scholarly journals Towards an understanding of the genetic basis behind 1080 (sodium fluoroacetate) tolerance and an investigation of the candidate gene ACO2

2013 ◽  
Vol 61 (1) ◽  
pp. 69 ◽  
Author(s):  
Janine E. Deakin ◽  
Desmond W. Cooper ◽  
Jennifer J. Sinclair ◽  
Catherine A. Herbert ◽  
Marilyn B. Renfree ◽  
...  

Sodium fluoroacetate, commonly referred to as 1080, is a pesticide heavily used to control vertebrate pests. The development of tolerance to this poison by target species is a critical concern raised by its intensive use. Tolerance to 1080 is common amongst many native vertebrates in south-west Western Australia and is thought to be the result of a long period of coevolution with plant species that produce 1080 in their seeds and flowers. Among those vertebrate species tolerant to 1080 exposure is a subspecies of the tammar wallaby (Macropus eugenii). Tammars from Western Australia are tolerant while the subspecies present on Kangaroo Island is susceptible to 1080 exposure. The availability of genetic and genomic information, combined with a distinct difference in tolerance to 1080 between subspecies, makes the tammar wallaby an ideal species in which to study the genetic basis behind 1080 resistance. To date, research in this area has focussed on a candidate gene approach. Since 1080 inhibits the action of the mitochondrial aconitase enzyme, the aconitase gene ACO2 was considered a prime candidate for involvement in 1080 tolerance. However, sequencing of the full-length ACO2 transcript failed to identify a sequence variant between the two subspecies that would result in an amino acid change in the active site of the enzyme. Future studies will need to take a genome-wide approach to identify the gene(s) responsible for 1080 tolerance.

2021 ◽  
Vol 11 (11) ◽  
pp. 1233
Author(s):  
Zulfan Zazuli ◽  
Corine de de Jong ◽  
Wei Xu ◽  
Susanne J. H. Vijverberg ◽  
Rosalinde Masereeuw ◽  
...  

This study aims to evaluate genetic risk factors for cisplatin-induced nephrotoxicity by investigating not previously studied genetic risk variants and further examining previously reported genetic associations. A genome-wide study (GWAS) was conducted in genetically estimated Europeans in a discovery cohort of cisplatin-treated adults from Toronto, Canada, followed by a candidate gene approach in a validation cohort from the Netherlands. In addition, previously reported genetic associations were further examined in both the discovery and validation cohorts. The outcome, nephrotoxicity, was assessed in two ways: (i) decreased estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) and (ii) increased serum creatinine according to the Common Terminology Criteria for Adverse Events v4.03 for acute kidney injury (AKI-CTCAE). Four different Illumina arrays were used for genotyping. Standard quality control was applied for pre- and post-genotype imputation data. In the discovery cohort (n = 608), five single-nucleotide polymorphisms (SNPs) reached genome-wide significance. The A allele in rs4388268 (minor allele frequency = 0.23), an intronic variant of the BACH2 gene, was consistently associated with increased risk of cisplatin-induced nephrotoxicity in both definitions, meeting genome-wide significance (β = −8.4, 95% CI −11.4–−5.4, p = 3.9 × 10−8) for decreased eGFR and reaching suggestive association (OR = 3.9, 95% CI 2.3–6.7, p = 7.4 × 10−7) by AKI-CTCAE. In the validation cohort of 149 patients, this variant was identified with the same direction of effect (eGFR: β = −1.5, 95% CI −5.3–2.4, AKI-CTCAE: OR = 1.7, 95% CI 0.8–3.5). Findings of our previously published candidate gene study could not be confirmed after correction for multiple testing. Genetic predisposition of BACH2 (rs4388268) might be important in the development of cisplatin-induced nephrotoxicity, indicating opportunities for mechanistic understanding, tailored therapy and preventive strategies.


