8,391 results
Search Results
2. Investigation of the Differences in the Pharmacokinetics of CYP2D6 Substrates, Desipramine, and Dextromethorphan in Healthy African Subjects Carrying the Allelic Variants CYP2D6*17 and CYP2D6*29, When Compared with Normal Metabolizers.
- Author
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Marasanapalle VP, Masimirembwa C, Sivasubramanian R, Sayyed S, Weinzierl-Hinum A, Mehta D, Kapungu NN, Kanji C, Thelingwani R, and Zack J
- Subjects
- Humans, Adult, Male, Female, Young Adult, Healthy Volunteers, Area Under Curve, Black People genetics, Middle Aged, Half-Life, Antidepressive Agents, Tricyclic pharmacokinetics, Antidepressive Agents, Tricyclic blood, Dextromethorphan pharmacokinetics, Dextromethorphan blood, Desipramine pharmacokinetics, Desipramine blood, Cytochrome P-450 CYP2D6 genetics, Cytochrome P-450 CYP2D6 metabolism, Genotype, Alleles
- Abstract
This study investigated the differences in the pharmacokinetics (PK) of dextromethorphan and desipramine in healthy African volunteers to understand the effect of allelic variants of the human cytochrome P450 2D6 (CYP2D6) enzyme, namely the diplotypes of CYP2D6*1/*2 (*1*1, *1*2, *2*2) and the genotypes of CYP2D6*17*17 and CYP2D6*29*29. Overall, 28 adults were included and split into 3 cohorts after genotype screening: CYP2D6*1/*2 (n = 12), CYP2D6*17*17 (n = 12), and CYP2D6*29*29 (n = 4). Each subject received a single oral dose of dextromethorphan 30 mg syrup on day 1 and desipramine 50 mg tablet on day 8. The PK parameters of area under the plasma concentration-time curve from time of dosing to time of last quantifiable concentration (AUC
last ), and extrapolated to infinity (AUCinf ), and the maximum plasma concentration (Cmax ) were determined. For both dextromethorphan and desipramine, AUCinf and Cmax were higher in subjects of the CYP2D6*29*29 and CYP2D6*17*17 cohorts, as compared with subjects in the CYP2D6*1/*2 diplotype cohort and with normal metabolizers from the literature. All PK parameters, including AUCinf , Cmax , and the elimination half-life, followed a similar trend: CYP2D6*17*17 > CYP2D6*29*29 > CYP2D6*1/*2. The plasma and urinary drug/metabolite exposure ratios of both drugs were higher in subjects of the CYP2D6*17*17 and CYP2D6*29*29 cohorts, when compared with subjects in the CYP2D6*1/*2 diplotype cohort. All adverse events were mild, except in 1 subject with CYP2D6*17*17 who had moderately severe headache with desipramine. These results indicate that subjects with CYP2D6*17*17 and CYP2D6*29*29 genotypes were 5-10 times slower metabolizers than those with CYP2D6*1/*2 diplotypes. These findings suggest that dose optimization may be required when administering CYP2D6 substrate drugs in African patients. Larger studies can further validate these findings., (© 2023, The American College of Clinical Pharmacology.)- Published
- 2024
- Full Text
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3. Learning genetics with paper pets
- Author
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Finnerty, Valerie Raunig
- Published
- 2006
4. Modeling Chromosomes: Building paper chromosomes to help understand five key terms in genetics
- Author
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Robertson, Carol
- Published
- 2016
5. Cumulative frequency-dependent selective episodes allow for rapid morph cycles and rock-paper-scissors dynamics in species with overlapping generations
- Author
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San-Jose, Luis M., Peñalver-Alcázar, Miguel, Milá, Borja, Gonzalez-Jimena, Virginia, and Fitze, Patrick S.
- Published
- 2014
6. Genetics, behavior and ecology of a paper wasp invasion: Polistes dominulus in North America
- Author
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Liebert, Aviva E., Gamboa, George J., Stamp, Nancy E., Curtis, Tracy R., Monnet, Kimberley M., Turillazzi, Stefano, and Starks, Philip T.
- Published
- 2006
7. Corrigendum for the Paper 'War and the Evolution of Belligerence and Bravery'
- Published
- 2009
- Full Text
- View/download PDF
8. Paper New Allele of HL6 Regulates Trichome Elongation in Rice.
- Author
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Fei, Shang, Wenbin, Mou, Hao, Wu, Furong, Xu, Chunyan, Xiang, and Jianfei, Wang
- Subjects
RICE ,PHYTOPATHOGENIC microorganisms ,ALLELES ,CELLULAR signal transduction ,PLANT development - Abstract
Trichomes are specialized epidermal cells that play multiple roles in plant development. However, knowledge about the molecular mechanism of trichome development in rice is limited. In this study, a hairy leaf locus HL6
SWWR of rice variety Suwangwanger (SWWR) was identified by map-based cloning. Transgenic complementation and knock-out mutation demonstrated that HL6SWWR regulated trichomes on leaves and expression levels of HL6SWWR affected trichome elongation. Transgenic experiments of PROSWWR :HL6NIP and PRONIP :HL6SWWR indicated that the promoter and coding sequences of HL6SWWR were indispensable for trichome regulation. Sequencing alignment of the promoter and coding regions of HL6 in 22 varieties showed that some cis -binding elements in the promoter region may be related to trichome development, while no decisive variation was found in the coding sequence. Furthermore, RNA-sequencing analysis revealed that 1 415 differential expression genes (DEGs) were detected in hl6SWWR mutant vs wild type and that 1 010 DEGs were found in HL6SWWR complementary transgenic line vs wild type. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that most of the DEGs were involved in metabolite pathway, secondary metabolite biosynthesis, plant pathogen interaction and phytohormone signal transduction in both the two groups. The results indicated that these enhanced pathways are critical during trichome development in rice. Taken together, our results provided new views into the regulatory mechanism of trichome formation in rice. [ABSTRACT FROM AUTHOR]- Published
- 2020
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9. A. Biometrics Invited Paper. Survey of Histocompatibility Testing: Biological Backgrounds, Probabilistic and Statistical Models and Problems
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Elandt-Johnson, Regina C.
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- 1969
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10. A Biometrics Invited Paper. Genetic Equilibrium under Selection
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Li, C. C.
- Published
- 1967
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11. National Academy of Sciences. Abstracts of Papers Presented at the Autumn Meeting, 16-18 November 1959, Bloomington, Indiana
- Published
- 1959
12. Filter paper grafted with epoxide-based copolymer brushes for activation-free peptide nucleic acid conjugation and its application for colorimetric DNA detection
- Author
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Voravee P. Hoven, Tirayut Vilaivan, Pornpen Sae-ung, and Malinee Leekrajang
- Subjects
Peptide Nucleic Acids ,Glycidyl methacrylate ,Magnetic Resonance Spectroscopy ,Polymers ,Surface Properties ,Epoxide ,02 engineering and technology ,Phenylenediamines ,Methacrylate ,01 natural sciences ,Polyethylene Glycols ,Polymerization ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,HLA Antigens ,Spectroscopy, Fourier Transform Infrared ,0103 physical sciences ,Copolymer ,Humans ,Physical and Theoretical Chemistry ,Alleles ,Horseradish Peroxidase ,010304 chemical physics ,Peptide nucleic acid ,Filter paper ,Nucleic Acid Hybridization ,Chain transfer ,DNA ,Surfaces and Interfaces ,General Medicine ,021001 nanoscience & nanotechnology ,Combinatorial chemistry ,chemistry ,Epoxy Compounds ,Methacrylates ,Colorimetry ,Adsorption ,0210 nano-technology ,Ethylene glycol ,Filtration ,Software ,Biotechnology - Abstract
Epoxide-bearing filter paper was first prepared by surface-initiated reversible addition-fragmentation chain transfer (RAFT) copolymerization of glycidyl methacrylate (GMA) and poly(ethylene glycol)methacrylate (PEGMA). Without the need for activation step, the capture peptide nucleic acid (PNA) probes carrying a C-terminal lysine modification can be directly immobilized on the surface-grafted poly[glycidyl methacrylate-ran-poly(ethylene glycol)methacrylate] (P(GMA-ran-PEGMA)) through ring-opening of epoxide groups in the GMA repeating units by amino groups in the PNA’s structure. The success of P(GMA-ran-PEGMA) grafting on the filter paper and subsequent PNA immobilization was confirmed by fluorescence microscopy, Fourier transform-infrared spectroscopy and X-ray photoelectron spectroscopy. Colorimetric detection with signal amplification upon DNA hybridization relies on sandwich-hybridization assay employing another biotinylated PNA strand as a reporter probe together with streptavidin-horseradish peroxidase conjugate (SA-HRP) and o-phenylenediamine (OPD) substrate. It was found that increasing ionic strength during the DNA hybridization step by addition of NaCl can increase the signal intensity, which can be visualized by naked eye. The sensing platform showed the best performance in preventing non-specific adsorption from the non-complementary DNA and discriminating between complementary and single-mismatched targets of at least 50 fmol without the requirement for stringent hybridization or washing condition. This superior ability to suppress non-specific adsorption of non-target DNA as well as other non-DNA components may be explained as a result of hydrophilic PEGMA repeating units in the surface-grafted copolymer.
