Linkage & Genetic Mapping in Eukaryotes
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Gene Mapping Techniques
Developmental Neurobiology, edited by Philippe Evrard and Alexandre Minkowski. Nestle Nutrition Workshop Series, Vol. 12. Nestec Ltd., Vevey/Raven Press, Ltd., New York © 1989. Gene Mapping Techniques Jean-Louis Guenet Institut Pasteur, 75724 Paris Cedex 15, France Very accurate gene mapping is essential in both man and laboratory mammals (1- 3). Several techniques have been used over the last 50 years to localize mammalian genes on the chromosomes of a given species. This chapter reviews these tech- niques, with special emphasis on the most recent ones that represent a true break- through in formal genetics. CLASSICAL GENE MAPPING TECHNIQUES AND THEIR LIMITATIONS When two genes are linked they have a tendency to cosegregate during successive generations. The closer the linkage, the more absolute is the cosegregation. This is the fundamental principle of gene mapping, which has been successfully applied to all species, including plants, over many years. In mammals such as humans and mice, the continued discovery of marker genes scattered throughout the genome has facilitated the mapping of new genes so that we now possess for these two species, particularly the mouse, linkage maps that are far more detailed than those existing for other mammals. In the mouse, special matings can be set up, with appropriate stocks, to test for possible autosomal linkage after two successive reproductive rounds: In general, cross-back crosses are used, cross-intercrosses being reserved for studies in which the viability or the fertility of the homozygous mutant under study is impaired. In humans investigations concerning linkage are based on pedigree analysis. In other words, for both species it is essential to define as a starting point a situa- tion where two genes are heterozygous and either in repulsion A + / + B or in cou- pling AB/ + +, then to look for changes in this configuration after a reproductive cycle (forms in coupling giving rise to forms in repulsion and vice versa), and fi- nally to count the percentage or frequency of these recombination events. -
Population Genetic Considerations for Using Biobanks As International
Carress et al. BMC Genomics (2021) 22:351 https://doi.org/10.1186/s12864-021-07618-x REVIEW Open Access Population genetic considerations for using biobanks as international resources in the pandemic era and beyond Hannah Carress1, Daniel John Lawson2 and Eran Elhaik1,3* Abstract The past years have seen the rise of genomic biobanks and mega-scale meta-analysis of genomic data, which promises to reveal the genetic underpinnings of health and disease. However, the over-representation of Europeans in genomic studies not only limits the global understanding of disease risk but also inhibits viable research into the genomic differences between carriers and patients. Whilst the community has agreed that more diverse samples are required, it is not enough to blindly increase diversity; the diversity must be quantified, compared and annotated to lead to insight. Genetic annotations from separate biobanks need to be comparable and computable and to operate without access to raw data due to privacy concerns. Comparability is key both for regular research and to allow international comparison in response to pandemics. Here, we evaluate the appropriateness of the most common genomic tools used to depict population structure in a standardized and comparable manner. The end goal is to reduce the effects of confounding and learn from genuine variation in genetic effects on phenotypes across populations, which will improve the value of biobanks (locally and internationally), increase the accuracy of association analyses and inform developmental efforts. Keywords: Bioinformatics, Population structure, Population stratification bias, Genomic medicine, Biobanks Background individuals, families, communities and populations, ne- Association studies aim to detect whether genetic vari- cessitated genomic biobanks. -
Gene Linkage and Genetic Mapping 4TH PAGES © Jones & Bartlett Learning, LLC
© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Gene Linkage and © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 4NOTGenetic FOR SALE OR DISTRIBUTIONMapping NOT FOR SALE OR DISTRIBUTION CHAPTER ORGANIZATION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR4.1 SALELinked OR alleles DISTRIBUTION tend to stay 4.4NOT Polymorphic FOR SALE DNA ORsequences DISTRIBUTION are together in meiosis. 112 used in human genetic mapping. 128 The degree of linkage is measured by the Single-nucleotide polymorphisms (SNPs) frequency of recombination. 113 are abundant in the human genome. 129 The frequency of recombination is the same SNPs in restriction sites yield restriction for coupling and repulsion heterozygotes. 114 fragment length polymorphisms (RFLPs). 130 © Jones & Bartlett Learning,The frequency LLC of recombination differs © Jones & BartlettSimple-sequence Learning, repeats LLC (SSRs) often NOT FOR SALE OR DISTRIBUTIONfrom one gene pair to the next. NOT114 FOR SALEdiffer OR in copyDISTRIBUTION number. 131 Recombination does not occur in Gene dosage can differ owing to copy- Drosophila males. 115 number variation (CNV). 133 4.2 Recombination results from Copy-number variation has helped human populations adapt to a high-starch diet. 134 crossing-over between linked© Jones alleles. & Bartlett Learning,116 LLC 4.5 Tetrads contain© Jonesall & Bartlett Learning, LLC four products of meiosis. -
