers is being rapidly turned into questionable 'tests', purporting to determine risk factors for complex disorders, by private companies that are eager to get their share of a profitable market of the future. The flow of money generated by such concerns looks likely to erode traditional research operations and small-scale projects, which risk becoming pebbles on the 'big science' landscape.
staff represents a range of expertise. For the review of -r Advanced Genetic Sciences’ (AGS) proposal to test ice-minus bacteria on k strawberry plants...organism that might protect strawberries against frost damage, the potential benefits included the economic gain from Page 59 GAO R(ED-48-27...commercial- scale use of the product included lowering farm production costs, free- ing land for other uses, and reducing the use of fertilizer . The
Full Text Available BACKGROUND: The liver function test (LFT is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI. AIMS: To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins--including alanine amino transaminase (ALT, Albumin, gamma glutamyl transpeptidase (GGT, total bilirubin, total protein, total globulin, aspartate transaminase (AST, and alkaline phosphotase (ALP--using the classical twin model. METHODS: Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach. RESULTS: Our results show that (1 variation in all the LFTs has a significant heritable basis (h(2 ranging from 20% to 77%; (2 other than GGT, the LFTs are all affected to some extent by common environmental factors (c(2 ranging from 24% to 54%; and (3 a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use. CONCLUSIONS: Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.
Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ
These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external
Background The dynamic re-emergence of visceral leishmaniasis (VL) in south Europe and the northward shift to Leishmania-free European countries are well-documented. However, the epidemiology of VL due to Leishmania infantum in southeastern (SE) Europe and the Balkans is inadequately examined. Herein, we aim to re-evaluate and compare the population structure of L. infantum in SE and southwestern (SW) Europe. Methods Leishmania strains collected from humans and canines in Turkey, Cyprus, Bulgaria, Greece, Albania and Croatia, were characterized by the K26-PCR assay and multilocus enzyme electrophoresis (MLEE). Genetic diversity was assessed by multilocus microsatellite typing (MLMT) and MLM Types were analyzed by model- and distance- based algorithms to infer the population structure of 128 L. infantum strains. Results L. infantum MON-1 was found predominant in SE Europe, whilst 16.8% of strains were MON-98. Distinct genetic populations revealed clear differentiation between SE and SW European strains. Interestingly, Cypriot canine isolates were genetically isolated and formed a monophyletic group, suggesting the constitution of a clonal MON-1 population circulating among dogs. In contrast, two highly heterogeneous populations enclosed all MON-1 and MON-98 strains from the other SE European countries. Structure sub-clustering, phylogenetic and Splitstree analysis also revealed two distinct Croatian subpopulations. A mosaic of evolutionary effects resulted in consecutive sub-structuring, which indicated substantial differentiation and gene flow among strains of both zymodemes. Conclusions This is the first population genetic study of L. infantum in SE Europe and the Balkans. Our findings demonstrate the differentiation between SE and SW European strains; revealing the partition of Croatian strains between these populations and the genetic isolation of Cypriot strains. This mirrors the geographic position of Croatia located in central Europe and the natural
Full Text Available Background: Genetic diversity is an essential resource for breeders to improve new cultivars with desirable characteristics. Recently, genotyping-by-sequencing (GBS, a next-generation sequencing (NGS technology that can simplify complex genomes, has now be used as a high-throughput and cost-effective molecular tool for routine breeding and screening in many crop species, including the species with a large genome.Results: We genotyped a diversity panel of 369 Iranian hexaploid wheat accessions including 270 landraces collected between 1931 and 1968 in different climate zones and 99 cultivars released between 1942 to 2014 using 16,506 GBS-based single nucleotide polymorphism (GBS-SNP markers. The B genome had the highest number of mapped SNPs while the D genome had the lowest on both the Chinese Spring and W7984 references. Structure and cluster analyses divided the panel into three groups with two landrace groups and one cultivar group, suggesting a high differentiation between landraces and cultivars and between landraces. The cultivar group can be further divided into four subgroups with one subgroup was mostly derived from Iranian ancestor(s. Similarly, landrace groups can be further divided based on years of collection and climate zones where the accessions were collected. Molecular analysis of variance indicated that the genetic variation was larger between groups than within group.Conclusion: Obvious genetic diversity in Iranian wheat was revealed by analysis of GBS-SNPs and thus breeders can select genetically distant parents for crossing in breeding. The diverse Iranian landraces provide rich genetic sources of tolerance to biotic and abiotic stresses, and they can be useful resources for the improvement of wheat production in Iran and other countries.
Tsao, Jack W
The availability of testing for identified risk genes for Alzheimer disease (AD) in patients with clinically probable AD or their at-risk family members raises important questions for the neurologist. Because the potential benefits and risks of testing vary for each patient, physicians need to evaluate whether it is appropriate on a case-by-case basis. This article outlines the testing decision process and serves as a guide to assist clinicians with associated counseling and result disclosure. Because genetic testing is relatively new and preventive and therapeutic options for AD remain limited, it is important to remain sensitive to and understand the specific challenges associated with obtaining these tests in the routine clinical setting.
Wasser, S. K.; Brown, L.; Mailand, C.; Mondol, S.; Clark, W.; Laurie, C.; Weir, B. S.
Poaching of elephants is now occurring at rates that threaten African populations with extinction. Identifying the number and location of Africa’s major poaching hotspots may assist efforts to end poaching and facilitate recovery of elephant populations. We genetically assign origin to 28 large ivory seizures (≥0.5 metric tons) made between 1996 and 2014, also testing assignment accuracy. Results suggest that the major poaching hotspots in Africa may be currently concentrated in as few as two...
Bernasconi, Barbara; Chiaravalli, Anna Maria; Finzi, Giovanna; Milani, Katia; Tibiletti, Maria Grazia
Prospective studies have demonstrated that approximately 20% of HER2 testing may be inaccurate. When carefully validated testing is conducted, available data do not clearly demonstrate the superiority of either IHC or fluorescence in situ hybridization (FISH) as a predictor of benefit from anti-HER2 therapy. In addition, the interpretation of the findings of HER2 tests according to international guidelines is not uniform. The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) recently published practice guidelines for a definition of HER2 amplification heterogeneity that can give rise to discrepant results between IHC and FISH assays for HER2. In this article, we compare the HER2 status of 291 non consecutive breast cancers. The status is determined by both IHC and FISH approaches, using a specific FISH strategy to investigate genetic heterogeneity. Our data demonstrate that HER2 amplified cells may be found as diffuse, clustered in a specific area or section, intermingled with non-amplified cells or confined to metastatic nodules. The correct evaluation of ratio value in the presence of genetic heterogeneity and of polysomy contributes to the accurate assessment of HER2 status and potentially affects the selection of appropriate anti-HER2 therapy. By taking into account the presence of different genetic cell populations, the immunotherapy eligibility criteria for HER2 FISH scoring proposed in the CAP (2009) and SIGU guidelines identify an additional subset of cases for trastuzumab or lapatinib therapy compared to the ASCO/CAP (2007) guidelines.
Cota Navin Gupta
Full Text Available It is becoming a consensus that white matter integrity is compromised in schizophrenia (SZ, however the underlying genetics remains elusive. Evidence suggests a polygenic basis of the disorder, which involves various genetic variants with modest individual effect sizes. In this work, we used a multivariate approach, parallel independent component analysis (P-ICA, to explore the genetic underpinnings of white matter abnormalities in SZ. A pre-filtering step was first applied to locate 6527 single nucleotide polymorphisms (SNPs discriminating patients from controls with a nominal uncorrected p-value of 0.01. These potential susceptibility loci were then investigated for associations with fractional anisotropy (FA images in a cohort consisting of 73 SZ patients and 87 healthy controls. A significant correlation (r=-0.37, p=1.25×E-6 was identified between one genetic factor and one FA component after controlling for scanning site, age and sex. The identified FA-SNP association remained stable in a 10-fold validation. A 5000-run permutation test yielded a p-value of 2.00×E-4. The FA component reflected decreased white matter integrity in the forceps major for SZ patients. The SNP component was overrepresented in genes whose products are involved in corpus callosum morphology (e.g., CNTNAP2, NPAS3 and NFIB as well as canonical pathways of synaptic long term depression and protein kinase A signaling. Taken together, our finding delineates a part of genetic architecture underlying SZ-related FA reduction, emphasizing the important role of genetic variants involved in neural development
It is important to stress that currently, the clinical validity and utility of genetic tests for complex multifactorial disorders such as type 2 diabetes mellitus and cardiovascular diseases is questionable. The majority of such tests are not scientifically validated and are based on a few preliminary studies. Potential consumers ...
Rudolf, Joseph; Jackson, Brian R; Wilson, Andrew R; Smock, Kristi J; Schmidt, Robert L
Health care organizations are under increasing pressure to deliver value by improving test utilization management. Many factors, including organizational factors, could affect utilization performance. Past research has focused on the impact of specific interventions in single organizations. The impact of organizational factors is unknown. The objective of this study is to determine whether testing patterns are subject to organizational effects, ie, are utilization patterns for individual tests correlated within organizations. Comparative analysis of ordering patterns (positivity rates for three genetic tests) across 659 organizations. Hierarchical regression was used to assess the impact of organizational factors after controlling for test-level factors (mutation prevalence) and hospital bed size. Test positivity rates were correlated within organizations. Organizations have a statistically significant impact on the positivity rate of three genetic tests.
Full Text Available The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, "genetical genomic" analyses have not yet addressed the degree to which their conclusions are affected by sex. We constructed and densely genotyped a large F2 intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an apolipoprotein E null (ApoE-/- background. This BXH.ApoE-/- population recapitulates several "metabolic syndrome" phenotypes. The cross consists of 334 animals of both sexes, allowing us to specifically test for the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significant proportion of which are sex-biased. We used these analyses to dissect the genetics of gonadal fat mass, a complex trait with sex-specific regulation. We present evidence for a remarkably high degree of sex-dependence on both the cis and trans regulation of gene expression. We demonstrate how these analyses can be applied to the study of the genetics underlying gonadal fat mass, a complex trait showing significantly female-biased heritability. These data have implications on the potential effects of sex on the genetic regulation of other complex traits.
Hoskins, Jessica L; Ritchie, Michael G; Bailey, Nathan W
The evolutionary maintenance of same-sex sexual behaviour (SSB) has received increasing attention because it is perceived to be an evolutionary paradox. The genetic basis of SSB is almost wholly unknown in non-human animals, though this is key to understanding its persistence. Recent theoretical work has yielded broadly applicable predictions centred on two genetic models for SSB: overdominance and sexual antagonism. Using Drosophila melanogaster, we assayed natural genetic variation for male SSB and empirically tested predictions about the mode of inheritance and fitness consequences of alleles influencing its expression. We screened 50 inbred lines derived from a wild population for male-male courtship and copulation behaviour, and examined crosses between the lines for evidence of overdominance and antagonistic fecundity selection. Consistent variation among lines revealed heritable genetic variation for SSB, but the nature of the genetic variation was complex. Phenotypic and fitness variation was consistent with expectations under overdominance, although predictions of the sexual antagonism model were also supported. We found an unexpected and strong paternal effect on the expression of SSB, suggesting possible Y-linkage of the trait. Our results inform evolutionary genetic mechanisms that might maintain low but persistently observed levels of male SSB in D. melanogaster, but highlight a need for broader taxonomic representation in studies of its evolutionary causes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H
Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.
Fejzo, Marlena Schoenberg; Myhre, Ronny; Colodro-Conde, Lucía; MacGibbon, Kimber W; Sinsheimer, Janet S; Reddy, M V Prasad Linga; Pajukanta, Päivi; Nyholt, Dale R; Wright, Margaret J; Martin, Nicholas G; Engel, Stephanie M; Medland, Sarah E; Magnus, Per; Mullin, Patrick M
Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG. Copyright Â© 2016 Elsevier Ireland Ltd. All rights reserved.
Khaire, Devendra; Atkulwar, Ashwin; Farah, Sameera; Baig, Mumtaz
The Indian wild ass Equus hemionus khur, belonging to ass-like equid branch, inhabits the dry and arid desert of the Little Rann of Kutch, Gujarat. The E. h. khur is the sole survivor of Asiatic wild ass species/subspecies in South Asia. To provide first ever insights into the genetic diversity, phylogeny, and demography of the endangered Indian wild ass, we sampled 52 free-ranging individuals from the Little Rann of Kutch by using a non-invasive methodology. The sequencing of 230 bp in cytochrome b (Cyt b) and displacement loop (D-loop) region revealed that current ∼4000 extant population of Indian wild ass harbours low genetic diversity. Phylogenetic analyses confirmed that E. h. khur, E. h. onager, and E. h. kulan belong to a single strict monophyletic clade. Therefore, we suggest the delimitation of the five E. hemionus subspecies in vogue to a single species E. hemionus. The application of molecular clock confirmed that the Asiatic wild ass had undergone diversification 0.65 Million years ago. Demographic measurements assessed using a Bayesian skyline plot demonstrated decline in the maternal effective population size of the Indian wild ass during different periods; these periods coincided with the origin and rise of the Indus civilization in the northwest of the Indian subcontinent during the Neolithic. In conclusion, maintaining high genetic diversity in the existing isolated population of 4000 Indian wild asses inhabiting the wild ass sanctuary is important compared with subspecies preservation alone.
Sara M. Coser
Full Text Available Charcoal rot (CR disease caused by Macrophomina phaseolina is responsible for significant yield losses in soybean production. Among the methods available for controlling this disease, breeding for resistance is the most promising. Progress in breeding efforts has been slow due to the insufficient information available on the genetic mechanisms related to resistance. Genome-wide association studies (GWAS enable unraveling the genetic architecture of resistance and identification of causal genes. The aims of this study were to identify new sources of resistance to CR in a collection of 459 diverse plant introductions from the USDA Soybean Germplasm Core Collection using field and greenhouse screenings, and to conduct GWAS to identify candidate genes and associated molecular markers. New sources for CR resistance were identified from both field and greenhouse screening from maturity groups I, II, and III. Five significant single nucleotide polymorphism (SNP and putative candidate genes related to abiotic and biotic stress responses are reported from the field screening; while greenhouse screening revealed eight loci associated with eight candidate gene families, all associated with functions controlling plant defense response. No overlap of markers or genes was observed between field and greenhouse screenings suggesting a complex molecular mechanism underlying resistance to CR in soybean with varied response to different environments; but our findings provide useful information for advancing breeding for CR resistance as well as the genetic mechanism of resistance.
Teng, Huajing; Zhang, Yaohua; Shi, Chengmin; Mao, Fengbiao; Hou, Lingling; Guo, Hongling; Sun, Zhongsheng; Zhang, Jianxu
Whole-genome sequencing of wild-derived rat species can provide novel genomic resources, which may help decipher the genetics underlying complex phenotypes. As a notorious pest, reservoir of human pathogens, and colonizer, the Asian house rat, Rattus tanezumi, is successfully adapted to its habitat. However, little is known regarding genetic variation in this species. In this study, we identified over 41,000,000 single-nucleotide polymorphisms, plus insertions and deletions, through whole-genome sequencing and bioinformatics analyses. Moreover, we identified over 12,000 structural variants, including 143 chromosomal inversions. Further functional analyses revealed several fixed nonsense mutations associated with infection and immunity-related adaptations, and a number of fixed missense mutations that may be related to anticoagulant resistance. A genome-wide scan for loci under selection identified various genes related to neural activity. Our whole-genome sequencing data provide a genomic resource for future genetic studies of the Asian house rat species and have the potential to facilitate understanding of the molecular adaptations of rats to their ecological niches. Copyright © 2016 Teng et al.
Zhang, Xuehai; Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Xiong, Lizhong; Yang, Wanneng; Yan, Jianbing
With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize (Zea mays) recombinant inbred line population (n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. © 2017 American Society of Plant Biologists. All Rights Reserved.
Hart Patrick J
Full Text Available Abstract Background The Hawaiian honeycreepers (Drepanidinae are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens, the apapane (Himatione sanguinea, and the iiwi (Vestiaria coccinea were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent.
Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.
Eggert, L.S.; Terwilliger, L.A.; Woodworth, B.L.; Hart, P.J.; Palmer, D.; Fleischer, R.C.
Background. The Hawaiian honeycreepers (Drepanidinae) are one of the best-known examples of an adaptive radiation, but their persistence today is threatened by the introduction of exotic pathogens and their vector, the mosquito Culex quinquefasciatus. Historically, species such as the amakihi (Hemignathus virens), the apapane (Himatione sanguinea), and the iiwi (Vestiaria coccinea) were found from the coastal lowlands to the high elevation forests, but by the late 1800's they had become extremely rare in habitats below 900 m. Recently, however, populations of amakihi and apapane have been observed in low elevation habitats. We used twelve polymorphic microsatellite loci to investigate patterns of genetic structure, and to infer responses of these species to introduced avian malaria along an elevational gradient on the eastern flanks of Mauna Loa and Kilauea volcanoes on the island of Hawaii. Results. Our results indicate that amakihi have genetically distinct, spatially structured populations that correspond with altitude. We detected very few apapane and no iiwi in low-elevation habitats, and genetic results reveal only minimal differentiation between populations at different altitudes in either of these species. Conclusion. Our results suggest that amakihi populations in low elevation habitats have not been recolonized by individuals from mid or high elevation refuges. After generations of strong selection for pathogen resistance, these populations have rebounded and amakihi have become common in regions in which they were previously rare or absent. ?? 2008 Eggert et al; licensee BioMed Central Ltd.
Full Text Available Abstract Background Multi-allelic microsatellite markers have become the markers of choice for the determination of genetic structure in plants. Synteny across cereals has allowed the cross-species and cross-genera transferability of SSR markers, which constitute a valuable and cost-effective tool for the genetic analysis and marker-assisted introgression of wild related species. Hordeum chilense is one of the wild relatives with a high potential for cereal breeding, due to its high crossability (both interspecies and intergenera and polymorphism for adaptation traits. In order to analyze the genetic structure and ecogeographical adaptation of this wild species, it is necessary to increase the number of polymorphic markers currently available for the species. In this work, the possibility of using syntenic wheat SSRs as a new source of markers for this purpose has been explored. Results From the 98 wheat EST-SSR markers tested for transferability and polymorphism in the wild barley genome, 53 primer pairs (54.0% gave cross-species transferability and 20 primer pairs (20.4% showed polymorphism. The latter were used for further analysis in the H. chilense germplasm. The H. chilense-Triticum aestivum addition lines were used to test the chromosomal location of the new polymorphic microsatellite markers. The genetic structure and diversity was investigated in a collection of 94 H. chilense accessions, using a set of 49 SSR markers distributed across the seven chromosomes. Microsatellite markers showed a total of 351 alleles over all loci. The number of alleles per locus ranged from two to 27, with a mean of 7.2 alleles per locus and a mean Polymorphic Information Content (PIC of 0.5. Conclusions According to the results, the germplasm can be divided into two groups, with morphological and ecophysiological characteristics being key determinants of the population structure. Geographic and ecological structuring was also revealed in the analyzed
Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I.; Taylor, Kent D.; Azziz, Ricardo; Goodarzi, Mark O.
Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227
Michelle R Jones
Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.
Clift, Kristin; Guthrie, Kimberly; Klee, Eric W; Boczek, Nicole; Cousin, Margot; Blackburn, Patrick; Atwal, Paldeep
Here we present a case of an asymptomatic 53-year-old woman who sought genetic testing for Familial Creutzfeldt-Jakob Disease (fCJD) after learning that her mother had fCJD. The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within ∼1 y of symptom onset. The cause of death was reported as "rapid onset dementia." The patient's family, unhappy with the vague diagnosis, researched prion disorders online and aggressively pursued causation and submitted frozen brain tissue from the mother to the National Prion Disease Surveillance Center, where testing revealed a previously described 5-octapeptide repeat insertion (5-OPRI) in the prion protein gene (PRNP) that is known to cause fCJD. The family had additional questions about the implications of this result and thus independently sought out genetic counseling. While rare, fCJD is likely underdiagnosed due to clinical heterogeneity, rapid onset, early non-specific symptomatology, and overlap in the differential diagnosis of Alzheimer disease and Lewy body dementias. When fCJD is identified, a multidisciplinary approach to return of results that includes the affected patient's provider, genetics professionals, and mental health professionals is key to the care of the family. We present an example case which discusses the psychosocial issues encountered and the role of genetic counseling in presymptomatic testing for incurable neurodegenerative conditions. Ordering physicians should be aware of the basic issues surrounding presymptomatic genetic testing and identify local genetic counseling resources for their patients.
Krayter, Lena; Schnur, Lionel F; Schönian, Gabriele
Leishmania (Leishmania) aethiopica and L. (L.) tropica cause cutaneous leishmaniases and appear to be related. L. aethiopica is geographically restricted to Ethiopia and Kenya; L. tropica is widely dispersed from the Eastern Mediterranean, through the Middle East into eastern India and in north, east and south Africa. Their phylogenetic inter-relationship is only partially revealed. Some studies indicate a close relationship. Here, eight strains of L. aethiopica were characterized genetically and compared with 156 strains of L. tropica from most of the latter species' geographical range to discern the closeness. Twelve unlinked microsatellite markers previously used to genotype strains of L. tropica were successfully applied to the eight strains of L. aethiopica and their microsatellite profiles were compared to those of 156 strains of L. tropica from various geographical locations that were isolated from human cases of cutaneous and visceral leishmaniasis, hyraxes and sand fly vectors. All the microsatellite profiles were subjected to various analytical algorithms: Bayesian statistics, distance-based and factorial correspondence analysis, revealing: (i) the species L. aethiopica, though geographically restricted, is genetically very heterogeneous; (ii) the strains of L. aethiopica formed a distinct genetic cluster; and (iii) strains of L. aethiopica are closely related to strains of L. tropica and more so to the African ones, although, by factorial correspondence analysis, clearly separate from them. The successful application of the 12 microsatellite markers, originally considered species-specific for the species L. tropica, to strains of L. aethiopica confirmed the close relationship between these two species. The Bayesian and distance-based methods clustered the strains of L. aethiopica among African strains of L. tropica, while the factorial correspondence analysis indicated a clear separation between the two species. There was no correlation between
Xie, Jianbo; Tian, Jiaxing; Du, Qingzhang; Chen, Jinhui; Li, Ying; Yang, Xiaohui; Li, Bailian; Zhang, Deqiang
Gibberellins (GAs) regulate a wide range of important processes in plant growth and development, including photosynthesis. However, the mechanism by which GAs regulate photosynthesis remains to be understood. Here, we used multi-gene association to investigate the effect of genes in the GA-responsive pathway, as constructed by RNA sequencing, on photosynthesis, growth, and wood property traits, in a population of 435 Populus tomentosa By analyzing changes in the transcriptome following GA treatment, we identified many key photosynthetic genes, in agreement with the observed increase in measurements of photosynthesis. Regulatory motif enrichment analysis revealed that 37 differentially expressed genes related to photosynthesis shared two essential GA-related cis-regulatory elements, the GA response element and the pyrimidine box. Thus, we constructed a GA-responsive pathway consisting of 47 genes involved in regulating photosynthesis, including GID1, RGA, GID2, MYBGa, and 37 photosynthetic differentially expressed genes. Single nucleotide polymorphism (SNP)-based association analysis showed that 142 SNPs, representing 40 candidate genes in this pathway, were significantly associated with photosynthesis, growth, and wood property traits. Epistasis analysis uncovered interactions between 310 SNP-SNP pairs from 37 genes in this pathway, revealing possible genetic interactions. Moreover, a structural gene-gene matrix based on a time-course of transcript abundances provided a better understanding of the multi-gene pathway affecting photosynthesis. The results imply a functional role for these genes in mediating photosynthesis, growth, and wood properties, demonstrating the potential of combining transcriptome-based regulatory pathway construction and genetic association approaches to detect the complex genetic networks underlying quantitative traits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights
Severin, Franziska; Borry, Pascal; Cornel, Martina C
Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set......, following the principles of accountability for reasonableness. We provide points to consider to stimulate this debate across the EU and to serve as a reference for improving patient management.European Journal of Human Genetics advance online publication, 24 September 2014; doi:10.1038/ejhg.2014.190....... testing services available in the next decade. Ethically and economically reflected prioritization criteria are needed. Prioritization should be based on considerations of medical benefit, health need and costs. Medical benefit includes evidence of benefit in terms of clinical benefit, benefit...
A captive Cercopithecus nictitans × C. cephus male was examined at loci on the X- and Y-chromosomes as a test of previously described phylogenetic methods for identifying hybrid Cercopithecus monkeys. The results confirm the reliability of such assays, indicating that they can be of immediate utility for studies of wild ...
Davis, Lea K.; Yu, Dongmei; Keenan, Clare L.; Gamazon, Eric R.; Konkashbaev, Anuar I.; Derks, Eske M.; Neale, Benjamin M.; Yang, Jian; Lee, S. Hong; Evans, Patrick; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrio, Gabriel Bedoya; Bienvenu, Oscar J.; Bloch, Michael H.; Blom, Rianne M.; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond; Cappi, Carolina; Cardona Silgado, Julio C.; Cath, Danielle C.; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Conti, David V.; Cook, Edwin H.; Coric, Vladimir; Cullen, Bernadette A.; Deforce, Dieter; Delorme, Richard; Dion, Yves; Edlund, Christopher K.; Egberts, Karin; Falkai, Peter; Fernandez, Thomas V.; Gallagher, Patience J.; Garrido, Helena; Geller, Daniel; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Haddad, Stephen; Heiman, Gary A.; Hemmings, Sian M. J.; Hounie, Ana G.; Illmann, Cornelia; Jankovic, Joseph; Jenike, Michael A.; Kennedy, James L.; King, Robert A.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Macciardi, Fabio; McCracken, James T.; McGrath, Lauren M.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Ochoa, William Cornejo; Ophoff, Roel A.; Osiecki, Lisa; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias J.; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosàrio, Maria C.; Rosenberg, David; Rouleau, Guy A.; Ruhrmann, Stephan; Ruiz-Linares, Andres; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, E.; Tischfield, Jay A.; Valencia Duarte, Ana V.; Vallada, Homero; Van Nieuwerburgh, Filip; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Miguel, Euripedes C.; McMahon, William; Wagner, Michael; Nicolini, Humberto; Posthuma, Danielle; Hanna, Gregory L.; Heutink, Peter; Denys, Damiaan; Arnold, Paul D.; Oostra, Ben A.; Nestadt, Gerald; Freimer, Nelson B.; Pauls, David L.; Wray, Naomi R.