- Published
- 2019
13. Addendum to a paper of W. Ewens.
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Karlin S and McGregor J
- Subjects
- Mathematics, Alleles, Gene Frequency, Probability
- Published
- 1972
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14. Letter to the editor on a paper by Kaivola et al. (2020): carriership of two copies of C9orf72 hexanucleotide repeat intermediate-length alleles is not associated with amyotrophic lateral sclerosis or frontotemporal dementia
- Author
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Sterre C M, de Boer, Lauren, Woolley, Merel O, Mol, Maria, Serpente, Lianne M, Reus, Rick, van Minkelen, Joke F A, van Vugt, Federica, Sorrentino, Jan H, Veldink, Harro, Seelaar, Daniela, Galimberti, Fred, van Ruissen, Simon, Mead, Ekaterina, Rogaeva, Yolande A L, Pijnenburg, and Sven J, van der Lee
- Subjects
DNA Repeat Expansion ,C9orf72 Protein ,Pick Disease of the Brain ,Risk Factors ,Frontotemporal Dementia ,Amyotrophic Lateral Sclerosis ,Humans ,Alleles ,Finland - Published
- 2022
15. Development of microsatellite loci and optimization of a multiplex assay for Latibulus argiolus (Hymenoptera: Ichneumonidae), the specialized parasitoid of paper wasps
- Author
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Anna Siekiera, Magdalena Czajkowska, Jan J. Pomorski, Agata Kostro-Ambroziak, and Hanna Panagiotopoulou
- Subjects
0106 biological sciences ,0301 basic medicine ,Genetic Markers ,Population ,Genome, Insect ,Wasps ,lcsh:Medicine ,Locus (genetics) ,Ectoparasitic Infestations ,Biology ,010603 evolutionary biology ,01 natural sciences ,03 medical and health sciences ,Animals ,Multiplex ,Genetic variability ,Allele ,education ,lcsh:Science ,Alleles ,education.field_of_study ,Multidisciplinary ,Polymorphism, Genetic ,lcsh:R ,biology.organism_classification ,Null allele ,Ichneumonidae ,030104 developmental biology ,Genetics, Population ,Evolutionary biology ,Genetic Loci ,Microsatellite ,lcsh:Q ,Multiplex Polymerase Chain Reaction ,Microsatellite Repeats - Abstract
Microsatellite loci are commonly used markers in population genetic studies. In this study, we present 40 novel and polymorphic microsatellite loci elaborated for the ichneumonid parasitoid Latibulus argiolus (Rossi, 1790). Reaction condition optimisation procedures allowed 14 of these loci to be co-amplified in two PCRs and loaded in two multiplex panels onto a genetic analyser. The assay was tested on 197 individuals of L. argiolus originating from ten natural populations obtained from the host nests of paper wasps. The validated loci were polymorphic with high allele numbers ranging from eight to 27 (average 17.6 alleles per locus). Both observed and expected heterozygosity values were high, ranging between 0.75 and 0.92 for HO (mean 0.83) and from 0.70 to 0.90 for HE (mean 0.85). The optimized assay showed low genotyping error rate and negligible null allele frequency. The designed multiplex panels could be successfully applied in relatedness analyses and genetic variability studies of L. argiolus populations, which would be particularly interesting considering the coevolutionary context of this species with its social host.
- Published
- 2020
16. Discovering new biology with drug-resistance alleles.
- Author
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Freedy AM and Liau BB
- Subjects
- Animals, Diazepam pharmacology, Drug Discovery, Drug Resistance, Humans, Mutant Proteins pharmacology, Mutation, Pharmaceutical Preparations, Protein Binding, Protein Conformation, Signal Transduction, Sulfonamides metabolism, Sulfonamides pharmacology, Alleles, Mutant Proteins genetics
- Abstract
Small molecule drugs form the backbone of modern medicine's therapeutic arsenal. Often less appreciated is the role that small molecules have had in advancing basic biology. In this Review, we highlight how resistance mutations have unlocked the potential of small molecule chemical probes to discover new biology. We describe key instances in which resistance mutations and related genetic variants yielded foundational biological insight and categorize these examples on the basis of their role in the discovery of novel molecular mechanisms, protein allostery, physiology and cell signaling. Next, we suggest ways in which emerging technologies can be leveraged to systematically introduce and characterize resistance mutations to catalyze basic biology research and drug discovery. By recognizing how resistance mutations have propelled biological discovery, we can better harness new technologies and maximize the potential of small molecules to advance our understanding of biology and improve human health., (© 2021. Springer Nature America, Inc.)
- Published
- 2021
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17. Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards
- Author
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Jaafar M.H. Abdulkadhim, Lika’a Fasih Y. Al-Kzayer, Le T.N. Uyen, M. Al-Ani, Hasanein H. Ghali, Salma Abbas Al-Hadad, Tariq Abadi Al-Shujairi, Zead Ismael I.K. Matti, Najiha Ahmed Ameen, Mazin Faisal Al-Jadiry, Toshi Inoshita, Paiman Ali I. Saber, Hussam M. Salih Al-Abdullah, Kenichi Koike, Hisham Maree Khalil, Janan Ghalib Hasan, Safaa A. F. Al‐Badri, Kazuyuki Matsuda, Minoru Kamata, Tingting Liu, and Kazuo Sakashita
- Subjects
Male ,Paper ,Acute promyelocytic leukemia ,Oncology ,NPM1 ,medicine.medical_specialty ,Adolescent ,Oncogene Proteins, Fusion ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Genetic analysis ,Leukemia, Myelomonocytic, Acute ,Translocation, Genetic ,Specimen Handling ,Bone Marrow ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Child ,Alleles ,Chromosome Aberrations ,Blood Specimen Collection ,Hematology ,Reverse Transcriptase Polymerase Chain Reaction ,business.industry ,Childhood Acute Myeloid Leukemia ,Infant ,Cancer ,DNA, Neoplasm ,Oncogenes ,Sequence Analysis, DNA ,General Medicine ,Prognosis ,medicine.disease ,Leukemia, Myeloid, Acute ,Treatment Outcome ,medicine.anatomical_structure ,Child, Preschool ,Iraq ,Mutation ,Immunology ,Female ,Bone marrow ,business ,Nucleophosmin - Abstract
The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.
- Published
- 2014
18. STR genotyping and mtDNA sequencing of latent fingerprint on paper
- Author
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Peter M. Schneider, Joachim Burger, Klaus Bender, Kurt W. Alt, and M.Kinga Balogh
- Subjects
Paper ,Mitochondrial DNA ,Genotype ,Sequence analysis ,Computational biology ,Biology ,DNA, Mitochondrial ,Polymerase Chain Reaction ,Latent fingerprint ,Pathology and Forensic Medicine ,law.invention ,law ,Humans ,Typing ,Dermatoglyphics ,Genotyping ,Alleles ,Polymerase chain reaction ,Electrophoresis, Agar Gel ,Genetics ,Sequence Analysis, DNA ,DNA Fingerprinting ,Tandem Repeat Sequences ,Microsatellite ,Low copy number ,Law - Abstract
A systematic study was conducted to investigate whether DNA can be successfully extracted from latent fingerprints deposited on ordinary paper and analysed using short tandem repeat profiling and mitochondrial DNA sequencing. In order to evaluate the performance of latent fingerprint analysis in a criminal case, experiments with varying conditions were carried out to improve our understanding of low copy number (LCN) DNA typing. After optimising the extraction methods to achieve increased sensitivity, the examination of touched paper can routinely yield the STR profile of the individual who has touched it. A fingerprint can therefore be considered as a potential source of DNA for genetic identification. Nevertheless, the findings of our "after enhancement experiment" (using chemically or physically pre-treated fingerprints), and our "mixture experiment" (using fingerprints from three to four people on the same sheet of paper) help to define the limitations of the low copy number PCR technique in forensic casework.