Genetic Mapping and Manipulation: Chapter 2-Two-Point Mapping with Genetic Markers* §
Genetic mapping and manipulation: Chapter 2-Two-point mapping with genetic markers* § David Fay , Department of Molecular Biology, University of Wyoming, Laramie, Wyoming 82071-3944 USA Table of Contents 1. The basics ..............................................................................................................................1 2. Calculating map distances ......................................................................................................... 3 3. Other considerations ................................................................................................................. 5 4. References ..............................................................................................................................6 1. The basics The basics. Two-point mapping, wherein a mutation in the gene of interest is mapped against a marker mutation, is primarily used to assign mutations to individual chromosomes. It can also give at least a rough indication of distance between the mutation and the markers used. On the surface, the concept of two-point mapping to determine chromosomal linkage is relatively straightforward. It can, however, be the source of some confusion when it comes to processing the actual data based on phenotypic frequencies to accurately determine genetic distances. It is also worth noting that most researchers don't bother much with exhaustive two-point mapping anymore. Once we've assigned our mutation to a linkage group, it's generally off to the races with three-point and SNP mapping -
Development of Novel SNP Assays for Genetic Analysis of Rare Minnow (Gobiocypris Rarus) in a Successive Generation Closed Colony
diversity Article Development of Novel SNP Assays for Genetic Analysis of Rare Minnow (Gobiocypris rarus) in a Successive Generation Closed Colony Lei Cai 1,2,3, Miaomiao Hou 1,2, Chunsen Xu 1,2, Zhijun Xia 1,2 and Jianwei Wang 1,4,* 1 The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430070, China; [email protected] (L.C.); [email protected] (M.H.); [email protected] (C.X.); [email protected] (Z.X.) 2 University of Chinese Academy of Sciences, Beijing 100049, China 3 Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou 510663, China 4 National Aquatic Biological Resource Center, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430070, China * Correspondence: [email protected] Received: 10 November 2020; Accepted: 11 December 2020; Published: 18 December 2020 Abstract: The complex genetic architecture of closed colonies during successive passages poses a significant challenge in the understanding of the genetic background. Research on the dynamic changes in genetic structure for the establishment of a new closed colony is limited. In this study, we developed 51 single nucleotide polymorphism (SNP) markers for the rare minnow (Gobiocypris rarus) and conducted genetic diversity and structure analyses in five successive generations of a closed colony using 20 SNPs. The range of mean Ho and He in five generations was 0.4547–0.4983 and 0.4445–0.4644, respectively. No significant differences were observed in the Ne, Ho, and He (p > 0.05) between the five closed colony generations, indicating well-maintained heterozygosity. -
Genetic Linkage Analysis
BASIC SCIENCE SEMINARS IN NEUROLOGY SECTION EDITOR: HASSAN M. FATHALLAH-SHAYKH, MD Genetic Linkage Analysis Stefan M. Pulst, MD enetic linkage analysis is a powerful tool to detect the chromosomal location of dis- ease genes. It is based on the observation that genes that reside physically close on a chromosome remain linked during meiosis. For most neurologic diseases for which the underlying biochemical defect was not known, the identification of the chromo- Gsomal location of the disease gene was the first step in its eventual isolation. By now, genes that have been isolated in this way include examples from all types of neurologic diseases, from neu- rodegenerative diseases such as Alzheimer, Parkinson, or ataxias, to diseases of ion channels lead- ing to periodic paralysis or hemiplegic migraine, to tumor syndromes such as neurofibromatosis types 1 and 2. Arch Neurol. 1999;56:667-672 With the advent of new genetic markers tin gene, diagnosis using flanking mark- and automated genotyping, genetic map- ers requires the analysis of several family ping can be conducted extremely rap- members. idly. Genetic linkage maps have been gen- erated for the human genome and for LINKAGE OF GENES model organisms and have provided the basis for the construction of physical maps When Mendel observed an “independent that permit the rapid mapping of disease assortment of traits” (Mendel’s second traits. law), he was fortunate to have chosen traits As soon as a chromosomal location that were not localized close to one an- for a disease phenotype has been estab- other on the same chromosome.1 Subse- lished, genetic linkage analysis helps quent studies revealed that many genes determine whether the disease pheno- were indeed linked, ie, that traits did not type is only caused by mutation in a assort or segregate independently, but that single gene or mutations in other genes traits encoded by these linked genes were can give rise to an identical or similar inherited together. -