2021 ◽  
Author(s):  
◽  
Noémie Valenza-Troubat

<p><b>Understanding the relationship between DNA sequence variation and the diversity of observable traits across the tree of life is a central research theme in biology. In all organisms, most traits vary continuously between individuals. Explaining the genetic basis of this quantitative variation requires disentangling genetic from non-genetic factors, as well as their interactions. The identification of causal genetic variants yields fundamental insights into how evolution creates diversity across the tree of life. Ultimately, this information can be used for medical, environmental and agricultural applications. Aquaculture is an industry that is experiencing significant global growth and is benefiting from the advances of genomic research. Genomic information helps to improve complex commercial phenotypes such as growth traits, which are easily quantified visually, but influenced by polygenes and multiple environmental factors, such as temperature. In the context of a global food crisis and environmental change, there is an urgent need not only to understand which genetic variants are potential candidates for selection gains, but also how the architecture of these traits are composed (e.g. monogenes, polygenes) and how they are influenced by and interact with the environment. The overall goal of this thesis research was to generate a genome-wide multi-omics dataset matched with exhaustive phenotypic information derived from a F0-F1 pedigree to investigate the quantitative genetic basis of growth in the New Zealand silver trevally (Pseudocaranx georgianus). These data were used to identify genomic regions that co-segregate with growth traits, and to describe the regulation of the genes involved in response to temperature fluctuations. The findings of this research helped gain fundamental insights into the genotype–phenotype map in an important teleost species and understand its ability to dynamically respond to temperature variations. This will ultimately support the establishment of a genomics-informed New Zealand aquaculture breeding programme. </b></p> <p>Chapter 1 of this thesis provides an overview of how genes interact with the environment to produce various growth phenotypes and how an understanding of this is important in aquaculture. This first chapter provides the deeper context for the research in subsequent data chapters. </p> <p>Chapter 2 describes the study population, the collection of phenotypic and genotypic data, and a first description of the genetic parameters of growth traits in trevally. A combination of Whole Genome Sequencing (WGS) and Genotyping-By-Sequencing (GBS) techniques were used to generate 60 thousand Single Nucleotide Polymorphism (SNP) markers for individuals in a two-generation pedigree. Together with phenotypic data, the genotyping data were used to reconstruct the pedigree, measure inbreeding levels, and estimate heritability for 10 growth traits. Parents were identified for 63% of the offspring and successful pedigree reconstruction indicated highly uneven contributions of each parent, and between the sexes, to the subsequent generation. The average inbreeding levels did not change between generations, but were significantly different between families. Growth patterns were found to be similar to that of other carangids and subject to seasonal variations. Heritability as well as genetic and phenotypic correlations were estimated using both a pedigree and a genomic relatedness matrix. All growth trait heritability estimates and correlations were found to be consistently high and positively correlated to each other. </p> <p>In Chapter 3, genotypic and phenotypic data were used to carry out linkage mapping and a genome-wide association study (GWAS) to map quantitative trait loci (QTLs) associated with growth differences in the F1 population. A linkage map was generated using the largest family, which allowed to scan for rare variants associated with the traits. The linkage map reported in this thesis is the first one for the Pseudocaranx genus and one of the densest for the carangid family. It included 19,861 SNPs contained in 24 linkage groups, which correspond to the 24 trevally chromosomes. Eight significant QTLs associated with height, length and weight were discovered on three linkage groups. Using GWAS, 113 SNPs associated with nine traits were identified and 29 genetic growth hot spots were uncovered. Two of the GWAS markers co-located with the QTLs discovered with the linkage mapping analysis. This demonstrates that combining QTL mapping and GWAS represents a powerful approach for the identification and validation of loci controlling complex phenotypes, such as growth, and provides important insights into the genetic architecture of these traits. </p> <p>Chapter 4, the last data chapter, investigates plasticity in gene expression patterns and growth of juvenile trevally, in response to different temperatures. Temperature conditions were experimentally manipulated for 1 month to mimic seasonal extremes. Phenotypic differences in growth were measured in 400 individuals, and the gene expression patterns of the pituitary gland and the liver were compared across treatments in a subset of 100 individuals, using RNA sequencing. Results showed that growth increased 50% more in the warmer compared with the colder condition, suggesting that temperature has a large impact on the metabolic activity associated with growth. We were able to annotate 27,887 gene models and found 39 differentially expressed genes (DEGs) in the pituitary, and 238 in the liver. Of these, 6 DEGs showed a common expression pattern between the tissues. Annotated blast matches of all DEGs revealed genes linked to major pathways affecting metabolism and reproduction. Our results indicate that native New Zealand trevally exhibit predictable plastic regulatory responses to temperature stress and the genes identified provide excellent for selective breeding objectives and studied how populations may adapt to increasing temperatures.</p> <p>Finally, Chapter 5 discusses the implications, future directions, and application of this research for trevally and other breeding programmes. It more broadly highlights the insights that were gained on the genetic architecture of growth, and the role of temperature in interacting and modulating genes involved in plastic growth responses.</p>