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures. PMID:24204291
Lea K Davis
Full Text Available The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD and Tourette Syndrome (TS, using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12 for TS, and 0.37 (se = 0.07, p = 1.5e-07 for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum for which we had available expression quantitative trait loci (eQTLs. Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002. These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Full Text Available Eukaryotic release factors 1 and 3, encoded by SUP45 and SUP35, respectively, in Saccharomyces cerevisiae, are required for translation termination. Recent studies have shown that, besides these two key factors, several genetic and epigenetic mechanisms modulate the efficiency of translation termination. These mechanisms, through modifying translation termination fidelity, were shown to affect various cellular processes, such as mRNA degradation, and in some cases could confer a beneficial phenotype to the cell. The most studied example of such a mechanism is [PSI+], the prion conformation of Sup35p, which can have pleiotropic effects on growth that vary among different yeast strains. However, genetic loci underlying such readthrough-dependent, background-specific phenotypes have yet to be identified. Here, we used sup35(C653R, a partial loss-of-function allele of the SUP35 previously shown to increase readthrough of stop codons and recapitulate some [PSI+]-dependent phenotypes, to study the genetic basis of phenotypes revealed by increased translational readthrough in two divergent yeast strains: BY4724 (a laboratory strain and RM11_1a (a wine strain. We first identified growth conditions in which increased readthrough of stop codons by sup35(C653R resulted in different growth responses between these two strains. We then used a recently developed linkage mapping technique, extreme QTL mapping (X-QTL, to identify readthrough-dependent loci for the observed growth differences. We further showed that variation in SKY1, an SR protein kinase, underlies a readthrough-dependent locus observed for growth on diamide and hydrogen peroxide. We found that the allelic state of SKY1 interacts with readthrough level and the genetic background to determine growth rate in these two conditions.
LeBlanc, Marissa A; McMaster, Christopher R
Saccharomyces cerevisiae remains an ideal organism for studying the cell biological roles of lipids in vivo, as yeast has phospholipid metabolic pathways similar to mammalian cells, is easy and economical to manipulate, and is genetically tractable. The availability of isogenic strains containing specific genetic inactivation of each non-essential gene allowed for the development of a high-throughput method, called synthetic genetic analysis (SGA), to identify and describe precise pathways or functions associated with specific genes. This review describes the use of SGA to aid in elucidating the function of two lipid-binding proteins that regulate vesicular transport, Sec14 and Kes1. Sec14 was first identified as a phosphatidylcholine (PC) - phosphatidylinositol (PI) transfer protein required for viability, with reduced Sec14 function resulting in diminished vesicular transport out of the trans-Golgi. Although Sec14 is required for cell viability, inactivating the KES1 gene that encodes for a member of the oxysterol binding protein family in cells lacking Sec14 function results in restoration of vesicular transport and cell growth. SGA analysis identified a role for Kes1 and Sec14 in regulating the level and function of Golgi PI-4-phosphate (PI-4-P). SGA also determined that Sec14 not only regulates vesicular transport out of the trans-Golgi, but also transport from endosomes to the trans-Golgi. Comparing SGA screens in databases, coupled with genetic and cell biological analyses, further determined that the PI-4-P pool affected by Kes1 is generated by the PI 4-kinase Pik1. An important biological role for Sec14 and Kes1 revealed by SGA is coordinate regulation of the Pik1-generated Golgi PI-4-P pool that in turn is essential for vesicular transport into and out of the trans-Golgi.
Glover, Kevin A.; Skaala, Øystein; Limborg, Morten
Glover, K. A., Skaala, Ø., Limborg, M., Kvamme, C., and Torstensen, E. Microsatellite DNA reveals population genetic differentiation among sprat (Sprattus sprattus) sampled throughout the Northeast Atlantic, including Norwegian fjords. – ICES Journal of Marine Science, 68: 2145–2151. Sprat (Sprat...... display population genetic differentiation throughout the Northeast Atlantic, and there may be limited connectivity between Norwegian fjord and sea-going populations....
Full Text Available Current ethical and legal issues with regard to abortion, prenatal genetic testing and managing pregnancy are discussed in this paper. These problems are considered from the legal theory point of view as well as from the standpoint of the Serbian Law, the European Convention for the Protection of Human Rights and Fundamental Freedoms, European Court of Human Rights, legal regulations of several EU countries, the USA, Japan, and their judicial practice. First, the pregnancy termination standards that exist in Serbia are introduced. Then the following issues are explained separately: the pro life and pro choice approaches to abortion; abortion according to the legal approach as a way of survival; the moral and legal status of the fetus; prenatal genetic testing, and finally matters regarding managing pregnancy today. Moral and legal principals of autonomy, namely freedom of choice of the individual, privacy and self-determination give women the right to terminate unwanted pregnancies. In addition, the basic question is whether the right of the woman to abortion clashes with the rights of others. Firstly, with the right of the "fetus to life". Secondly, with the right of the state to intervene in the interest of protecting "the life of the fetus". Third, with the rights of the woman’s partner. The fetus has the moral right to life, but less in relation to the same right of the woman as well as in relation to her right to control her life and her physical and moral integrity. On the other hand, the value of the life of the fetus increases morally and legally with the maturity of gestation; from the third trimester, the interest of the state prevails in the protection of the "life of the fetus" except when the life or health of the pregnant woman are at risk. As regards the rights of the woman’s partner, namely the husband’s opinion, there is no legal significance. The law does not request his participation in the decision on abortion because
Keogh, Louise A; Otlowski, Margaret F A
Currently, there is debate about life insurance companies' use of genetic information for assessing applicants. In his early 20s, James (pseudonym) was denied full life insurance cover because he revealed that he had discussed genetic testing with a genetic counsellor. He was later tested and found to carry a mutation in the MSH6 gene; after disclosing this, he was denied cover for cancer by two other life insurance companies. Unsatisfied with the insurance companies' risk assessments, and based on his understanding that regular colonoscopy significantly reduced his risk of cancer, James made a complaint to the Australian Human Rights Commission. After informing the third insurance company that he had done so, he was offered full coverage, which suggests that the company did not have actuarial data to justify its decision. This case provides evidence of the high level of initiative and proactivity required for a consumer to achieve a fair result. Few Australians would be in a position to pursue the level of research and advocacy undertaken by James (a professional with scientific training). We call on a collaborative approach between industry, government and researchers to address the issues that James's case raises about genetic testing and life insurance.
Morling, Niels; Allen, Robert W; Carracedo, Angel
The International Society for Forensic Genetics (ISFG) has established a Paternity Testing Commission (PTC) with the purpose of formulating international recommendations concerning genetic investigations in paternity testing. The PTC recommends that paternity testing be performed in accordance...... with the ISO 17025 standards. The ISO 17025 standards are general standards for testing laboratories and the PTC offers explanations and recommendations concerning selected areas of special importance to paternity testing....
Full Text Available Background: Cystic fibrosis (CF is an autosomal recessive disease caused by mutations in gene encoding cystic fibrosis transmembrane regulator (CFTR protein. Over 1400 mutations found in the gene contribute to the complexity of the CF phenotypes ranging from a classic multiorgan disease commonly involving respiratory, gastrointestinal and reproductive tract to mild and monosymptomatic presentations. Pilocarpine iontophoresis is considered as standard diagnostic test for CF, but it often fails in atypical forms of CF.Methods: In order to provide an additional diagnostic test to assure the diagnosis and provide patients with a proper medical care, we performed a genetic testing on 16 adults suspected to have atypical form of CF. Following counselling, parents of patients with possible homozygote variant of mutations were tested. On a personal request testing was also performed in an adult sibling of a patient with two known mutations to investigate possible carrier hood. The allele specific polymerase chain reaction method (PCR was used to detect 29 most common mutations in the cftr gene.Results: The diagnosis was proved in 3 individuals, a homozygote for Δ F508, and two compound heterozygotes Δ F508/R1162X and Δ F508/3849+10kbC>T. In three cases only one mutation was found: I148T, 2789+5G>A and Δ F508 in a heterozygote form.Conclusions: The genetic testing for CF is a valuable diagnostic tool in atypical forms of CF. Exclusion of possible differential diagnosis is warranted because of a variable CF phenotype. In cases where only one or no mutation was detected a necessity of whole gene sequencing is indicated to exclude rare mutations and polymorphisms that could be implicated in the pathogenesis of atypical CF.
Listyasari, Nurin Aisyiyah; Sihombing, Nydia Rena Benita; Winarni, Tri Indah; Belladona, Maria; Faradz, Sultana MH
Background Spinocerebellar ataxia (SCA) is neurodegenerative disorders with autosomal dominant inheritance, characterized by progressive ataxia. More than 30 types of SCA are known caused by various causative genes. SCA3 (MJD1 gene) is the most common form of SCA. We present an SCA3 family with complicated genetic counseling issue. Methods A 44-year-old female was referred to our service for genetic consultation. Pedigree construction, physical examination, and gene mutation analyses were performed on specimens from the patient and some family members. CAG repeat analysis of ataxin1 (SCA1), ataxin2 (SCA2), MJD1 (SCA3), and CACNA1A (SCA6) genes were done, followed by fragment length analysis, and sequencing. Genetic counseling was provided. Results The patient was already bedridden and she had a brother with the same condition. Neurological examination showed multiple cranial nerve palsy, right eye twitching, spastic paraplegia, limb atrophy, numbness, and bowel-bladder incontinence. CAG repeat expansion (>44) of MJD1 gene was found (28/76 repeats alleles), confirming SCA3. As requested by her family, carrier testing was done for her 15-year-old daughter, 12-year-old nephew, and 10-year-old niece. Her daughter had CAG repeat expansion (27/77 repeats alleles), while the nephew and niece revealed normal alleles. Problem arose when patient died prior to mutation analysis was complete and her husband divorced, leaving the daughter being an orphan. Risk and consequences of positive testing were explained to her uncle, who decided to keep information until the child would have reached legally adult age. Conclusions Genetic counseling is needed, especially in situation which involves many affected members. Carrier testing ethically should be taken for adult who can signs consent for themselves and should be discouraged for under aged individuals. Nevertheless, test was done as parent’s request, because of family anxiety and curiosity. Complexity and adult onset of SCA
Creel, David B; Schuh, Leslie M; Newton, Robert L; Stote, Joseph J; Cacucci, Brenda M
Few studies have quantified cardiorespiratory fitness among individuals seeking bariatric surgery. Treadmill testing allows researchers to determine exercise capacity through metabolic equivalents. These findings can assist clinicians in understanding patients' capabilities to carry out various activities of daily living. The purpose of this study was to determine exercise tolerance and the variables associated with fitness, among individuals seeking bariatric surgery. Bariatric surgery candidates completed submaximal treadmill testing and provided ratings of perceived exertion. Each participant also completed questionnaires related to history of exercise, mood, and perceived barriers/benefits of exercise. Over half of participants reported that exercise was "hard to very hard" before reaching 70% of heart rate reserve, and one-third of participants reported that exercise was "moderately hard" at less than 3 metabolic equivalents (light activity). Body mass index and age accounted for the majority of the variance in exercise tolerance, but athletic history, employment status, and perceived health benefits also contributed. Perceived benefit scores were higher than barrier scores. Categories commonly used to describe moderate-intensity exercise (3-6 metabolic equivalents) do not coincide with perceptions of intensity among many bariatric surgery candidates, especially those with a body mass index of 50 or more.
Brownstein, C A; Margulies, D M; Manzi, S F
23andme has suspended marketing of health-related reports due to US Food and Drug Administration approval violations. This has fostered discussions on the actual risks associated with consumer use of these reports. In the case described below, rare genotypes for the gene encoding thiopurine methyltransferase (TPMT) were misinterpreted by a direct-to-consumer (DTC) company, and risk calculations for breast cancer were offered when accuracy was not possible from the available information. Politics aside, these examples illustrate risks associated with DTC genetic testing without professional interpretation.
Myers, Melanie F; Bernhardt, Barbara A
This issue of the Journal of Genetic Counseling is devoted to direct-to-consumer (DTC) genetic testing. The 15 articles in this special issue address practice considerations for genetic counselors and other health care professionals; the benefits and limitations of DTC genetic testing; consumer and provider attitudes towards and experience with DTC testing; and the roles and educational needs of genetic counselors and other health care providers in providing and interpreting DTC genetic testing. In this introduction to the special issue, we provide a brief background on DTC genetic testing, summarize the important contribution of the articles included in this issue, and outline the essential work that still needs to be done as genetic counselors are increasingly engaged in discussions, education, and research about DTC genetic testing.
Wasser, S K; Brown, L; Mailand, C; Mondol, S; Clark, W; Laurie, C; Weir, B S
Poaching of elephants is now occurring at rates that threaten African populations with extinction. Identifying the number and location of Africa's major poaching hotspots may assist efforts to end poaching and facilitate recovery of elephant populations. We genetically assign origin to 28 large ivory seizures (≥0.5 metric tons) made between 1996 and 2014, also testing assignment accuracy. Results suggest that the major poaching hotspots in Africa may be currently concentrated in as few as two areas. Increasing law enforcement in these two hotspots could help curtail future elephant losses across Africa and disrupt this organized transnational crime. Copyright © 2015, American Association for the Advancement of Science.
Lu, Mengfei; Lewis, Cathryn M; Traylor, Matthew
Rapid advances in scientific research have led to an increase in public awareness of genetic testing and pharmacogenetics. Direct-to-consumer (DTC) genetic testing companies, such as 23andMe, allow consumers to access their genetic information directly through an online service without the involvement of healthcare professionals. Here, we evaluate the clinical relevance of pharmacogenetic tests reported by 23andMe in their UK tests. The research papers listed under each 23andMe report were evaluated, extracting information on effect size, sample size and ethnicity. A wider literature search was performed to provide a fuller assessment of the pharmacogenetic test and variants were matched to FDA recommendations. Additional evidence from CPIC guidelines, PharmGKB, and Dutch Pharmacogenetics Working Group was reviewed to determine current clinical practice. The value of the tests across ethnic groups was determined, including information on linkage disequilibrium between the tested SNP and causal pharmacogenetic variant, where relevant. 23andMe offers 12 pharmacogenetic tests to their UK customers, some of which are in standard clinical practice, and others which are less widely applied. The clinical validity and clinical utility varies extensively between tests. The variants tested are likely to have different degrees of sensitivity due to different risk allele frequencies and linkage disequilibrium patterns across populations. The clinical relevance depends on the ethnicity of the individual and variability of pharmacogenetic markers. Further research is required to determine causal variants and provide more complete assessment of drug response and side effects. 23andMe reports provide some useful pharmacogenetics information, mirroring clinical tests that are in standard use. Other tests are unspecific, providing limited guidance and may not be useful for patients without professional interpretation. Nevertheless, DTC companies like 23andMe act as a powerful
Jeong, Hyeonsoo; Song, Ki-Duk; Seo, Minseok; Caetano-Anollés, Kelsey; Kim, Jaemin; Kwak, Woori; Oh, Jae-Don; Kim, EuiSoo; Jeong, Dong Kee; Cho, Seoae; Kim, Heebal; Lee, Hak-Kyo
Natural and artificial selection following domestication has led to the existence of more than a hundred pig breeds, as well as incredible variation in phenotypic traits. Berkshire pigs are regarded as having superior meat quality compared to other breeds. As the meat production industry seeks selective breeding approaches to improve profitable traits such as meat quality, information about genetic determinants of these traits is in high demand. However, most of the studies have been performed using trained sensory panel analysis without investigating the underlying genetic factors. Here we investigate the relationship between genomic composition and this phenotypic trait by scanning for signatures of positive selection in whole-genome sequencing data. We generated genomes of 10 Berkshire pigs at a total of 100.6 coverage depth, using the Illumina Hiseq2000 platform. Along with the genomes of 11 Landrace and 13 Yorkshire pigs, we identified genomic variants of 18.9 million SNVs and 3.4 million Indels in the mapped regions. We identified several associated genes related to lipid metabolism, intramuscular fatty acid deposition, and muscle fiber type which attribute to pork quality (TG, FABP1, AKIRIN2, GLP2R, TGFBR3, JPH3, ICAM2, and ERN1) by applying between population statistical tests (XP-EHH and XP-CLR). A statistical enrichment test was also conducted to detect breed specific genetic variation. In addition, de novo short sequence read assembly strategy identified several candidate genes (SLC25A14, IGF1, PI4KA, CACNA1A) as also contributing to lipid metabolism. Results revealed several candidate genes involved in Berkshire meat quality; most of these genes are involved in lipid metabolism and intramuscular fat deposition. These results can provide a basis for future research on the genomic characteristics of Berkshire pigs.
Machado, R Grecco; Eames, B Frank
Genome-wide association studies (GWASs) opened an innovative and productive avenue to investigate the molecular basis of human craniofacial disease. However, GWASs identify candidate genes only; they do not prove that any particular one is the functional villain underlying disease or just an unlucky genomic bystander. Genetic manipulation of animal models is the best approach to reveal which genetic loci identified from human GWASs are functionally related to specific diseases. The purpose of this review is to discuss the potential of zebrafish to resolve which candidate genetic loci are mechanistic drivers of craniofacial diseases. Many anatomic, embryonic, and genetic features of craniofacial development are conserved among zebrafish and mammals, making zebrafish a good model of craniofacial diseases. Also, the ability to manipulate gene function in zebrafish was greatly expanded over the past 20 y, enabling systems such as Gateway Tol2 and CRISPR-Cas9 to test gain- and loss-of-function alleles identified from human GWASs in coding and noncoding regions of DNA. With the optimization of genetic editing methods, large numbers of candidate genes can be efficiently interrogated. Finding the functional villains that underlie diseases will permit new treatments and prevention strategies and will increase understanding of how gene pathways operate during normal development.
Sánchez, Arancha; Roguev, Assen; Krogan, Nevan J; Russell, Paul
Brc1, which was first identified as a high-copy, allele-specific suppressor of a mutation impairing the Smc5-Smc6 holocomplex in Schizosaccharomyces pombe, protects genome integrity during normal DNA replication and when cells are exposed to toxic compounds that stall or collapse replication forks. The C-terminal tandem BRCT (BRCA1 C-terminus) domain of fission yeast Brc1 docks with phosphorylated histone H2A (γH2A)-marked chromatin formed by ATR/Rad3 checkpoint kinase at arrested and damaged replication forks; however, how Brc1 functions in relation to other genome protection modules remains unclear. Here, an epistatic mini-array profile reveals critical requirements for Brc1 in mutants that are defective in multiple DNA damage response pathways, including checkpoint signaling by Rad3-Rad26/ATR-ATRIP kinase, DNA repair by Smc5-Smc6 holocomplex, replication fork stabilization by Mrc1/claspin and Swi1-Swi3/Timeless-Tipin, and control of ubiquitin-regulated proteolysis by the COP9 signalosome (CSN). Exogenous genotoxins enhance these negative genetic interactions. Rad52 and RPA foci are increased in CSN-defective cells, and loss of γH2A increases genotoxin sensitivity, indicating a critical role for the γH2A-Brc1 module in stabilizing replication forks in CSN-defective cells. A negative genetic interaction with the Nse6 subunit of Smc5-Smc6 holocomplex indicates that the DNA repair functions of Brc1 and Smc5-Smc6 holocomplex are at least partially independent. Rtt107, the Brc1 homolog in Saccharomyces cerevisiae, has a very different pattern of genetic interactions, indicating evolutionary divergence of functions and DNA damage responses. Copyright © 2015 Sánchez et al.
Full Text Available Abstract Background Inbreeding can slow population growth and elevate extinction risk. A small number of unrelated immigrants to an inbred population can substantially reduce inbreeding and improve fitness, but little attention has been paid to the sex-specific effects of immigrants on such "genetic rescue". We conducted two subsequent experiments to investigate demographic consequences of inbreeding and genetic rescue in guppies. Results Populations established from pairs of full siblings that were descended either from two generations of full-sibling inbreeding or unrelated outbred guppies did not grow at different rates initially, but when the first generation offspring started breeding, outbred-founded populations grew more slowly than inbred-founded populations. In a second experiment, adding two outbred males to the inbred populations resulted in significantly faster population growth than in control populations where no immigrants were added. Adding females resulted in growth at a rate intermediate to the control and male-immigrant treatments. Conclusion The slower growth of the outbred-founded than inbred-founded populations is the opposite of what would be expected under inbreeding depression unless many deleterious recessive alleles had already been selectively purged in the inbreeding that preceded the start of the experiment, and that significant inbreeding depression occurred when the first generation offspring in outbred-founded populations started to inbreed. The second experiment revealed strong inbreeding depression in the inbred founded populations, despite the apparent lack thereof in these populations earlier on. Moreover, the fact that the addition of male immigrants resulted in the highest levels of population growth suggests that sex-specific genetic rescue may occur in promiscuous species, with male rescue resulting in higher levels of outbreeding than female rescue.
Naumova, Elena S; Naumov, Gennadi I; Michailova, Yulia V; Martynenko, Nikolay N; Masneuf-Pomarède, Isabelle
Intraspecies polymorphism of the yeast Saccharomyces bayanus var. uvarum was studied using the polymerase chain reaction with a microsatellite primer (GTG)(5). Sixty-nine strains of different origins were analyzed. There existed a correlation between PCR patterns of the strains and the source of their isolation: the type of wine and the particular winemaking region. Southern hybridization analysis revealed for the first time introgression between Saccharomyces cerevisiae and S. bayanus var. uvarum. Two strains isolated from alcoholic beverages in Hungary and identified by genetic analysis as S. bayanus var. uvarum were found to harbor a number of S. cerevisiae subtelomeric sequences: Y', SUC, RTM and MAL. Copyright © 2010 Institut Pasteur. Published by Elsevier SAS. All rights reserved.
Miah, Andy; Rich, Emma
This paper explores the prospect of genetic tests for performance in physical activity and sports practices. It investigates the terminology associated with genetics, testing, selection and ability as a means towards a socio-ethical analysis of its value within sport, education and society. Our argument suggests that genetic tests need not even be…
Cui, Zhenhai; Luo, Jinhong; Qi, Chuangye; Ruan, Yanye; Li, Jing; Zhang, Ao; Yang, Xiaohong; He, Yan
Maize (Zea mays) husk referring to the leafy outer enclosing the ear, plays an important role in grain production by directly contributing photosynthate and protecting ear from pathogen infection. Although the physiological functions related to husk have been extensively studied, little is known about its morphological variation and genetic basis in natural population. Here we utilized a maize association panel including 508 inbred lines with tropical, subtropical and temperate backgrounds to decipher the genetic architecture attributed to four husk traits, i.e. number of layers, length, width and thickness. Evaluating the phenotypic diversity at two different environments showed that four traits exhibit broadly natural variations and moderate levels of heritability with 0.64, 0.74, 0.49 and 0.75 for number, length, width and thickness, respectively. Diversity analysis indicated that different traits have dissimilar responses to subpopulation effects. A series of significantly positive or negative correlations between husk phenotypes and other agronomic traits were identified, indicating that husk growth is coordinated with other developmental processes. Combining husk traits with about half of a million of single nucleotide polymorphisms (SNPs) via genome-wide association study revealed a total of 9 variants significantly associated with traits at P husk development, and further studies on identified candidate genes facilitate to illuminate molecular pathways regulating maize husk growth.
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
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.
Eder, Thomas; Kobus, Stefanie; Stallmann, Sonja; Stepanow, Stefanie; Köhrer, Karl; Hegemann, Johannes H; Rattei, Thomas
Chlamydia trachomatis (Ctr) is a bacterial pathogen that causes ocular, urogenital and lymph system infections in humans. It is highly abundant and among its serovars, E, F and D are most prevalent in sexually transmitted disease. However, the number of publicly available genome sequences of the serovars E and F, and thereby our knowledge about the molecular architecture of these serovars, is low. Here we sequenced the genomes of six E and F clinical isolates and one E lab strain, in order to study the genetic variance in these serovars. As observed before, the genomic variation inside the Ctr genomes is very low and the phylogenetic placement in comparison to publicly available genomes is as expected by ompA gene serotyping. However, we observed a large InDel carrying four to five open reading frames in one clinical E sample and in the E lab strain. We have also observed substantial variation on nucleotide and amino acid levels, especially in membrane proteins and secreted proteins. Furthermore, these two groups of proteins are also target for recombination events. One clinical F isolate was genetically heterogeneous and revealed the highest differences on nucleotide level in the pmpE gene. © FEMS 2017.
Sarno, Stefania; Harmant, Christine; Useli, Antonella; Sanz, Paula; Yang-Yao, Daniele; Manry, Jeremy; Ciani, Graziella; Luiselli, Donata; Quintana-Murci, Lluis; Comas, David; Pettener, Davide
Located in the center of the Mediterranean landscape and with an extensive coastal line, the territory of what is today Italy has played an important role in the history of human settlements and movements of Southern Europe and the Mediterranean Basin. Populated since Paleolithic times, the complexity of human movements during the Neolithic, the Metal Ages and the most recent history of the two last millennia (involving the overlapping of different cultural and demic strata) has shaped the pattern of the modern Italian genetic structure. With the aim of disentangling this pattern and understanding which processes more importantly shaped the distribution of diversity, we have analyzed the uniparentally-inherited markers in ∼900 individuals from an extensive sampling across the Italian peninsula, Sardinia and Sicily. Spatial PCAs and DAPCs revealed a sex-biased pattern indicating different demographic histories for males and females. Besides the genetic outlier position of Sardinians, a North West–South East Y-chromosome structure is found in continental Italy. Such structure is in agreement with recent archeological syntheses indicating two independent and parallel processes of Neolithisation. In addition, date estimates pinpoint the importance of the cultural and demographic events during the late Neolithic and Metal Ages. On the other hand, mitochondrial diversity is distributed more homogeneously in agreement with older population events that might be related to the presence of an Italian Refugium during the last glacial period in Europe. PMID:23734255
Full Text Available Two hundred and fifty bread wheat lines, mainly Chinese mini core accessions, were assayed for polymorphism and linkage disequilibrium (LD based on 512 whole-genome microsatellite loci representing a mean marker density of 5.1 cM. A total of 6,724 alleles ranging from 1 to 49 per locus were identified in all collections. The mean PIC value was 0.650, ranging from 0 to 0.965. Population structure and principal coordinate analysis revealed that landraces and modern varieties were two relatively independent genetic sub-groups. Landraces had a higher allelic diversity than modern varieties with respect to both genomes and chromosomes in terms of total number of alleles and allelic richness. 3,833 (57.0% and 2,788 (41.5% rare alleles with frequencies of 0.05 (P<0.001 than the landraces. Mean LD decay distance for the landraces at the whole genome level was <5 cM, while a higher LD decay distance of 5-10 cM in modern varieties. LD decay distances were also somewhat different for each of the 21 chromosomes, being higher for most of the chromosomes in modern varieties (<5 ∼ 25 cM compared to landraces (<5 ∼ 15 cM, presumably indicating the influences of domestication and breeding. This study facilitates predicting the marker density required to effectively associate genotypes with traits in Chinese wheat genetic resources.