HUMAN GENE MAPPING WORKSHOPS C.1973–C.1991
HUMAN GENE MAPPING WORKSHOPS c.1973–c.1991 The transcript of a Witness Seminar held by the History of Modern Biomedicine Research Group, Queen Mary University of London, on 25 March 2014 Edited by E M Jones and E M Tansey Volume 54 2015 ©The Trustee of the Wellcome Trust, London, 2015 First published by Queen Mary University of London, 2015 The History of Modern Biomedicine Research Group is funded by the Wellcome Trust, which is a registered charity, no. 210183. ISBN 978 1 91019 5031 All volumes are freely available online at www.histmodbiomed.org Please cite as: Jones E M, Tansey E M. (eds) (2015) Human Gene Mapping Workshops c.1973–c.1991. Wellcome Witnesses to Contemporary Medicine, vol. 54. London: Queen Mary University of London. CONTENTS What is a Witness Seminar? v Acknowledgements E M Tansey and E M Jones vii Illustrations and credits ix Abbreviations and ancillary guides xi Introduction Professor Peter Goodfellow xiii Transcript Edited by E M Jones and E M Tansey 1 Appendix 1 Photographs of participants at HGM1, Yale; ‘New Haven Conference 1973: First International Workshop on Human Gene Mapping’ 90 Appendix 2 Photograph of (EMBO) workshop on ‘Cell Hybridization and Somatic Cell Genetics’, 1973 96 Biographical notes 99 References 109 Index 129 Witness Seminars: Meetings and publications 141 WHAT IS A WITNESS SEMINAR? The Witness Seminar is a specialized form of oral history, where several individuals associated with a particular set of circumstances or events are invited to meet together to discuss, debate, and agree or disagree about their memories. The meeting is recorded, transcribed, and edited for publication. -
Inference and Analysis of Population Structure Using Genetic Data and Network Theory
| INVESTIGATION Inference and Analysis of Population Structure Using Genetic Data and Network Theory Gili Greenbaum,*,†,1 Alan R. Templeton,‡,§ and Shirli Bar-David† *Department of Solar Energy and Environmental Physics and †Mitrani Department of Desert Ecology, Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, 84990 Midreshet Ben-Gurion, Israel, ‡Department of Biology, Washington University, St. Louis, Missouri 63130, and §Department of Evolutionary and Environmental Ecology, University of Haifa, 31905 Haifa, Israel ABSTRACT Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance- based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition’s modularity, a network theory measure indicating the quality of community partitions. -
Genetic Linkage of the Huntington's Disease Gene to a DNA Marker James F
LE JOURNAL CANADIEN DES SCIENCES NEUROLOG1QUES SPECIAL FEATURE Genetic Linkage of the Huntington's Disease Gene to a DNA Marker James F. Gusella ABSTRACT: Recombinant DNA techniques have provided the means to generate large numbers of new genetic linkage markers. This technology has been used to identify a DNA marker that coinherits with the Huntington's Disease (HD) gene in family studies. The HD locus has thereby been mapped to human chromosome 4. The discovery of a genetic marker for the inheritance of HD has implications both for patient care and future research. The same approach holds considerable promise for the investigation of other genetic diseases, including Dystonia Musculorum Deformans. RESUME: Les techniques d'ADN recombine ont fourni le moyen de g£nerer un grand nombre de nouveux marqueurs a liason g6n£tique. Cette technologie a He employe" afin d'identifier un marqueur d'ADN qui co-herite avec le gene de la maladie de Huntington (MH) dans les etudes familiales. Le lieu du gene de la MH a ainsi 6te localise sur le chromosome humain numero 4. La d6couverte d'un marqueur g6n6tique pour I'her6dit6 de MH a des implications pour la soin de patients ainsi que pour la recherche dans le futur. La meme approche semble pleine de promesses pour l'investigation d'autres maladies g6ndtiques, incluant la dystonie musculaire deTormante. Can. J. Neurol. Sci. 1984; 11:421-425 Huntington's Disease currently no effective therapy to cure this devastating disease, Huntington's disease (HD) is a genetic neurodegenerative or to slow its inexorable progression. disorder first described by George Huntington in 1873 (Hunting ton, 1972;Hayden, 1981;Chaseetal., 1979). -
Cancer Genomics Terminology
