Profiling of warfarin pharmacokinetics‐associated genetic variants: Black Africans portray unique genetic markers important for an African specific warfarin pharmacogenetics‐dosing algorithm

The main objective of this paper is to measure the relationships between the ecotypes belonging to the Tigai and Tsurcana breeds of Romania and to quantify the genetic diversity within them from the informational statistics point of view, depending on the relief forms of the biotope in which they live, using the genetic variants of some selective genetic markers. The researches were carried out on ecotypes of the most ubiquitous sheep breeds in Romania, Tsigai and Tsurcana whose biotopes are circumscribed by more relief forms: plain, hilly, sub-mountainous and mountainous. The sheep were electrophoretically typified at the determinant loci of haemoglobin and transferrin. Using the allelic frequencies of the haemoglobin and transferrin systems that have been processed by concepts of informational statistics, the differentiation / similarity degree among ecotypes within the two breeds was quantified by the genetic distance (D) and the informational correlation coefficient (Rx,y), as well as the diversity level (d) of the genetic structures of these ecotypes on the basis of informational energy (e). Also, the heterozygosity degree (Ht) at the Hb and Tf loci was calculated in relation to the genetic diversity level. The paper analyzes the causes of genetic similarities and differentiations among the ecotypes of these two breeds at the level of the two biochemical-genetic loci: allelic distribution of haemoglobin and transferrin, altitude of relief forms, habitat conditions etc. The benefits of such studies are also presented for the improvement, breeding and conservation of the ecotypes of these two sheep breeds from Romania.

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New perspectives on multilocus ancestry informativeness

10.1101/273466 ◽

2018 ◽

Author(s):

Omri Tal ◽

Tat Dat Tran

Keyword(s):

Mutual Information ◽

Genetic Markers ◽

Genetic Variants ◽

Population Genetic ◽

Finite Population ◽

Axiomatic Approach ◽

Amount Of Information ◽

Individual Ancestry

AbstractWe present an axiomatic approach for multilocus informativeness measures for determining the amount of information that a set of polymorphic genetic markers provides about individual ancestry. We then reveal several surprising properties of a decision-theoretic based measure that is consistent with the set of proposed criteria for multilocus informativeness. In particular, these properties highlight the interplay between information originating from population priors and the information extractable from the population genetic variants. This analysis then reveals a certain deficiency of mutual information based multilocus informativeness measures when such population priors are incorporated. Finally, we analyse and quantify the inevitable inherent decrease in informativeness due to learning from finite population samples.

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Genetic markers of canine hip dysplasia

Medycyna Weterynaryjna ◽

10.21521/mw.6069 ◽

2018 ◽

Vol 74 (2) ◽

pp. 6069-2018

Author(s):

PAULINA KRZEMIŃSKA ◽

MACIEJ GOGULSKI ◽

ROMAN ALEKSIEWICZ ◽

MAREK ŚWITOŃSKI

Keyword(s):

Genetic Markers ◽

Genetic Variants ◽

Hip Dysplasia ◽

Skeletal Development ◽

Molecular Testing ◽

Gene Pools ◽

German Shepherd ◽

Skeletal Malformation ◽

Early Risk ◽

Canine Hip Dysplasia

Canine hip dysplasia is a complex skeletal malformation caused by genetic and environmental factors. The prevalence of hip dysplasia in different canine breeds ranges widely, from 1% (for Whippet and Borzoi) to over 70% (for Bulldog and Pug). These differences indicate the presence of genetic variants predisposing to or preventing this disorder in gene pools of particular breeds. The importance of genetic factors is also confirmed by a high coefficient of heritability (h2) of canine hip dysplasia, which for most breeds oscillates around 0.5 – 0.6. Application of modern genomic methods, that is, mainly genome scanning (based previously on microsatellite markers and currently on SNP microarrays) has led in recent years to the identification of potential genetic markers associated with this disorder. Such studies were carried out mostly in two breeds: Labrador retriever and German shepherd. Some of the markers were found in the vicinity of genes involved in skeletal development. Following these achievements, the use of some markers has been suggested for early risk diagnosis of hip dysplasia. This shows that molecular testing is becoming important for not only monogenic, but also polygenic canine diseases and disorders. Identification of genetic markers associated with predisposition to hip dysplasia offers an opportunity for an early risk evaluation of this disorder (prior to its first signs). Moreover, it facilitates effective breeding selection aimed at eradicating undesirable genetic variants from the gene pool of a given breed..