- Published
- 2003
19. Whole Genome Amplification on DNA from Filter Paper Blood Spot Samples: An Evaluation of Selected Systems
- Author
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Bent Nørgaard-Pedersen, Cathrine Jespersgaard, Jens Vuust, David M. Hougaard, Karina Meden Sørensen, and Paal Skytt Andersen
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Paper ,Whole Genome Amplification ,Genetics ,Genome ,Multiple displacement amplification ,DNA ,Biology ,Molecular Inversion Probe ,Polymerase Chain Reaction ,SNP genotyping ,chemistry.chemical_compound ,Blood ,chemistry ,biology.protein ,Humans ,DNA fragmentation ,Applications of PCR ,Alleles ,Genetics (clinical) ,Polymerase - Abstract
As the number of single-nucleotide polymorphism (SNP) screening and other mutation scanning studies have increased explosively, following the development of high-throughput instrumentation, it becomes even more important to have sufficient template DNA. The source of DNA is often limited, especially in epidemiological studies, which require many samples as well as enough DNA to perform numerous SNP screenings or mutation scannings. Therefore, the aim is to solve the problem of stock DNA limitation. This need has been an important reason for the development of whole genome amplification (WGA) methods. Several systems are based on Phi29 polymerase multiple displacement amplification (MDA) or on DNA fragmentation (OmniPlex). Using TaqMan SNP genotyping assays, we have tested four WGA systems -- AmpliQ Genomic Amplifier Kit, GenomiPhi, Repli-g, and GenomePlex -- on DNA extracted from Guthrie cards to evaluate the amplification bias, concordance- and call rates, cost efficiency, and flexibility. All systems successfully amplified picograms of DNA from Guthrie cards to micrograms of product without loss of heterozygosity and with minimal allelic bias. A modified AmpliQ set up was chosen for further evaluation. In all, 2,000 SNP genotyping results from amplified and nonamplified samples were compared and the concordance rates between the samples were 99.7%. The call rate using the TaqMan system was 99.8%. DNA extracted from Guthrie cards and amplified with one of the four evaluated WGA systems is applicable in epidemiological genetic screenings. System choice should be based on requirements for system flexibility, product yield, and use in subsequent analysis.
- Published
- 2007
20. Phenol oxidase activity and the lozenge locus of Drosophila melanogaster.
- Author
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Warner CK, Grell EH, and Jacobson KB
- Subjects
- Animals, Chromatography, Paper, Chromosome Mapping, Dihydroxyphenylalanine, Drosophila melanogaster enzymology, Electrophoresis, Polyacrylamide Gel, Female, Male, Mutation, Phenotype, Pupa, Time Factors, Tyrosine, Alleles, Catechol Oxidase metabolism
- Published
- 1974
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21. Rapid, Cost-effective Gene Mutation Screening for Carnitine Palmitoyltransferase II Deficiency Using Whole Blood on Filter Paper
- Author
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Christopher Boles, David Smail, Leah Gambino, and Georgirene D. Vladutiu
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Male ,Paper ,DNA Mutational Analysis ,Clinical Biochemistry ,Population ,Biology ,Gene mutation ,medicine.disease_cause ,Polymerase Chain Reaction ,medicine ,Humans ,Carnitine palmitoyltransferase II ,Genetic Testing ,Carnitine O-palmitoyltransferase ,Myopathy ,education ,Alleles ,Chromatography, High Pressure Liquid ,Blood Specimen Collection ,Mutation ,education.field_of_study ,Carnitine O-Palmitoyltransferase ,Biochemistry (medical) ,medicine.disease ,Molecular biology ,Costs and Cost Analysis ,Female ,Carnitine palmitoyltransferase II deficiency ,medicine.symptom ,Restriction fragment length polymorphism ,Oligonucleotide Probes - Abstract
Carnitine palmitoyltransferase II (CPT II; EC 2.3.1.21), an enzyme associated with the inner mitochondrial membrane, is important in the transport of long-chain fatty acids from the cytosol into the mitochondrial matrix for β-oxidation (1). CPT II deficiency presents as three distinct clinical phenotypes: adult myopathic (MIM 255110), lethal neonatal (MIM 600649), and a severe infantile phenotype (2). The adult form is the most common lipid myopathy in humans and is characterized by muscle pain, stiffness, and myoglobinuria triggered by exercise, fasting, anesthesia, or other metabolic stressors (3). CPT II is a homotetramer (4) encoded by a gene (MIM 600650) on chromosome 1p32 (5) that spans 20 kb and contains five exons ranging in length from 81 to 1305 bp (6). At least 15 mutations in CPT2 are associated with the adult and infantile disorders (7)(8)(9). CPT II deficiency is an autosomal recessive disorder (3)(9); however, recent biochemical and molecular evidence suggests the existence of manifesting carriers, predicting that the prevalence of the disease may be even higher than previously believed (9). Screening for mutations in CPT2 has been performed using DNA isolated from biopsied muscle tissue (9), venous blood (10), lymphoblasts (11), or fibroblasts (8). Isolation of DNA from these specimens is time-consuming, and mutation screening generally has been performed using restriction fragment length polymorphisms (12) or allele-specific oligonucleotide (ASO) detection (9), requiring portions of several days for completion (9). Large-scale screening has not been performed to determine the carrier frequency of the common mutations in the general population. Although the methods for DNA isolation, PCR amplification, and ASO analysis developed previously by our laboratory are effective for detecting known mutations in the CPT2 gene (9), they were too costly and laborious for application to large family studies or population screening. We proposed …
- Published
- 1999
22. Ribosomal proteins. XXXVII. Determination of allelle types and amino acid exchanges in protein S12 of three streptomycin-resistant mutants of Escherichia coli.
- Author
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Funatsu G, Nierhaus K, and Wittmann HG
- Subjects
- Amino Acid Sequence, Amino Acids analysis, Arginine analysis, Asparagine analysis, Carbon Radioisotopes, Centrifugation, Zonal, Chromatography, Ion Exchange, Chromatography, Paper, Drug Resistance, Microbial, Escherichia coli drug effects, Lysine analysis, Peptide Fragments, Phenylalanine metabolism, Ribosomes drug effects, Ribosomes metabolism, Species Specificity, Spectrophotometry, Ultraviolet, Trypsin, Alleles, Bacterial Proteins biosynthesis, Escherichia coli metabolism, Mutation, Protein Biosynthesis, Streptomycin pharmacology
- Published
- 1972
- Full Text
- View/download PDF
23. Genetic control of lactate dehydrogenase synthesis in the somatic and gametic tissues of pigeons.
- Author
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Zinkham WH and Isensee H
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- Animals, Biological Evolution, Breeding, Electrophoresis, Paper, Female, Gene Frequency, Genetic Complementation Test, Genotype, Isoenzymes, Male, Myocardium enzymology, Peptides analysis, Peptides metabolism, Phenotype, Polymorphism, Genetic, Recombination, Genetic, Testis enzymology, Tissue Extracts, Alleles, Columbidae enzymology, L-Lactate Dehydrogenase analysis, L-Lactate Dehydrogenase biosynthesis
- Published
- 1972
24. Effect of 1,2-indanedione on PCR-STR typing of fingerprints deposited on thermal and carbonless paper
- Author
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Pei-Hua Yu and Margaret M. Wallace
- Subjects
Genetics ,Paper ,Chromatography ,Surface Properties ,Extraction (chemistry) ,Substrate (chemistry) ,Biology ,DNA Fingerprinting ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,law.invention ,chemistry.chemical_compound ,DNA profiling ,chemistry ,law ,Indans ,Microsatellite ,Humans ,Str typing ,Typing ,Dermatoglyphics ,Law ,Polymerase chain reaction ,DNA ,Alleles - Abstract
1,2-Indanedione treated fingerprints deposited on two substrates (thermal and carbonless paper) were swabbed and tested to determine the effect of the chemical on PCR-STR DNA typing. Samples from 10 post-treatment intervals were analyzed. Two extraction methods, Chelex ® and Qiamp, were used to determine the effect of extraction procedure on the quality of the DNA profiles. The LCN DNA samples were concentrated using Microcon ® 100 and amplified using the Profiler Plus amplification kit. 1,2-Indanedione did not adversely affect the DNA profiles obtained from the treated fingerprints. Partial DNA profiles were obtained at all post-development time frames. Both extraction methods produced comparable profiles although more "drop-ins" were observed with the Qiamp method. More "drop-outs" occurred in the DNA profiles from samples deposited on the thermal substrate compared with carbonless substrate.
- Published
- 2005
25. Identification of sequence variation in the oocyte-derived bone morphogenetic protein 15 (BMP15) gene (BMP15) associated with litter size in New Zealand sheep (Ovis aries) breeds.