Gustafsson, Daniel R; Price, David A; Erséus, Christer
Genetic variation in the freshwater oligochaete Lumbriculus variegatus from Europe, North America and Japan was studied by sequencing and analysing the mitochondrial 16S and COI genes, and the nuclear ITS region. What hitherto has been regarded as L. variegatus was found to consist of at least two distinct clades (I and II), both of which occur in Europe as well as North America (clade I also in Japan). Specimens from a single locality in Sierra Nevada, California, also morphologically identified as L. variegatus, represent a third clade, which appears to be more closely related to clade II than to clade I, based on 16S data only. Average COI genetic distances were 17.7% between clades I and II, 0.6% within clade I, and 1.3% within clade II. Further, for these two clades, the mitochondrial (16S and COI) gene trees, which consider only the maternal lineages, are congruent with the ITS gene tree, which is the result of recombinations of paternal as well as maternal genomes. Finally, chromosome counts revealed clade I specimens to be highly polyploid, and clade II specimens to be diploid. We therefore conclude that clades I-II are separately evolving lineages, and that they should be regarded as separate species. This will have to be taken into account in the continued use of L. variegatus as a model organism in biological sciences.
Starkenburg, Shawn R; Kwon, Kyungyoon J; Jha, Ramesh K; McKay, Cedar; Jacobs, Michael; Chertkov, Olga; Twary, Scott; Rocap, Gabrielle; Cattolico, Rose Ann
Microalgae in the genus Nannochloropsis are photosynthetic marine Eustigmatophytes of significant interest to the bioenergy and aquaculture sectors due to their ability to efficiently accumulate biomass and lipids for utilization in renewable transportation fuels, aquaculture feed, and other useful bioproducts. To better understand the genetic complement that drives the metabolic processes of these organisms, we present the assembly and comparative pangenomic analysis of the chloroplast and mitochondrial genomes from Nannochloropsis salina CCMP1776. The chloroplast and mitochondrial genomes of N. salina are 98.4% and 97% identical to their counterparts in Nannochloropsis gaditana. Comparison of the Nannochloropsis pangenome to other algae within and outside of the same phyla revealed regions of significant genetic divergence in key genes that encode proteins needed for regulation of branched chain amino synthesis (acetohydroxyacid synthase), carbon fixation (RuBisCO activase), energy conservation (ATP synthase), protein synthesis and homeostasis (Clp protease, ribosome). Many organellar gene modifications in Nannochloropsis are unique and deviate from conserved orthologs found across the tree of life. Implementation of secondary and tertiary structure prediction was crucial to functionally characterize many proteins and therefore should be implemented in automated annotation pipelines. The exceptional similarity of the N. salina and N. gaditana organellar genomes suggests that N. gaditana be reclassified as a strain of N. salina.
Alba Linero, C; Rodríguez Calvo de Mora, M; España Contreras, M; Hernando Ayala, C
Our objective is to describe a multifocal vitelliform presentation of Best's disease. The lesions in this disease may vary in size and shape, some may be a disc diameter in size, and often have some irregularity in their contour. The case is described of a 21-year-old male patient referred to our ophthalmology department due to a progressive loss of vision. His poor visual acuity was confirmed, and a complete examination was performed, in which macular flecks were observed, with yellow pigment arranged in oval distribution near their periphery. Due to the suspicion of Best's multifocal disease, genetic tests were performed. Multifocal vitelliform disease with the same features as those in Best's disease occurs most frequently in patients with a normal electro-oculogram (EOG), and a normal family history. Best's multifocal disease must be suspected in case of multiple vitelliruptive lesions close to the posterior pole. Genetic testing is essential for its diagnosis. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.
Sharma, Sandeep; Dutta, Trishna; Maldonado, Jesús E; Wood, Thomas C; Panwar, Hemendra Singh; Seidensticker, John
We investigated the spatial genetic structure of the tiger meta-population in the Satpura-Maikal landscape of central India using population- and individual-based genetic clustering methods on multilocus genotypic data from 273 individuals. The Satpura-Maikal landscape is classified as a global-priority Tiger Conservation Landscape (TCL) due to its potential for providing sufficient habitat that will allow the long-term persistence of tigers. We found that the tiger meta-population in the Satpura-Maikal landscape has high genetic variation and very low genetic subdivision. Individual-based Bayesian clustering algorithms reveal two highly admixed genetic populations. We attribute this to forest connectivity and high gene flow in this landscape. However, deforestation, road widening, and mining may sever this connectivity, impede gene exchange, and further exacerbate the genetic division of tigers in central India.
Sharma, Sandeep; Dutta, Trishna; Maldonado, Jesús E; Wood, Thomas C; Panwar, Hemendra Singh; Seidensticker, John
We investigated the spatial genetic structure of the tiger meta-population in the Satpura–Maikal landscape of central India using population- and individual-based genetic clustering methods on multilocus genotypic data from 273 individuals. The Satpura–Maikal landscape is classified as a global-priority Tiger Conservation Landscape (TCL) due to its potential for providing sufficient habitat that will allow the long-term persistence of tigers. We found that the tiger meta-population in the Satpura–Maikal landscape has high genetic variation and very low genetic subdivision. Individual-based Bayesian clustering algorithms reveal two highly admixed genetic populations. We attribute this to forest connectivity and high gene flow in this landscape. However, deforestation, road widening, and mining may sever this connectivity, impede gene exchange, and further exacerbate the genetic division of tigers in central India. PMID:23403813
Full Text Available The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas 'sensu stricto' isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA of four core housekeeping genes (rrs, gyrB, rpoB and rpoD. A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1; P. fluorescens, P. lutea and P. syringae (NG 2; and P. rhizosphaerae (NG 3. Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria.
Howard, Heidi Carmen; Borry, Pascal
Over the last couple of years, many commercial companies, the majority of which are based in the USA, have been advertising and offering direct-to-consumer (DTC) genetic testing services outside of the established health care system, and often without any involvement from a health care professional. In the last year, however, a number of DTC genetic testing companies have changed their provision model such that consumers must now contact a health care professional before being able to order the genetic testing service. In discussing the advent of this new model of service provision, this article also reviews the ethical and social issues surrounding DTC genetic testing and addresses the potential motivations for change, some barriers to achieving truly appropriate medical supervision and the present reality of DTC genetic testing for some psychiatric and neurological disorders. Since the advent of these commercial activities, critics have pointed a finger at the lack of medical supervision surrounding these services. The discussion herein, however, reveals how difficult it may be, despite the addition of a physician, to actually achieve adequate medical supervision within the present context of DTC genetic testing.
Symula Rebecca E
Full Text Available Abstract Background Wolbachia pipientis, a diverse group of α-proteobacteria, can alter arthropod host reproduction and confer a reproductive advantage to Wolbachia-infected females (cytoplasmic incompatibility (CI. This advantage can alter host population genetics because Wolbachia-infected females produce more offspring with their own mitochondrial DNA (mtDNA haplotypes than uninfected females. Thus, these host haplotypes become common or fixed (selective sweep. Although simulations suggest that for a CI-mediated sweep to occur, there must be a transient phase with repeated initial infections of multiple individual hosts by different Wolbachia strains, this has not been observed empirically. Wolbachia has been found in the tsetse fly, Glossina fuscipes fuscipes, but it is not limited to a single host haplotype, suggesting that CI did not impact its population structure. However, host population genetic differentiation could have been generated if multiple Wolbachia strains interacted in some populations. Here, we investigated Wolbachia genetic variation in G. f. fuscipes populations of known host genetic composition in Uganda. We tested for the presence of multiple Wolbachia strains using Multi-Locus Sequence Typing (MLST and for an association between geographic region and host mtDNA haplotype using Wolbachia DNA sequence from a variable locus, groEL (heat shock protein 60. Results MLST demonstrated that some G. f. fuscipes carry Wolbachia strains from two lineages. GroEL revealed high levels of sequence diversity within and between individuals (Haplotype diversity = 0.945. We found Wolbachia associated with 26 host mtDNA haplotypes, an unprecedented result. We observed a geographical association of one Wolbachia lineage with southern host mtDNA haplotypes, but it was non-significant (p = 0.16. Though most Wolbachia-infected host haplotypes were those found in the contact region between host mtDNA groups, this association was non
Herrick, Nicole; Davis, Christopher; Vargas, Lisa; Dietz, Hal; Grossfeld, Paul
Basketball and volleyball attract individuals with a characteristic biophysical profile, mimicking features of Marfan syndrome. Consequently, identification of these abnormalities can be lifesaving. To determine how physical examination, echocardiography, and genetic screening can identify elite volleyball players with a previously undiagnosed aortopathy. We have performed cardiac screening on 90 US Volleyball National Team members and identified four individuals with dilated sinuses of Valsalva. This case series reports on three individuals who underwent a comprehensive genetics evaluation, including gene sequencing. Cardiac screening combined with genetic testing can identify previously undiagnosed tall athletes with an aortopathy, in the absence of noncardiac findings of a connective tissue disorder. Subject 1 had a revised Ghent systems (RGS) score of 2 and a normal aortopathy gene panel. Subject 2 had a RGS score of 1 and genetic testing revealed a de novo disease causing mutation in the gene encoding fibrillin-1 (FBN1). Subject 3 had an RGS score of 4.0 and had a normal aortopathy gene panel. Despite variable clinical features of Marfan syndrome, dilated sinuses of Valsalva were found in 4.9% of the athletes. A disease-causing mutation in the FBN1 gene was identified in subject 2, who had the lowest RGS but the largest aortic root measurement. Subjects 1 and 3, with the highest RGS, had a normal aortopathy gene panel. Our findings provide further evidence suggesting that a cardiac evaluation, including a screening echocardiogram, should be performed on all elite tall adult athletes independent of other physical findings. Genetic testing should be considered for athletes with dilated sinuses of Valsalva (male, >4.2 cm; female, >3.4 cm), regardless of other extracardiac findings.
Ornelas, Juan Francisco; González, Clementina; Hernández-Baños, Blanca E; García-Moreno, Jaime
The present day distribution and spatial genetic diversity of Mesoamerican biota reflects a long history of responses to habitat change. The hummingbird Lampornis amethystinus is distributed in northern Mesoamerica, with geographically disjunct populations. Based on sampling across the species range using mitochondrial DNA (mtDNA) sequences and nuclear microsatellites jointly analysed with phenotypic and climatic data, we (1) test whether the fragmented distribution is correlated with main evolutionary lineages, (2) assess body size and plumage color differentiation of populations in geographic isolation, and (3) evaluate a set of divergence scenarios and demographic patterns of the hummingbird populations. Analysis of genetic variation revealed four main groups: blue-throated populations (Sierra Madre del Sur); two groups of amethyst-throated populations (Trans-Mexican Volcanic Belt and Sierra Madre Oriental); and populations east of the Isthmus of Tehuantepec (IT) with males showing an amethyst throat. The most basal split is estimated to have originated in the Pleistocene, 2.39-0.57 million years ago (MYA), and corresponded to groups of populations separated by the IT. However, the estimated recent divergence time between blue- and amethyst-throated populations does not correspond to the 2-MY needed to be in isolation for substantial plumage divergence, likely because structurally iridescent colors are more malleable than others. Results of species distribution modeling and Approximate Bayesian Computation analysis fit a model of lineage divergence west of the Isthmus after the Last Glacial Maximum (LGM), and that the species' suitable habitat was disjunct during past and current conditions. These results challenge the generality of the contraction/expansion glacial model to cloud forest-interior species and urges management of cloud forest, a highly vulnerable ecosystem to climate change and currently facing destruction, to prevent further loss of genetic
Cortés, Kamila Caraballo; Zagordi, Osvaldo; Perlejewski, Karol; Laskus, Tomasz; Maroszek, Krzysztof; Bukowska-Ośko, Iwona; Pawełczyk, Agnieszka; Płoski, Rafał; Berak, Hanna; Horban, Andrzej; Radkowski, Marek
Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-α (pegylated interferon α) and ribavirin treatment. HVR1 sequences were amplified from pretreatment serum samples of 25 patients infected with genotype 1b HCV (12 responders and 13 non-responders) and were subjected to pyrosequencing (GS Junior, 454/Roche). Reads were corrected for sequencing error using ShoRAH software, while population reconstruction was done using three different minimal variant frequency cut-offs of 1%, 2% and 5%. Statistical analysis was done using Mann-Whitney and Fisher's exact tests. Complexity, Shannon entropy, nucleotide diversity per site, genetic distance and the number of genetic substitutions were not significantly different between responders and non-responders, when analyzing viral populations at any of the three frequencies (≥1%, ≥2% and ≥5%). When clonal sample was used to determine pyrosequencing error, 4% of reads were found to be incorrect and the most abundant variant was present at a frequency of 1.48%. Use of ShoRAH reduced the sequencing error to 1%, with the most abundant erroneous variant present at frequency of 0.5%. While deep sequencing revealed complex genetic heterogeneity of HVR1 in chronic hepatitis C patients, there was no correlation between treatment outcome and any of the analyzed quasispecies parameters.
Harbison, Susan T; Serrano Negron, Yazmin L; Hansen, Nancy F; Lobell, Amanda S
Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.
Full Text Available We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G-protein coupled receptor (GPCR signaling involving G-alphaq (G-protein alpha subunit. Our studies suggest that the small molecules act at the level of the RGS/G-alphaq signaling complex, and define new mutations in both RGS and G-alphaq, including a unique hypo-adapation allele of G-alphaq. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation.
Thomas, Jibu; Vijayan, Deepu; Joshi, Sarvottam D; Joseph Lopez, S; Raj Kumar, R
Adoption of inter simple sequence repeats (ISSR) technique to analyze the genetic variability of somatic embryo derived tea plants was evaluated. Morphological characterisation of the field grown plants revealed no identical character aligning with the parent, UPASI-10. Out of 40 primers, 15 exhibited concurrent polymorphism were selected for the study. Genetic variability of somaclones derived from single line cotyledonary culture ranged from 33.0 to 55.0%. A unique fragment of 1.2Kb was visible in majority of the accessions whereas the fragments below the length of 0.6Kb were noticed only in 50% of the variants. Out of 120 interactions attempted using Pearson's coefficient correlation, only 9.2% of somaclones exhibited significant similarity at genetic level. Dendrogram constructed based on simple matching coefficient revealed a distance of 2.257-3.317 between the final clusters. This strengthens the existence of wide genetic variation among the somaclones.
Full Text Available The Goto-Kakizaki (GK rat, which has been developed by repeated inbreeding of glucose-intolerant Wistar rats, is the most widely studied rat model for Type 2 diabetes (T2D. However, the detailed genetic background of T2D phenotype in GK rats is still largely unknown. We report a survey of T2D susceptible variations based on high-quality whole genome sequencing of GK and Wistar rats, which have generated a list of GK-specific variations (228 structural variations, 2660 CNV amplification and 2834 CNV deletion, 1796 protein affecting SNVs or indels by comparative genome analysis and identified 192 potential T2D-associated genes. The genes with variants are further refined with prior knowledge and public resource including variant polymorphism of rat strains, protein-protein interactions and differential gene expression. Finally we have identified 15 genetic mutant genes which include seven known T2D related genes (Tnfrsf1b, Scg5, Fgb, Sell, Dpp4, Icam1, and Pkd2l1 and eight high-confidence new candidate genes (Ldlr, Ccl2, Erbb3, Akr1b1, Pik3c2a, Cd5, Eef2k, and Cpd. Our result reveals that the T2D phenotype may be caused by the accumulation of multiple variations in GK rat, and that the mutated genes may affect biological functions including adipocytokine signaling, glycerolipid metabolism, PPAR signaling, T cell receptor signaling and insulin signaling pathways. We present the genomic difference between two closely related rat strains (GK and Wistar and narrow down the scope of susceptible loci. It also requires further experimental study to understand and validate the relationship between our candidate variants and T2D phenotype. Our findings highlight the importance of sequenced-based comparative genomics for investigating disease susceptibility loci in inbreeding animal models.
Villa, Francesco; Carrizzo, Albino; Spinelli, Chiara C; Ferrario, Anna; Malovini, Alberto; Maciąg, Anna; Damato, Antonio; Auricchio, Alberto; Spinetti, Gaia; Sangalli, Elena; Dang, Zexu; Madonna, Michele; Ambrosio, Mariateresa; Sitia, Leopoldo; Bigini, Paolo; Calì, Gaetano; Schreiber, Stefan; Perls, Thomas; Fucile, Sergio; Mulas, Francesca; Nebel, Almut; Bellazzi, Riccardo; Madeddu, Paolo; Vecchione, Carmine; Puca, Annibale A
Long living individuals show delay of aging, which is characterized by the progressive loss of cardiovascular homeostasis, along with reduced endothelial nitric oxide synthase activity, endothelial dysfunction, and impairment of tissue repair after ischemic injury. Exploit genetic analysis of long living individuals to reveal master molecular regulators of physiological aging and new targets for treatment of cardiovascular disease. We show that the polymorphic variant rs2070325 (Ile229Val) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) associates with exceptional longevity, under a recessive genetic model, in 3 independent populations. Moreover, the expression of BPIFB4 is instrumental to maintenance of cellular and vascular homeostasis through regulation of protein synthesis. BPIFB4 phosphorylation/activation by protein-kinase-R-like endoplasmic reticulum kinase induces its complexing with 14-3-3 and heat shock protein 90, which is facilitated by the longevity-associated variant. In isolated vessels, BPIFB4 is upregulated by mechanical stress, and its knock-down inhibits endothelium-dependent vasorelaxation. In hypertensive rats and old mice, gene transfer of longevity-associated variant-BPIFB4 restores endothelial nitric oxide synthase signaling, rescues endothelial dysfunction, and reduces blood pressure levels. Furthermore, BPIFB4 is implicated in vascular repair. BPIFB4 is abundantly expressed in circulating CD34(+) cells of long living individuals, and its knock-down in endothelial progenitor cells precludes their capacity to migrate toward the chemoattractant SDF-1. In a murine model of peripheral ischemia, systemic gene therapy with longevity-associated variant-BPIFB4 promotes the recruitment of hematopoietic stem cells, reparative vascularization, and reperfusion of the ischemic muscle. Longevity-associated variant-BPIFB4 may represent a novel therapeutic tool to fight endothelial dysfunction and promote vascular
Full Text Available The common carp is an important aquaculture species that is widely distributed across the world. During the long history of carp domestication, numerous carp strains with diverse skin colors have been established. Skin color is used as a visual criterion to determine the market value of carp. However, the genetic basis of common carp skin color has not been extensively studied.In this study, we performed Illumina sequencing on two common carp strains: the reddish Xingguo red carp and the brownish-black Yellow River carp. A total of 435,348,868 reads were generated, resulting in 198,781 assembled contigs that were used as reference sequences. Comparisons of skin transcriptome files revealed 2,012 unigenes with significantly different expression in the two common carp strains, including 874 genes that were up-regulated in Xingguo red carp and 1,138 genes that were up-regulated in Yellow River carp. The expression patterns of 20 randomly selected differentially expressed genes were validated using quantitative RT-PCR. Gene pathway analysis of the differentially expressed genes indicated that melanin biosynthesis, along with the Wnt and MAPK signaling pathways, is highly likely to affect the skin pigmentation process. Several key genes involved in the skin pigmentation process, including TYRP1, SILV, ASIP and xCT, showed significant differences in their expression patterns between the two strains.In this study, we conducted a comparative transcriptome analysis of Xingguo red carp and Yellow River carp skins, and we detected key genes involved in the common carp skin pigmentation process. We propose that common carp skin pigmentation depends upon at least three pathways. Understanding fish skin color genetics will facilitate future molecular selection of the fish skin colors with high market values.
Full Text Available Genetics and organic chemistry are areas of science that students regard as difficult to learn. Part of this difficulty is derived from the disciplines having representations as part of their discourses. In order to optimally support students’ meaning-making, teachers need to use representations to structure the meaning-making experience in thoughtful ways that consider the variation in students’ prior knowledge. Using a focus group setting, we explored 43 university students’ reasoning on representations in introductory chemistry and genetics courses. Our analysis of eight focus group discussions revealed how students can construct somewhat bewildered relations with disciplinary-specific representations. The students stated that they preferred familiar representations, but without asserting the meaning-making affordances of those representations. Also, the students were highly aware of the affordances of certain representations, but nonetheless chose not to use those representations in their problem solving. We suggest that an effective representation is one that, to some degree, is familiar to the students, but at the same time is challenging and not too closely related to “the usual one”. The focus group discussions led the students to become more aware of their own and others ways of interpreting different representations. Furthermore, feedback from the students’ focus group discussions enhanced the teachers’ awareness of the students’ prior knowledge and limitations in students’ representational literacy. Consequently, we posit that a focus group setting can be used in a university context to promote both student meaning-making and teacher professional development in a fruitful way.
Wolfe, Kate; Stueber, Kerstin; McQuillin, Andrew; Jichi, Fatima; Patch, Christine; Flinter, Frances; Strydom, André; Bass, Nick
Background: An increasing number of genetic causes of intellectual disabilities (ID) are identifiable by clinical genetic testing, offering the prospect of bespoke patient management. However, little is known about the practices of psychiatrists and their views on genetic testing. Method: We undertook an online survey of 215 psychiatrists, who…
Sun, Rongxi; Lin, Furong; Huang, Ping; Zheng, Yongqi
Chinese sweetgum ( Liquidambar formosana ) is a relatively fast-growing ecological pioneer species. It is widely used for multiple purposes. To assess the genetic diversity and genetic differentiation of the species, genic SSR markers were mined from transcriptome data for subsequent analysis of the genetic diversity and population structure of natural populations. A total of 10645 potential genic SSR loci were identified in 80482 unigenes. The average frequency was one SSR per 5.12 kb, and the dinucleotide unit was the most abundant motif. A total of 67 alleles were found, with a mean of 6.091 alleles per locus and a mean polymorphism information content of 0.390. Moreover, the species exhibited a relatively moderate level of genetic diversity ( He = 0.399), with the highest was found in population XY ( He = 0.469). At the regional level, the southwestern region displayed the highest genetic diversity ( He = 0.435) and the largest number of private alleles (n = 5), which indicated that the Southwestern region may be the diversity hot spot of L. formosana. The AMOVA results showed that variation within populations (94.02%) was significantly higher than among populations (5.98%), which was in agreement with the coefficient of genetic differentiation ( Fst = 0.076). According to the UPGMA analysis and principal coordinate analysis and confirmed by the assignment test, 25 populations could be divided into three groups, and there were different degrees of introgression among populations. No correlation was found between genetic distance and geographic distance (P > 0.05). These results provided further evidence that geographic isolation was not the primary factor leading to the moderate genetic differentiation of L. formosana . As most of the genetic diversity of L. formosana exists among individuals within a population, individual plant selection would be an effective way to use natural variation in genetic improvement programs. This would be helpful to not only
Full Text Available Spatial genetics is a relatively new field in wildlife and conservation biology that is becoming an essential tool for unravelling the complexities of animal population processes, and for designing effective strategies for conservation and management. Conceptual and methodological developments in this field are therefore critical. Here we present two novel methodological approaches that further the analytical possibilities of STRUCTURE and DResD. Using these approaches we analyse structure and migrations in a grey wolf (Canislupus population in north-eastern Europe. We genotyped 16 microsatellite loci in 166 individuals sampled from the wolf population in Estonia and Latvia that has been under strong and continuous hunting pressure for decades. Our analysis demonstrated that this relatively small wolf population is represented by four genetic groups. We also used a novel methodological approach that uses linear interpolation to statistically test the spatial separation of genetic groups. The new method, which is capable of using program STRUCTURE output, can be applied widely in population genetics to reveal both core areas and areas of low significance for genetic groups. We also used a recently developed spatially explicit individual-based method DResD, and applied it for the first time to microsatellite data, revealing a migration corridor and barriers, and several contact zones.
Paul R. Brezina MD, MBA
The past hundred years have given birth to arguably the most profound changes in society, medicine, and technology the world has ever witnessed. Genetics is one such field that has enjoyed a meteoric rise during this time. Progressing from Mendelian genetics to the discovery of DNA to the ability to sequence the human genome, perhaps no other discipline holds more promise to affect future change than genetics. Technology currently exists to evaluate some of the genetic information held by dev...
The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.
Hoerner, Rebecca; Feldpausch, Jill; Gray, R Lucas; Curry, Stephanie; Islam, Zahidul; Goldy, Tim; Klein, Frank; Tadese, Theodros; Rice, Jennifer; Mozola, Mark
Reveal Salmonella 2.0 is an improved version of the original Reveal Salmonella lateral flow immunoassay and is applicable to the detection of Salmonella enterica serogroups A-E in a variety of food and environmental samples. A Performance Tested Method validation study was conducted to compare performance of the Reveal 2.0 method with that of the U.S. Department of Agriculture-Food Safety and Inspection Service or U.S. Food and Drug Administration/Bacteriological Analytical Manual reference culture methods for detection of Salmonella spp. in chicken carcass rinse, raw ground turkey, raw ground beef, hot dogs, raw shrimp, a ready-to-eat meal product, dry pet food, ice cream, spinach, cantaloupe, peanut butter, stainless steel surface, and sprout irrigation water. In a total of 17 trials performed internally and four trials performed in an independent laboratory, there were no statistically significant differences in performance of the Reveal 2.0 and reference culture procedures as determined by Chi-square analysis, with the exception of one trial with stainless steel surface and one trial with sprout irrigation water where there were significantly more positive results by the Reveal 2.0 method. Considering all data generated in testing food samples using enrichment procedures specifically designed for the Reveal method, overall sensitivity of the Reveal method relative to the reference culture methods was 99%. In testing environmental samples, sensitivity of the Reveal method relative to the reference culture method was 164%. For select foods, use of the Reveal test in conjunction with reference method enrichment resulted in overall sensitivity of 92%. There were no unconfirmed positive results on uninoculated control samples in any trials for specificity of 100%. In inclusivity testing, 102 different Salmonella serovars belonging to serogroups A-E were tested and 99 were consistently positive in the Reveal test. In exclusivity testing of 33 strains of non
The author inquires into the relation between the production of genetic knowledge on the one hand, and human autonomy and self-determination on the other. He does so by specifying the notions of “genetic test” and “human autonomy”; by discussing the epistemic status of genetic knowledge, given its importance for the ...