2019 ◽  
Vol 116 (12) ◽  
pp. 5653-5658 ◽  
Author(s):  
Lin Shao ◽  
Feng Xing ◽  
Conghao Xu ◽  
Qinghua Zhang ◽  
Jian Che ◽  
...  

Utilization of heterosis has greatly increased the productivity of many crops worldwide. Although tremendous progress has been made in characterizing the genetic basis of heterosis using genomic technologies, molecular mechanisms underlying the genetic components are much less understood. Allele-specific expression (ASE), or imbalance between the expression levels of two parental alleles in the hybrid, has been suggested as a mechanism of heterosis. Here, we performed a genome-wide analysis of ASE by comparing the read ratios of the parental alleles in RNA-sequencing data of an elite rice hybrid and its parents using three tissues from plants grown under four conditions. The analysis identified a total of 3,270 genes showing ASE (ASEGs) in various ways, which can be classified into two patterns: consistent ASEGs such that the ASE was biased toward one parental allele in all tissues/conditions, and inconsistent ASEGs such that ASE was found in some but not all tissues/conditions, including direction-shifting ASEGs in which the ASE was biased toward one parental allele in some tissues/conditions while toward the other parental allele in other tissues/conditions. The results suggested that these patterns may have distinct implications in the genetic basis of heterosis: The consistent ASEGs may cause partial to full dominance effects on the traits that they regulate, and direction-shifting ASEGs may cause overdominance. We also showed that ASEGs were significantly enriched in genomic regions that were differentially selected during rice breeding. These ASEGs provide an index of the genes for future pursuit of the genetic and molecular mechanism of heterosis.


2019 ◽  
Vol 36 (12) ◽  
pp. 2890-2905 ◽  
Author(s):  
Christos Vlachos ◽  
Robert Kofler

Abstract Evolve and resequence (E&R) studies are frequently used to dissect the genetic basis of quantitative traits. By subjecting a population to truncating selection for several generations and estimating the allele frequency differences between selected and nonselected populations using next-generation sequencing (NGS), the loci contributing to the selected trait may be identified. The role of different parameters, such as, the population size or the number of replicate populations has been examined in previous works. However, the influence of the selection regime, that is the strength of truncating selection during the experiment, remains little explored. Using whole genome, individual based forward simulations of E&R studies, we found that the power to identify the causative alleles may be maximized by gradually increasing the strength of truncating selection during the experiment. Notably, such an optimal selection regime comes at no or little additional cost in terms of sequencing effort and experimental time. Interestingly, we also found that a selection regime which optimizes the power to identify the causative loci is not necessarily identical to a regime that maximizes the phenotypic response. Finally, our simulations suggest that an E&R study with an optimized selection regime may have a higher power to identify the genetic basis of quantitative traits than a genome-wide association study, highlighting that E&R is a powerful approach for finding the loci underlying complex traits.


PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0137087 ◽  
Author(s):  
Biao Chen ◽  
Jiguo Xu ◽  
Xiaomei He ◽  
Haiping Xu ◽  
Guihuan Li ◽  
...  