- Author
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Najafabadi HA, Khansefid M, Mahmoud GG, Haruna IL, Zhou H, and Hickford JGH
- Subjects
- Animals, Base Sequence genetics, Bone Morphogenetic Protein 15 metabolism, Exons, Female, Fertility genetics, Heterozygote, Homozygote, Mutation, New Zealand, Polymerase Chain Reaction veterinary, Pregnancy, Sequence Analysis, DNA methods, Alleles, Bone Morphogenetic Protein 15 genetics, Litter Size genetics, Oocytes metabolism, Polymorphism, Genetic, Reproduction genetics, Sheep, Domestic genetics
- Abstract
Advances in the study of reproductive traits indicate that functional variation in fertility genes may be useful for improving sheep fertility. The aim of this study was to search for variation in the bone morphogenetic protein 15 gene (BMP15) and ascertain any association with litter size in purebred Finnish Landrace sheep (n = 148), Finnish Landrace × Texel-cross sheep (n = 45), and composite sheep (of varying breed background; n = 58) from New Zealand (NZ). A 482 bp and 312 bp fragment of exon 1 and 2, respectively, of BMP15 were analysed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). The additive and dominance effect of BMP15 variation on litter size were estimated using animal and sire models. Two variants (A and B) were detected in exon 1; no sequence variation was detected in exon 2. Variant A had the nucleotide sequence CTT between positions c.31 and c.33, while variant B had a deletion (c.31_33del). The observed frequency for variant A in the Finnish Landrace sheep, Finnish Landrace × Texel-cross sheep and the composite sheep, was 0.77, 0.92, and 0.68, respectively while the frequency of variant B (c.31_33del) was 0.23, 0.08, and 0.32, respectively. An association between litter size and c.31_33del (P < 0.001) was observed in composite sheep. Analysis of more sheep will be required to confirm these results. Litter size did not differ significantly between sheep breeds regardless of the presence/absence of c.31_33del. Results suggested that c.31_33del might be a genetic marker for improving fecundity in some NZ sheep., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2021
- Full Text
- View/download PDF
26. Surveillance of Plasmodium falciparum pfcrt haplotypes in southwestern uganda by high‐resolution melt analysis.
- Author
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Kassaza, Kennedy, Long, Anna C., McDaniels, Jennifer M., Andre, Mharlove, Fredrickson, Wasswa, Nyehangane, Dan, Orikiriza, Patrick, Operario, Darwin J., Bazira, Joel, Mwanga-Amumpaire, Juliet A., Moore, Christopher C., Guler, Jennifer L., and Boum II, Yap
- Subjects
PLASMODIUM falciparum ,HAPLOTYPES ,FILTER paper ,DETECTION limit ,ALLELES - Abstract
Background: Chloroquine (CQ) resistance is conferred by mutations in the Plasmodium falciparum CQ resistance transporter (pfcrt). Following CQ withdrawal for anti-malarial treatment, studies across malaria-endemic countries have shown a range of responses. In some areas, CQ sensitive parasites re-emerge, and in others, mutant haplotypes persist. Active surveillance of resistance mutations in clinical parasites is essential to inform treatment regimens; this effort requires fast, reliable, and cost-effective methods that work on a variety of sample types with reagents accessible in malaria-endemic countries. Methods: Quantitative PCR followed by High-Resolution Melt (HRM) analysis was performed in a field setting to assess pfcrt mutations in two groups of clinical samples from Southwestern Uganda. Group 1 samples (119 in total) were collected in 2010 as predominantly Giemsa-stained slides; Group 2 samples (125 in total) were collected in 2015 as blood spots on filter paper. The Rotor-Gene Q instrument was utilized to assess the impact of different PCR-HRM reagent mixes and the detection of mixed haplotypes present in the clinical samples. Finally, the prevalence of the wild type (CVMNK) and resistant pfcrt haplotypes (CVIET and SVMNT) was evaluated in this understudied Southwestern region of Uganda. Results: The sample source (i.e. Giemsa-stained slides or blood spots) and type of LCGreen-based reagent mixes did not impact the success of PCR-HRM. The detection limit of 10
− 5 ng and the ability to identify mixed haplotypes as low as 10 % was similar to other HRM platforms. The CVIET haplotype predominated in the clinical samples (66 %, 162/244); however, there was a large regional variation between the sample groups (94 % CVIET in Group 1 and 44 % CVIET in Group 2). Conclusions: The HRM-based method exhibits the flexibility required to conduct reliable assessment of resistance alleles from various sample types generated during the clinical management of malaria. Large regional variations in CQ resistance haplotypes across Southwestern Uganda emphasizes the need for continued local parasite genotype assessment to inform anti-malarial treatment policies. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
27. Delineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense variant.
- Author
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Poole RL, Curry PDK, Marcinkute R, Brewer C, Coman D, Hobson E, Johnson D, Lynch SA, Saggar A, Searle C, Scurr I, Turnpenny PD, Vasudevan P, and Tatton-Brown K
- Subjects
- Adolescent, Amino Acid Substitution, Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder genetics, Child, Child, Preschool, Facies, Female, Genetic Loci, Humans, Intellectual Disability diagnosis, Intellectual Disability genetics, Male, Megalencephaly diagnosis, Megalencephaly genetics, Syndrome, Alleles, Genetic Association Studies, Mutation, Missense, Phenotype, TOR Serine-Threonine Kinases genetics
- Abstract
Smith-Kingsmore Syndrome (SKS) is a rare genetic syndrome associated with megalencephaly, a variable intellectual disability, autism spectrum disorder, and MTOR gain of function variants. Only 30 patients with MTOR missense variants are published, including 14 (47%) with the MTOR c.5395G>A p.(Glu1799Lys) variant. Limited phenotypic data impacts the quality of information delivered to families and the robustness of interpretation of novel MTOR missense variation. This study aims to improve our understanding of the SKS phenotype through the investigation of 16 further patients with the MTOR c.5395G>A p.(Glu1799Lys) variant. Through the careful phenotypic evaluation of these 16 patients and integration with data from 14 previously reported patients, we have defined major (100% patients) and frequent (>15%) SKS clinical characteristics and, using these data, proposed guidance for evidence-based management. In addition, in the absence of functional studies, we suggest that the combination of the SKS major clinical features of megalencephaly (where the head circumference is at least 3SD) and an intellectual disability with a de novo MTOR missense variant (absent from population databases) should be considered diagnostic for SKS., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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28. Sequence and haplotypes of ankyrin 1 gene (ANK1) and their association with carcass and meat quality traits in yak.
- Author
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Hu J, Gao X, Shi B, Chen H, Zhao Z, Wang J, Liu X, Li S, and Luo Y
- Subjects
- Animals, Cattle, Genetic Association Studies, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Alleles, Ankyrins genetics, Haplotypes, Meat standards, Nutritive Value genetics, Quantitative Trait, Heritable
- Abstract
Ankyrin 1 (ANK1) gene has been demonstrated to be a functional candidate gene for meat quality that helps to constitute and maintain the structure of the cell skeleton. In this study, three contiguous ANK1 regions from yak were analyzed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP). As a result, nine single-nucleotide polymorphisms (SNPs) were identified, four of them in the coding region and three (c.179 C/A, c.250 G/C, and c.313 C/T) putatively resulting in amino acid changes (p. Ala 60 Glu, p. Asp 84 His, and p. Pro 105 Ser). Some SNPs in promoter region were located within or nearby the putative transcription factor binding sites, such as Sp1 and GATA, which might have an impact on the expression of the yak ANK1 gene. The presence of C
1 -D3 and C1 -A3 were associated with an increased hot carcass weight (p = 0.0045) and a decreased drip loss rate (p = 0.0046). The presence of B1 -B3 , C1 -A3 and C1 -D3 had decreased Warner-Bratzler shear force (p = 0.0066, p = 0.0343 and p = 0.0004). The presence of one and two copies of B1 -B3 and C1 -A3 had decreased Warner-Bratzler shear force (p = 0.0005 and p = 0.0443), and C1 -A3 had also decreased drip loss rate (p = 0.0164). These findings indicated that genetic variations of the ANK1 gene would be a preferable biomarker for the improvement of yak meat quality.- Published
- 2021
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29. Title of presented paper: A review of recent findings in the dietary treatment of prediabetes, and type 2 diabetes with a focus on low carbohydrate intake.