Latch, Emily K.; William I Boarman; Andrew Walde; Robert C Fleischer
Characterizing the effects of landscape features on genetic variation is essential for understanding how landscapes shape patterns of gene flow and spatial genetic structure of populations. Most landscape genetics studies have focused on patterns of gene flow at a regional scale. However, the genetic structure of populations at a local scale may be influenced by a unique suite of landscape variables that have little bearing on connectivity patterns observed at broader spatial scales. We inves...
Lim, Phaik-Eem; Tan, Ji; Suana, I Wayan; Eamsobhana, Praphathip; Yong, Hoi Sen
The fruit fly Bactrocera caudata is a pest species of economic importance in Asia. Its larvae feed on the flowers of Cucurbitaceae such as Cucurbita moschata. To-date it is distinguished from related species based on morphological characters. Specimens of B. caudata from Peninsular Malaysia and Indonesia (Bali and Lombok) were analysed using the partial DNA sequences of cytochrome c oxidase subunit I (COI) and 16S rRNA genes. Both gene sequences revealed that B. caudata from Peninsular Malaysia was distinctly different from B. caudata of Bali and Lombok, without common haplotype between them. Phylogenetic analysis revealed two distinct clades, indicating distinct genetic lineage. The uncorrected 'p' distance for COI sequences between B. caudata of Malaysia-Thailand-China and B. caudata of Bali-Lombok was 5.65%, for 16S sequences from 2.76 to 2.99%, and for combined COI and 16S sequences 4.45 to 4.46%. The 'p' values are distinctly different from intraspecific 'p' distance (0-0.23%). Both the B. caudata lineages are distinctly separated from related species in the subgenus Zeugodacus - B. ascita, B. scutellata, B. ishigakiensis, B. diaphora, B. tau, B. cucurbitae, and B. depressa. Molecular phylogenetic analysis indicates that the B. caudata lineages are closely related to B. ascita sp. B, and form a clade with B. scutellata, B. ishigakiensis, B. diaphora and B. ascita sp. A. This study provides additional baseline for the phylogenetic relationships of Bactrocera fruit flies of the subgenus Zeugodacus. Both the COI and 16S genes could be useful markers for the molecular differentiation and phylogenetic analysis of tephritid fruit flies.
Lim, Phaik-Eem; Tan, Ji; Suana, I. Wayan; Eamsobhana, Praphathip; Yong, Hoi Sen
The fruit fly Bactrocera caudata is a pest species of economic importance in Asia. Its larvae feed on the flowers of Cucurbitaceae such as Cucurbita moschata. To-date it is distinguished from related species based on morphological characters. Specimens of B. caudata from Peninsular Malaysia and Indonesia (Bali and Lombok) were analysed using the partial DNA sequences of cytochrome c oxidase subunit I (COI) and 16S rRNA genes. Both gene sequences revealed that B. caudata from Peninsular Malaysia was distinctly different from B. caudata of Bali and Lombok, without common haplotype between them. Phylogenetic analysis revealed two distinct clades, indicating distinct genetic lineage. The uncorrected ‘p’ distance for COI sequences between B. caudata of Malaysia-Thailand-China and B. caudata of Bali-Lombok was 5.65%, for 16S sequences from 2.76 to 2.99%, and for combined COI and 16S sequences 4.45 to 4.46%. The ‘p’ values are distinctly different from intraspecific ‘p’ distance (0–0.23%). Both the B. caudata lineages are distinctly separated from related species in the subgenus Zeugodacus – B. ascita, B. scutellata, B. ishigakiensis, B. diaphora, B. tau, B. cucurbitae, and B. depressa. Molecular phylogenetic analysis indicates that the B. caudata lineages are closely related to B. ascita sp. B, and form a clade with B. scutellata, B. ishigakiensis, B. diaphora and B. ascita sp. A. This study provides additional baseline for the phylogenetic relationships of Bactrocera fruit flies of the subgenus Zeugodacus. Both the COI and 16S genes could be useful markers for the molecular differentiation and phylogenetic analysis of tephritid fruit flies. PMID:22615962
Full Text Available The fruit fly Bactrocera caudata is a pest species of economic importance in Asia. Its larvae feed on the flowers of Cucurbitaceae such as Cucurbita moschata. To-date it is distinguished from related species based on morphological characters. Specimens of B. caudata from Peninsular Malaysia and Indonesia (Bali and Lombok were analysed using the partial DNA sequences of cytochrome c oxidase subunit I (COI and 16S rRNA genes. Both gene sequences revealed that B. caudata from Peninsular Malaysia was distinctly different from B. caudata of Bali and Lombok, without common haplotype between them. Phylogenetic analysis revealed two distinct clades, indicating distinct genetic lineage. The uncorrected 'p' distance for COI sequences between B. caudata of Malaysia-Thailand-China and B. caudata of Bali-Lombok was 5.65%, for 16S sequences from 2.76 to 2.99%, and for combined COI and 16S sequences 4.45 to 4.46%. The 'p' values are distinctly different from intraspecific 'p' distance (0-0.23%. Both the B. caudata lineages are distinctly separated from related species in the subgenus Zeugodacus - B. ascita, B. scutellata, B. ishigakiensis, B. diaphora, B. tau, B. cucurbitae, and B. depressa. Molecular phylogenetic analysis indicates that the B. caudata lineages are closely related to B. ascita sp. B, and form a clade with B. scutellata, B. ishigakiensis, B. diaphora and B. ascita sp. A. This study provides additional baseline for the phylogenetic relationships of Bactrocera fruit flies of the subgenus Zeugodacus. Both the COI and 16S genes could be useful markers for the molecular differentiation and phylogenetic analysis of tephritid fruit flies.
To determine the genetic architecture of trout in Albania, 87 individuals were collected from 19 riverine and lacustrine sites in Albania, FYROM and Greece. All individuals were analyzed for sequence variation in the mtDNA control region. Among fourteen haplotypes detected, four previously unpublished haplotypes, bearing a close relationship to haplotypes of the Adriatic and marmoratus lineages of Salmo trutta, were revealed. Ten previously described haplotypes, characteristic of S. ohridanus, S. letnica and the Adriatic and Mediterranean lineages of S. trutta, were also detected. Haplotypes detected in this study were placed in a well supported branch of S. ohridanus, and a cluster of Mediterranean – Adriatic – marmoratus haplotypes, which were further delimited into three subdivisions of Mediterranean, marmoratus, and a previously non-described formation of four Adriatic haplotypes (Balkan cluster). Haplotypes of the Balkan cluster and the other Adriatic haplotypes, do not represent a contiguous haplotype lineage and appear not to be closely related, indicating independent arrivals into the Adriatic drainage and suggesting successive colonization events. Despite the presence of marmoratus haplotypes in Albania, no marbled phenotype was found, confirming previously reported findings that there is no association between this phenotype and marmoratus haplotypes. PMID:19284692
Guo, Jianhua; Li, Jie; Chen, Hui; Bond, Philip L; Yuan, Zhiguo
The intensive use of antibiotics results in their continuous release into the environment and the subsequent widespread occurrence of antibiotic resistant bacteria (ARB), antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). This study used Illumina high-throughput sequencing to investigate the broad-spectrum profiles of both ARGs and MGEs in activated sludge and anaerobically digested sludge from a full-scale wastewater treatment plant. A pipeline for identifying antibiotic resistance determinants was developed that consisted of four categories: gene transfer potential, ARG potential, ARGs pathway and ARGs phylogenetic origin. The metagenomic analysis showed that the activated sludge and the digested sludge exhibited different microbial communities and changes in the types and occurrence of ARGs and MGEs. In total, 42 ARGs subtypes were identified in the activated sludge, while 51 ARG subtypes were detected in the digested sludge. Additionally, MGEs including plasmids, transposons, integrons (intI1) and insertion sequences (e.g. ISSsp4, ISMsa21 and ISMba16) were abundant in the two sludge samples. The co-occurrence pattern between ARGs and microbial taxa revealed by network analysis indicated that some environmental bacteria (e.g. Clostridium and Nitrosomonas) might be potential hosts of multiple ARGs. The findings increase our understanding of WWTPs as hotspots of ARGs and MGEs, and contribute towards preventing their release into the downstream environment. Copyright © 2017 Elsevier Ltd. All rights reserved.
Full Text Available The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs are considered as important reservoirs for antibiotic resistance genes (ARGs and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT via mobile genetic elements (MGEs. However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In this study, the transposon aided capture (TRACA system was employed to isolate novel plasmids from activated sludge of one STP in Hong Kong, China. We also used Illumina Hiseq 2000 high-throughput sequencing and metagenomics analysis to investigate the plasmid metagenome. Two novel plasmids were acquired from the sludge microbiome by using TRACA system and one novel plasmid was identified through metagenomics analysis. Our results revealed high levels of various ARGs as well as MGEs for HGT, including integrons, transposons and plasmids. The application of the TRACA system to isolate novel plasmids from the environmental metagenome, coupled with subsequent high-throughput sequencing and metagenomic analysis, highlighted the prevalence of ARGs and MGEs in microbial community of STPs.
Zhang, Tong; Zhang, Xu-Xiang; Ye, Lin
The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs) are considered as important reservoirs for antibiotic resistance genes (ARGs) and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT) via mobile genetic elements (MGEs). However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In this study, the transposon aided capture (TRACA) system was employed to isolate novel plasmids from activated sludge of one STP in Hong Kong, China. We also used Illumina Hiseq 2000 high-throughput sequencing and metagenomics analysis to investigate the plasmid metagenome. Two novel plasmids were acquired from the sludge microbiome by using TRACA system and one novel plasmid was identified through metagenomics analysis. Our results revealed high levels of various ARGs as well as MGEs for HGT, including integrons, transposons and plasmids. The application of the TRACA system to isolate novel plasmids from the environmental metagenome, coupled with subsequent high-throughput sequencing and metagenomic analysis, highlighted the prevalence of ARGs and MGEs in microbial community of STPs.
Fan, Wenqiao; Jiang, Yusong; Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Sun, Hanchang; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan
Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians.
Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan
Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians. PMID:29267366
da Silva, Flavio R C; Daudt, Cíntia; Streck, André F; Weber, Matheus N; Filho, Ronaldo V Leite; Driemeier, David; Canal, Cláudio W
Papillomaviruses are small and complex viruses that belong to the Papillomaviridae family, which comprises 39 genera. The bovine papillomavirus (BPV) causes an infectious disease that is characterized by chronic and proliferative benign tumors that affect cattle worldwide. Different genotypes of BPVs can cause distinct skin and mucosal lesions and the immunity they raise has low cross-protection. This report aimed to genotype BPVs in cattle from Northern Brazil based on nucleotide partial sequences of the L1 ORF. Skin wart samples from 39 bovines clinically and histopathologically diagnosed as cutaneous papillomatosis from Acre and Rondônia States were analyzed. The results revealed four already reported BPV types (BPVs 1, 2, 11, and 13), nine putative new BPV subtypes and four putative new BPV types as well as two putative new BPV types that were already reported. To our knowledge, this is the first record of BPVs from the Brazilian Amazon region that identified new possible BPV types and subtypes circulating in this population. These findings point to the great genetic diversity of BPVs that are present in this region and highlight the importance of this knowledge before further studies about vaccination are attempted.
Batts, William N; Falk, Knut; Winton, James R
Viruses with the morphological and biochemical characteristics of the family Paramyxoviridae (paramyxoviruses) have been isolated from adult salmon returning to rivers along the Pacific coast of North America since 1982. These Pacific salmon paramyxoviruses (PSPV), which have mainly been isolated from Chinook salmon Oncorhynchus tshawytscha, grow slowly in established fish cell lines and have not been associated with disease. Genetic analysis of a 505-base-pair region of the polymerase gene from 47 PSPV isolates produced 17 nucleotide sequence types that could be grouped into two major sublineages, designated A and B. The two independently co-circulating sublineages differed by 12.1-13.9% at the nucleotide level but by only 1.2% at the amino acid level. Isolates of PSPV from adult Pacific salmon returning to rivers from Alaska to California over a 25-year period showed little evidence of geographic or temporal grouping. Phylogenetic analyses revealed that these paramyxoviruses of Pacific salmon were most closely related to the Atlantic salmon paramyxovirus (ASPV) from Norway, having a maximum nucleotide diversity of 26.1% and an amino acid diversity of 19.0%. When compared with homologous sequences of other paramyxoviruses, PSPV and ASPV were sufficiently distinct to suggest that they are not clearly members of any of the established genera in the family Paramyxoviridae. In the course of this study, a polymerase chain reaction assay was developed that can be used for confirmatory identification of PSPV.
Bai, Xufeng; Zhao, Hu; Huang, Yong; Xie, Weibo; Han, Zhongmin; Zhang, Bo; Guo, Zilong; Yang, Lin; Dong, Haijiao; Xue, Weiya; Li, Guangwei; Hu, Gang; Hu, Yong; Xing, Yongzhong
Panicle architecture determines the number of spikelets per panicle (SPP) and is highly associated with grain yield in rice ( L.). Understanding the genetic basis of panicle architecture is important for improving the yield of rice grain. In this study, we dissected panicle architecture traits into eight components, which were phenotyped from a germplasm collection of 529 cultivars. Multiple regression analysis revealed that the number of secondary branch (NSB) was the major factor that contributed to SPP. Genome-wide association analysis was performed independently for the eight particle architecture traits observed in the and rice subpopulations compared with the whole rice population. In total, 30 loci were associated with these traits. Of these, 13 loci were closely linked to known panicle architecture genes, and 17 novel loci were repeatedly identified in different environments. An association signal cluster was identified for NSB and number of spikelets per secondary branch (NSSB) in the region of 31.6 to 31.7 Mb on chromosome 4. In addition to the common associations detected in both and subpopulations, many associated loci were unique to one subpopulation. For example, and were specifically associated with panicle length (PL) in and rice, respectively. Moreover, the -mediated flowering genes and were associated with the formation of panicle architecture in rice. These results suggest that different gene networks regulate panicle architecture in and rice. Copyright © 2016 Crop Science Society of America.
Full Text Available The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity. Glycobiological approaches revealed that mutations in DS-biosynthetic enzymes cause reductions in enzymatic activities and in the amount of synthesized DS and also disrupt the formation of collagen bundles. This review focused on the growing number of glycobiological studies on recently reported genetic diseases caused by defects in the biosynthesis of DS and DS-PGs.
Shagalov, Devorah R; Ferzli, Georgina M; Wildman, Temima; Glick, Sharon A
The past several decades have witnessed unprecedented advances in genomic technology, bringing genetic testing to the forefront of medical practice and moving us towards the practice of personalized medicine. Genetic testing has become an important aspect in preempting and successfully treating diseases in dermatology, yet difficulty remains in regards to obtaining genetic testing for patients. We conducted a survey for pediatric dermatologists in order to try to gauge and understand where difficulties lie in obtaining genetic testing and to analyze how best these issues can be resolved. An 18-question survey was emailed to 480 dermatologists who have attended at least one of the last three annual Society for Pediatric Dermatology (SPD) meetings. Virtually all providers encountered at least one situation in which they required genetic testing for a patient (97.3% [n = 108]) and 37.4% indicated needing genetic testing more than six times per year. Of the respondents who had attempted to obtain genetic testing, half were unsuccessful in obtaining coverage more than 75% of the time (45% [n = 32]) and only 7.0% (n = 5) achieved success 75% to 100% of the time. The most common reasons for obtaining genetic testing included the need to provide an accurate diagnosis, followed by the need to provide prognostic information and appropriate medical management. The role of genetic testing in the practice of dermatology is expanding, yet obtaining coverage for genetic testing remains a challenge. We propose several solutions as to how this can be remedied. © 2016 Wiley Periodicals, Inc.
Full Text Available Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity.
Ren, Jing; Sun, Daokun; Chen, Liang; You, Frank M.; Wang, Jirui; Peng, Yunliang; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua
Evaluation of genetic diversity and genetic structure in crops has important implications for plant breeding programs and the conservation of genetic resources. Newly developed single nucleotide polymorphism (SNP) markers are effective in detecting genetic diversity. In the present study, a worldwide durum wheat collection consisting of 150 accessions was used. Genetic diversity and genetic structure were investigated using 946 polymorphic SNP markers covering the whole genome of tetraploid wheat. Genetic structure was greatly impacted by multiple factors, such as environmental conditions, breeding methods reflected by release periods of varieties, and gene flows via human activities. A loss of genetic diversity was observed from landraces and old cultivars to the modern cultivars released during periods of the Early Green Revolution, but an increase in cultivars released during the Post Green Revolution. Furthermore, a comparative analysis of genetic diversity among the 10 mega ecogeographical regions indicated that South America, North America, and Europe possessed the richest genetic variability, while the Middle East showed moderate levels of genetic diversity. PMID:23538839
Full Text Available Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set of mutation(s that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo.
Guy, Endrick; Genissel, Anne; Hajri, Ahmed; Chabannes, Matthieu; David, Perrine; Carrere, Sébastien; Lautier, Martine; Roux, Brice; Boureau, Tristan; Arlat, Matthieu; Poussier, Stéphane; Noël, Laurent D.
ABSTRACT The pathogenic bacterium Xanthomonas campestris pv. campestris, the causal agent of black rot of Brassicaceae, manipulates the physiology and the innate immunity of its hosts. Association genetic and reverse-genetic analyses of a world panel of 45 X. campestris pv. campestris strains were used to gain understanding of the genetic basis of the bacterium’s pathogenicity to Arabidopsis thaliana. We found that the compositions of the minimal predicted type III secretome varied extensively, with 18 to 28 proteins per strain. There were clear differences in aggressiveness of those X. campestris pv. campestris strains on two Arabidopsis natural accessions. We identified 3 effector genes (xopAC, xopJ5, and xopAL2) and 67 amplified fragment length polymorphism (AFLP) markers that were associated with variations in disease symptoms. The nature and distribution of the AFLP markers remain to be determined, but we observed a low linkage disequilibrium level between predicted effectors and other significant markers, suggesting that additional genetic factors make a meaningful contribution to pathogenicity. Mutagenesis of type III effectors in X. campestris pv. campestris confirmed that xopAC functions as both a virulence and an avirulence gene in Arabidopsis and that xopAM functions as a second avirulence gene on plants of the Col-0 ecotype. However, we did not detect the effect of any other effector in the X. campestris pv. campestris 8004 strain, likely due to other genetic background effects. These results highlight the complex genetic basis of pathogenicity at the pathovar level and encourage us to challenge the agronomical relevance of some virulence determinants identified solely in model strains. PMID:23736288
Blanco, Eleonora Zambrano; Bajay, Miklos Maximiliano; Siqueira, Marcos Vinícius Bohrer Monteiro; Zucchi, Maria Imaculada; Pinheiro, José Baldin
Ginger is a vegetable with medicinal and culinary properties widely cultivated in the Southern and Southeastern Brazil. The knowledge of ginger species' genetic variability is essential to direct correctly future studies of conservation and genetic improvement, but in Brazil, little is known about this species' genetic variability. In this study, we analyzed the genetic diversity and structure of 55 Brazilian accessions and 6 Colombian accessions of ginger, using AFLP (Amplified Fragment Length Polymorphism) molecular markers. The molecular characterization was based on 13 primers combinations, which generated an average of 113.5 polymorphic loci. The genetic diversity estimates of Nei (Hj), Shannon-Weiner index (I) and an effective number of alleles (n e ) were greater in the Colombian accessions in relation to the Brazilian accessions. The analysis of molecular variance showed that most of the genetic variation occurred between the two countries while in the Brazilian populations there is no genetic structure and probably each region harbors 100 % of genetic variation found in the samples. The bayesian model-based clustering and the dendrogram using the dissimilarity's coefficient of Jaccard were congruent with each other and showed that the Brazilian accessions are highly similar between themselves, regardless of the geographic region of origin. We suggested that the exploration of the interspecific variability and the introduction of new varieties of Z.officinale are viable alternatives for generating diversity in breeding programs in Brazil. The introduction of new genetic materials will certainly contribute to a higher genetic basis of such crop.
Botkin, Jeffrey R; Belmont, John W; Berg, Jonathan S; Berkman, Benjamin E; Bombard, Yvonne; Holm, Ingrid A; Levy, Howard P; Ormond, Kelly E; Saal, Howard M; Spinner, Nancy B; Wilfond, Benjamin S; McInerney, Joseph D
In 1995, the American Society of Human Genetics (ASHG) and American College of Medical Genetics and Genomics (ACMG) jointly published a statement on genetic testing in children and adolescents. In the past 20 years, much has changed in the field of genetics, including the development of powerful new technologies, new data from genetic research on children and adolescents, and substantial clinical experience. This statement represents current opinion by the ASHG on the ethical, legal, and social issues concerning genetic testing in children. These recommendations are relevant to families, clinicians, and investigators. After a brief review of the 1995 statement and major changes in genetic technologies in recent years, this statement offers points to consider on a broad range of test technologies and their applications in clinical medicine and research. Recommendations are also made for record and communication issues in this domain and for professional education. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Atkinson Carter T
Full Text Available Abstract Background The relatively recent introduction of a highly efficient mosquito vector and an avian pathogen (Plasmodium relictum to an isolated island ecosystem with naïve, highly susceptible avian hosts provides a unique opportunity to investigate evolution of virulence in a natural system. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct impacts on virulence. Toward further understanding of how host-parasite and parasite-parasite relationships may impact virulence, this study characterizes within-host diversity of malaria parasite populations based on genetic analysis of the trap (thrombospondin-related anonymous protein gene in isolates originating from Hawaii, Maui and Kauai Islands. Methods A total of 397 clones were produced by nested PCR amplification and cloning of a 1664 bp fragment of the trap gene from two malarial isolates, K1 (Kauai and KV115 (Hawaii that have been used for experimental studies, and from additional isolates from wild birds on Kauai, Maui and Hawaii Islands. Diversity of clones was evaluated initially by RFLP-based screening, followed by complete sequencing of 33 selected clones. Results RFLP analysis of trap revealed a minimum of 28 distinct RFLP haplotypes among the 397 clones from 18 birds. Multiple trap haplotypes were detected in every bird evaluated, with an average of 5.9 haplotypes per bird. Overall diversity did not differ between the experimental isolates, however, a greater number of unique haplotypes were detected in K1 than in KV115. We detected high levels of clonal diversity with clear delineation between isolates K1 and KV115 in a haplotype network. The patterns of within-host haplotype clustering are consistent with the possibility of a clonal genetic structure and rapid within-host mutation after infection. Conclusion Avian malaria (P. relictum and Avipoxvirus are the significant infectious diseases currently affecting the native Hawaiian
Jarvi, S.I.; Farias, M.E.M.; Atkinson, C.T.
Background: The relatively recent introduction of a highly efficient mosquito vector and an avian pathogen (Plasmodium relictum) to an isolated island ecosystem with nai??ve, highly susceptible avian hosts provides a unique opportunity to investigate evolution of virulence in a natural system. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct impacts on virulence. Toward further understanding of how host-parasite and parasite-parasite relationships may impact virulence, this study characterizes within-host diversity of malaria parasite populations based on genetic analysis of the trap (thrombospondin-related anonymous protein) gene in isolates originating from Hawaii, Maui and Kauai Islands. Methods: A total of 397 clones were produced by nested PCR amplification and cloning of a 1664 bp fragment of the trap gene from two malarial isolates, K1 (Kauai) and KV115 (Hawaii) that have been used for experimental studies, and from additional isolates from wild birds on Kauai, Maui and Hawaii Islands. Diversity of clones was evaluated initially by RFLP-based screening, followed by complete sequencing of 33 selected clones. Results: RFLP analysis of trap revealed a minimum of 28 distinct RFLP haplotypes among the 397 clones from 18 birds. Multiple trap haplotypes were detected in every bird evaluated, with an average of 5.9 haplotypes per bird. Overall diversity did not differ between the experimental isolates, however, a greater number of unique haplotypes were detected in K1 than in KV115. We detected high levels of clonal diversity with clear delineation between isolates K1 and KV115 in a haplotype network. The patterns of within-host haplotype clustering are consistent with the possibility of a clonal genetic structure and rapid within-host mutation after infection. Conclusion: Avian malaria (P. relictum) and Avipoxvirus are the significant infectious diseases currently affecting the native Hawaiian avifauna. This
Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.
Full Text Available The objective of this work was to evaluate the genetic diversity, its organization and the genetic relationships within oil palm (Elaeis oleifera (Kunth Cortés, from America, and E. guineensis (Jacq., from Africa germplasm using Restriction Fragment Length Polymorphism (RFLP and Amplified Fragment Length Polymorphism (AFLP. In complement to a previous RFLP study on 241 E. oleifera accessions, 38 E. guineensis accessions were analyzed using the same 37 cDNA probes. These accessions covered a large part of the geographical distribution areas of these species in America and Africa. In addition, AFLP analysis was performed on a sub-set of 40 accessions of E. oleifera and 22 of E. guineensis using three pairs of enzyme/primer combinations. Data were subjected to Factorial Analysis of Correspondence (FAC and cluster analysis, with parameters of genetic diversity being also studied. Results appeared congruent between RFLP and AFLP. In the E. oleifera, AFLP confirmed the strong structure of genetic diversity revealed by RFLP, according to geographical origin of the studied material, with the identification of the same four distinct genetic groups: Brazil, French Guyana/Surinam, Peru, north of Colombia/Central America. Both markers revealed that genetic divergence between the two species is of the same magnitude as that among provenances of E. oleifera. This finding is in discrepancy with the supposed early tertiary separation of the two species.
Vinh, Nguyen Xuan
It is widely recognized nowadays that complex diseases are caused by, amongst the others, multiple genetic factors. The recent advent of genome-wide association study (GWA) has triggered a wave of research aimed at discovering genetic factors underlying common complex diseases. While the number of reported susceptible genetic variants is increasing steadily, the application of such findings into diseases prognosis for the general population is still unclear, and there are doubts about whether...
Ruggeri, Paolo; Splendiani, Andrea; Bonanomi, Sara
) that explain the genetic diversity variation, while the same parameters turned out to be more stable in the southern samples. In addition, we detected the presence of a genetic bottleneck and low effective population size ( Ne) values in several northern samples. Even if the northern and southern Adriatic...... of otoliths and scales from sampling locations of northern (Chioggia) and southern (Vieste) Adriatic Sea, with the aim to investigate the genetic effects of these stock biomass fluctuations. The northern samples showed significant reduction in observed heterozygosity ( HO) and mean number of alleles ( Na...... sardine samples belong to the same genetic stock, the more pronounced decrease in genetic variability recorded in the northern sample led us to speculate that a more intensive fishing pressure and a more pronounced oceanographic isolation of this area could have accentuated the effects of the genetic...
