Novel genotyping assay for the nt230 (del4) ABCB1 gene mutation and its allele frequency in Border Collie dogs in Mexico

A 4-bp deletion in the ATP-binding cassette subfamily B member 1 ( ABCB1) gene, also referred to as the multidrug resistance gene ( MDR1), produces stop codons that cause premature termination of P-glycoprotein 1 (P-gp) synthesis. Dogs with the homozygous mutation do not express functional P-gp, which increases their sensitivity markedly to many common veterinary drugs. We detected the nt230 (del4) ABCB1 mutation in Border Collie dogs in western Mexico with a simple and affordable primer-introduced restriction analysis PCR (PIRA-PCR). PIRA-PCR clearly identified all genotypes in our sample of 104 dogs. Genotype frequencies were 0.952 (wild/wild), 0.029 (wild/mut) and 0.019 (mut/mut). Allele frequencies were 0.033 (mutant alleles) and 0.966 (wild-type alleles). In this small subset of the Mexican dog population, we found a higher prevalence of the nt230 (del4) MDR1/ABCB1 gene mutation than reported in other countries.

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Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01895-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Keping Chen ◽

Peng Xiao ◽

Guochun Li ◽

Chunling Wang ◽

Chuankun Yang

Keyword(s):

Genetic Polymorphisms ◽

Venous Blood ◽

Gene Chip ◽

Han Chinese ◽

Genotype Frequency ◽

Wild Type ◽

Angiotensin Ii Receptor ◽

Hypertensive Patients ◽

Genotype Frequencies ◽

Combined Genotypes

Abstract Background There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. Methods Totally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively. Results The gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients. Conclusions These data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.

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Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)84675-6 ◽

1989 ◽

Vol 264 (30) ◽

pp. 18031-18040

Author(s):

L A Mickley ◽

S E Bates ◽

N D Richert ◽

S Currier ◽

S Tanaka ◽

...

Keyword(s):

Multidrug Resistance ◽

Resistance Gene ◽

Multidrug Resistance Gene ◽

P Glycoprotein ◽

Differentiating Agents ◽

Mdr 1

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P-glycoprotein Has Differential Effects on the Disposition of Statin Acid and Lactone Forms in mdr1a/b Knockout and Wild-Type Mice

Drug Metabolism and Disposition ◽

10.1124/dmd.107.015677 ◽

2007 ◽

Vol 35 (10) ◽

pp. 1725-1729 ◽

Cited By ~ 33

Author(s):

Cuiping Chen ◽

Jian Lin ◽

Teresa Smolarek ◽

Larry Tremaine

Keyword(s):

Wild Type ◽

Differential Effects ◽

P Glycoprotein

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Predicting P-Glycoprotein Effects on Oral Absorption: Correlation of Transport in Caco-2 with Drug Pharmacokinetics in Wild-Type and mdr1a(-/-) Mice in Vivo

Pharmaceutical Research ◽

10.1023/b:pham.0000026434.82855.69 ◽

2004 ◽

Vol 21 (5) ◽

pp. 819-826 ◽

Cited By ~ 48

Author(s):

Andrew Collett ◽

Jolanta Tanianis-Hughes ◽

David Hallifax ◽

Geoff Warhurst

Keyword(s):

Oral Absorption ◽

Wild Type ◽

P Glycoprotein ◽

Drug Pharmacokinetics

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COL1A1 GENE POLYMORPHISM IN MATERNITY PATIENTS WITH SOFT TISSUE INJURIES

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2021-4-54-58 ◽

2021 ◽

pp. 54-58

Author(s):

Kh.M. Laypanova ◽

N.A. Zharkin ◽

Yu.A. Shatilova

Keyword(s):