- Author
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Andryszko, Krystian, Krowiak, Karolina, and Krowiak, Anita
- Subjects
PREDIABETIC state ,CARBOHYDRATES ,ALLELES ,WEIGHT loss ,MEDITERRANEAN diet - Abstract
Introduction and aim. This research paper examines the advantages and disadvantages of a low-carbohydrate diet, specifically the ketogenic or Atkins diet, in treating prediabetic states and type 2 diabetes. Material and methods. We carried out a systematic review by searching both English and Polish literature databases up to December 31, 2022. The following search words were used: diabetes mellitus, prediabetic state, ketogenic diet, low carbohydrate diet and treatment. Articles focusing on clinical aspects were selected. Analysis of literature. Studies show that a ketogenic diet reduces abdominal obesity, improves insulin resistance, and accelerates weight loss more efficiently than other diets with a caloric deficit, without adverse effects on liver and kidney health. Additionally, adherence to the diet allows for the cessation of hyperglycemic biguanides and a significant reduction in insulin dependence. However, the ketogenic diet has unwanted effects, specifically increasing total cholesterol and low-density lipoprotein levels, especially in patients with lipoproteinemia, allele mutations, and dysbetalipoproteinemia. These effects can lead to palmar xanthomas and a greater risk of atherosclerosis, myocardial infarctions, and strokes. Therefore, a cautious approach to implementing the ketogenic diet includes quarterly medical visits, preliminary genetic testing, and the use of statins or plant-derived felisterols to control lipoprotein levels. Contrastingly to the Mediterranean diet, which is rich in omega-3 fats and B12, the ketogenic diet shows similar outcomes. For this reason, switching from the Mediterranean to the keto diet is contraindicated. Conclusions. This research suggests that a low-carbohydrate diet can be beneficial in treating prediabetic states and type 2 diabetes but must be managed with caution, especially in patients with lipoproteinemia and hereditary diseases. Although the ketogenic diet seems better than rich carbohydrate diets, its long-term effects beyond 12 months remain unknown and require further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2023
30. Epigenetic regulation of MdMYB1 is associated with paper bagging-induced red pigmentation of apples.
- Author
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Bai, Songling, Tuan, Pham, Saito, Takanori, Honda, Chikako, Hatsuyama, Yoshimichi, Ito, Akiko, and Moriguchi, Takaya
- Subjects
EPIGENETICS ,ALLELES ,BIOSYNTHESIS ,ANIMAL coloration ,DNA methylation - Abstract
Main conclusion : Paper-bagging treatment can transform non-transcribed MdMYB1 - 2 and MdMYB1 - 3 alleles into transcribed alleles through epigenetic regulations, resulting in the red pigmentation of a normally non-red apple cultivar 'Mutsu.' Anthocyanin biosynthesis in apples is regulated by MdMYB1/ A/ 10, an R2R3-Type MYB gene. 'Mutsu,' a triploid apple cultivar harboring non-transcribed MdMYB1- 2 and MdMYB1- 3 alleles, retains green skin color under field conditions. However, it can show red/pink pigmentation under natural or artificial ultraviolet-B (UV-B) light exposure after paper-bagging and bag removal treatment. In the present study, we found that in 'Mutsu,' paper bagging-induced red pigmentation was due to the activation of non-transcribed MdMYB1- 2/- 3 alleles, which triggered the expression of downstream anthocyanin biosynthesis genes in a UV-B-dependent manner. By monitoring the epigenetic changes during UV-B-induced pigmentation, no significant differences in DNA methylation and histone modifications in the 5′ upstream region of MdMYB1- 2/-3 were recorded between the UV-B-treated fruit skin (red) and the fruit skin treated only by white light (green). In contrast, bag treatment lowered the DNA methylation in this region of MdMYB1- 2/- 3 alleles. Similarly, higher levels of histone H3 acetylation and trimethylation of H3 tail at lysine 4, and lower level of trimethylation of H3 tail at lysine 27 were observed in the 5′ upstream region of MdMYB1- 2/-3 in the skin of the fruit immediately after bag removal. These results suggest that bagging treatment can induce epigenetic changes, facilitating the binding of trans factor(s) to MdMYB1- 2/- 3 alleles, resulting in the activation of these MYBs after bag removal. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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31. Examination of Hardy-Weinberg equilibrium in papers of Kidney International: An underused tool
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Éva Németh, Barna Vásárhelyi, István Kocsis, and Balazs Gyorffy
- Subjects
Biometry ,gene polymorphism ,Population ,Population genetics ,Hardy-Weinberg equilibrium ,Kidney ,symbols.namesake ,Gene Frequency ,Genotype ,Humans ,Medicine ,education ,Alleles ,Genetic association ,Publishing ,Genetics ,education.field_of_study ,Polymorphism, Genetic ,Models, Genetic ,business.industry ,population genetics ,Hardy–Weinberg principle ,Genotype frequency ,Genetics, Population ,Nephrology ,Mendelian inheritance ,symbols ,business ,Demography - Abstract
Examination of Hardy-Weinberg equilibrium in papers of Kidney International : An underused tool. Background Population-genetic studies investigating genetic polymorphisms of Mendelian inheritance should always test whether the measured genotype frequencies deviate from the expected one. For this purpose Hardy-Weinberg (HW) criteria are generally used. If genotype distribution of control population misses HW equilibrium, the results should be treated cautiously because the observed genotype distribution in control population does not represent genotype distribution in the overall population. If HW criteria are not fulfilled in the investigated population, this may be further evidence for the correlation between genotype and investigated condition. Methods Between September, 1998, and September, 2003, we tested papers published in Kidney International if HW criteria were ordinarily and correctly checked in studies investigating genetic polymorphisms. Seventy-five genotype distributions of the selected 39 articles were reanalyzed. Results HW calculation was reportedly performed in 25 papers (64%). The observed genotype distribution deviated significantly from the expected one in three control, and in 16 patient populations and in three populations of association studies of 15 papers overall; however, this fact was not mentioned in 12 papers. Conclusion Although the deviation of genotype distribution from the expected one is important information, HW calculations are not performed routinely for each investigated subject groups in these papers investigating genetic polymorphisms.
- Published
- 2004
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32. A Sweet Dive into the Gene Pool : An Easy Look at p & q
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- 2015
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33. [Screening program for alpha-1 antitrypsin deficiency in patients with chronic obstructive pulmonary disease, using dried blood spots on filter paper]
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C, de la Roza, X, Costa, R, Vidal, S, Vilá, F, Rodríguez-Frías, R, Jardí, and M, Miravitlles
- Subjects
Male ,Pulmonary Disease, Chronic Obstructive ,Genotype ,Spain ,alpha 1-Antitrypsin ,alpha 1-Antitrypsin Deficiency ,Humans ,Mass Screening ,Female ,Middle Aged ,Alleles ,Aged - Abstract
Alpha-1 antitrypsin (AAT) deficiency is an under-diagnosed disease and screening programs have therefore been recommended for patients with chronic obstructive pulmonary disease (COPD). We present the results of the pilot phase of a screening program for AAT deficiency in order to evaluate the technique used, the procedures for transporting samples and the results obtained. Over a period of one month, five centers collected samples from all COPD patients for whom plasma concentrations of AAT or Pi phenotype had not yet been determined. Capillary blood spots were dried on filter paper and then sent by surface mail to a central laboratory for study. An immunonephelometric assay was used to determine AAT and DNA phenotyping was done by use of a Light Cycler. Samples were analyzed from 86 COPD patients (76 men, 10 women) with a mean age of 68.2 years. AAT deficiency was ruled out for 74 patients (86%) who had concentrations above the cutoff established, although one of them was MZ heterozygote by genotype. Among the 12 remaining patients (13.9%), only two also had a Z allele. The rest were individuals with concentrations below the established threshold and no evidence of a Z allele (10 patients, 11.6%). The Z allele frequency observed (3/172; 1.74%) was very similar to that found in the general population. The results of this pilot study allowed us to confirm that the method used to collect samples worked well. The sampling method is applicable, easy and well-accepted by participating physicians. It allowed AAT concentrations and Z allele deficiency to be determined. The method correlates well with standard techniques used for samples in whole blood.
- Published
- 2003
34. Letter to the Editor regarding Mörkl et al.’s paper: Gut microbiota, dietary intakes and intestinal permeability reflected by serum zonulin in women.
- Author
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Scheffler, Lucas, Kovacs, Peter, Fasano, Alessio, and Heiker, John T.
- Subjects
- *
INTESTINAL physiology , *ALLELES , *BIOMARKERS , *BLOOD proteins , *C-reactive protein , *DIET , *ENZYME-linked immunosorbent assay , *GLOBULINS , *INFLAMMATION , *INGESTION , *WESTERN immunoblotting , *WOMEN , *GUT microbiome - Published
- 2018
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35. Special Speciation
- Published
- 2015
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36. Evolutionary games, climate and the generation of diversity.
- Author
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Friedman, Daniel, Magnani, Jacopo, Paranjpe, Dhanashree, and Sinervo, Barry
- Subjects
BIODIVERSITY ,GAME theory in biology ,HEALTH outcome assessment ,MAXIMUM likelihood statistics ,ROCK-paper-scissors (Game) ,OSCILLATIONS - Abstract
Environmental stochasticity and climate affect outcomes in evolutionary games, which can thereby affect biological diversity. Our maximum likelihood (ML) estimates of replicator dynamics for morph frequency data from control (25 years) and three experimentally perturbed populations (14 years) of side-blotched lizards yield a 3 × 3 payoff matrix in the generalized Rock-Paper-Scissors family; it has intransitive best replies, and each strategy is its own worst reply. ML estimates indicate significant interactive effects of density and temperature on morph frequency. Implied dynamics feature a powerful interior attractor and recover (for the first time) observed 4-5 year oscillations. Our evolutionary experiment on morph frequency confirms that oscillations are driven by frequency dependent selection, but climate entrains the cycles across the perturbed and control populations within 10 generations. Applying the model across the species range, we find that climate also accounts for morph fixation and mating system diversity, suggesting climate may similarly impact ecosystem diversity. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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37. Shared Genetic Risk of Schizophrenia and Gray Matter Reduction in 6p22.1.