Mellor, Greg; Laksman, Zachary W M; Tadros, Rafik; Roberts, Jason D; Gerull, Brenda; Simpson, Christopher S; Klein, George J; Champagne, Jean; Talajic, Mario; Gardner, Martin; Steinberg, Christian; Arbour, Laura; Birnie, David H; Angaran, Paul; Leather, Richard; Sanatani, Shubhayan; Chauhan, Vijay S; Seifer, Colette; Healey, Jeffrey S; Krahn, Andrew D
Unexplained cardiac arrest may be because of an inherited arrhythmia syndrome. The role of genetic testing in cardiac arrest survivors without a definite clinical phenotype is unclear. The CASPER (Cardiac Arrest Survivors with Preserved Ejection Fraction Registry) is a large registry of cardiac arrest survivors where initial assessment reveals normal coronary arteries, left ventricular function, and resting ECG. Of 375 cardiac arrest survivors in CASPER from 2006 to 2015, 174 underwent genetic testing. Patients were classified as phenotype-positive (n=72) or phenotype-negative (n=102). Genetic testing was performed at treating physicians' discretion in line with contemporary guidelines and availability. All genetic variants identified from original laboratory reports were reassessed by the investigators in line with modern criteria. Pathogenic variants were identified in 29 (17%) patients (60% channelopathy-associated and 40% cardiomyopathy-associated genes) and 70 variants of unknown significance were identified in 32 (18%) patients. Prior syncope (odds ratio, 4.0; 95% confidence interval, 1.6-9.7) and a family history of sudden death (odds ratio, 3.2; 95% confidence interval, 1.1-9.4) were independently associated with the presence of a pathogenic variant. In phenotype-negative patients, broad multiphenotype genetic testing led to higher yields (21% versus 8%; P=0.04) but was associated with more variants of unknown significance (55% versus 5%; Pcardiac arrest survivors. Prior syncope and family history of sudden death are predictors of a positive genetic test. Both arrhythmia and cardiomyopathy genes are implicated. Broad, multiphenotype testing revealed the highest frequency of pathogenic variants in phenotype-negative patients. https://www.clinicaltrials.gov. Unique Identifier: NCT00292032. © 2017 American Heart Association, Inc.
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 provision of predictive genetic tests by such DTC companies: (1) clinical utility of a genetic test shall be an essential criterion for deciding to offer this test to a person or a group of persons; (2) laboratories providing genetic tests should comply with accepted quality standards, including those regarding laboratory personnel qualifications; (3) information about the purpose and appropriateness of testing should be given before the test is done; (4) genetic counselling appropriate to the type of test and disease should be offered; and for some tests psychosocial evaluation and follow-up should be available; (5) privacy and confidentiality of sensitive genetic information should be secured and the data safely guarded; (6) special measures should be taken to avoid inappropriate testing of minors and other legally incapacitated persons; (7) all claims regarding genetic tests should be transparent; advertisement should be unbiased and marketing of genetic tests should be fair; (8) in biomedical research, health care and marketing, respect should be given to relevant ethical principles, as well as international treaties and recommendations regarding genetic testing; and (9) nationally approved guidelines considering all the above-mentioned aspects should be made and followed.
Simon, Laura; Lavallée, Vincent-Philippe; Bordeleau, Marie-Eve; Krosl, Jana; Baccelli, Irène; Boucher, Geneviève; Lehnertz, Bernhard; Chagraoui, Jalila; MacRae, Tara; Ruel, Réjean; Chantigny, Yves; Lemieux, Sébastien; Marinier, Anne; Hébert, Josée; Sauvageau, Guy
Purpose:RUNX1-mutated (RUNX1mut) acute myeloid leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Toward this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup.Experimental Design: RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML.Results: We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the glucocorticoid receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that coassociating mutations as well as GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells.Conclusions: Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Clin Cancer Res; 23(22); 6969-81. ©2017 AACR. ©2017 American Association for Cancer Research.
Full Text Available A qualitative pilot study on the attitudes of some citizens in southern Sweden toward predictive genetic testing – and a quantitative nation wide opinion poll targeting the same issues, was initiated by the Cultural Scientific Research Team of BAGADILICO. The latter is an international biomedical research environment on neurological disease at Lund University. The data of the two studies crystallized through analysis into themes around which the informants’ personal negotiations of opinions and emotions in relation to the topic centred: Concept of Risk,‘Relations and Moral Multi-layers, Worry, Agency and Autonomy, Authority, and Rationality versus Emotion. The studies indicate that even groups of people that beforehand are non-engaged in the issue, harbour complex and ambivalent emotions and opinions toward questions like this. A certain kind of situation bound pragmatism that with difficulty could be shown by quantitative methods alone emerges. This confirms our belief that methodological consideration of combining quantitative and qualitative methods is crucial for gaining a more complex representation of attitudes, as well as for problematizing the idea of a unified public open to inquiry.
Full Text Available Data were obtained from 17,968 records from 2,130 first lactations of Holstein cows calving between 1988 and 1991. The subjects were daughters of 136 sires monitored by Brazilian Breeders Association, Animal Science Institute, Department of Agriculture, a branch of the State of São Paulo. Data were divided into 10 subsets based on the number of days in milk yield. Test day milk yields (M1 to M10 and 305-day milk yield (M305 were the traits studied. These traits were adjusted for several environmental effects: class of cow age at calving, interval from calving to first test day, and herd-year-season. Restricted maximum likelihood estimates of (covariance components were obtained from one and two-traits analysis under a sire model. Estimates of heritabilities for M ranged from 0.04 to 0.32. The highest values were found in the second half of lactation (M5 to M7. Heritability estimate for M305 was 0.32. Genetic correlations between individual test days and M305 ranged from 0.78 to 1.00. Results suggested that test day milk yields, mainly in mid-lactation, can be used instead of 305-day milk yield in genetic evaluations, because estimates of these two-trait heritabilities are nearly alike. Moreover, early selection can reduce generation intervals.No presente estudo foram utilizados 17.968 registros de produção de leite, referentes a 2130 primeiras lactações de vacas da raça Holandesa, paridas nos anos de 1988 a 1991, filhas de 136 touros e controladas pela Associação Brasileira de Criadores (ABC. Os dados foram distribuídos em dez sub-arquivos de acordo com o número do controle (M1 a M10. As características estudadas foram: produção de leite no dia do controle (M e produção aos 305 dias de lactação (M305, as quais foram ajustadas para os seguintes fatores de variação: idade da vaca ao parto em classes, intervalo parto-primeiro controle e subclasses de rebanho-ano-estação de parto. Os componentes de (covariância foram obtidos a
Full Text Available Abstract Background Understanding the evolution of cultivated barley is important for two reasons. First, the evolutionary relationships between different landraces might provide information on the spread and subsequent development of barley cultivation, including the adaptation of the crop to new environments and its response to human selection. Second, evolutionary information would enable landraces with similar traits but different genetic backgrounds to be identified, providing alternative strategies for the introduction of these traits into modern germplasm. Results The evolutionary relationships between 651 barley landraces were inferred from the genotypes for 24 microsatellites. The landraces could be divided into nine populations, each with a different geographical distribution. Comparisons with ear row number, caryopsis structure, seasonal growth habit and flowering time revealed a degree of association between population structure and phenotype, and analysis of climate variables indicated that the landraces are adapted, at least to some extent, to their environment. Human selection and/or environmental adaptation may therefore have played a role in the origin and/or maintenance of one or more of the barley landrace populations. There was also evidence that at least some of the population structure derived from geographical partitioning set up during the initial spread of barley cultivation into Europe, or reflected the later introduction of novel varieties. In particular, three closely-related populations were made up almost entirely of plants with the daylength nonresponsive version of the photoperiod response gene PPD-H1, conferring adaptation to the long annual growth season of northern Europe. These three populations probably originated in the eastern Fertile Crescent and entered Europe after the initial spread of agriculture. Conclusions The discovery of population structure, combined with knowledge of associated phenotypes and
Paul De Barro
Full Text Available BACKGROUND: A challenge within the context of cryptic species is the delimitation of individual species within the complex. Statistical parsimony network analytics offers the opportunity to explore limits in situations where there are insufficient species-specific morphological characters to separate taxa. The results also enable us to explore the spread in taxa that have invaded globally. METHODOLOGY/PRINCIPAL FINDINGS: Using a 657 bp portion of mitochondrial cytochrome oxidase 1 from 352 unique haplotypes belonging to the Bemisia tabaci cryptic species complex, the analysis revealed 28 networks plus 7 unconnected individual haplotypes. Of the networks, 24 corresponded to the putative species identified using the rule set devised by Dinsdale et al. (2010. Only two species proposed in Dinsdale et al. (2010 departed substantially from the structure suggested by the analysis. The analysis of the two invasive members of the complex, Mediterranean (MED and Middle East - Asia Minor 1 (MEAM1, showed that in both cases only a small number of haplotypes represent the majority that have spread beyond the home range; one MEAM1 and three MED haplotypes account for >80% of the GenBank records. Israel is a possible source of the globally invasive MEAM1 whereas MED has two possible sources. The first is the eastern Mediterranean which has invaded only the USA, primarily Florida and to a lesser extent California. The second are western Mediterranean haplotypes that have spread to the USA, Asia and South America. The structure for MED supports two home range distributions, a Sub-Saharan range and a Mediterranean range. The MEAM1 network supports the Middle East - Asia Minor region. CONCLUSION/SIGNIFICANCE: The network analyses show a high level of congruence with the species identified in a previous phylogenetic analysis. The analysis of the two globally invasive members of the complex support the view that global invasion often involve very small portions of
Guo, Xu; Li, Ying; Li, Chunfang; Luo, Hongmei; Wang, Lizhi; Qian, Jun; Luo, Xiang; Xiang, Li; Song, Jingyuan; Sun, Chao; Xu, Haibin; Yao, Hui; Chen, Shilin
Dendrobium officinale Kimura et Migo (Orchidaceae) is a traditional Chinese medicinal plant. The stem contains an alkaloid that is the primary bioactive component. However, the details of alkaloid biosynthesis have not been effectively explored because of the limited number of expressed sequence tags (ESTs) available in GenBank. In this study, we analyzed RNA isolated from the stem of D. officinale using a single half-run on the Roche 454 GS FLX Titanium platform to generate 553,084 ESTs with an average length of 417 bases. The ESTs were assembled into 36,407 unique putative transcripts. A total of 69.97% of the unique sequences were annotated, and a detailed view of alkaloid biosynthesis was obtained. Functional assignment based on Kyoto Encyclopedia of Genes and Genomes (KEGG) terms revealed 69 unique sequences representing 25 genes involved in alkaloid backbone biosynthesis. A series of qRT-PCR experiments confirmed that the expression levels of 5 key enzyme-encoding genes involved in alkaloid biosynthesis are greater in the leaves of D. officinale than in the stems. Cytochrome P450s, aminotransferases, methyltransferases, multidrug resistance protein (MDR) transporters and transcription factors were screened for possible involvement in alkaloid biosynthesis. Furthermore, a total of 1061 simple sequence repeat motifs (SSR) were detected from 36,407 unigenes. Dinucleotide repeats were the most abundant repeat type. Of these, 179 genes were associated with a metabolic pathway in KEGG. This study is the first to produce a large volume of transcriptome data from D. officinale. It extends the foundation to facilitate gene discovery in D. officinale and provides an important resource for the molecular genetic and functional genomic studies in this species. Copyright © 2013 Elsevier B.V. All rights reserved.
Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.
Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M
Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.
Zhai, Weiwei; Nielsen, Rasmus; Slatkin, Montgomery
In this report, we investigate the statistical power of several tests of selective neutrality based on patterns of genetic diversity within and between species. The goal is to compare tests based solely on population genetic data with tests using comparative data or a combination of comparative...
Liou, Yu-Ligh; Zhang, Tao-Lan; Yan, Tian; Yeh, Ching-Tung; Kang, Ya-Nan; Cao, Lanqin; Wu, Nayiyuan; Chang, Chi-Feng; Wang, Huei-Jen; Yen, Carolyn; Chu, Tang-Yuan; Zhang, Yi; Zhang, Yu; Zhou, Honghao
Opportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy. The delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methylation-specific PCR in a training set (57 CIN2- and 43 cervical intraepithelial neoplasia ≥grade 3 (CIN3+) women), and the individual and combination gene sensitivities and specificities were determined. The detection accuracy of three algorithms combining gynecologic findings and genetic test results was then compared in a randomized case-control study comprising 449 women referred for colposcopic examination by gynecologists in the outpatient department of Xiangya Hospital between November 2011 and March 2013. Significant association was observed between CIN3+ and methylated PAX1 or ZNF582 in combination with HPV16/18 (OR:15.52, 95 % CI:7.73-31.18). The sensitivities and specificities of methylated PAX1 or ZNF582 combined with HPV16/18 for CIN3+ women were 89.2 and 76.0 %, or 85.4 and 80.1 %, respectively. Of the three algorithms applied to cohort data and validated in the study, two indicated 100 % sensitivity in detecting cervical cancer and a low rate of referrals for colposcopy. These algorithms might contribute to precise and objective cervical cancer diagnostics in the outpatient departments of hospitals in countries with high mortality and low screening rates or areas with uneven resource distribution.
He, Yajun; Wu, Daoming; Wei, Dayong; Fu, Ying; Cui, Yixin; Dong, Hongli; Tan, Chuandong; Qian, Wei
Branch number is an important trait in plant architecture that can influence crop yield and quality in Brassica napus. Here, we detected the QTLs responsible for branch number in a DH population and its reconstructed F2 population over two years. Further, a GWAS research on branch number was performed using a panel of 327 accessions with 33186 genomic SNPs from the 60 K Brassica Illumina® Infinium SNP array. Through combining linkage analysis and association mapping, a new QTL was fine mapped onto C03. Subsequently, we tested the correlations between the SNP polymorphisms and mRNA expression levels of genes in the target interval to identify potential loci or genes that control branch number through expression. The results show that 4 SNP loci are associated with the corresponding gene expression levels, and one locus (BnaC03g63480D) exhibited a significant correlation between the phenotype variation and gene expression levels. Our results provide insights into the genetic basis for branching morphogenesis and may be valuable for optimizing architecture in rapeseed breeding.
Al-Sadi, Abdullah M; Al-Oweisi, Fatma A; Edwards, Simon G; Al-Nadabi, Hamed; Al-Fahdi, Ahmed M
Trichoderma is one of the most common fungi in soil. However, little information is available concerning the diversity of Trichoderma in soil with no previous history of cultivation. This study was conducted to investigate the most common species and the level of genetic relatedness of Trichoderma species from uncultivated soil in relation to cultivated soil and potting media. A total of 24, 15 and 13 Trichoderma isolates were recovered from 84 potting media samples, 45 cultivated soil samples and 65 uncultivated soil samples, respectively. Analysis based on the internal transcribed spacer region of the ribosomal RNA (rRNA) and the translation elongation factor gene (EF1) indicated the presence of 9 Trichoderma species: T. harzianum (16 isolates), T. asperellum (13), T. citrinoviride (9), T. orientalis (3), T. ghanense (3), T. hamatum (3), T. longibrachiatum (2), T. atroviride (2), and T. viride (1). All species were found to occur in potting media samples, while five Trichoderma species were recovered from the cultivated soils and four from the uncultivated soils. AFLP analysis of the 52 Trichoderma isolates produced 52 genotypes and 993 polymorphic loci. Low to moderate levels of genetic diversity were found within populations of Trichoderma species (H = 0.0780 to 0.2208). Analysis of Molecular Variance indicated the presence of very low levels of genetic differentiation (Fst = 0.0002 to 0.0139) among populations of the same Trichoderma species obtained from the potting media, cultivated soil and uncultivated soil. The study provides evidence for occurrence of Trichoderma isolates in soil with no previous history of cultivation. The lack of genetic differentiation among Trichoderma populations from potting media, cultivated soil and uncultivated soil suggests that some factors could have been responsible for moving Trichoderma propagules among the three substrates. The study reports for the first time the presence of 4 Trichoderma species in Oman: T
Lopez-Pujalte, Cristina; Guerrero Bote, Vicente P.; Moya Anegon, Felix de
Discussion of information retrieval, query optimization techniques, and relevance feedback focuses on genetic algorithms, which are derived from artificial intelligence techniques. Describes an evaluation of different genetic algorithms using a residual collection method and compares results with the Ide dec-hi method (Salton and Buckley, 1990…
Arnos, Kathleen S.
Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in…
Morahan, Grant; Mehta, Munish; James, Ian
Interactions between genetic and environmental factors lead to immune dysregulation causing type 1 diabetes and other autoimmune disorders. Recently, many common genetic variants have been associated with type 1 diabetes risk, but each has modest individual effects. Familial clustering of type 1...
Strandberg, B.; Kjær, C.
The report contains the proceedings from the conference Genetically Modified Organisms in Nordic Habitats - Sustainable Use or Loss of Diversity? in Helsinki, 1998......The report contains the proceedings from the conference Genetically Modified Organisms in Nordic Habitats - Sustainable Use or Loss of Diversity? in Helsinki, 1998...
A.C.J.W. Janssens (Cécile); M.J. Khoury (Muin Joseph)
textabstractMultifactorial diseases such as type 2 diabetes, osteoporosis, and cardiovascular disease are caused by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. Unraveling the genetic origins of these diseases is
Accurate estimates of genetic parameters are essential for genetic improvement of milk yield in dairy cattle and for setting up breeding programmes. Estimates of genetic parameters from test-day models, particularly for Holstein Friesian cattle maintained in tropical environments, are scant in the literature. The objective of ...
Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R
peoples' expectations as regards to genetic testing are too high. Having more medical education was related to having less 'cannot say' and missing responses. Our results do not suggest that major conflicts about the direction of genetic testing and screening would arise in near future. However, different......The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions...
Campbell, E; Ross, L F
Although no genetic tests for violent behaviour are currently available, research is ongoing to isolate genes related to a propensity for violence. We explored the attitudes of parents and healthcare professionals toward behavioural genetic testing for violence. The attitudes of healthcare professionals and the lay public about genetic testing of children were elicited for a range of conditions through interviews with healthcare professionals and focus groups with parents. All participants were informed that behavioural genetic testing was the only hypothetical genetic test in our script and it was presented as the last condition. The healthcare professionals included both genetic professionals and paediatricians. Focus group participants were recruited through various community institutions in the southside of Chicago and nearby suburbs. The healthcare professionals tended to medicalise behavioural genetics, and were opposed to testing unless treatment was available. They were also uniformly concerned about the potential harms of this information, including unintentional adverse effects from environmental changes. In contrast, parents wanted genetic testing for behavioural traits to be available even in the absence of proved medical treatments. Not all parents wanted to test their own children, and some parents were concerned about self-fulfilling prophecies. Some parents, however, felt the information was important for their understanding, and could be used to support environmental changes. While healthcare professionals medicalised behavioural genetics, parents focused on environmental causes and influences. Consequently, healthcare professionals do not want to offer testing if there is no clear treatment, while parents may want this information to shape environmental influences.
Snoek, L.B.; Terpstra, I.R.|info:eu-repo/dai/nl/311456049; Dekter, R.; van den Ackerveken, A.F.J.M.|info:eu-repo/dai/nl/113853254; Peeters, A.J.M.|info:eu-repo/dai/nl/089258886
One of the major goals of quantitative genetics is to unravel the complex interactions between molecular genetic factors and the environment.The effects of these genotype-byenvironment interactions also affect and cause variation in gene expression.The regulatory loci responsible for this variation
Snoek, L.B.; Terpstra, I.R.; Dekter, R.; Ackerveken, van den G.; Peeters, A.J.
One of the major goals of quantitative genetics is to unravel the complex interactions between molecular genetic factors and the environment. The effects of these genotype-by-environment interactions also affect and cause variation in gene expression. The regulatory loci responsible for this
James W Kijas
Full Text Available The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.
Kijas, James W; Townley, David; Dalrymple, Brian P; Heaton, Michael P; Maddox, Jillian F; McGrath, Annette; Wilson, Peter; Ingersoll, Roxann G; McCulloch, Russell; McWilliam, Sean; Tang, Dave; McEwan, John; Cockett, Noelle; Oddy, V Hutton; Nicholas, Frank W; Raadsma, Herman
The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability.
Stine H Kresse
Full Text Available BACKGROUND: Osteosarcomas are the most common non-haematological primary malignant tumours of bone, and all conventional osteosarcomas are high-grade tumours showing complex genomic aberrations. We have integrated genome-wide genetic and epigenetic profiles from the EuroBoNeT panel of 19 human osteosarcoma cell lines based on microarray technologies. PRINCIPAL FINDINGS: The cell lines showed complex patterns of DNA copy number changes, where genomic copy number gains were significantly associated with gene-rich regions and losses with gene-poor regions. By integrating the datasets, 350 genes were identified as having two types of aberrations (gain/over-expression, hypo-methylation/over-expression, loss/under-expression or hyper-methylation/under-expression using a recurrence threshold of 6/19 (>30% cell lines. The genes showed in general alterations in either DNA copy number or DNA methylation, both within individual samples and across the sample panel. These 350 genes are involved in embryonic skeletal system development and morphogenesis, as well as remodelling of extracellular matrix. The aberrations of three selected genes, CXCL5, DLX5 and RUNX2, were validated in five cell lines and five tumour samples using PCR techniques. Several genes were hyper-methylated and under-expressed compared to normal osteoblasts, and expression could be reactivated by demethylation using 5-Aza-2'-deoxycytidine treatment for four genes tested; AKAP12, CXCL5, EFEMP1 and IL11RA. Globally, there was as expected a significant positive association between gain and over-expression, loss and under-expression as well as hyper-methylation and under-expression, but gain was also associated with hyper-methylation and under-expression, suggesting that hyper-methylation may oppose the effects of increased copy number for detrimental genes. CONCLUSIONS: Integrative analysis of genome-wide genetic and epigenetic alterations identified dependencies and relationships between
Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz
Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...
Caroline E. Dubé
Full Text Available Quantifying the genetic diversity in natural populations is crucial to address ecological and evolutionary questions. Despite recent advances in whole-genome sequencing, microsatellite markers have remained one of the most powerful tools for a myriad of population genetic approaches. Here, we used the 454 sequencing technique to develop microsatellite loci in the fire coral Millepora platyphylla, an important reef-builder of Indo-Pacific reefs. We tested the cross-species amplification of these loci in five other species of the genus Millepora and analysed its success in correlation with the genetic distances between species using mitochondrial 16S sequences. We succeeded in discovering fifteen microsatellite loci in our target species M. platyphylla, among which twelve were polymorphic with 2–13 alleles and a mean observed heterozygosity of 0.411. Cross-species amplification in the five other Millepora species revealed a high probability of amplification success (71% and polymorphism (59% of the loci. Our results show no evidence of decreased heterozygosity with increasing genetic distance. However, only one locus enabled measures of genetic diversity in the Caribbean species M. complanata due to high proportions of null alleles for most of the microsatellites. This result indicates that our novel markers may only be useful for the Indo-Pacific species of Millepora. Measures of genetic diversity revealed significant linkage disequilibrium, moderate levels of observed heterozygosity (0.323–0.496 and heterozygote deficiencies for the Indo-Pacific species. The accessibility to new polymorphic microsatellite markers for hydrozoan Millepora species creates new opportunities for future research on processes driving the complexity of their colonisation success on many Indo-Pacific reefs.
Laegsgaard, Mett Marri; Mors, Ole
as a guide in this field, but the optimal utilization of genetic testing has also been recognized to depend on knowledge of the potential consumers' attitudes. To provide knowledge to inform the public debate on mental illness and genetics, and the future conducting of psychiatric genetic testing...... contradictions mirroring the bioethical dilemmas recognized in the field and variations in attitudes between groups with different levels of knowledge of genetics, different kinds of experience with mental illness, and different motives and preconceptions regarding psychiatric genetics. The contradictions...... and differences in attitudes among possible future users and providers of psychiatric genetic testing and counseling indicate ambivalence, insecurity, and perceived lack of knowledge in relation to psychiatric genetics. These results should inform further research and the future integration of psychiatric...
Yan, Boqian; Li, Zuozhou; Huang, Hongwen; Qin, Ling
Seventeen Cryphonectria parasitica populations sampled from six regions in China were investigated using RAPD. Across all 169 isolates from the 17 populations evaluated, 52 of the 71 markers (73%) were polymorphic, total genetic diversity (h) was 0.1463, and Shannon's index was 0.2312. Diversity within populations accounted for 74% of total genetic diversity, and genetic differentiation among populations was 0.26 (G (ST) = 0.26). Gene flow was 1.4 among the populations; higher gene flow was found among populations within regions and among regions [N (m) (G (SR)) = 2.8 and N (m) (G (RT)) = 3.5]. The unweighted pair group mean analysis (UPGMA) dendrogram revealed two distinct clusters: the northern China group and the southern China group. The spatial autocorrelation analysis revealed that the variation at most loci was randomly distributed and lacked spatial structure, but several loci and closer distances were spatially structured. Human activity and habitat could also be important factors affecting genetic structure among C. parasitica populations in China. Genetic diversity was highest in Southwest China, descending in an orderly fashion to Northeast China. This pattern indicated that Southwest China might be the center of origin of C. parasitica in China. The present study provides useful information for understanding the origin and spread of chestnut blight fungus in China and valuable data for formulating relevant strategies for controlling the disease in China.
Full Text Available In Europe, there is a wide variety of genetic tests that various private companies offer to patients or to consumers. More and more people have become curious about their genetic predisposition and susceptibility. Most public health-care systems, however, are not adequately prepared for responding to these new demands and to the results of these genetic tests as, quite often, there is no available therapy for the identified genetic condition. This discrepancy between the newly emerging expectations and the insufficient responses contributes to a further rift between the public and private sectors of health care. Individual genetic test results may also trigger the need for personalized medicine and may open up a competition between the two fields in offering further genetic tests and medical exams. Pro-active patients may need a different kind of information on genetic tests and their implications. In this context, how should the public health system deal with the challenges of private testing? Will private genetic testing transform health care from a solidarity-based system to an individualistic one? In this paper, I would like to explore the emerging legal and ethical issues related to genetic testing and the relevant legal framework that has developed so far. In the conclusion, I will examine the possibilities of further legal development.