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Cumulative Small Effect Genetic Markers and the Risk of Colorectal Cancer in Poland, Estonia, Lithuania, and Latvia

Gastroenterology Research and Practice ◽

10.1155/2015/204089 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Pablo Serrano-Fernandez ◽

Dagmara Dymerska ◽

Grzegorz Kurzawski ◽

Róża Derkacz ◽

Tatiana Sobieszczańska ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Practice ◽

High Risk ◽

Genetic Markers ◽

Genetic Variants ◽

Cumulative Effect ◽

Low Risk ◽

Cumulative Effects ◽

Risk Markers ◽

Individual Effects

The continued identification of new low-penetrance genetic variants for colorectal cancer (CRC) raises the question of their potential cumulative effect among compound carriers. We focused on 6 SNPs (rs380284, rs4464148, rs4779584, rs4939827, rs6983267, and rs10795668), already described as risk markers, and tested their possible independent and combined contribution to CRC predisposition.Material and Methods.DNA was collected and genotyped from 2330 unselected consecutive CRC cases and controls from Estonia (166 cases and controls), Latvia (81 cases and controls), Lithuania (123 cases and controls), and Poland (795 cases and controls).Results.Beyond individual effects, the analysis revealed statistically significant linear cumulative effects for these 6 markers for all samples except of the Latvian one (correctedPvalue = 0.018 for the Estonian, correctedPvalue = 0.0034 for the Lithuanian, and correctedPvalue = 0.0076 for the Polish sample).Conclusions.The significant linear cumulative effects demonstrated here support the idea of using sets of low-risk markers for delimiting new groups with high-risk of CRC in clinical practice that are not carriers of the usual CRC high-risk markers.

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Whole-genome sequencing reveals KRTAP1-1 as a novel genetic variant associated with antidepressant treatment outcomes

Scientific Reports ◽

10.1038/s41598-021-83887-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jong-Ho Park ◽

Shinn-Won Lim ◽

Woojae Myung ◽

Inho Park ◽

Hyeok-Jae Jang ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Treatment Outcomes ◽

Genetic Markers ◽

Genome Sequencing ◽

Genetic Variants ◽

Selective Serotonin Reuptake Inhibitors ◽

Remission Rate ◽

Antidepressant Treatment ◽

Whole Genome ◽

Loss Of Function

AbstractAchieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic studies do not provide robust evidence to aid pharmacogenetic decision-making in clinical settings. Thus, the objective of this study was to perform whole-genome sequencing (WGS) using genomic DNA to identify genetic variants associated with the treatment outcomes of selective serotonin reuptake inhibitors (SSRIs). We performed WGS on 100 patients with MDD who were treated with escitalopram (discovery set: 36 remitted and 64 non-remitted). The findings were applied to an additional 553 patients with MDD who were treated with SSRIs (replication set: 185 remitted and 368 non-remitted). A novel loss-of-function variant (rs3213755) in keratin-associated protein 1–1 (KRTAP1-1) was identified in this study. This rs3213755 variant was significantly associated with remission following antidepressant treatment (p = 0.0184, OR 3.09, 95% confidence interval [CI] 1.22–7.80 in the discovery set; p = 0.00269, OR 1.75, 95% CI 1.22–2.53 in the replication set). Moreover, the expression level of KRTAP1-1 in surgically resected human temporal lobe samples was significantly associated with the rs3213755 genotype. WGS studies on a larger sample size in various ethnic groups are needed to investigate genetic markers useful in the pharmacogenetic prediction of remission following antidepressant treatment.

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Genomic Regions and Candidate Genes Linked to Capped Hock in Pig

Life ◽

10.3390/life11060510 ◽

2021 ◽

Vol 11 (6) ◽

pp. 510

Author(s):

Lyubov Getmantseva ◽

Maria Kolosova ◽

Faridun Bakoev ◽

Anna Zimina ◽

Siroj Bakoev

Keyword(s):

Candidate Genes ◽

Genetic Markers ◽

Genetic Variants ◽

San Diego ◽

Negative Impact ◽

Carcass Traits ◽

Blood Parameters ◽

Pilot Studies ◽

Research Results ◽

Genomic Regions

Capped hock affects the exterior of pedigree pigs, making them unsalable and resulting in a negative impact on the efficiency of pig-breeding centers. The purpose of this paper was to carry out pilot studies aimed at finding genomic regions and genes linked to the capped hock in pigs. The studies were carried out on Landrace pigs (n = 75) and Duroc pigs (n = 70). To identify genomic regions linked to capped hock in pigs, we used smoothing FST statistics. Genotyping was performed with GeneSeek® GGP Porcine HD Genomic Profiler v1 (Illumina Inc, San Diego, CA, USA). The research results showed 70 SNPs linked to capped hock in Landrace (38 SNPs) and Duroc (32 SNPs). The identified regions overlapped with QTLs related with health traits (blood parameters) and meat and carcass traits (fatness). In total, 31 genes were identified (i.e., 17 genes in Landrace, 14 genes in Durocs). Three genes appeared in both the Landrace and Duroc groups, including A2ML1 (SSC5), ROBO2 (SSC13), and MSI1 (SSC14). We identified genomic regions directly or indirectly linked to capped hock, which thus might contribute to identifying genetic variants and using them as genetic markers in pig breeding.