- Author
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Chen, Jiayu, Calhoun, Vince D, Lin, Dongdong, Perrone-Bizzozero, Nora I, Bustillo, Juan R, Pearlson, Godfrey D, Potkin, Steven G, Erp, Theo G M van, Macciardi, Fabio, Ehrlich, Stefan, Ho, Beng-Choon, Sponheim, Scott R, Wang, Lei, Stephen, Julia M, Mayer, Andrew R, Hanlon, Faith M, Jung, Rex E, Clementz, Brett A, Keshavan, Matcheri S, and Gershon, Elliot S
- Subjects
BRAIN anatomy ,GENETICS of schizophrenia ,SCHIZOPHRENIA risk factors ,ALLELES ,CEREBRAL cortex ,DNA ,FRONTAL lobe ,GENE expression ,GENETIC polymorphisms ,METHYLATION ,MULTIVARIATE analysis ,NUCLEOTIDES ,PAPER chromatography ,PARIETAL lobe ,SALIVA ,TEMPORAL lobe ,FUNERAL industry ,PHENOTYPES ,GENOMICS ,GRAY matter (Nerve tissue) ,IN vivo studies - Abstract
Genetic factors are known to influence both risk for schizophrenia (SZ) and variation in brain structure. A pressing question is whether the genetic underpinnings of brain phenotype and the disorder overlap. Using multivariate analytic methods and focusing on 1,402 common single-nucleotide polymorphisms (SNPs) mapped from the Psychiatric Genomics Consortium (PGC) 108 regions, in 777 discovery samples, we identified 39 SNPs to be significantly associated with SZ-discriminating gray matter volume (GMV) reduction in inferior parietal and superior temporal regions. The findings were replicated in 609 independent samples. These 39 SNPs in chr6:28308034-28684183 (6p22.1), the most significant SZ-risk region reported by PGC, showed regulatory effects on both DNA methylation and gene expression of postmortem brain tissue and saliva. Furthermore, the regulated methylation site and gene showed significantly different levels of methylation and expression in the prefrontal cortex between cases and controls. In addition, for one regulated methylation site we observed a significant in vivo methylation-GMV association in saliva, suggesting a potential SNP-methylation-GMV pathway. Notably, the risk alleles inferred for GMV reduction from in vivo imaging are all consistent with the risk alleles for SZ inferred from postmortem data. Collectively, we provide evidence for shared genetic risk of SZ and regional GMV reduction in 6p22.1 and demonstrate potential molecular mechanisms that may drive the observed in vivo associations. This study motivates dissecting SZ-risk variants to better understand their associations with focal brain phenotypes and the complex pathophysiology of the illness. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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38. Real-time PCR detection of PI*S and PI*Z alleles of SERPINA1 gene using SYBR green.
- Author
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Ramos-Díaz R, Escuela-Escobar A, Díaz-Usera A, Hernández Pérez JM, González-Carracedo MA, and Pérez-Pérez JA
- Subjects
- Humans, alpha 1-Antitrypsin Deficiency genetics, Polymorphism, Single Nucleotide, Genotyping Techniques methods, Genotype, Fluorescent Dyes chemistry, alpha 1-Antitrypsin genetics, Real-Time Polymerase Chain Reaction methods, Alleles, Diamines, Benzothiazoles, Quinolines, Organic Chemicals
- Abstract
Background: Alpha-1 antitrypsin deficiency is an underdiagnosed genetic condition that predisposes to pulmonary complications and is mainly caused by rs28929474 (PI*Z allele) and rs17580 (PI*S allele) mutations in the SERPINA1 gene., Objective: Development of a homogeneous genotyping test for detection of PI*S and PI*Z alleles based on the principles of allele-specific PCR and amplicon melting analysis with a fluorescent dye., Methods: Sixty individuals, which included all possible genotypes that result from combinations of rs28929474 and rs17580 single nucleotide variants, were assayed with tailed allele-specific primers and SYBR Green dye in a real-time PCR machine., Results: A clear discrimination of mutant and wild-type variants was achieved in the genetic loci that define PI*S and PI*Z alleles. Specific amplicons showed a difference of 2.0 °C in melting temperature for non-S and S variants and of 2.9 °C for non-Z and Z variants., Conclusions: The developed genotyping method is robust, fast, and easily scalable on a standard real-time PCR platform. While it overcomes the handicaps of non-homogeneous approaches, it greatly reduces genotyping costs compared with other homogeneous approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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39. p67 gene alleles sequence analysis reveals Theileria parva parasites associated with East Coast fever and Corridor disease in buffalo from Zambia.
- Author
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Choopa CN, Muleya W, Fandamu P, Mukolwe LD, and Sibeko-Matjila KP
- Subjects
- Animals, Zambia epidemiology, Cattle, Phylogeny, Cattle Diseases parasitology, Cattle Diseases epidemiology, Protozoan Proteins, Buffaloes parasitology, Theileria parva genetics, Theileria parva immunology, Theileriasis parasitology, Theileriasis epidemiology, Alleles, Antigens, Protozoan genetics
- Abstract
Theileriosis caused by Theileria parva infections is responsible for high cattle mortalities in Zambia. Although infected buffalo are a risk to cattle, the characterization of T. parva parasites occurring in this host in Zambia has not been reported. Furthermore, considering the advances in the development of a p67 subunit vaccine, the knowledge of p67 genetic and antigenic diversity in both cattle and buffalo associated T. parva is crucial. Therefore, blood samples from buffalo (n=43) from Central, Eastern and Southern provinces, and cattle (n=834) from Central, Copperbelt, Eastern, Lusaka, and Southern provinces, were tested for T. parva infection and the parasites characterized by sequencing the gene encoding the p67 antigen. About 76.7 % of buffalo and 19.3 % of cattle samples were PCR positive for T. parva. Three of the four known p67 allele types (1, 2 and 3) were identified in parasites from buffalo, of which two (allele types 2 and 3) are associated with T. parva parasites responsible for Corridor disease. Only allele type 1, associated with East Coast fever, was identified from cattle samples, consistent with previous reports from Zambia. Phylogenetic analysis revealed segregation between allele type 1 sequences from cattle and buffalo samples as they grouped separately within the same sub-clade. The high occurrence of T. parva infection in buffalo samples investigated demonstrates the risk of Corridor disease infection, or even outbreaks, should naïve cattle co-graze with infected buffalo in the presence of the tick vector. In view of a subunit vaccine, the antigenic diversity in buffalo associated T. parva should be considered to ensure broad protection. The current disease control measures in Zambia may require re-evaluation to ensure that cattle are protected against buffalo-derived T. parva infections. Parasite stocks used in 'infection and treatment' immunization in Zambia, have not been evaluated for protection against buffalo-derived T. parva parasites currently circulating in the buffalo population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kgomotso P. Sibeko-Matjila reports financial support was provided by National Research Foundation, South Africa. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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40. The minor allele of ANGPTL8 rs2278426 has a protective effect against CAD in T2DM patients.
- Author
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Bilgin AG, Ekici B, Ozuynuk-Ertugrul AS, Erkan AF, and Coban N
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Peptide Hormones genetics, Genetic Predisposition to Disease, Turkey, Coronary Angiography, Gene Frequency, Risk Factors, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 complications, Coronary Artery Disease genetics, Angiopoietin-Like Protein 8, Angiopoietin-like Proteins genetics, Polymorphism, Single Nucleotide, Alleles
- Abstract
Background: Coronary artery disease (CAD) is the leading cause of death worldwide despite advanced treatment and diagnosis strategies. Angiopoietin-like protein 8 (ANGPTL8) mainly functions in the lipid mechanism, which is a dysregulated mechanism during CAD pathogenesis. In this study, we aimed to determine the associations between an ANGPTL8 polymorphism rs2278426 and the severity, presence, and risk factors of CAD., Methods: A total of 1367 unrelated Turkish individuals who underwent coronary angiography were recruited for the study and grouped as CAD (n = 736, ≥50 stenosis) and non-CAD (n = 549, ≤30 stenosis). Also, subjects were further divided into groups regarding type 2 diabetes mellitus (T2DM) status. Subjects were genotyped for rs2278426 (C/T) by quantitative real-time PCR. Secondary structure analyses of protein interactions were revealed using I-TASSER and PyMOL., Results: Among CAD patients, T allele carriage frequency was lower in the T2DM group (p = 0.046). Moreover, in male non-CAD group, T allele carriage was more prevalent among T2DM patients than non-T2DM (p = 0.033). In logistic regression analysis adjusted for obesity, T allele carrier males had an increased risk for T2DM in non-CAD group (OR = 2.244, 95 % CI: 1.057-4.761, p = 0.035). Also, in T2DM group, stenosis (p = 0.002) and SYNTAX score (p = 0.040) were lower in T allele carrier males than in non-carriers. Analyzes of secondary structure showed that ANGPTL8 could not directly form complexes with ANGPTL3 or ANGPTL4., Conclusion: In conclusion, T allele carriage of ANGPTL8 rs2278426 has a protective effect on CAD in T2DM patients. Further research should be conducted to explore the association between ANGPTL8 polymorphism (rs2778426) and CAD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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41. Comprehensive analysis of thalassemia alleles (CATSA) based on third-generation sequencing is a comprehensive and accurate approach for neonatal thalassemia screening.