Full Text Available In cultivated commercial crop species, genetic diversity tends to decrease because of the extensive breeding processes. Therefore, germplasm of commercial crop species, such as Brassica napus L. should be evaluated and the genotypes, which have higher genetic diversity index, should be addressed as potential parental cross materials in breeding programs. In this study, the genetic diversity was analysed by using randomly amplified polymorphic DNA analysis (RAPD technique in nine Turkish commercial rapeseed varieties. The RAPD primers (10-mer oligonucleotides produced 51 scorable loci, 31 loci of which were polymorphic (60.78% and 20 loci (39.22% were monomorphic The RAPD bands were scored as binary matrix data and were analysed using POPGENE version 1.32. At locus level, the values of genetic diversity within population (Hs and total (HT were 0.15 and 0.19 respectively. The genetic differentiation (GST and the gene flow (Nm values between the populations were 0.20 and 2.05 respectively. The mean number of alleles (na, the mean number of effective alleles (nae, and the mean value of genetic diversity (He were 2.00, 1.26, and 0.19 respectively. According to Pearson’s correlation, multiple regression and principal component analyses, eco-geographical conditions in combination had significant effect on genetic indices of commercial B. napus L. varieties were discussed.
Emily K Latch
Full Text Available Characterizing the effects of landscape features on genetic variation is essential for understanding how landscapes shape patterns of gene flow and spatial genetic structure of populations. Most landscape genetics studies have focused on patterns of gene flow at a regional scale. However, the genetic structure of populations at a local scale may be influenced by a unique suite of landscape variables that have little bearing on connectivity patterns observed at broader spatial scales. We investigated fine-scale spatial patterns of genetic variation and gene flow in relation to features of the landscape in desert tortoise (Gopherus agassizii, using 859 tortoises genotyped at 16 microsatellite loci with associated data on geographic location, sex, elevation, slope, and soil type, and spatial relationship to putative barriers (power lines, roads. We used spatially explicit and non-explicit Bayesian clustering algorithms to partition the sample into discrete clusters, and characterize the relationships between genetic distance and ecological variables to identify factors with the greatest influence on gene flow at a local scale. Desert tortoises exhibit weak genetic structure at a local scale, and we identified two subpopulations across the study area. Although genetic differentiation between the subpopulations was low, our landscape genetic analysis identified both natural (slope and anthropogenic (roads landscape variables that have significantly influenced gene flow within this local population. We show that desert tortoise movements at a local scale are influenced by features of the landscape, and that these features are different than those that influence gene flow at larger scales. Our findings are important for desert tortoise conservation and management, particularly in light of recent translocation efforts in the region. More generally, our results indicate that recent landscape changes can affect gene flow at a local scale and that their
Kimberly R Andrews
Full Text Available The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200-360 m in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787 and E. "marshi" (formerly E. carbunculus; N = 770 with 436-490 bp of mtDNA cytochrome b and 10-11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus and a submesophotic grouper (Hyporthodus quernus. Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management
Full Text Available Ovine and dromedary Echinococcus granulosus isolates from Tunisia were identified as G1 and G6 strains based on polymorphism of the mitochondrial cytochrome C oxydase CO1. Single strand conformation polymorphism (SSCP was used in order to examine the genetic variation within and between Tunisian G1 and G6 strains and to estimate the extent of selfing. The dromedary isolates are genetically distinct from sheep isolates (high value of genetic variation between populations: Fst = 0.46. No significant deficiency in heterozygotes was found in sheep isolates, whereas heterozygote deficiency (suggesting selfing was found in a limited number of camel isolates.
Wade, Christopher H; Shiloh, Shoshana; Woolford, Samuel W; Roberts, J Scott; Alford, Sharon Hensley; Marteau, Theresa M; Biesecker, Barbara B
New genetic tests reveal risks for multiple conditions simultaneously, although little is understood about the psychological factors that affect testing uptake. We assessed a conceptual model called the multiplex genetic testing model (MGTM) using structural equation modelling. The MGTM delineates worry, perceived severity, perceived risk, response efficacy and attitudes towards testing as predictors of intentions and behaviour. Participants were 270 healthy insured adults aged 25-40 from the Multiplex Initiative conducted within a health care system in Detroit, MI, USA. Participants were offered a genetic test that assessed risk for eight common health conditions. Confirmatory factor analysis revealed that worry, perceived risk and severity clustered into two disease domains: cancer or metabolic conditions. Only perceived severity of metabolic conditions was correlated with general response efficacy (β = 0.13, ptesting (β = 0.24, ptesting were the strongest predictors of intentions to undergo testing (β = 0.49, ptesting uptake (OR 17.7, β = 0.97, ptesting for multiple health conditions.
Full Text Available The broadleaved evergreen forests of the East Asian warm temperate zone are characterised by their high biodiversity and endemism, and there is therefore a need to extend our understanding of its genetic diversity and phylogeographic patterns. Castanopsis (Fagaceae is one of the dominant tree species in the broadleaved evergreen forests of Japan. In this study we investigate the genetic diversity, genetic structure and leaf epidermal morphology of 63 natural populations of C. sieboldii and C. cuspidata, using 32 Expressed Sequence Tag associated microsatellites. The overall genetic differentiation between populations was low (GST = 0.069 in C. sieboldii and GST = 0.057 in C. cuspidata. Neighbor-joining tree and Bayesian clustering analyses revealed that the populations of C. sieboldii and C. cuspidata were genetically clearly differentiated, a result which is consistent with the morphology of their epidermal cell layers. This suggests that C. sieboldii and C. cuspidata should be treated as independent species, although intermediate morphologies are often observed, especially at sites where the two species coexist. The higher level of genetic diversity observed in the Kyushu region (for both species and the Ryukyu Islands (for C. sieboldii is consistent with the available fossil pollen data for Castanopsis-type broadleaved evergreen trees during the Last Glacial Maximum and suggests the existence of refugia for Castanopsis forests in southern Japan. Within the C. sieboldii populations, Bayesian clustering analyses detected three clusters, in the western and eastern parts of the main islands and in the Ryukyu Islands. The west-east genetic differentiation observed for this species in the main islands, a pattern which is also found in several plant and animal species inhabiting Castanopsis forests in Japan, suggests that they have been isolated from each other in the western and eastern populations for an extended period of time, and may
Elizabeth T. Ables
Full Text Available Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets. More recently, genome-wide approaches have identified hundreds of putative ecdysone-responsive targets. Determining whether these putative targets represent bona fide targets in vivo, however, requires that they be tested via traditional mutant analysis in a cell-type specific fashion. To investigate the molecular mechanisms whereby ecdysone signaling regulates oogenesis, we used genetic mosaic analysis to screen putative ecdysone-responsive genes for novel roles in the control of the earliest steps of oogenesis. We identified a cohort of genes required for stem cell maintenance, stem and progenitor cell proliferation, and follicle encapsulation, growth, and survival. These genes encode transcription factors, chromatin modulators, and factors required for RNA transport, stability, and ribosome biogenesis, suggesting that ecdysone might control a wide range of molecular processes during oogenesis. Our results suggest that, although ecdysone target genes are known to have cell type-specific roles, many ecdysone response genes that control larval or pupal cell types at developmental transitions are used reiteratively in the adult ovary. These results provide novel insights into the molecular mechanisms by which ecdysone signaling controls oogenesis, laying new ground for future studies.
Ables, Elizabeth T; Hwang, Grace H; Finger, Danielle S; Hinnant, Taylor D; Drummond-Barbosa, Daniela
Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets. More recently, genome-wide approaches have identified hundreds of putative ecdysone-responsive targets. Determining whether these putative targets represent bona fide targets in vivo, however, requires that they be tested via traditional mutant analysis in a cell-type specific fashion. To investigate the molecular mechanisms whereby ecdysone signaling regulates oogenesis, we used genetic mosaic analysis to screen putative ecdysone-responsive genes for novel roles in the control of the earliest steps of oogenesis. We identified a cohort of genes required for stem cell maintenance, stem and progenitor cell proliferation, and follicle encapsulation, growth, and survival. These genes encode transcription factors, chromatin modulators, and factors required for RNA transport, stability, and ribosome biogenesis, suggesting that ecdysone might control a wide range of molecular processes during oogenesis. Our results suggest that, although ecdysone target genes are known to have cell type-specific roles, many ecdysone response genes that control larval or pupal cell types at developmental transitions are used reiteratively in the adult ovary. These results provide novel insights into the molecular mechanisms by which ecdysone signaling controls oogenesis, laying new ground for future studies. Copyright © 2016 Ables et al.
Barlow-Stewart, Kristine; Taylor, Sandra D; Treloar, Susan A; Stranger, Mark; Otlowski, Margaret
To undertake a systematic process of verification of consumer accounts of alleged genetic discrimination. Verification of incidents reported in life insurance and other contexts that met the criteria of genetic discrimination, and the impact of fear of such treatment, was determined, with consent, through interview, document analysis and where appropriate, direct contact with the third party involved. The process comprised obtaining evidence that the alleged incident was accurately reported and determining whether the decision or action seemed to be justifiable and/or ethical. Reported incidents of genetic discrimination were verified in life insurance access, underwriting and coercion (9), applications for worker's compensation (1) and early release from prison (1) and in two cases of fear of discrimination impacting on access to genetic testing. Relevant conditions were inherited cancer susceptibility (8), Huntington disease (3), hereditary hemochromatosis (1), and polycystic kidney disease (1). In two cases, the reversal of an adverse underwriting decision to standard rate after intervention with insurers by genetics health professionals was verified. The mismatch between consumer and third party accounts in three life insurance incidents involved miscommunication or lack of information provision by financial advisers. These first cases of verified genetic discrimination make it essential for policies and guidelines to be developed and implemented to ensure appropriate use of genetic test results in insurance underwriting, to promote education and training in the financial industry, and to provide support for consumers and health professionals undertaking challenges of adverse decisions.
Tariq, Muhammad; Ware, Stephanie M
Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for significant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathy. There is substantial evidence for a genetic contribution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been problematic because of the large number of genes, the private nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardiomyopathy and their diagnostic relevance in clinical settings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype-phenotype correlations may help delineate the molecular and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children. PMID:25429328
Yanase, Tohru; Aizawa, Maki; Kato, Tomoko; Yamakawa, Makoto; Shirafuji, Hiroaki; Tsuda, Tomoyuki
Sequence determination and phylogenetic analysis were conducted using the S, M and L RNA segments of the 10 Aino, 6 Peaton and 1 Sango virus (AINOV, PEAV and SANV) field isolates of the genus Orthobunyavirus in the family Bunyaviridae, respectively. The Japanese AINOV strains were genetically stable, but the sequence differences between the Japanese and Australian AINOV strains were considerably larger than those among the Japanese AINOV strains. A similar result was found in the genetic relationship among Japanese and Australian PEAVs, and SANV which was isolated in Nigeria and was thought as a synonym of PEAV, suggesting that geographic separation contributed significantly to the evolution of those viruses. The Australian AINOV strain B7974 is more closely related to the Australian PEAV strain CSIRO110 than to the Japanese AINOV strains in the S and L RNA segments, while the phylogenetic position of the M RNA segment of the B7974 strain was clustered with those of the Japanese AINOV strains. Our findings indicate that the B7974 strain is a reassortment with the M RNA segment derived from AINOV and the S and L RNA segments derived from an Australian PEAV. (c) 2010 Elsevier B.V. All rights reserved.
Rahm, Alanna Kulchak; Feigelson, Heather Spencer; Wagner, Nicole; Le, Anh Quynh; Halterman, Eve; Cornish, Nadine; Dearing, James W
This small qualitative study was designed to determine possible attitudes toward and understanding of direct-to-consumer (DTC) genetic testing among members of a large managed care organization, and whether differences might exist between population groups. Ten focus groups were conducted by population type (high risk, White, African American, Hispanic/Latino) to determine knowledge, attitudes and beliefs about DTC genetics. Focus group transcripts were coded for attitudes toward and framing of the issue. Study results found participants were negative towards DTC genetic testing but they also found some aspects useful. Participants framed the issue mainly in terms of disease prevention and uncertainty of reaction to results, with some variation between population types. The concept of an "Informed Consumer," or process to seek information when the issue becomes personally relevant, emerged. This concept suggests that individuals may seek additional assistance to make personally-appropriate choices when faced with a DTC advertisement or genetic test.
Zhu, Wensheng; Zhang, Heping
In studies of complex disorders such as nicotine dependence, it is common that researchers assess multiple variables related to a disorder as well as other disorders that are potentially correlated with the primary disorder of interest. In this work, we refer to those variables and disorders broadly as multiple traits. The multiple traits may or may not have a common causal genetic variant. Intuitively, it may be more powerful to accommodate multiple traits in genetic traits, but the analysis...
Xie, Hailiang; Guo, Ruijin; Zhong, Huanzi
The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing...
Ahsyee Salem R.
Full Text Available Alfalfa (Medicago sativa L. is an important forage legume in Libya. The genetic diversity of nine alfalfa domesticated varietal populations was studied using thirteen RAPD primer combinations. The number of polymorphic fragments detected per primer combination ranged from 8 to 46 bands with an average of 24 bands. The number of polymorphic bands detected was from 6 (Atalia population to 37 (Gabsia population. The lowest genetic distance was 0.058 and the highest was 0.655. The average genetic distance was (0.356. The dendrogram based on Ward’s minimum variance clustering method grouped the nine populations into the two main clusters. The first group included Fazania, Atalia, Masratia, Zawia, Denamo Ferade and Arezona. The second group was composed of Tagoria, Gabsia and Wade Alrabeh. The simplicity of RAPD assays for detection of genetic polymorphisms is confirmed in our study, and results can be utilized in breeding practice.
Lighten, Jackie; Papadopulos, Alexander S. T.; Mohammed, Ryan S.; Ward, Ben J.; G. Paterson, Ian; Baillie, Lyndsey; Bradbury, Ian R.; Hendry, Andrew P.; Bentzen, Paul; van Oosterhout, Cock
Red Queen host-parasite co-evolution can drive adaptations of immune-genes by positive selection that erodes genetic variation (Red Queen Arms Race), or result in a balanced polymorphism (Red Queen Dynamics) and the long-term preservation of genetic variation (trans-species polymorphism). These two Red Queen processes are opposite extremes of the co-evolutionary spectrum. Here we show that both Red Queen processes can operate simultaneously, analyzing the Major Histocompatibility Complex (MHC...
Fadhlaoui-Zid, Karima; Rodríguez-Botigué, Laura; Naoui, Nejib; Benammar-Elgaaied, Amel; Calafell, Francesc; Comas, David
Human population movements in North Africa have been mostly restricted to an east-west direction due to the geographical barriers imposed by the Sahara Desert and the Mediterranean Sea. Although these barriers have not completely impeded human migrations, genetic studies have shown that an east-west genetic gradient exists. However, the lack of genetic information of certain geographical areas and the focus of some studies in parts of the North African landscape have limited the global view of the genetic pool of North African populations. To provide a global view of the North African genetic landscape and population structure, we have analyzed ∼2,300 North African mitochondrial DNA lineages (including 269 new sequences from Libya, in the first mtDNA study of the general Libyan population). Our results show a clinal distribution of certain haplogroups, some of them more frequent in Western (H, HV0, L1b, L3b, U6) or Eastern populations (L0a, R0a, N1b, I, J) that might be the result of human migrations from the Middle East, sub-Saharan Africa, and Europe. Despite this clinal pattern, a genetic discontinuity is found in the Libyan/Egyptian border, suggesting a differential gene flow in the Nile River Valley. Finally, frequency of the post-LGM subclades H1 and H3 is predominant in Libya within the H sequences, highlighting the magnitude of the LGM expansion in North Africa. Copyright © 2011 Wiley-Liss, Inc.
Witt, S H; Streit, F; Jungkunz, M
overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score......Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report...... describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic...
Lavínia Schuler-Faccini; Claudio Maria Osorio; Flavia Romariz; Milena Paneque; Jorge Sequeiros; Laura Bannach Jardim
Machado-Joseph disease (MJD) is an autosomal dominant, late-onset neurological disorder and the most common form of spinocerebellar ataxia (SCA) worldwide. Diagnostic genetic testing is available to detect the disease-causing mutation by direct sizing of the CAG repeat tract in the ataxin 3 gene. Presymptomatic testing (PST) can be used to identify persons at risk of developing the disease. Genetic counseling provides patients with information about the disease, genetic risks, PST, and the de...
Allen, Jill Fonda; Stoll, Katie; Bernhardt, Barbara A
Genetic carrier screening, prenatal screening for aneuploidy and prenatal diagnostic testing have expanded dramatically over the past two decades. Driven in part by powerful market forces, new complex testing modalities have become available after limited clinical research. The responsibility for offering these tests lies primarily on the obstetrical care provider, and has become more burdensome as the number of testing options expands. Genetic testing in pregnancy is optional, and decisions about undergoing tests, as well as follow-up testing, should be informed and based on individual patients’ values and needs. Careful pre- and post-test counseling is central to supporting informed decision-making. This article explores three areas of technical expansion in genetic testing: expanded carrier screening, non-invasive prenatal screening for fetal aneuploidies using cell-free DNA, and diagnostic testing using fetal chromosomal microarray testing, and provides insights aimed at enabling the obstetrical practitioner to better support patients considering these tests. PMID:26718445
Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard
We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.
Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard
We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk. PMID:28051113
Vlahovich, Nicole; Hughes, David C; Griffiths, Lyn R; Wang, Guan; Pitsiladis, Yannis P; Pigozzi, Fabio; Bachl, Nobert; Eynon, Nir
There has been considerable growth in basic knowledge and understanding of how genes are influencing response to exercise training and predisposition to injuries and chronic diseases. On the basis of this knowledge, clinical genetic tests may in the future allow the personalisation and optimisation of physical activity, thus providing an avenue for increased efficiency of exercise prescription for health and disease. This review provides an overview of the current status of genetic testing for the purposes of exercise prescription and injury prevention. As such there are a variety of potential uses for genetic testing, including identification of risks associated with participation in sport and understanding individual response to particular types of exercise. However, there are many challenges remaining before genetic testing has evidence-based practical applications; including adoption of international standards for genomics research, as well as resistance against the agendas driven by direct-to-consumer genetic testing companies. Here we propose a way forward to develop an evidence-based approach to support genetic testing for exercise prescription and injury prevention. Based on current knowledge, there is no current clinical application for genetic testing in the area of exercise prescription and injury prevention, however the necessary steps are outlined for the development of evidence-based clinical applications involving genetic testing.
Kapa, Suraj; Tester, David J.; Salisbury, Benjamin A.; Harris-Kerr, Carole; Pungliya, Manish S.; Alders, Marielle; Wilde, Arthur A. M.; Ackerman, Michael J.
Background-Genetic testing for long-QT syndrome (LQTS) has diagnostic, prognostic, and therapeutic implications. Hundreds of causative mutations in 12 known LQTS-susceptibility genes have been identified. Genetic testing that includes the 3 most commonly mutated genes is available clinically.
Vashlishan Murray, Amy B; Carson, Michael J; Morris, Corey A; Beckwith, Jon
Marketers of genetic tests often openly or implicitly misrepresent the utility of genetic information. Scientists who are well aware of the current limitations to the utility of such tests are best placed to publicly counter misrepresentations of the science. Copyright © 2010 Elsevier Ltd. All rights reserved.
Janssens, A C J W; Wilde, A A M; van Langen, I M
Expectations are high that increasing knowledge of the genetic basis of cardiovascular disease will eventually lead to personalised medicine-to preventive and therapeutic interventions that are targeted to at-risk individuals on the basis of their genetic profiles. Most cardiovascular diseases are caused by a complex interplay of many genetic variants interacting with many non-genetic risk factors such as diet, exercise, smoking and alcohol consumption. Since several years, genetic susceptibility testing for cardiovascular diseases is being offered via the internet directly to consumers. We discuss five reasons why these tests are not useful, namely: (1) the predictive ability is still limited; (2) the risk models used by the companies are based on assumptions that have not been verified; (3) the predicted risks keep changing when new variants are discovered and added to the test; (4) the tests do not consider non-genetic factors in the prediction of cardiovascular disease risk; and (5) the test results will not change recommendations of preventive interventions. Predictive genetic testing for multifactorial forms of cardiovascular disease clearly lacks benefits for the public. Prevention of disease should therefore remain focused on family history and on non-genetic risk factors as diet and physical activity that can have the strongest impact on disease risk, regardless of genetic susceptibility.
Ngene, Samuel O; Adedokun, Babatunde; Adejumo, Prisca; Olopade, Olufunmilayo
Genetic testing services for breast cancer are well established in developed countries compared to African populations that bear a disproportionate burden of breast cancer (BC). The objective of this study is to examine the knowledge of professional Nigerian women about BC genetics and their intentions to utilize genetic testing services when it is made available in Nigeria. In this study, 165 lecturers and 189 bankers were recruited and studied using a validated self-administered questionnaire. The respondents' mean age was 34.9 years (SD = 10.9), 6.5% had family history of BC, and 84.7% had limited knowledge of breast cancer genetics. The proportion of women with genetic testing intentions for breast cancer was 87.3%. Health care access (OR = 2.35, 95% CI, 1.07-5.13), religion (OR = 3.51, 95% CI, 1.03-11.92), and perceived personal risk if a close relative had breast cancer (OR = 2.31, 95% CI, 1.05-5.08) independently predicted testing intentions. The genetic testing intentions for BC were high despite limited knowledge about breast cancer genetics. Promotion of BC genetics education as well as efforts to make BC genetic testing services available in Nigeria at reduced cost remains essential.
Sun, Ye; Wen, Xiangying; Huang, Hongwen
Seven polymorphic and transferable nuclear microsatellites were used to investigate the population structure of genetic diversity of Schisandra chinensis and Schisandra sphenanthera for facilitating their conservation and sustainable utilization. High levels of gene diversity were revealed in these two medicinal species, the majority of genetic diversity was harbored within populations, and population structure was might due to restricted gene flow among populations. Isolation by distance was close to significance in S. chinensis but not in S. sphenanthera. In S. chinensis, null alleles were identified as a cause for excess of homozygotes at loci G24 and WGA60, but inbreeding might also be partly responsible for the positive F ( IS ) values in this species. In contrast, null allele frequencies were high at all the seven loci in S. sphenanthera and resulted in overestimation of fixation index. The strategy for ex situ conservation of these two medicinal species is discussed based on the genetic results.
Huang, Chenglong; Wu, Di; Qiao, Feng; Li, Wenqiang; Duan, Lingfeng; Wang, Ke; Xiao, Yingjie; Chen, Guoxing; Liu, Qian; Yang, Wanneng
With increasing demand for novel traits in crop breeding, the plant research community faces the challenge of quantitatively analyzing the structure and function of large numbers of plants. A clear goal of high-throughput phenotyping is to bridge the gap between genomics and phenomics. In this study, we quantified 106 traits from a maize (Zea mays) recombinant inbred line population (n = 167) across 16 developmental stages using the automatic phenotyping platform. Quantitative trait locus (QTL) mapping with a high-density genetic linkage map, including 2,496 recombinant bins, was used to uncover the genetic basis of these complex agronomic traits, and 988 QTLs have been identified for all investigated traits, including three QTL hotspots. Biomass accumulation and final yield were predicted using a combination of dissected traits in the early growth stage. These results reveal the dynamic genetic architecture of maize plant growth and enhance ideotype-based maize breeding and prediction. PMID:28153923
de Paor, Aisling
With rapid scientific and technological advances, the past few years has witnessed the emergence of a new genetic era and a growing understanding of the genetic make-up of human beings. These advances have propelled the introduction of companies offering direct to consumer (DTC) genetic testing, which facilitates the direct provision of such tests to consumers, (for example, via the internet). Although DTC genetic testing offers benefits by enhancing consumer accessibility to such technology, promoting proactive healthcare and increasing genetic awareness, it presents a myriad of challenges, from an ethical, legal and regulatory perspective. As DTC genetic testing usually eliminates the need for a medical professional in accessing genetic tests, this lack of professional guidance and counselling may result in misinterpretation and confusion regarding results. In addition, an evident concern relates to the scientific validity and quality of these tests. A further problem arising is the lack or inadequacy of regulation in this field. Despite the increasing accessibility of DTC genetic testing, this legislative vacuum is apparent in Ireland, where there is no concrete legislation. This article explores the main ethical, legal and regulatory issues arising with the advent of rapid advances in DTC genetic testing in Ireland. Further, with inevitable future advances in genetic science, as well as increasing internet accessibility, the challenges presented are likely to become more amplified. In consideration of the ethical and legal challenges, this paper highlights the regulation of DTC genetic testing as a growing concern in Ireland, recognising its importance to both the scientific community as well as in respect of enhancing consumer confidence in such technologies.
Frånberg, Mattias; Strawbridge, Rona J; Hamsten, Anders; de Faire, Ulf; Lagergren, Jens; Sennblad, Bengt
A complex disease has, by definition, multiple genetic causes. In theory, these causes could be identified individually, but their identification will likely benefit from informed use of anticipated interactions between causes. In addition, characterizing and understanding interactions must be considered key to revealing the etiology of any complex disease. Large-scale collaborative efforts are now paving the way for comprehensive studies of interaction. As a consequence, there is a need for methods with a computational efficiency sufficient for modern data sets as well as for improvements of statistical accuracy and power. Another issue is that, currently, the relation between different methods for interaction inference is in many cases not transparent, complicating the comparison and interpretation of results between different interaction studies. In this paper we present computationally efficient tests of interaction for the complete family of generalized linear models (GLMs). The tests can be applied for inference of single or multiple interaction parameters, but we show, by simulation, that jointly testing the full set of interaction parameters yields superior power and control of false positive rate. Based on these tests we also describe how to combine results from multiple independent studies of interaction in a meta-analysis. We investigate the impact of several assumptions commonly made when modeling interactions. We also show that, across the important class of models with a full set of interaction parameters, jointly testing the interaction parameters yields identical results. Further, we apply our method to genetic data for cardiovascular disease. This allowed us to identify a putative interaction involved in Lp(a) plasma levels between two 'tag' variants in the LPA locus (p = 2.42 ⋅ 10-09) as well as replicate the interaction (p = 6.97 ⋅ 10-07). Finally, our meta-analysis method is used in a small (N = 16,181) study of interactions in myocardial
Mathew, Lisa S; Spannagl, Manuel; Al-Malki, Ameena; George, Binu; Torres, Maria F; Al-Dous, Eman K; Al-Azwani, Eman K; Hussein, Emad; Mathew, Sweety; Mayer, Klaus F X; Mohamoud, Yasmin Ali; Suhre, Karsten; Malek, Joel A
The date palm is one of the oldest cultivated fruit trees. It is critical in many ways to cultures in arid lands by providing highly nutritious fruit while surviving extreme heat and environmental conditions. Despite its importance from antiquity, few genetic resources are available for improving the productivity and development of the dioecious date palm. To date there has been no genetic map and no sex chromosome has been identified. Here we present the first genetic map for date palm and identify the putative date palm sex chromosome. We placed ~4000 markers on the map using nearly 1200 framework markers spanning a total of 1293 cM. We have integrated the genetic map, derived from the Khalas cultivar, with the draft genome and placed up to 19% of the draft genome sequence scaffolds onto linkage groups for the first time. This analysis revealed approximately ~1.9 cM/Mb on the map. Comparison of the date palm linkage groups revealed significant long-range synteny to oil palm. Analysis of the date palm sex-determination region suggests it is telomeric on linkage group 12 and recombination is not suppressed in the full chromosome. Based on a modified genotyping-by-sequencing approach we have overcome challenges due to lack of genetic resources and provide the first genetic map for date palm. Combined with the recent draft genome sequence of the same cultivar, this resource offers a critical new tool for date palm biotechnology, palm comparative genomics and a better understanding of sex chromosome development in the palms.