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Glucagon-like peptide-1 receptor and sarcoglycan delta genetic variants can affect cardiovascular risk in chronic kidney disease patients under hemodialysis

Clinical Kidney Journal ◽

10.1093/ckj/sfz182 ◽

2020 ◽

Vol 13 (4) ◽

pp. 666-673

Author(s):

Annalisa Terranegra ◽

Teresa Arcidiacono ◽

Lorenza Macrina ◽

Caterina Brasacchio ◽

Francesca Pivari ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Gene Ontology ◽

Kidney Disease ◽

Genetic Markers ◽

Genetic Variants ◽

Fixation Index ◽

Gene Ontology Analysis ◽

Cox Regression Analysis ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Abstract Background Chronic kidney disease (CKD) patients under hemodialysis show a higher risk of cardiovascular (CV) mortality and morbidity than the general population. This study aims to identify genetic markers that could explain the increased CV risk in hemodialysis. Methods A total of 245 CKD patients under hemodialysis were recruited and followed up for 5 years to record CV events. Genetic analysis was performed using single-nucleotide polymorphisms (SNPs) genotyping by Infinium Expanded Multi-Ethnic Genotyping Array (Illumina, San Diego, CA, USA) comparing patients with and without a history of CV events [161 cardiovascular diseases (CVDs) and 84 no CVDs]. The fixation index (Fst) measure was used to identify the most differentiated SNPs, and gene ontology analysis [Protein Analysis THrough Evolutionary Relationships (PANTHER) and Ingenuity Pathway Analysis (IPA)] was applied to define the biological/pathological roles of the associated SNPs. Partitioning tree analysis interrogated the genotype–phenotype relationship between discovered genetic variants and CV phenotypes. Cox regression analysis measured the effect of these SNPs on new CV events during the follow-up (FU). Results Fst analysis identified 3218 SNPs that were significantly different between CVD and no CVD. Gene ontology analysis identified two of these SNPs as involved in cardiovascular disease pathways (Ingenuity Pathway) and heart development (Panther) and belonging to 2 different genes: Glucagon-like peptide-1 receptor (GLP1R) and Sarcoglycan delta (SGCD). The phenotype–genotype analysis found a higher percentage of CVD patients carrying the GLP1R rs10305445 allele A (P = 0.03) and lower percentages of CVD patients carrying the SGCD rs145292439 allele A (P = 0.038). Moreover, SGCD rs145292439 was associated with higher levels of high-density lipoprotein (P = 0.015). Cox analysis confirmed the increased frequency of CV events during the 5-year FU in patients carrying GLP1R rs1035445 allele A but it did not show any significant association with SGCD rs145292439. Conclusions This study identified GLP1R rs10305445 and SCGD rs145292439 as potential genetic markers that may explain the higher risk of CVD in hemodialysis patients.

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Onco-fertility and personalized testing for potential for loss of ovarian reserve in patients undergoing chemotherapy: proposed next steps for development of genetic testing to predict changes in ovarian reserve

Fertility Research and Practice ◽

10.1186/s40738-021-00105-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Bei Sun ◽

John Yeh

Keyword(s):