2016 ◽  
Author(s):  
Mark Barash ◽  
Philipp E. Bayer ◽  
Angela van Daal

AbstractDespite intensive research on genetics of the craniofacial morphology using animal models and human craniofacial syndromes, the genetic variation that underpins normal human facial appearance is still largely elusive. Recent development of novel digital methods for capturing the complexity of craniofacial morphology in conjunction with high-throughput genotyping methods, show great promise for unravelling the genetic basis of such a complex trait.As a part of our efforts on detecting genomic variants affecting normal craniofacial appearance, we have implemented a candidate gene approach by selecting 1,201 single nucleotide polymorphisms (SNPs) and 4,732 tag SNPs in over 170 candidate genes and intergenic regions. We used 3-dimentional (3D) facial scans and direct cranial measurements of 587 volunteers to calculate 104 craniofacial phenotypes. Following genotyping by massively parallel sequencing, genetic associations between 2,332 genetic markers and 104 craniofacial phenotypes were tested.An application of a Bonferroni–corrected genome–wide significance threshold produced significant associations between five craniofacial traits and six SNPs. Specifically, associations of nasal width with rs8035124 (15q26.1), cephalic index with rs16830498 (2q23.3), nasal index with rs37369 (5q13.2), transverse nasal prominence angle with rs59037879 (10p11.23) and rs10512572 (17q24.3), and principal component explaining 73.3% of all the craniofacial phenotypes, with rs37369 (5p13.2) and rs390345 (14q31.3) were observed.Due to over-conservative nature of the Bonferroni correction, we also report all the associations that reached the traditional genome-wide p-value threshold (<5.00E-08) as suggestive. Based on the genome-wide threshold, 8 craniofacial phenotypes demonstrated significant associations with 34 intergenic and extragenic SNPs. The majority of associations are novel, except PAX3 and COL11A1 genes, which were previously reported to affect normal craniofacial variation.This study identified the largest number of genetic variants associated with normal variation of craniofacial morphology to date by using a candidate gene approach, including confirmation of the two previously reported genes. These results enhance our understanding of the genetics that determines normal variation in craniofacial morphology and will be of particular value in medical and forensic fields.Author SummaryThere is a remarkable variety of human facial appearances, almost exclusively the result of genetic differences, as exemplified by the striking resemblance of identical twins. However, the genes and specific genetic variants that affect the size and shape of the cranium and the soft facial tissue features are largely unknown. Numerous studies on animal models and human craniofacial disorders have identified a large number of genes, which may regulate normal craniofacial embryonic development.In this study we implemented a targeted candidate gene approach to select more than 1,200 polymorphisms in over 170 genes that are likely to be involved in craniofacial development and morphology. These markers were genotyped in 587 DNA samples using massively parallel sequencing and analysed for association with 104 traits generated from 3-dimensional facial images and direct craniofacial measurements. Genetic associations (p-values<5.00E-08) were observed between 8 craniofacial traits and 34 single nucleotide polymorphisms (SNPs), including two previously described genes and 26 novel candidate genes and intergenic regions. This comprehensive candidate gene study has uncovered the largest number of novel genetic variants affecting normal facial appearance to date. These results will appreciably extend our understanding of the normal and abnormal embryonic development and impact our ability to predict the appearance of an individual from a DNA sample in forensic criminal investigations and missing person cases.


2021 ◽  
Author(s):  
Bo Peng ◽  
Xiaolei Zhao ◽  
Yi Wang ◽  
Chunhui Li ◽  
Yongxiang Li ◽  
...  

Abstract Compact plant-type with small leaf angle has increased canopy light interception, which is conducive to the photosynthesis of the population and higher population yield at high density planting in maize. In this study, a panel of 285 diverse maize inbred lines genotyped with 56,000 SNPs was used to investigate the genetic basis of leaf angle across three consecutive years using a genome-wide association study (GWAS). The leaf angle showed broad phenotypic variation and high heritability across different years. Population structure analysis subdivided the panel into four subgroups that correspond to the four major empirical germplasm origins in China, i.e., Tangsipingtou, Reid, Lancaster and P. When tested with the optimal GWAS model, we found that the Q+K model was the best in reducing false positive. In total, 96 SNPs accounting for 5.54%-10.44% of phenotypic variation were significantly (P<0.0001) associated with leaf angle across three years. According to the linkage disequilibrium decay distance, 96 SNPs were binned in 43 QTLs for leaf angle. Seven major QTLs with R2>8% stably detected in at least two years and BLUP values were clustered in four genomic regions (bins 2.01, 2.07, 5.06, and 10.04). Seven important candidate genes, Zm00001d001961, Zm00001d006348, Zm00001d006463, Zm00001d017618, Zm00001d024919, Zm00001d025018, and Zm00001d025033 were predicted for the seven stable major QTLs, respectively. The markers identified in this study can be used for molecular breeding for leaf angle, and the candidate genes would contribute to further understanding of the genetic basis of leaf angle.


Sign in / Sign up

Export Citation Format

Share Document