Soft Tissue ◽

Gene Polymorphism ◽

Gene Mutation ◽

Pelvic Floor Muscle ◽

Soft Tissue Injuries ◽

Birth Trauma ◽

Homozygous Mutation ◽

Col1a1 Gene ◽

Tissue Injuries ◽

The Impact

The aim of the paper is to determine the impact of COL1A1 gene polymorphism on soft tissue injuries in maternity patients. Materials and Methods. The study involved 62 maternity patients who were divided into 2 groups. The first group included 45 patients (72.5 %) without type 1 collagen mutation, alpha 1 Sp1-polymorphism (G2046T) G/G. The second group consisted of 16 patients (27.5 %) with mutation in COL1A1 gene, Sp1-polymorphism (G2046T) G/T. During the study, a homozygous mutation, Sp1-polymorphism (G2046T) T/T was observed in one patient. Age, parity and mean fetal weight of women were comparable. Results. In patients with the COL1A1 mutation, Sp1-polymorphism (G2046T), the incidence of soft tissue birth injuries was 2.3 times higher than in those without such a mutation. Thus, it was confirmed that COL1A1 gene mutation contributes to the soft tissue trauma of the birth canal. It can be regarded as a prognostic criterion and as a basis for preventive measures during pregnancy. Conclusion. Birth trauma risks remain a controversial issue. One of the factors may be COL1A1 gene mutation. Key words: birth trauma, pelvic floor muscle insufficiency, collagen 1 gene polymorphism (COL1A1). Цель работы – определить роль полиморфизма гена COL1A1 у женщин с родовыми травмами мягких тканей родовых путей. Материалы и методы. В исследовании приняло участие 62 родильницы, которые были разделены на 2 группы. В первую группу включены 45 (72,5 %) родильниц, у которых мутация коллагена типа 1, альфа 1 Sp1-polymorphism (G2046T) G/G не обнаружена. Во второй группе, состоящей из 16 (27,5 %) родильниц, обнаружена мутация гена COL1A1 Sp1-polymorphism (G2046T) G/T. В процессе проведения исследования у одной пациентки обнаружена гомозиготная мутация Sp1-polymorphism (G2046T) T/T. Пациентки были сопоставимы по возрасту, паритету и средней массе плода. Результаты. У пациенток с мутацией COL1A1 Sp1-polymorphism (G2046T) частота родовых травм мягких тканей оказалась в 2,3 раза выше, чем у пациенток без мутации. Таким образом, подтверждено, что мутация данного гена имеет определенное значение в реализации риска травм мягких тканей родовых путей, что может послужить прогностическим критерием и основанием для проведения профилактических мероприятий в период беременности. Выводы. Вопрос о рисках родового травматизма остается спорным. Одним их факторов может явиться мутация гена COL1A1. Ключевые слова: родовой травматизм, недостаточность мышц тазового дна, полиморфизм гена коллагена 1 (COL1A1).

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Sucrose Transporter Gene AtSUC4 Responds to Drought Stress by Regulating the Sucrose Distribution and Metabolism in Arabidopsis thaliana

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.765-767.2971 ◽

2013 ◽

Vol 765-767 ◽

pp. 2971-2975 ◽

Cited By ~ 4

Author(s):

Xue Gong ◽

Ming Li Liu ◽

Li Jun Zhang ◽

Wei Liu ◽

Che Wang

Keyword(s):

Arabidopsis Thaliana ◽

Drought Stress ◽

Plant Stress ◽

Homozygous Mutation ◽

Transporter Gene ◽

Wild Type ◽

Sucrose Transporters ◽

Whole Plant ◽

Plant Stress Tolerance ◽

Plant Level

Sucrose transporters (SUCs or SUTs) are considered as the important carriers and responsible for the loading, unloading and distribution of sucrose, but at present there is no report that SUCs are involved in sucrose distribution and metabolism under drought stress at the whole-plant level. AtSUC4, as the unique member of SUT4-clade inArabidopsis thaliana, may be important for plant stress tolerance. Here, by analyzing two homozygous mutation lines ofAtSUC4(Atsuc4-1andAtsuc4-2), we found drought stress induced higher sucrose, lower fructose and glucose contents in shoots, and lower sucrose, higher fructose and glucose contents in roots of these mutants compared with the wild-type (WT), leading to an imbalance of sucrose distribution, fructose and glucose (sucrose metabolites) accumulation changes at the whole-plant level. Thus we believe thatAtSUC4regulates sucrose distribution and metabolism in response to drought stress.

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CRISPR knockouts of pmela and pmelb engineered a golden tilapia by regulating relative pigment cell abundance

10.1101/2021.12.09.471900 ◽

2021 ◽

Author(s):

Chenxu Wang ◽

Jia Xu ◽

Thomas D. Kocher ◽

Minghui Li ◽

Deshou Wang

Keyword(s):

Pigment Cell ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Homozygous Mutation ◽

Body Color ◽

Wild Type ◽

Double Mutation ◽

Vertical Bars ◽

White Plumage ◽

New Strategies

Premelanosome protein (pmel) is a key gene for melanogenesis in vertebrates. Mutations in this gene are responsible for white plumage in chicken, but its role in pigmentation of fish remains to be demonstrated. In this study we found that most fishes have two pmel genes arising from the teleost-specific whole genome duplication. Both pmela and pmelb were expressed at high levels in the eyes and skin of Nile tilapia. We mutated both genes in tilapia using CRISPR/Cas9 gene editing. Homozygous mutation of pmela resulted in yellowish body color with weak vertical bars and a hypo-pigmented retinal pigment epithelium (RPE) due to significantly reduced number and size of melanophores. In contrast, we observed an increased number and size of xanthophores in mutants compared to wild-type fish. Homozygous mutation of pmelb resulted in a similar, but milder phenotype than pmela -/- mutants, without effects on RPE pigmentation. Double mutation of pmela and pmelb resulted in loss of additional melanophores compared to the pmela -/- mutants, and also an increase in the number and size of xanthophores, producing a strong golden body color without bars in the trunk. The RPE pigmentation of pmela -/ - ;pmelb -/- was similar to pmela -/- mutants, with much less pigmentation than pmelb -/- mutants and wild-type fish. Taken together, our results indicate that, while both pmel genes are important for the formation of body color in tilapia, pmela plays a more important role than pmelb. To our knowledge, this is the first report on mutation of pmelb or both pmela;pmelb in fish. Studies on these mutants suggest new strategies for breeding golden tilapia, and also provide a new model for studies of pmel function in vertebrates.