Genetic Testing ◽

Genetic Markers ◽

Ovarian Reserve ◽

Genetic Variants ◽

Reproductive Potential ◽

Ovarian Failure ◽

Primary Ovarian Insufficiency ◽

Reproductive Age ◽

Ovarian Insufficiency ◽

Ovarian Damage

AbstractWomen of reproductive age undergoing chemotherapy face the risk of irreversible ovarian insufficiency. Current methods of ovarian reserve testing do not accurately predict future reproductive potential for patients undergoing chemotherapy. Genetic markers that more accurately predict the reproductive potential of each patient undergoing chemotherapy would be critical tools that would be useful for evidence-based fertility preservation counselling. To assess the possible approaches to take to develop personalized genetic testing for these patients, we review current literature regarding mechanisms of ovarian damage due to chemotherapy and genetic variants associated with both the damage mechanisms and primary ovarian insufficiency. The medical literature point to a number of genetic variants associated with mechanisms of ovarian damage and primary ovarian insufficiency. Those variants that appear at a higher frequency, with known pathways, may be considered as potential genetic markers for predictive ovarian reserve testing. We propose developing personalized testing of the potential for loss of ovarian function for patients with cancer, prior to chemotherapy treatment. There are advantages of using genetic markers complementary to the current ovarian reserve markers of AMH, antral follicle count and day 3 FSH as predictors of preservation of fertility after chemotherapy. Genetic markers will help identify upstream pathways leading to high risk of ovarian failure not detected by present clinical markers. Their predictive value is mechanism-based and will encourage research towards understanding the multiple pathways contributing to ovarian failure after chemotherapy.

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Molecular techniques used in the search for genetic determinants to improve meat quality

Canadian Journal of Animal Science ◽

10.4141/a98-095 ◽

1998 ◽

Vol 78 (4) ◽

pp. 483-492 ◽

Cited By ~ 1

Author(s):

W. Jon Meadus

Keyword(s):

Gene Mapping ◽

Meat Quality ◽

Genetic Markers ◽

Genetic Variants ◽

Red Meat ◽

Molecular Techniques ◽

Pedigree Information ◽

Meat Industry ◽

Genetic Trait ◽

Microsatellite Mapping

An objective of the red meat industry is to improve the eating qualities of their product. This article focuses on some of the newer techniques used in identifying the genetic factors controlling the eating qualities of red meat animals. Identifying genes in an animal can be achieved either directly, or by linking with genetic markers. Linking a trait with genetic markers has become much easier with the recent development of microsatellite DNA-based genomic maps. The ultimate goal of most molecular biologists is to identify the DNA sequence that defines a unique genetic variant. If the actual sequence mutation is known, animals can be conclusively genotyped without pedigree information. Using microsatellite mapping, genetic variants can be defined in a range of DNA of approximately 100 to 1000 kilobases, which can include more the 50 to 100 genes. Current methods available for identifying specific genetic mutations can analyze approximately 0.4 to 2 kilobases per reaction, but a gene can be more than 60 kilobases long. To conclude, gene mapping can fix a genetic trait quickly, which is useful in controlled breeding programs, but the next step of identifying the genetic variants is very difficult. However, if a trait is defined biochemically, alternative molecular techniques can be applied to a few candidate genes, which might be a riskier approach, but it can give the best result of a simple genetic test. These tests can then be applied to identify and design meat animals according to specific food markets. Key words: Meat quality, gene mapping, genetic testing

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Genomic Study of Cardiovascular Continuum Comorbidity

Acta Naturae ◽

10.32607/20758251-2015-7-3-89-99 ◽

2015 ◽

Vol 7 (3) ◽

pp. 89-99 ◽

Cited By ~ 11

Author(s):

O. A. Makeeva ◽

A. A. Sleptsov ◽

E. V. Kulish ◽

O. L. Barbarash ◽

A. M. Mazur ◽

...

Keyword(s):

Genetic Markers ◽

Genetic Variants ◽

Association Studies ◽

Control Group ◽

Genetic Profile ◽

Genomic Study ◽

Disease Predisposition ◽

Cardiovascular Continuum ◽

Modern Technologies

Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non-random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted. Patients were selected as follows: presence of only one disease, ischemic heart disease (IHD); a combination of two diseases, IHD and arterial hypertension (AH); and a combination of several diseases, including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia (HC). Genotyping was performed using the My Gene genomic service (www.i-gene.ru). An analysis of 1,400 polymorphic genetic variants and their associations with the studied phenotypes are presented. A total of 14 polymorphic variants were associated with the phenotype IHD only, including those in the APOB, CD226, NKX2-5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total of 13 genetic markers were associated with the IHD and AH phenotype, including variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and rs1160312. A total of 14 genetic variants were associated with a combination of several diseases of cardiovascular continuum (CVC), including those in the TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic marker was identified for the IHD only and IHD and AH phenotypes: rs4765623 in the SCARB1 gene; two common genetic markers, rs663048 in SEZ6L and intragenic rs6501455, were identified for the IHD and AH phenotype and a combination of several diseases (syntropy); there were no common genetic markers for the syntropy and IHD only phenotypes. Classificatory analysis of the relationships between the associated genes and metabolic pathways revealed that lipid-metabolizing genes are involved in the development of all three CVC variants, whereas immunity-response genes are specific to the IHD only phenotype. The study demonstrated that comorbidity presents additional challenges in association studies of disease predisposition, since the genetic profile of combined forms of pathology can be markedly different from those for isolated single forms of a disease.

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