- Author
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Long J, Yu C, Sun L, Peng M, Song C, Mao A, Zhan J, and Liu E
- Subjects
- Humans, Infant, Newborn, Electrophoresis, Capillary, alpha-Globins genetics, High-Throughput Nucleotide Sequencing, Neonatal Screening, Thalassemia genetics, Thalassemia diagnosis, Alleles
- Abstract
Thalassemia is one of the most common and damaging monogenic diseases in the world. It is caused by pathogenic variants of α- and/or β-globin genes, which disrupt the balance of these two protein chains and leads to α-thalassemia or β-thalassemia, respectively. Patients with α-thalassemia or β-thalassemia could exhibit a severe phenotype, with no simple and effective treatment. A three-tiered strategy of carrier screening, prenatal diagnosis and newborn screening has been established in China for the prevention and control of thalassemia, of which the first two parts have been studied thoroughly. The implementation of neonatal thalassemia screening is lagging, and the effectiveness of various screening programs has not yet been demonstrated. In this study, hemoglobin capillary electrophoresis (CE), hotspot testing method, and third-generation sequencing (TGS) were used in the variant detection of 2000 newborn samples, to assess the efficacy of these methods in neonatal thalassemia screening. Compared with CE (249, 12.45 %) and hotspot analysis (424, 21.2 %), CATSA detected the largest number of thalassemia variants (535, 26.75 %), which included 24 hotspot variants, increased copy number of α-globin gene, rare pathogenic variants, and three unreported potentially disease-causing variants. More importantly, CATSA directly determined the cis-trans relationship of variants in three newborns, which greatly shortens the clinical diagnosis time of thalassemia. CATSA showed a great advantage over other genetic tests and could become the most powerful technical support for the three-tiered prevention and control strategy of thalassemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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42. Frequency-Dependent Selection Can Lead to Evolution of High Mutation Rates
- Author
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Rosenbloom, Daniel I. S. and Allen, Benjamin
- Published
- 2014
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43. How Flowering Plants Discriminate between Self and Non-Self Pollen to Prevent Inbreeding
- Author
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Kao, Teh-Hui and McCubbin, Andrew G.
- Published
- 1996
44. Dopamine genes and ADHD
- Author
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Swanson, JM, Flodman, Pamela, Kennedy, James, Spence, M Anne, Moyzis, Robert, Schuck, Sabrina, Murias, Michael, Moriarity, Joan, Barr, Cathy, Smith, Moyra, and Posner, Michael
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Attention Deficit Hyperactivity Disorder (ADHD) ,Genetics ,Mental Health ,Neurosciences ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Alleles ,Attention Deficit Disorder with Hyperactivity ,Carrier Proteins ,Dopamine ,Dopamine Plasma Membrane Transport Proteins ,Ethnicity ,Gene Frequency ,Haplotypes ,Humans ,Membrane Glycoproteins ,Membrane Transport Proteins ,Nerve Tissue Proteins ,Phenotype ,Receptors ,Dopamine D2 ,Receptors ,Dopamine D4 ,Risk Assessment ,dopamine genes ,ADHD ,alleles ,Dopamine genes ,dopamine ,dopamine 4 receptor ,dopamine receptor ,dopamine transporter ,allele ,attention deficit disorder ,conference paper ,dopaminergic transmission ,gene ,gene frequency ,high risk population ,human ,hypothesis ,nerve cell network ,priority journal ,Ethnic Groups ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Behavioral Science & Comparative Psychology ,Biomedical and clinical sciences ,Health sciences - Abstract
Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.
- Published
- 2000
45. Developmental Validation of the ANDE 6C System for Rapid DNA Analysis of Forensic Casework and DVI Samples
- Author
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Rosemary S. Turingan, Yeshwanthi Estari, Greice Krautz-Peterson, Hua Jiang, Jessi Brown, Eugene Tan, and Richard F. Selden
- Subjects
Male ,Computer science ,I‐Chip ,computer.software_genre ,01 natural sciences ,Polymerase Chain Reaction ,FlexPlex assay ,Identification system ,Chewing Gum ,0302 clinical medicine ,Rapid dna ,Limit of Detection ,developmental validation ,disaster victim identification ,Quality Assurance Standards ,Papers ,Microsatellite ,Female ,Data mining ,Databases, Nucleic Acid ,Paper ,Concordance ,short tandem repeat ,ANDE ,Bone and Bones ,Pathology and Forensic Medicine ,Specimen Handling ,03 medical and health sciences ,Species Specificity ,Semen ,Genetics ,Humans ,030216 legal & forensic medicine ,Expert System ,Saliva ,Alleles ,business.industry ,010401 analytical chemistry ,Mouth Mucosa ,Reproducibility of Results ,Disaster victim identification ,Rapid DNA Identification ,DNA ,DNA analysis/testing ,DNA Fingerprinting ,Expert system ,0104 chemical sciences ,Forensic science ,Disaster Victims ,business ,Quality assurance ,computer ,Tooth ,Criminalistics ,Blood Chemical Analysis ,Microsatellite Repeats - Abstract
A developmental validation was performed to demonstrate reliability, reproducibility, and robustness of the ANDE Rapid DNA Identification System for processing of crime scene and disaster victim identification (DVI) samples. A total of 1705 samples were evaluated, including blood, oral epithelial samples from drinking containers, samples on FTA and untreated paper, semen, bone, and soft tissues. This study was conducted to address the FBI’s Quality Assurance Standards on developmental validation and to accumulate data from a sufficient number of unique donors and sample types to meet NDIS submission requirements for acceptance of the ANDE Expert System for casework use. To date, no Expert System has been approved for such samples, but the results of this study demonstrated that the automated Expert System performs similarly to conventional laboratory data analysis. Furthermore, Rapid DNA analysis demonstrated accuracy, precision, resolution, concordance, and reproducibility that were comparable to conventional processing along with appropriate species specificity, limit of detection, performance in the presence of inhibitors. No lane‐to‐lane or run‐to‐run contamination was observed, and the system correctly identified the presence of mixtures. Taken together, the ANDE instrument, I‐Chip consumable, FlexPlex chemistry (a 27‐locus STR assay compatible with all widely used global loci, including the CODIS core 20 loci), and automated Expert System successfully processed and interpreted more than 1200 unique samples with over 99.99% concordant CODIS alleles. This extensive developmental validation data provides support for broad use of the system by agencies and accredited forensic laboratories in single‐source suspect‐evidence comparisons, local database searches, and DVI.