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the Prevalence of UGT1A1*93 and ABCC5 Polymorphisms in Cancer Patients Receiving Irinotecan-Based Chemotherapy at Al-Najaf Al-Ashraf

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol28iss2pp24-29 ◽

2019 ◽

Vol 28 (2) ◽

pp. 24-29

Author(s):

Ahmed F. Al_talkani ◽

Sarmed H. Kathem

Keyword(s):

Cancer Patients ◽

Topoisomerase I ◽

Antineoplastic Agent ◽

Limiting Factors ◽

Cancer Center ◽

Heterozygous Mutation ◽

Homozygous Mutation ◽

Wild Type ◽

Isolation And Purification ◽

Wide Range

Irinotecan (CPT-11) is a semisynthetic derivative of the antineoplastic agent camptothecin used in a wide range as an anti-cancer agent in many solid tumors because of its cytotoxic effect through the interaction with the topoisomerase I enzyme. The major limiting factors for irinotecan treatment are its association with potentially life-threatening toxicities including neutropenia and acute or delayed-type diarrhea, results from distinct interindividual and interethnic variability due to gene polymorphism. This is a cross sectional pharmacogentics study was conducted on 25 cancer patients to estimate the prevalence of UGT1A1*93 and ABCC5 allele single nucleotide polymorphism (SNP) in Iraqi cancer patients treated with irinotecan-based therapy at Middle Euphrates Cancer Center. Four drops of venous blood was drawn for each patient and was applied onto the FTA classic card to perform a genotyping assay for the 2 SNPs. After DNA isolation and purification, real time PCR was performed to detect the SNPs of each gene. Results of this study showed the prevalence of one allele variant (heterozygous mutation) of UGT1A1*93 was 64% compared to 36% of patients were wild type to this SNP. No patient (0%) could be detected with homozygous polymorphism of the UGT1A1*93. For the ABCC5 polymorphism, results revealed that 32% of patients have one polymorphic allele (heterozygous), while 28% of them have two polymorphic alleles (homozygous mutation). Wild type ABCC5 gene constitutes 40% of patients. As a conclusion, high prevalence of UGT1A1*93 and ABCC5 polymorphic alleles were detected in patients at Middle Euphrates Cancer Center which may explain the high toxicity features associated with irinotecan therapy.

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STRUCTURAL DIFFERENTIATION OF STACKED AND UNSTACKED CHLOROPLAST MEMBRANES

The Journal of Cell Biology ◽

10.1083/jcb.48.3.594 ◽

1971 ◽

Vol 48 (3) ◽

pp. 594-619 ◽

Cited By ~ 130

Author(s):

Ursula W. Goodenough ◽

L. Andrew Staehelin

Keyword(s):

Gene Mutation ◽

Growth Conditions ◽

Salt Medium ◽

Wild Type ◽

Dense Population ◽

Structural Differentiation ◽

Chloroplast Membranes ◽

Particle Distributions ◽

Low Salt

Wild-type chloroplast membranes from Chlamydomonas reinhardi exhibit four faces in freeze-etchreplicas: the complementary Bs and Cs faces are found where the membranes are stacked together; the complementary Bu and Cu faces are found in unstacked membranes. The Bs face carries a dense population of regularly spaced particles containing the large, 160 ± 10 A particles that appear to be unique to chloroplast membranes. Under certain growth conditions, membrane stacking does not occur in the ac-5 strain. When isolated, these membranes remain unstacked, exhibit only Bu and Cu faces, and retain the ability to carry out normal photosynthesis. Membrane stacking is also absent in the ac-31 strain, and, when isolated in a low-salt medium, these membranes remain unstacked and exhibit only Bu and Cu faces. When isolated in a high-salt medium, however, they stack normally, and Bs and Cs faces are produced by this in vitro stacking process. We conclude that certain particle distributions in the chloroplast membrane are created as a consequence of the stacking process, and that the ability of membranes to stack can be modified both by gene mutation and by the ionic environment in which the membranes are found.

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