Carro, Belén; Quintela, María; Ruiz, José Miguel; Barreiro, Rodolfo
Dispersal has received growing attention in marine ecology, particularly since evidence obtained with up-to-date techniques challenged the traditional view. The dogwhelk Nucella lapillus L., a sedentary gastropod with direct development, is a good example: dispersal was traditionally assumed to be limited until studies with microsatellites disputed this idea. To shed some light on this controversy, the genetic structure of dogwhelk populations in northwest Spain was investigated with highly polymorphic AFLP markers giving special attention to the influence of hydrodynamic stress. In agreement with the expectations for a poor disperser, our results show a significant genetic structure at regional (<200 km) and areal scales (<15 km). However, the spatial genetic structure varied with wave-exposure in the present case study: IBD was evident under sheltered conditions but absent from the exposed area where genetic differentiation was stronger. Our results provide evidence that differences in wave-exposure can exert a detectable influence on the genetic structure of coastal organisms, even in species without a planktonic larva.
Full Text Available Dispersal has received growing attention in marine ecology, particularly since evidence obtained with up-to-date techniques challenged the traditional view. The dogwhelk Nucella lapillus L., a sedentary gastropod with direct development, is a good example: dispersal was traditionally assumed to be limited until studies with microsatellites disputed this idea. To shed some light on this controversy, the genetic structure of dogwhelk populations in northwest Spain was investigated with highly polymorphic AFLP markers giving special attention to the influence of hydrodynamic stress. In agreement with the expectations for a poor disperser, our results show a significant genetic structure at regional (<200 km and areal scales (<15 km. However, the spatial genetic structure varied with wave-exposure in the present case study: IBD was evident under sheltered conditions but absent from the exposed area where genetic differentiation was stronger. Our results provide evidence that differences in wave-exposure can exert a detectable influence on the genetic structure of coastal organisms, even in species without a planktonic larva.
Dikshit, Harsh Kumar; Singh, Akanksha; Singh, Dharmendra; Aski, Muraleedhar Sidaram; Prakash, Prapti; Jain, Neelu; Meena, Suresh; Kumar, Shiv; Sarker, Ashutosh
Low productivity of pilosae type lentils grown in South Asia is attributed to narrow genetic base of the released cultivars which results in susceptibility to biotic and abiotic stresses. For enhancement of productivity and production, broadening of genetic base is essentially required. The genetic base of released cultivars can be broadened by using diverse types including bold seeded and early maturing lentils from Mediterranean region and related wild species. Genetic diversity in eighty six accessions of three species of genus Lens was assessed based on twelve genomic and thirty one EST-SSR markers. The evaluated set of genotypes included diverse lentil varieties and advanced breeding lines from Indian programme, two early maturing ICARDA lines and five related wild subspecies/species endemic to the Mediterranean region. Genomic SSRs exhibited higher polymorphism in comparison to EST SSRs. GLLC 598 produced 5 alleles with highest gene diversity value of 0.80. Among the studied subspecies/species 43 SSRs detected maximum number of alleles in L. orientalis. Based on Nei’s genetic distance cultivated lentil L. culinaris subsp. culinaris was found to be close to its wild progenitor L. culinaris subsp. orientalis. The Prichard’s structure of 86 genotypes distinguished different subspecies/species. Higher variability was recorded among individuals within population than among populations. PMID:26381889
Teodoro, S. S. A.; Terossi, M.; Costa, R. C.; Mantelatto, F. L.
The pink shrimp Farfantepenaeus paulensis is one of the most commercially exploited species in Brazil's South and Southeastern regions. Specific information about the status of its genetic variation is necessary to promote more effective management procedures. The genetic variation of the population of F. paulensis was investigated in five localities along southern and southeastern coast of Brazil. Sampling was performed with a commercial fishing boat. Total genomic DNA was extracted from abdominal muscle tissues and was used to DNA amplification by PCR. The COI gene was used as a DNA barcoding marker. The 570 bp COI gene sequences were obtained from all 45 individuals. The haplotype network showed no genetic variability among the population stocks, which was confirmed by Molecular Variance Analysis. The final alignment showed that inside species there is haplotype sharing among the sampled localities, since one haplotype is shared by 38 individuals belonging to all the five sampled regions, with no biogeographic pattern. This result is reasonable since there are no geographical barriers or habitat disjunction that might serve as a barrier to gene flow among the sampled localities. Possible reasons and consequences of the genetic homogeneity found are discussed. The results complement ecological studies concerning the offseason: since it is a single stock, the same protection strategy can be applied. However, the genetic homogeneity found in this study combined with the intensive fishery effort and the species biology can result in severe consequences for the F. paulensis.
Harsh Kumar Dikshit
Full Text Available Low productivity of pilosae type lentils grown in South Asia is attributed to narrow genetic base of the released cultivars which results in susceptibility to biotic and abiotic stresses. For enhancement of productivity and production, broadening of genetic base is essentially required. The genetic base of released cultivars can be broadened by using diverse types including bold seeded and early maturing lentils from Mediterranean region and related wild species. Genetic diversity in eighty six accessions of three species of genus Lens was assessed based on twelve genomic and thirty one EST-SSR markers. The evaluated set of genotypes included diverse lentil varieties and advanced breeding lines from Indian programme, two early maturing ICARDA lines and five related wild subspecies/species endemic to the Mediterranean region. Genomic SSRs exhibited higher polymorphism in comparison to EST SSRs. GLLC 598 produced 5 alleles with highest gene diversity value of 0.80. Among the studied subspecies/species 43 SSRs detected maximum number of alleles in L. orientalis. Based on Nei's genetic distance cultivated lentil L. culinaris subsp. culinaris was found to be close to its wild progenitor L. culinaris subsp. orientalis. The Prichard's structure of 86 genotypes distinguished different subspecies/species. Higher variability was recorded among individuals within population than among populations.
Hudec, Ján; Gramatová, Elena
The paper presents a new functional test generation method for processors testing based on genetic algorithms and evolutionary strategies. The tests are generated over an instruction set architecture and a processor description. Such functional tests belong to the software-oriented testing. Quality of the tests is evaluated by code coverage of the processor description using simulation. The presented test generation method uses VHDL models of processors and the professional simulator ModelSim. The rules, parameters and fitness functions were defined for various genetic algorithms used in automatic test generation. Functionality and effectiveness were evaluated using the RISC type processor DP32.
Carneiro, Ana Carolina Aguiar Vasconcelos; Andrade, Gláucia Manzan; Costa, Júlia Gatti Ladeia; Pinheiro, Breno Veloso; Vasconcelos-Santos, Daniel Vitor; Ferreira, Adriana Melo; Su, Chunlei; Januário, José Nélio; Vitor, Ricardo Wagner Almeida
Recent studies of Toxoplasma gondii isolates from animals in Brazil have revealed high genetic diversity. Many of these isolates are virulent to mice. It is speculated that these isolates may also be virulent to humans. However, there is very limited data regarding T. gondii strains from human infection. Therefore, it is not clear whether there is any association between parasite genotypes and disease phenotypes. In this study, a total of 27 T. gondii strains were isolated from humans with congenital toxoplasmosis in Minas Gerais state, Brazil. The genetic variability was assessed by restricted fragment length polymorphism in 11 loci (SAG1, 5' plus 3' SAG2, alternative [alt.] SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). Genetic analysis of 24 strains revealed 14 different genotypes, including 7 previously identified from animals and 7 new types. The widespread genotype BrII accounted for 29% (7/24) of the isolates and was the dominant genotype involved in this study. This is the first report of genotyping of T. gondii isolates obtained from blood samples from newborns with congenital toxoplasmosis. Genotypic characterization of these isolates suggests high genetic diversity of T. gondii in this human population in Brazil. Future studies are needed to determine the source of contamination of this human population.
Bradbury, A R; Patrick-Miller, L; Fetzer, D; Egleston, B; Cummings, S A; Forman, A; Bealin, L; Peterson, C; Corbman, M; O'Connell, J; Daly, M B
BRCA1/2 test disclosure has, historically, been conducted in-person by genetics professionals. Given increasing demand for, and access to, genetic testing, interest in telephone and Internet genetic services, including disclosure of test results, has increased. Semi-structured interviews with genetic counselors were conducted to determine interest in, and experiences with telephone disclosure of BRCA1/2 test results. Descriptive data are summarized with response proportions. One hundred and ninety-four genetic counselors completed self-administered surveys via the web. Although 98% had provided BRCA1/2 results by telephone, 77% had never provided pre-test counseling by telephone. Genetic counselors reported perceived advantages and disadvantages to telephone disclosure. Thirty-two percent of participants described experiences that made them question this practice. Genetic counselors more frequently reported discomfort with telephone disclosure of a positive result or variant of uncertain significance (p disadvantages to telephone disclosure, and recognize the potential for testing and patient factors to impact patient outcomes. Further research evaluating the impact of testing and patient factors on cognitive, affective, social and behavioral outcomes of alternative models of communicating genetic information is warranted. © 2010 John Wiley & Sons A/S.
Uhlmann, Wendy R; Schwalm, Katie; Raymond, Victoria M
Obtaining genetic testing insurance authorizations for patients is a complex, time-involved process often requiring genetic counselor (GC) and physician involvement. In an effort to mitigate this complexity and meet the increasing number of genetic testing insurance authorization requests, GCs formed a novel partnership with an industrial engineer (IE) and a patient services associate (PSA) to develop a streamlined work flow. Eight genetics clinics and five specialty clinics at the University of Michigan were surveyed to obtain benchmarking data. Tasks needed for genetic testing insurance authorization were outlined and time-saving work flow changes were introduced including 1) creation of an Excel password-protected shared database between GCs and PSAs, used for initiating insurance authorization requests, tracking and follow-up 2) instituting the PSAs sending GCs a pre-clinic email noting each patients' genetic testing insurance coverage 3) inclusion of test medical necessity documentation in the clinic visit summary note instead of writing a separate insurance letter and 4) PSAs development of a manual with insurance providers and genetic testing laboratories information. These work flow changes made it more efficient to request and track genetic testing insurance authorizations for patients, enhanced GCs and PSAs communication, and reduced tasks done by clinicians.
Full Text Available Although Colombia presents an enormous biological diversity, few studies have been conducted on the population genetics of Trypanosoma cruzi. This study was carried out with 23 Colombian stocks of this protozoa analyzed for 13 isoenzymatic loci. The Hardy-Weinberg equilibrium, the genetic diversity and heterogeneity, the genetic relationships and the possible spatial structure of these 23 Colombian stocks of T. cruzi were estimated. The majority of results obtained are in agreement with a clonal population structure. Nevertheless, two aspects expected in a clonal structure were not discovered in the Colombian T. cruzi stocks. There was an absence of given zymodemes over-represented from a geographical point of view and the presumed temporal stabilizing selective phenomena was not observed either in the Colombian stocks sampled several times through the years of the study. Some hypotheses are discussed in order to explain the results found.
Zhang, Xu; Hause, Ronald J; Borevitz, Justin O
Leaf growth and development determines a plant's capacity for photosynthesis and carbon fixation. These morphological traits are the integration of genetic and environmental factors through time. Yet fine dissection of the developmental genetic basis of leaf expansion throughout a growing season is difficult, due to the complexity of the trait and the need for real time measurement. In this study, we developed a time-lapse image analysis approach, which traces leaf expansion under seasonal light variation. Three growth traits, rosette leaf area, circular area, and their ratio as compactness, were measured and normalized on a linear timescale to control for developmental heterogeneity. We found high heritability for all growth traits that changed over time. Our study highlights a cost-effective, high-throughput phenotyping approach that facilitates the dissection of genetic basis of plant shoot growth and development under dynamic environmental conditions.
Busemeyer, Lucas; Ruckelshausen, Arno; Möller, Kim; Melchinger, Albrecht E.; Alheit, Katharina V.; Maurer, Hans Peter; Hahn, Volker; Weissmann, Elmar A.; Reif, Jochen C.; Würschum, Tobias
To extend agricultural productivity by knowledge-based breeding and tailor varieties adapted to specific environmental conditions, it is imperative to improve our ability to assess the dynamic changes of the phenome of crops under field conditions. To this end, we have developed a precision phenotyping platform that combines various sensors for a non-invasive, high-throughput and high-dimensional phenotyping of small grain cereals. This platform yielded high prediction accuracies and heritabilities for biomass of triticale. Genetic variation for biomass accumulation was dissected with 647 doubled haploid lines derived from four families. Employing a genome-wide association mapping approach, two major quantitative trait loci (QTL) for biomass were identified and the genetic architecture of biomass accumulation was found to be characterized by dynamic temporal patterns. Our findings highlight the potential of precision phenotyping to assess the dynamic genetics of complex traits, especially those not amenable to traditional phenotyping.
Peter D Paré
Full Text Available The human genome project promised a revolution in health care – the development of ‘personalized medicine’, where knowledge of an individual’s genetic code enables the prediction of risk for specific diseases and the potential to alter that risk based on preventive measures and lifestyle modification. The present brief review provides a report card on the progress toward that goal with respect to respiratory disease. Should generalized population screening for genetic risk factors for respiratory disease be instituted? Or not?
This paper considers the extent to which the geneticization of 'race' and ethnicity is the prevailing outcome of genetic testing for genealogical purposes. The decoding of the human genome precipitated a change of paradigms in genetics research, from an emphasis on genetic similarity to a focus on molecular-level differences among individuals and groups. This shift from lumping to splitting spurred ongoing disagreements among scholars about the significance of 'race' and ethnicity in the genetics era. I characterize these divergent perspectives as 'pragmatism' and 'naturalism'. Drawing upon ethnographic fieldwork and interviews, I argue that neither position fully accounts for how understandings of 'race' and ethnicity are being transformed with genetic genealogy testing. While there is some acquiescence to genetic thinking about ancestry, and by implication, 'race', among African-American and black British consumers of genetic genealogy testing, test-takers also adjudicate between sources of genealogical information and from these construct meaningful biographical narratives. Consumers engage in highly situated 'objective' and 'affiliative' self-fashioning, interpreting genetic test results in the context of their 'genealogical aspirations'. I conclude that issues of site, scale, and subjectification must be attended to if scholars are to understand whether and to what extent social identities are being transformed by recent developments in genetic science.
Snoek, L Basten; Terpstra, Inez R; Dekter, René; Van den Ackerveken, Guido; Peeters, Anton J M
One of the major goals of quantitative genetics is to unravel the complex interactions between molecular genetic factors and the environment. The effects of these genotype-by-environment interactions also affect and cause variation in gene expression. The regulatory loci responsible for this variation can be found by genetical genomics that involves the mapping of quantitative trait loci (QTLs) for gene expression traits also called expression-QTL (eQTLs). Most genetical genomics experiments published so far, are performed in a single environment and hence do not allow investigation of the role of genotype-by-environment interactions. Furthermore, most studies have been done in a steady state environment leading to acclimated expression patterns. However a response to the environment or change therein can be highly plastic and possibly lead to more and larger differences between genotypes. Here we present a genetical genomics study on 120 Arabidopsis thaliana, Landsberg erecta × Cape Verde Islands, recombinant inbred lines (RILs) in active response to the environment by treating them with 3 h of shade. The results of this experiment are compared to a previous study on seedlings of the same RILs from a steady state environment. The combination of two highly different conditions but exactly the same RILs with a fixed genetic variation showed the large role of genotype-by-environment interactions on gene expression levels. We found environment-dependent hotspots of transcript regulation. The major hotspot was confirmed by the expression profile of a near isogenic line. Our combined analysis leads us to propose CSN5A, a COP9 signalosome component, as a candidate regulator for the gene expression response to shade.
L. Basten eSnoek
Full Text Available One of the major goals of quantitative genetics is to unravel the complex interactions between molecular genetic factors and the environment. The effects of these genotype-by-environment interactions also affect and cause variation in gene expression. The regulatory loci responsible for this variation can be found by genetical genomics that involves the mapping of quantitative trait loci (QTLs for gene expression traits also called expression QTL (eQTLs. Most genetical genomics experiments published so far, are performed in a single environment and hence do not allow investigation of the role of genotype-by-environment interactions. Furthermore, most studies have been done in a steady state environment leading to acclimated expression patterns. However a response to the environment or change therein can be highly plastic and possibly lead to more and larger differences between genotypes. Here we present a genetical genomics study on 120 Arabidopsis thaliana, Landsberg erecta x Cape Verde Islands, recombinant inbred lines (RILs in active response to the environment by treating them with 3 hours of shade. The results of this experiment are compared to a previous study on seedlings of the same RILs from a steady state environment. The combination of two highly different conditions but exactly the same RILs with a fixed genetic variation showed the large role of genotype-by-environment interactions on gene expression levels.We found environment-dependent hotspots of transcript regulation. The major hotspot was confirmed by the expression profile of a near isogenic line. Our combined analysis leads us to propose CSN5A, a COP9 signalosome component, as a candidate regulator for the gene expression response to shade.
Russell J. Ferland
Full Text Available Epilepsy has many causes and comorbidities affecting as many as 4% of people in their lifetime. Both idiopathic and symptomatic epilepsies are highly heritable, but genetic factors are difficult to characterize among humans due to complex disease etiologies. Rodent genetic studies have been critical to the discovery of seizure susceptibility loci, including Kcnj10 mutations identified in both mouse and human cohorts. However, genetic analyses of epilepsy phenotypes in mice to date have been carried out as acute studies in seizure-naive animals or in Mendelian models of epilepsy, while humans with epilepsy have a history of recurrent seizures that also modify brain physiology. We have applied a repeated seizure model to a genetic reference population, following seizure susceptibility over a 36-d period. Initial differences in generalized seizure threshold among the Hybrid Mouse Diversity Panel (HMDP were associated with a well-characterized seizure susceptibility locus found in mice: Seizure susceptibility 1. Remarkably, Szs1 influence diminished as subsequent induced seizures had diminishing latencies in certain HMDP strains. Administration of eight seizures, followed by an incubation period and an induced retest seizure, revealed novel associations within the calmodulin-binding transcription activator 1, Camta1. Using systems genetics, we have identified four candidate genes that are differentially expressed between seizure-sensitive and -resistant strains close to our novel Epileptogenesis susceptibility factor 1 (Esf1 locus that may act individually or as a coordinated response to the neuronal stress of seizures.
Al-Abadi, Shaikha Y; Al-Sadi, Abdullah M; Dickinson, Matthew; Al-Hammadi, Mohammed S; Al-Shariqi, Rashid; Al-Yahyai, Rashid A; Kazerooni, Elham A; Bertaccini, Assunta
Witches' broom disease of lime (WBDL) is a serious phytoplasma disease of acid lime in Oman, the UAE and Iran. Despite efforts to study it, no systemic study attempted to characterize the relationship among the associated phytoplasma, 'Candidatus Phytoplasma aurantifolia', from the three countries. This study utilized sequences of the 16S rRNA, imp and secA genes to characterize 57 strains collected from Oman (38), the UAE (9) and Iran (10). Phylogenetic analysis based on the 16S rRNA gene showed that the 57 strains shared 98.5-100 % nucleotide similarity to each other and to strains of 'Ca. P. aurantifolia' available in GenBank. The level of genetic diversity was low based on the 16S rRNA (0-0.011), imp (0-0.002) and secA genes (0-0.015). The presence of low level of diversity among phytoplasma strains from Oman, the UAE and Iran can be explained by the movement of infected lime seedlings from one country to another through trading and exchange of infected plants. The study discusses implication of the findings on WBDL spread and management.
Fredsted, T; Pertoldi, C; Schierup, MH
Information on genetic structure can be used to complement direct inferences on social systems and behaviour. We studied the genetic structure of the solitary grey mouse lemur (Microcebus murinus), a small, nocturnal primate endemic to western Madagascar, with the aim of getting further insight...... distribution of identical homozygotes was found, supporting the notion that dispersal distance for breeding was shorter than that for foraging, i.e. the breeding neighbourhood size is smaller than the foraging neighbourhood size. In conclusion, we found a more complex population structure than what has been...
Vincent, P.; Larsen, S.; Galloway, D.; Laczniak, R.J.; Walter, W.R.; Foxall, W.; Zucca, J.J.
New observations of surface displacement caused by past underground nuclear tests at the Nevada Test Site (NTS) are presented using interferometric synthetic aperture radar (InSAR). The InSAR data reveal both coseismic and postseismic subsidence signals that extend one kilometer or more across regardless of whether or not a surface crater was formed from each test. While surface craters and other coseismic surface effects (ground cracks, etc.) may be detectable using high resolution optical or other remote sensing techniques, these broader, more subtle subsidence signals (one to several centimeters distributed over an area 1-2 kilometers across) are not detectable using other methods [Barker et al., 1998]. A time series of interferograms reveal that the postseismic signals develop and persist for months to years after the tests and that different rates and styles of deformation occur depending on the geologic and hydrologic setting and conditions of the local test area.
Thomas, Geethu E; Geetha, Kiran A; Augustine, Lesly; Mamiyil, Sabu; Thomas, George
Mode of reproduction is generally considered to have long-range evolutionary implications on population survival. Because sexual reproduction produces genetically diverse genotypes, this mode of reproduction is predicted to positively influence the success potential of offspring in evolutionary arms race with parasites (Red queen) whereas, without segregation and recombination, the obligate asexual multiplication may push a species into extinction due to the steady accumulation of deleterious mutations (Muller's ratchet). However, the extent of linearity between reproductive strategies, genetic diversity and population fitness, and the contributions of different breeding strategies to population fitness are yet to be understood clearly. Genus Zingiber belonging to the pan-tropic family Zingiberaceae represents a good system to study contributions of different breeding behavior on genetic diversity and population fitness, as this genus comprises species with contrasting breeding systems. In this study, we analyzed breeding behavior, amplified fragment length polymorphism diversity and response to the soft-rot pathogen Pythium aphanidermatum in 18 natural populations of three wild Zingiber spp.: Z. neesanum, Z. nimmonii, and Z. zerumbet, together with the obligately asexual cultivated congener, ginger (Z. officinale). Ginger showed an exceptionally narrow genetic base, and adding to this, all the tested cultivars were uniformly susceptible to soft-rot. Concordant with the postulates of Muller's ratchet, the background selection may be continuously pushing ginger into the ancestral state, rendering it inefficient in host-pathogen coevolution. Z. neesanum and Z. nimmonii populations were sexual and genetically diverse; however, contrary to Red Queen expectations, the populations were highly susceptible to soft-rot. Z. zerumbet showed a hemiclonal breeding behavior. The populations inhabiting forest understory were large and continuous, sexual and genetically diverse
Thomas, Geethu E.; Geetha, Kiran A.; Augustine, Lesly; Mamiyil, Sabu; Thomas, George
Mode of reproduction is generally considered to have long-range evolutionary implications on population survival. Because sexual reproduction produces genetically diverse genotypes, this mode of reproduction is predicted to positively influence the success potential of offspring in evolutionary arms race with parasites (Red queen) whereas, without segregation and recombination, the obligate asexual multiplication may push a species into extinction due to the steady accumulation of deleterious mutations (Muller’s ratchet). However, the extent of linearity between reproductive strategies, genetic diversity and population fitness, and the contributions of different breeding strategies to population fitness are yet to be understood clearly. Genus Zingiber belonging to the pan-tropic family Zingiberaceae represents a good system to study contributions of different breeding behavior on genetic diversity and population fitness, as this genus comprises species with contrasting breeding systems. In this study, we analyzed breeding behavior, amplified fragment length polymorphism diversity and response to the soft-rot pathogen Pythium aphanidermatum in 18 natural populations of three wild Zingiber spp.: Z. neesanum, Z. nimmonii, and Z. zerumbet, together with the obligately asexual cultivated congener, ginger (Z. officinale). Ginger showed an exceptionally narrow genetic base, and adding to this, all the tested cultivars were uniformly susceptible to soft-rot. Concordant with the postulates of Muller’s ratchet, the background selection may be continuously pushing ginger into the ancestral state, rendering it inefficient in host-pathogen coevolution. Z. neesanum and Z. nimmonii populations were sexual and genetically diverse; however, contrary to Red Queen expectations, the populations were highly susceptible to soft-rot. Z. zerumbet showed a hemiclonal breeding behavior. The populations inhabiting forest understory were large and continuous, sexual and genetically
Hursch, Thomas Mercer
Two statistical tools, the Chi-square and standard error approaches, are compared for use in Mendelian genetics experiments. Although the Chi-square technique is more often used, the standard error approach is to be preferred for both research investigations and student experiments. (BB)
The thought of genetically engineered (GE) trees might conjure images of mutant trees with unnatural and invasive tendencies, but there is much more to the story. GE trees are a new reality that, like it or not, will probably be part of the future of forestry. The basic inclination of most Forest Guild stewards is to reject GE trees as violating our principle to...
National Research Council Staff
... on Scientific Evaluation of the Introduction of Genetically Modified Microoganisms and Plants into the Environment Board on Biology Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1989 i Copyrightthe cannot be not from book, paper however, version for formatting, original authoritative the typesetting-s...
A genetic predisposition for this relatively common autosomal recessive disease has been identified in approximately 1 in 100 South Africans of European descent. If left untreated, this condition may lead to organ damage presenting as cirrhosis, liver cancer, diabetes, arthritis, impotence, sterility and/or cardiac disease.