- Published
- 2020
46. Mining the 99 Lives Cat Genome Sequencing Consortium database implicates genes and variants for the Ticked locus in domestic cats (Felis catus)
- Author
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Lyons, L., Buckley, R., Harvey, R., Abitbol, Marie, Aberdein, Danielle, Alves, Paulo, Ohlsson Andersson, Asa, Bellone, Rebecca, Bergström, Tomas, Bilgen, Nuket, Boyko, Adam, Brockman, Jeffrey, Casal, Margret, Castelhano, Marta, Davis, Brian, Davison, Lucy, Distl, Ottmar, Dodman, Nicholas, Ellinwood, N. Matthew, Fogle, Jonathan, Forman, Oliver, Garrick, Dorian, Ginns, Edward, Häggström, Jens, Hasegawa, Daisuke, Haase, Bianca, Jagannathan, Vidhya, Lait, Philippa, Hernandez, Isabel, Hytönen, Marjo, Kaukonen, Maria, Kosho, Tomoki, Leclerc, Emilie, Lear, Teri, Leeb, Tosso, Li, Ronald H.L., Lohi, Hannes, Longeri, Maria, Magnuson, Mark, Malik, Richard, Mane, Shrinivasrao, Middleton, Rondo, Munday, John, Murphy, William, Myers, Alexandra, Pedersen, Niels, Peterson‐Jones, Simon, Rothschild, Max, Rusbridge, Clare, Schoenebeck, Jeffrey, Shapiro, Beth, Stern, Joshua, Swanson, William, Terio, Karen, Todhunter, Rory, Warren, Wesley, Wilcox, Elizabeth, Wildschutte, Julia, Yu, Yoshihiko, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,Candidate gene ,Abyssinian ,Locus (genetics) ,Biology ,Breeding ,Genome ,DNA sequencing ,03 medical and health sciences ,Genetics ,Tabby ,Animals ,Amino Acid Sequence ,Allele ,coat pattern ,Hair Color ,Gene ,ComputingMilieux_MISCELLANEOUS ,Dickkopf Wnt Signaling Pathway Inhibitor 4 ,Alleles ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Full Paper ,0402 animal and dairy science ,Chromosome ,04 agricultural and veterinary sciences ,General Medicine ,Full Papers ,DKK4 ,040201 dairy & animal science ,030104 developmental biology ,Phenotype ,Cats ,Intercellular Signaling Peptides and Proteins ,Animal Science and Zoology ,Reference genome - Abstract
Summary Tabby patterns of fur coats are defining characteristics in wild and domestic felids. Historically, three autosomal alleles at one locus (Tabby): Abyssinian (Ta; a.k.a. ticked), mackerel (Tm; a.k.a. striped) and blotched (tb; a.k.a. classic, blotched) were thought to control these patterns in domestic cats and their breeds. Currently, at least three loci influence cat tabby markings, two of which are designated Tabby and Ticked. The Tabby locus is laeverin (LVRN) and affects the mackerel and blotched patterns. The unidentified gene for the Ticked locus on cat chromosome B1 was suggested to control the presence or absence of the ticked pattern (Tabby – Abyssinian (Ta; a.k.a. ticked). The cat reference genome (Cinnamon, the Abyssinian) has the ticked phenotype and the variant dataset and coat phenotypes from the 99 Lives Cat Genome Consortium (195 cats) were used to identify candidate genes and variants associated with the Ticked locus. Two strategies were used to find the Ticked allele(s), one considered Cinnamon with the reference allele or heterozygous (Strategy A) and the other considered Cinnamon as having the variant allele or heterozygous (Strategy B). For Strategy A, two variants in Dickkopf Wnt Signaling Pathway Inhibitor 4 (DKK4), a p.Cys63Tyr (B1:41621481, c.188G>A) and a less common p.Ala18Val (B1:42620835, c.53C>T) variant are suggested as two alleles influencing the Ticked phenotype. Bioinformatic and molecular modeling analysis suggests that these changes disrupt a key disulfide bond in the Dkk4 cysteine‐rich domain 1 or Dkk4 signal peptide cleavage respectively. All coding variants were excluded as Ticked alleles using Strategy B.
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- 2021
47. Correlations of FUT3 gene polymorphisms with colon polyps
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Xiaotian, Hu, Fang, Chen, Wenjuan, Ji, and Yingying, Wang
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Polymorphism, Genetic ,Genotype ,Colon ,Colonic Polyps ,Cell Biology ,Fucosyltransferases ,Polymorphism, Single Nucleotide ,Gene Frequency ,Humans ,Genetic Predisposition to Disease ,Molecular Biology ,Alleles ,Research Paper ,Developmental Biology - Abstract
Objective: To explore the relationship between fut3 gene polymorphism and colonic polyps. Methods: Two hundred patients with colonic polyps and 200 healthy people in our hospital in recent 3 years were taken as the research objects, as the disease group and the control group, respectively. The disease group was divided into cancerous colonic polyps group (n = 50) and non-cancerous colonic polyps group (n = 150). The peripheral blood nucleated cells of the subjects were collected and isolated. The fut3 gene polymorphism was obtained by sequencing and analyzed combined with the expression of fut3 gene and the level of tumor markers. Results: The frequency of allele C at rs2561796 locus in the disease group was significantly higher than that in the control group (P
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- 2021
48. DiGAS: Differential gene allele spectrum as a descriptor in genetic studies.
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Aparo A, Bonnici V, Avesani S, Cascione L, and Giugno R
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- Humans, Computational Biology methods, Databases, Genetic, Software, Polymorphism, Single Nucleotide, Alzheimer Disease genetics, Alleles, Genome-Wide Association Study
- Abstract
Diagnosing individuals with complex genetic diseases is a challenging task. Computational methodologies exploit information at the genotype level by taking into account single nucleotide polymorphisms (SNPs) leveraging the results of genome-wide association studies analysis to assign a statistical significance to each SNP. Recent methodologies extend such an approach by aggregating SNP significance at the genetic level to identify genes that are related to the condition under study. However, such methodologies still suffer from the initial SNP analysis limitations. Here, we present DiGAS, a tool for diagnosing genetic conditions by computing significance, by means of SNP information, directly at the complex level of genetic regions. Such an approach is based on a generalized notion of allele spectrum, which evaluates the complete genetic alterations of the SNP set belonging to a genetic region at the population level. The statistical significance of a region is then evaluated through a differential allele spectrum analysis between the conditions of individuals belonging to the population. Tests, performed on well-established datasets regarding Alzheimer's disease, show that DiGAS outperforms the state of the art in distinguishing between sick and healthy subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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49. An induced pluripotent stem cell line carrying a silencing-resistant calcium reporter allele.
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Durens M, Baljinnyam E, Grisanti L, Hu R, and Marro SG
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- Humans, Cell Differentiation, Cell Line, Gene Silencing, Genes, Reporter, Induced Pluripotent Stem Cells metabolism, Induced Pluripotent Stem Cells cytology, Calcium metabolism, Alleles
- Abstract
Calcium indicators are sensitive tools to image neural activity. However, their use in human induced pluripotent stem cells (iPSC)-derived neurons is limited by silencing of the transgene. We generated the iPSC line MSE2336A carrying heterozygous insertion in the safe-harbor locus AAVS1 of the ultrasensitive protein calcium sensor (GCaMP6) under the control of CAG promoter and UCOE to maintain robust transgene expression in differentiated cells. The iPSC exhibited normal cell morphology, expression of pluripotency markers, genome integrity, and the ability to differentiate into the three primary germ layers. This line provides a powerful model to study activity in human neurons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Samuele Marro is an active editor for Stem Cell Research Lab Resources. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
- Full Text
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50. Roan, ticked and clear coat patterns in the canine are associated with three haplotypes near usherin on CFA38
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Kerstin Lindblad-Toh, Claire M. Wade, Cali E. Willet, Hamutal Mazrier, Lillian Brancalion, Frode Lingaas, and Bianca Haase
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0301 basic medicine ,coat‐color ,Male ,Coat ,usherin ,Genotype ,Locus (genetics) ,Biology ,03 medical and health sciences ,USH2A ,Dogs ,Genetics ,Missense mutation ,Animals ,pigmentation ,coat-color ,Allele ,Genetik ,Hair Color ,Gene ,Alleles ,Genetic Association Studies ,Full Paper ,Haplotype ,0402 animal and dairy science ,04 agricultural and veterinary sciences ,General Medicine ,Full Papers ,040201 dairy & animal science ,White (mutation) ,030104 developmental biology ,Phenotype ,Haplotypes ,Epistasis ,Animal Science and Zoology ,Female - Abstract
White coat patterning is a feature of many dog breeds and is known to be coded primarily by the gene micropthalmia-associated transcription factor (MITF). This patterning in the coat can be modified by other factors to produce the attractive phenotypes termed ‘ticked’ and ‘roan’ that describe the presence of flecks of color that vary in distribution and intensity within otherwise ‘clear’ white markings. The appearance of the pigment in the white patterning caused by ticking and roaning intensifies in the weeks after birth. We applied genome-wide association to compare English Cocker Spaniels of roan phenotype (N = 34) with parti-color (non-roan) English Cocker Spaniels (N = 9) and identified an associated locus on CFA 38, CFA38:11 057 040 (Praw = 8.9 × 10−10, Pgenome = 2.7 × 10−5). A local case–control association in English Springer Spaniels comparing 11 ticked and six clear dogs identified indicative association with a different haplotype, CFA38:11 122 467G>T (Praw = 1.7 × 10−5) and CFA38:11 124 294A>C (Praw = 1.7 × 10−5). We characterize three haplotypes in Spaniels according to their putative functional variant profiles at CFA38:11 111 286C>T (missense), CFA38:11 131 841–11 143 239DUP.insTTAA (using strongly linked marker CFA38:11 143 243C>T) and CFA38:11 156 425T>C (splice site). In Spaniels, the haplotypes work as an allelic series including alleles (t, recessive clear; T, dominant ticked/parti-color; and TR, incomplete dominant roan) to control the appearance of pigmented spots or flecks in otherwise white areas of the canine coat. In Spaniels the associated haplotypes are t (CCT), T (TCC) and TR (TTT) for SNP markers on CFA38 at 11 111 286C>T, 11 143 243C>T and 11 156 425T>C respectively. It is likely that other alleles exist in this series and together the haplotypes result in a complex range of patterning that is only visible when dogs have white patterning resulting from the epistatic gene Micropthalmia-associated transcription factor (the S-locus).
- Published
- 2021
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