Cancer Genomics Terminology Acquired Susceptibility Mutation: A mutation in a gene that occurs after birth from a carcinogenic insult. Allele: One of the variant forms of a gene. Different alleles may produce variation in inherited characteristics. Allele Heterogeneity: A phenotype that can be produced by different genetic mechanisms. Amino Acid: The building blocks of protein, for which DNA carries the genetic code. Analytical Sensitivity: The proportion of positive test results correctly reported by the laboratory among samples with a mutation(s) that the laboratory’s test is designed to detect. Analytic Specificity: The proportion of negative test results correctly reported among samples when no detectable mutation is present. Analytic Validity: A test’s ability to accurately and reliably measure the genotype of interest. Apoptosis: Programmed cell death. Ashkenazi: Individuals of Eastern European Jewish ancestry/decent (For example-Germany and Poland). Non-assortative mating occurred in this population. Association: When significant differences in allele frequencies are found between a disease and control population, the disease and allele are said to be in association. Assortative Mating: In population genetics, selective mating in a population between individuals that are genetically related or have similar characteristics. Autosome: Any chromosome other than a sex chromosome. Humans have 22 pairs numbered 1-22. Base Excision Repair Gene: The gene responsible for the removal of a damaged base and replacing it with the correct nucleotide. Base Pair: Two bases, which form a “rung on the DNA ladder”. Bases are the “letters” (Adenine, Thymine, Cytosine, Guanine) that spell out the genetic code. Normally adenine pairs with thymine and cytosine pairs with guanine. -
Mapping Genomes
472 Chapter 17 | Biotechnology and Genomics the bacterium Agrobacterium tumefaciens occur by DNA transfer from the bacterium to the plant. Although the tumors do not kill the plants, they stunt the plants and they become more susceptible to harsh environmental conditions. A. tumefaciens affects many plants such as walnuts, grapes, nut trees, and beets. Artificially introducing DNA into plant cells is more challenging than in animal cells because of the thick plant cell wall. Researchers used the natural transfer of DNA from Agrobacterium to a plant host to introduce DNA fragments of their choice into plant hosts. In nature, the disease-causing A. tumefaciens have a set of plasmids, Ti plasmids (tumor-inducing plasmids), that contain genes to produce tumors in plants. DNA from the Ti plasmid integrates into the infected plant cell’s genome. Researchers manipulate the Ti plasmids to remove the tumor-causing genes and insert the desired DNA fragment for transfer into the plant genome. The Ti plasmids carry antibiotic resistance genes to aid selection and researchers can propagate them in E. coli cells as well. The Organic Insecticide Bacillus thuringiensis Bacillus thuringiensis (Bt) is a bacterium that produces protein crystals during sporulation that are toxic to many insect species that affect plants. Insects need to ingest Bt toxin in order to activate the toxin. Insects that have eaten Bt toxin stop feeding on the plants within a few hours. After the toxin activates in the insects' intestines, they die within a couple of days. Modern biotechnology has allowed plants to encode their own crystal Bt toxin that acts against insects. -
Physical Mapping Technologies for the Identification and Characterization of Mutated Genes Contributing to Crop Quality
to Crop Quality for the Identification for the Identification and Characterization of Mutated Genes Contributing Physical Mapping Technologies Physical Mapping Technologies IAEA-TECDOC-1664 spine: 7,75 mm - 120 pages IAEA-TECDOC-1664 n PHYSICAL MAPPING TECHNOLOGIES FOR THE IDENTIFICATION AND CHARACTERIZATION OF MUTATED GENES CONTRIBUTING TO CROP QUALITY VIENNA ISSN 1011–4289 ISBN 978–92–0–119610–1 INTERNATIONAL ATOMIC AGENCY ENERGY ATOMIC INTERNATIONAL Physical Mapping Technologies for the Identification and Characterization of Mutated Genes Contributing to Crop Quality The following States are Members of the International Atomic Energy Agency: AFGHANISTAN GHANA NORWAY ALBANIA GREECE OMAN ALGERIA GUATEMALA PAKISTAN ANGOLA HAITI PALAU ARGENTINA HOLY SEE PANAMA ARMENIA HONDURAS PARAGUAY AUSTRALIA HUNGARY PERU AUSTRIA ICELAND PHILIPPINES AZERBAIJAN INDIA POLAND BAHRAIN INDONESIA PORTUGAL BANGLADESH IRAN, ISLAMIC REPUBLIC OF QATAR BELARUS IRAQ REPUBLIC OF MOLDOVA BELGIUM IRELAND ROMANIA BELIZE ISRAEL RUSSIAN FEDERATION BENIN ITALY SAUDI ARABIA BOLIVIA JAMAICA BOSNIA AND HERZEGOVINA JAPAN SENEGAL BOTSWANA JORDAN SERBIA BRAZIL KAZAKHSTAN SEYCHELLES BULGARIA KENYA SIERRA LEONE BURKINA FASO KOREA, REPUBLIC OF SINGAPORE BURUNDI KUWAIT SLOVAKIA CAMBODIA KYRGYZSTAN SLOVENIA CAMEROON LATVIA SOUTH AFRICA CANADA LEBANON SPAIN CENTRAL AFRICAN LESOTHO SRI LANKA REPUBLIC LIBERIA SUDAN CHAD LIBYAN ARAB JAMAHIRIYA SWEDEN CHILE LIECHTENSTEIN SWITZERLAND CHINA LITHUANIA SYRIAN ARAB REPUBLIC COLOMBIA LUXEMBOURG TAJIKISTAN CONGO MADAGASCAR THAILAND COSTA RICA