C.H.M. Leenen (Celine); M.D. Heijer (Mariska den); C.A. van der Meer (Conny); E.J. Kuipers (Ernst); M.E. van Leerdam (Monique); A. Wagner (Anja)
textabstractCurrent genetic counselling practice for Lynch syndrome (LS) relies on diagnosed index patients to inform their biological family about LS, referred to as the family-mediated approach. The objective of this study was to evaluate this approach and to identify factors influencing the
Schäfer, Mike Steffen
Full Text Available Purpose: The study aimed to describe students' attitudes towards human genome research and towards genetic counselling and testing at cancer patients. The background of this investigation provided the increasing relevance ob human genetics research for clinical practice.Methods: A total of 167 medical students (54% female, aged 24 +/- 2 years from the second phase of their studies were surveyed in obligatory courses at the University of Leipzig, using a standardized questionnaire. Topics of the survey were attitudes towards human genome research and genetic counselling and testing at cancer patients as well as general values and socio-demographic data of the students.Results: The students consider human genome research as relevant and evaluate it positively, mainly based on expectations of medical uses. Genetic counselling and testing at cancer patients as an application of human genetics is also evaluated as important. The students attribute high relevance to clinical procedures for identification of genetic backgrounds for cancer (family history, information about genetic diagnostic. Nevertheless, deficits in their medical education are highlighted und reflected upon: the increased integration of human genetic content into medical curricula is demanded.Discussion: In accordance with the newly formulated „Approbationsordnung für Ärzte", the results suggest that current human genetic development should be more emphasized in medical education. This could be realized by an enlarged ratio of human genetic courses within curricula and by the transformation of these courses from facultative into obligatory.
Population genetic structure and approximate Bayesian computation analyses reveal the southern origin and northward dispersal of the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) in its native range.
Wei, Shu-Jun; Cao, Li-Jun; Gong, Ya-Jun; Shi, Bao-Cai; Wang, Su; Zhang, Fan; Guo, Xiao-Jun; Wang, Yuan-Min; Chen, Xue-Xin
The oriental fruit moth (OFM) Grapholita molesta is one of the most destructive orchard pests. Assumed to be native to China, the moth is now distributed throughout the world. However, the evolutionary history of this moth in its native range remains unknown. In this study, we explored the population genetic structure, dispersal routes and demographic history of the OFM in China and South Korea based on mitochondrial genes and microsatellite loci. The Mantel test indicated a significant correlation between genetic distance and geographical distance in the populations. Bayesian analysis of population genetic structure (baps) identified four nested clusters, while the geneland analysis inferred five genetic groups with spatial discontinuities. Based on the approximate Bayesian computation approach, we found that the OFM was originated from southern China near the Shilin area of Yunnan Province. The early divergence and dispersal of this moth was dated to the Penultimate glaciation of Pleistocene. Further dispersal from southern to northern region of China occurred before the last glacial maximum, while the expansion of population size in the derived populations in northern region of China occurred after the last glacial maximum. Our results indicated that the current distribution and structure of the OFM were complicatedly influenced by climatic and geological events and human activities of cultivation and wide dissemination of peach in ancient China. We provide an example on revealing the origin and dispersal history of an agricultural pest insect in its native range as well as the underlying factors. © 2015 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.
Lappegård, Knut Tore; Christiansen, Dorte; Pharo, Anne
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 knock...
Sun, Ye; Wen, Xiangying; Huang, Hongwen
Michelia maudiae Dunn. is a Magnoliaceae species threatened by habitat destruction and over-exploitation. Genetic diversity and differentiation, population contribution to total diversity and allelic/haplotypic richness, and the relative importance of pollen- and seed-mediated gene flow were investigated in nine populations (192 individuals) of M. maudiae using nuclear and chloroplast microsatellites to further our understanding of the genetic structure and evolutionary history of this tree species and to provide a genetic perspective for its conservation. The species had strong pollen mediated gene flow in the past. The ratio of pollen to seed gene flow was 25.4. Three clusters from the western, central, and eastern China were identified by both chloroplast and nuclear microsatellites. Western populations at Xiaodanjiang and Daoxian were phylogenetically divergent from the remaining populations and might be particularly important for the conservation of this species. The populations of Xiaodanjiang, Daoxian, and Minjiangyuan made positive contribution to the total diversity and allelic/haplotypic richness, and were worthy of being conserved with priority. In the central cluster, population at Laopengding should be protected since it harbored the greatest genetic diversity.
Ariyarathna, Chandima; Gunasekare, Kumudini
An understanding of genetic diversity and relationships among breeding materials is a prerequisite for crop improvement. Coefficient of parentage (COP) can be used to measure the genetic diversity among genotypes on the basis of pedigree information. In the present study, COP was estimated for 56 cultivars, including commercial tea cultivars developed by the Tea Research Institute of Sri Lanka and their parental lines. Mean COP of the 56 accessions studied was 0.097 and the value was raised up to 0.272 when non-related pair-wise comparisons were excluded. A single cultivar (Assam/Cambod introduction) was the nucleus of the commercial cultivars. Group mean COP of the cultivars derived from Assam/Cambod parentage was 0.17. Thirty-three percent of the pair-wise comparisons had 0.00 COP, highlighting that many cultivars were unrelated. Within the pedigree, 2 major COP clusters were identified: Assam/Cambod open-pollinated half-sib progenies, and full-sib progenies derived from crosses between Assam/Cambod and other parental lines. The elite groups within the pedigree, where Assam/Cambod parentage was concentrated, were also identified. Information generated in this study should be useful for effective utilization of available diversity in future breeding programmes as well as for proper conservation of genetic diversity in the adapted germplasm. This is the first report on estimates of genetic diversity based on COP in a woody perennial crop, such as tea.
Harakalova, Magdalena; Kummeling, Gijs; Sammani, Arjan; Linschoten, Marijke; Baas, Annette F.; van der Smagt, Jasper; Doevendans, Pieter A.; van Tintelen, J. Peter; Dooijes, Dennis; Mokry, Michal; Asselbergs, Folkert W.
Despite considerable progress being made in genetic diagnostics for dilated cardiomyopathy (DCM) using panels of the most prevalent genes, the cause remains unsolved in a substantial percentage of patients. We hypothesize that several previously described DCM genes with low or unknown prevalence
Mona, Stefano; Grunz, Katharina E; Brauer, Silke; Pakendorf, Brigitte; Castrì, Loredana; Sudoyo, Herawati; Marzuki, Sangkot; Barnes, Robert H; Schmidtke, Jörg; Stoneking, Mark; Kayser, Manfred
Eastern Indonesia possesses more linguistic diversity than any other region in Southeast Asia, with both Austronesian (AN) languages that are of East Asian origin, as well as non-Austronesian (NAN) languages of likely Melanesian origin. Here, we investigated the genetic history of human populations from seven eastern Indonesian islands, including AN and NAN speakers, as well as the relationship between languages and genes, by means of nonrecombining Y-chromosomal (NRY) and mitochondrial DNA (mtDNA) analysis. We found that the eastern Indonesian gene pool consists of East Asian as well as Melanesian components, as might be expected based on linguistic evidence, but also harbors putative indigenous eastern Indonesian signatures that perhaps reflect the initial occupation of the Wallacea by aboriginal hunter-gatherers already in Palaeolithic times. Furthermore, both NRY and mtDNA data showed a complete lack of correlation between linguistic and genetic relationships, most likely reflecting genetic admixture and/or language shift. In addition, we noted a small fraction of the NRY and mtDNA data shared between eastern Indonesians and Australian Aborigines likely reflecting an ancient link between Asia and Australia. Our data thus provide insights into the complex genetic ancestry history of eastern Indonesian islanders characterized by several admixture episodes and demonstrate a clear example of the lack of the often-assumed correlation between the genes and languages of human populations.
Erica M. Goss; Meg Larsen; Ignazio Carbone; Donald R. Givens; Gary A. Chastagner; Niklaus J. Gr& uuml; nwald
Phytophthora ramorum populations in North America and Europe are comprised of three clonal lineages based on several different genetic marker systems (Ivors and others 2006, Martin 2008). Whether these lineages are ancient or a recent artifact of introduction has been unclear. We analyzed DNA sequence variation at five nuclear loci in order to...
Savage, Wesley K; Fremier, Alexander K; Shaffer, H Bradley
Quantifying the influence of the landscape on the genetic structure of natural populations remains an important empirical challenge, particularly for poorly studied, ecologically cryptic species. We conducted an extensive microsatellite analysis to examine the population genetics of the southern long-toed salamander (Ambystoma macrodactylum sigillatum) in a naturally complex landscape. Using spatially explicit modelling, we investigated the influence of the Sierra Nevada topography on potential dispersal corridors between sampled populations. Our results indicate very high-genetic divergence among populations, high within-deme relatedness, and little evidence of recent migration or population admixture. We also discovered unexpectedly high between-year genetic differentiation (F(ST)) for breeding sites, suggesting that breeding groups vary over localized space and time. While environmental factors associated with high-elevation montane habitats apparently play an important role in shaping population differentiation, additional, species-specific biological processes must also be operating to account for observed deviations from temporal, among-year panmixia. Our study emphasizes the population-level insights that can be gained from high-density sampling in space and time, and the highly substructured population biology that may characterize amphibians in extreme montane habitats.
Craig S. Echt; L.L. DeVerno; M. Anzidei; G.G. Vendramin
Variation in paternally inherited chloroplast microsatellite (cpSSR) DNA was used to study population genetic structure in red pine (Pinus resinosa Ait.), a species characterized by morphological uniformity, no allozyme variation, and limited RAPD variation. Using nine cpSSR loci, a total of 23 chloroplast haplotypes and 25 cpSSR alleles were were...
S. Reppe (Sjur); Y. Wang (Yunpeng); W.K. Thompson (Wesley K.); L.K. McEvoy (Linda K.); N.J. Schork (Nicholas); V. Zuber (Verena); M. Leblanc (Marissa); F. Bettella (Francesco); I.G. Mills (Ian G.); R.S. Desikan (Rahul S.); S. Djurovic (Srdjan); K.M. Gautvik (Kaare); A.M. Dale (Anders); O.A. Andreassen (Ole); K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James F); V. Aalto (Ville); M. Alen (Markku); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. Lacroix (Andrea Z.); S.H. Lee (Seung Hun); P.C. Leung (Ping C.); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); J. Woo (Jean); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William D.); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E. Slagboom (Eline); N.L.S. Tang (Nelson L.S.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S.T. Palsson (Stefan Th); J.I. Rotter (Jerome I.); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S.R. Cummings (Steven R.); P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K.T. Khaw; T. Lehtimäki (Terho); Y. Liu (YongMei); M. Lorentzon (Mattias); E. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huib); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak Chung); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cornelia); N.J. Wareham (Nicholas J.); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara B.); A.W.C. Kung (Annie Wai Chee); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John P.A.); D.P. Kiel (Douglas P.); F. Rivadeneira Ramirez (Fernando)
textabstractBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown.
Bowl, Michael R.; Simon, Michelle M.; Ingham, Neil J.
The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. O...
Espley, R.V.; Bovy, A.G.; Bava, C.; Jaeger, S.R.; Tomes, S.; Norling, C.; Crawford, J.; Rowan, D.; McGhie, T.K.; Brendolise, C.; Putterill, J.; Schouten, H.J.; Hellens, R.P.; Allan, A.C.
Consumers of whole foods, such as fruits, demand consistent high quality and seek varieties with enhanced health properties, convenience or novel taste. We have raised the polyphenolic content of apple by genetic engineering of the anthocyanin pathway using the apple transcription factor MYB10.
Diets, I J; Nagtegaal, I D; Loeffen, J; de Blaauw, I; Waanders, E; Hoogerbrugge, N; Jongmans, M C J
BACKGROUND: Neuroendocrine tumours (NETs) are rare in children and limited data are available. We aimed to specify tumour and patient characteristics and to investigate the role of genetic predisposition in the aetiology of paediatric NETs. METHODS: Using the Dutch Pathology Registry PALGA, we
Yanagida, Tetsuya; Carod, Jean-François; Sako, Yasuhito; Nakao, Minoru; Hoberg, Eric P; Ito, Akira
An intricate history of human dispersal and geographic colonization has strongly affected the distribution of human pathogens. The pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serious neglected tropical diseases. Discrete genetic lineages of T. solium in Asia and Africa/Latin America are geographically disjunct; only in Madagascar are they sympatric. Linguistic, archaeological and genetic evidence has indicated that the people in Madagascar have mixed ancestry from Island Southeast Asia and East Africa. Hence, anthropogenic introduction of the tapeworm from Southeast Asia and Africa had been postulated. This study shows that the major mitochondrial haplotype of T. solium in Madagascar is closely related to those from the Indian Subcontinent. Parasitological evidence presented here, and human genetics previously reported, support the hypothesis of an Indian influence on Malagasy culture coinciding with periods of early human migration onto the island. We also found evidence of nuclear-mitochondrial discordance in single tapeworms, indicating unexpected cross-fertilization between the two lineages of T. solium. Analyses of genetic and geographic populations of T. solium in Madagascar will shed light on apparently rapid evolution of this organism driven by recent (<2,000 yr) human migrations, following tens of thousands of years of geographic isolation.
Lee, P H; Baker, J T; Holmes, A J; Jahanshad, N; Ge, T; Jung, J-Y; Cruz, Y; Manoach, D S; Hibar, D P; Faskowitz, J; McMahon, K L; de Zubicaray, G I; Martin, N H; Wright, M J; Öngür, D; Buckner, R; Roffman, J; Thompson, P M; Smoller, J W
Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.
Fernandez-Lopez, J.; Monteagudo, A. B.
The genetic variability within and among 17 wild Spanish chestnut stands was examined by isozyme analysis, with the goals of describing their geographic structure and designing conservation and management strategies. Measures of genetic diversity such as allelic richness, heterozygosity, polymorphism, F-statistics, D-statistics, gene flow and the contributions of each stand to diversity and allelic richness were calculated, clustering using Nei's genetic distances and a method based on an Monte Carlo Markov Chain algorithm were used. Wild Spanish chestnut populations displayed heterogeneity of allele frequencies between them, high levels of genetic diversity and high differentiation (Fst = 0.15) compared with populations from other western European countries. Two clustering methods allowed identification of three clusters: The highest heterozygosity and allelic richness were found in the North and especially in the Galician cluster close to Portugal. These results indicate that probably the northern chestnut populations are relictual originated from a North Iberian refuge. Several areas can be recommended for inclusion in the network of Conservation Units: Fraga de Catasos, representing the southern Galician cluster; Fragas do Eume, representing the northern Spanish cluster; and Hervas or El Tiemblo, representing the Mediterranean cluster. Key words: relict populations, diversity, allelic richness, conservation. (Author)
Reddy, Uma M; Page, Grier P; Saade, George R; Silver, Robert M; Thorsten, Vanessa R; Parker, Corette B; Pinar, Halit; Willinger, Marian; Stoll, Barbara J; Heim-Hall, Josefine; Varner, Michael W; Goldenberg, Robert L; Bukowski, Radek; Wapner, Ronald J; Drews-Botsch, Carolyn D; O'Brien, Barbara M; Dudley, Donald J; Levy, Brynn
Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants. The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery. In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies. Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).
Greenbaum, Gili; Renan, Sharon; Templeton, Alan R; Bouskila, Amos; Saltz, David; Rubenstein, Daniel I; Bar-David, Shirli
Effective population size, a central concept in conservation biology, is now routinely estimated from genetic surveys, and can also be theoretically-predicted from demographic, life-history and mating-system hypotheses. However, by evaluating the consistency of theoretical predictions with empirically-estimated effective size, insights can be gained regarding life-history characteristics, as well as the relative impact of different life-history traits on genetic drift. These insights can be used to design and inform management strategies aimed at increasing effective population size. Here we describe and demonstrate this approach by addressing the conservation of a reintroduced population of Asiatic wild ass (Equus hemionus). We estimate the variance effective size (Nev ) from genetic data (Nev = 24.3), and we formulate predictions for the impacts on Nev of demography, polygyny, female variance in life-time reproductive success, and heritability of female reproductive success. By contrasting the genetic estimation with theoretical predictions, we find that polygyny is the strongest factor effecting genetic drift, as only when accounting for polygyny were predictions consistent with the genetically-measured Nev , with 10.6% mating males per generation when heritability of female RS was unaccounted for (polygyny responsible for 81% decrease in Nev ), and 19.5% when it was accounted for (polygyny responsible for 67% decrease in Nev ). Heritability of female reproductive success was also found to affect Nev , with hf2 = 0.91 (heritability responsible for 41% decrease in Nev ). The low effective population size is of concern, and we suggest specific management actions focusing on factors identified as strongly affecting Nev -increasing the availability of artificial water sources to increase number of dominant males contributing to the gene pool. This approach - evaluating life-history hypotheses, in light of their impact on effective population size, and contrasting
Full Text Available We have created a high-resolution linkage map of Miscanthus sinensis, using genotyping-by-sequencing (GBS, identifying all 19 linkage groups for the first time. The result is technically significant since Miscanthus has a very large and highly heterozygous genome, but has no or limited genomics information to date. The composite linkage map containing markers from both parental linkage maps is composed of 3,745 SNP markers spanning 2,396 cM on 19 linkage groups with a 0.64 cM average resolution. Comparative genomics analyses of the M. sinensis composite linkage map to the genomes of sorghum, maize, rice, and Brachypodium distachyon indicate that sorghum has the closest syntenic relationship to Miscanthus compared to other species. The comparative results revealed that each pair of the 19 M. sinensis linkages aligned to one sorghum chromosome, except for LG8, which mapped to two sorghum chromosomes (4 and 7, presumably due to a chromosome fusion event after genome duplication. The data also revealed several other chromosome rearrangements relative to sorghum, including two telomere-centromere inversions of the sorghum syntenic chromosome 7 in LG8 of M. sinensis and two paracentric inversions of sorghum syntenic chromosome 4 in LG7 and LG8 of M. sinensis. The results clearly demonstrate, for the first time, that the diploid M. sinensis is tetraploid origin consisting of two sub-genomes. This complete and high resolution composite linkage map will not only serve as a useful resource for novel QTL discoveries, but also enable informed deployment of the wealth of existing genomics resources of other species to the improvement of Miscanthus as a high biomass energy crop. In addition, it has utility as a reference for genome sequence assembly for the forthcoming whole genome sequencing of the Miscanthus genus.
Pedreschi, Debbi; Kelly-Quinn, Mary; Caffrey, Joe; O’Grady, Martin; Mariani, Stefano; Phillimore, Albert
Aim We investigated genetic variation of Irish pike populations and their relationship with European outgroups, in order to elucidate the origin of this species to the island, which is largely assumed to have occurred as a human-mediated introduction over the past few hundred years. We aimed thereby to provide new insights into population structure to improve fisheries and biodiversity management in Irish freshwaters. Location Ireland, Britain and continental Europe. Methods A total of 752 pike (Esox lucius) were sampled from 15 locations around Ireland, and 9 continental European sites, and genotyped at six polymorphic microsatellite loci. Patterns and mechanisms of population genetic structure were assessed through a diverse array of methods, including Bayesian clustering, hierarchical analysis of molecular variance, and approximate Bayesian computation. Results Varying levels of genetic diversity and a high degree of population genetic differentiation were detected. Clear substructure within Ireland was identified, with two main groups being evident. One of the Irish populations showed high similarity with British populations. The other, more widespread, Irish strain did not group with any European population examined. Approximate Bayesian computation suggested that this widespread Irish strain is older, and may have colonized Ireland independently of humans. Main conclusions Population genetic substructure in Irish pike is high and comparable to the levels observed elsewhere in Europe. A comparison of evolutionary scenarios upholds the possibility that pike may have colonized Ireland in two ‘waves’, the first of which, being independent of human colonization, would represent the first evidence for natural colonization of a non-anadromous freshwater fish to the island of Ireland. Although further investigations using comprehensive genomic techniques will be necessary to confirm this, the present results warrant a reappraisal of current management strategies
Neumann, Kerstin; Zhao, Yusheng; Chu, Jianting; Keilwagen, Jens; Reif, Jochen C; Kilian, Benjamin; Graner, Andreas
Genetic mapping of phenotypic traits generally focuses on a single time point, but biomass accumulates continuously during plant development. Resolution of the temporal dynamics that affect biomass recently became feasible using non-destructive imaging. With the aim to identify key genetic factors for vegetative biomass formation from the seedling stage to flowering, we explored growth over time in a diverse collection of two-rowed spring barley accessions. High heritabilities facilitated the temporal analysis of trait relationships and identification of quantitative trait loci (QTL). Biomass QTL tended to persist only a short period during early growth. More persistent QTL were detected around the booting stage. We identified seven major biomass QTL, which together explain 55% of the genetic variance at the seedling stage, and 43% at the booting stage. Three biomass QTL co-located with genes or QTL involved in phenology. The most important locus for biomass was independent from phenology and is located on chromosome 7HL at 141 cM. This locus explained ~20% of the genetic variance, was significant over a long period of time and co-located with HvDIM, a gene involved in brassinosteroid synthesis. Biomass is a dynamic trait and is therefore orchestrated by different QTL during early and late growth stages. Marker-assisted selection for high biomass at booting stage is most effective by also including favorable alleles from seedling biomass QTL. Selection for dynamic QTL may enhance genetic gain for complex traits such as biomass or, in the future, even grain yield.
Van der Zande, Paul; Akkerman, Sanne F.; Brekelmans, Mieke; Waarlo, Arend Jan; Vermunt, Jan D.
Contemporary genomics research will impact the daily practice of biology teachers who want to teach up-to-date genetics in secondary education. This article reports on a research project aimed at enhancing biology teachers' expertise for teaching genetics situated in the context of genetic testing. The increasing body of scientific knowledge concerning genetic testing and the related consequences for decision-making indicate the societal relevance of an educational approach based on situated learning. What expertise do biology teachers need for teaching genetics in the personal health context of genetic testing? This article describes the required expertise by exploring the educational practice. Nine experienced teachers were interviewed about the pedagogical content, moral and interpersonal expertise areas concerning how to teach genetics in the personal health context of genetic testing, and the lessons of five of them were observed. The findings showed that the required teacher expertise encompasses specific pedagogical content expertise, interpersonal expertise and a preference for teacher roles and teaching approaches for the moral aspects of teaching in this context. A need for further development of teaching and learning activities for (reflection on) moral reasoning came to the fore. Suggestions regarding how to apply this expertise into context-based genetics education are discussed.
Katapodi, Maria C; Northouse, Laurel; Pierce, Penny; Milliron, Kara J; Liu, Guipeng; Merajver, Sofia D
To (a) examine differences in appraisals of hereditary breast and ovarian cancer (HBOC), psychological distress, family environment, and decisional conflict between women who pursued genetic testing and their at-risk relatives who did not, and (b) examine correlations among appraisals of HBOC, psychological distress, family environment, and decisional conflict regarding genetic testing in these two cohorts of women. Descriptive, cross-sectional cohort study. Two clinics affiliated with a major research university in the midwestern United States. 372 women aged 18 years and older. 200 pursued genetic testing for BRCA1 and BRCA2 mutations (probands) and 172 of their female relatives who had a greater than 10% prior probability of being a mutation carrier but had not pursued testing. After providing informed consent, probands and relatives were mailed self-administered questionnaires. Perceived risk, knowledge of HBOC risk factors and modes of gene inheritance, perceived severity, perceived controllability, psychological distress, family relationships, family communication, and decisional conflict about genetic testing. T tests revealed that probands perceived higher risk and had more psychological distress associated with breast cancer. Probands had more knowledge regarding risk factors and gene inheritance, and greater decisional conflict regarding genetic testing. Relatives reported higher perceived severity and controllability. No differences were observed in family relationships and family communication between probands and relatives. Pearson correlations revealed different patterns in knowledge, perceived controllability, family relationships, and decisional conflict between probands and relatives. Significant differences exist between women who pursue genetic testing and those who do not. The family environment influences adjustment to HBOC and decisions about genetic testing. Enhancing the family communication process about HBOC can provide informational and
Full Text Available Forty-five Xanthomonas arboricola pv. juglandis (Xaj strains originating from Juglans regia cultivation in different countries were molecularly typed by means of MultiLocus Sequence Typing (MLST, using acnB, gapA, gyrB and rpoD gene fragments. A total of 2.5 kilobases was used to infer the phylogenetic relationship among the strains and possible recombination events. Haplotype diversity, linkage disequilibrium analysis, selection tests, gene flow estimates and codon adaptation index were also assessed. The dendrograms built by maximum likelihood with concatenated nucleotide and amino acid sequences revealed two major and two minor phylotypes. The same haplotype was found in strains originating from different continents, and different haplotypes were found in strains isolated in the same year from the same location. A recombination breakpoint was detected within the rpoD gene fragment. At the pathovar level, the Xaj populations studied here are clonal and under neutral selection. However, four Xaj strains isolated from walnut fruits with apical necrosis are under diversifying selection, suggesting a possible new adaptation. Gene flow estimates do not support the hypothesis of geographic isolation of the strains, even though the genetic diversity between the strains increases as the geographic distance between them increases. A triplet deletion, causing the absence of valine, was found in the rpoD fragment of all 45 Xaj strains when compared with X. axonopodis pv. citri strain 306. The codon adaptation index was high in all four genes studied, indicating a relevant metabolic activity.
Martis W Cowles
Full Text Available Members of the COE family of transcription factors are required for central nervous system (CNS development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenotype, we knocked down their expression by RNAi and uncovered a set of coe-regulated genes implicated in CNS regeneration and patterning, including orthologs of sodium channel alpha-subunit and pou4. Our study broadens the knowledge of gene expression programs regulated by COE that are required for maintenance of neural subtypes and nervous system architecture in adult animals.
Cowles, Martis W; Omuro, Kerilyn C; Stanley, Brianna N; Quintanilla, Carlo G; Zayas, Ricardo M
Members of the COE family of transcription factors are required for central nervous system (CNS) development. However, the function of COE in the post-embryonic CNS remains largely unknown. An excellent model for investigating gene function in the adult CNS is the freshwater planarian. This animal is capable of regenerating neurons from an adult pluripotent stem cell population and regaining normal function. We previously showed that planarian coe is expressed in differentiating and mature neurons and that its function is required for proper CNS regeneration. Here, we show that coe is essential to maintain nervous system architecture and patterning in intact (uninjured) planarians. We took advantage of the robust phenotype in intact animals to investigate the genetic programs coe regulates in the CNS. We compared the transcriptional profiles of control and coe RNAi planarians using RNA sequencing and identified approximately 900 differentially expressed genes in coe knockdown animals, including 397 downregulated genes that were enriched for nervous system functional annotations. Next, we validated a subset of the downregulated transcripts by analyzing their expression in coe-deficient planarians and testing if the mRNAs could be detected in coe+ cells. These experiments revealed novel candidate targets of coe in the CNS such as ion channel, neuropeptide, and neurotransmitter genes. Finally, to determine if loss of any of the validated transcripts underscores the coe knockdown phenoty