Over the last two decades, we have extensively studied the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and have performed 8,290 DNA analyses of the CYP21A2 ...gene on members of 4,857 families at risk for CAH—the largest cohort of CAH patients reported to date. Of the families studied, 1,507 had at least one member affected with one of three known forms of CAH, namely salt wasting, simple virilizing, or nonclassical CAH. Here, we report the genotype and phenotype of each affected patient, as well as the ethnic group and country of origin for each patient. We showed that 21 of 45 genotypes yielded a phenotypic correlation in our patient cohort. In particular, contrary to what is generally reported in the literature, we found that certain mutations, for example, the P30L, I2G, and I172N mutations, yielded different CAH phenotypes. In salt wasting and nonclassical CAH, a phenotype can be attributed to a genotype; however, in simple virilizing CAH, we observe wide phenotypic variability, particularly with the exon 4 I172N mutation. Finally, there was a high frequency of homozygous I2G and V281L mutations in Middle Eastern and Ashkenazi Jewish populations, respectively. By identifying the predominant phenotype for a given genotype, these findings should assist physicians in prenatal diagnosis and genetic counseling of parents who are at risk for having a child with CAH.
In plant breeding, heritability is often calculated (i) as a measure of precision of trials and/or (ii) to compute the response to selection. It is usually estimated on an entry-mean basis, since
is ...usually an aggregated value, as genotypes are replicated in trials, which stands in contrast with animal breeding and human genetics. When this was first proposed, assumptions such as balanced data and independent genotypic effects were made that are often violated in modern plant breeding trials/analyses. Due to this, multiple alternative methods have been proposed, aiming to generalize heritability on an entry-mean basis. In this study, we propose an extension of the concept for heritability on an entry-mean to an entry-difference basis, which allows for more detailed insight and is more meaningful in the context of selection in plant breeding, because the correlation among entry means can be accounted for. We show that under certain circumstances our method reduces to other popular generalized methods for heritability estimation on an entry-mean basis. The approach is exemplified via four examples that show different levels of complexity, where we compare six methods for heritability estimation on an entry-mean basis to our approach (example codes: https://github.com/PaulSchmidtGit/Heritability). Results suggest that heritability on an entry-difference basis is a well-suited alternative for obtaining an overall heritability estimate, and in addition provides one heritability per genotype as well as one per difference between genotypes.
Genetic diversity is key to crop improvement. Owing to pervasive genomic structural variation, a single reference genome assembly cannot capture the full complement of sequence diversity of a crop ...species (known as the 'pan-genome'
). Multiple high-quality sequence assemblies are an indispensable component of a pan-genome infrastructure. Barley (Hordeum vulgare L.) is an important cereal crop with a long history of cultivation that is adapted to a wide range of agro-climatic conditions
. Here we report the construction of chromosome-scale sequence assemblies for the genotypes of 20 varieties of barley-comprising landraces, cultivars and a wild barley-that were selected as representatives of global barley diversity. We catalogued genomic presence/absence variants and explored the use of structural variants for quantitative genetic analysis through whole-genome shotgun sequencing of 300 gene bank accessions. We discovered abundant large inversion polymorphisms and analysed in detail two inversions that are frequently found in current elite barley germplasm; one is probably the product of mutation breeding and the other is tightly linked to a locus that is involved in the expansion of geographical range. This first-generation barley pan-genome makes previously hidden genetic variation accessible to genetic studies and breeding.
Improving grain yield in cereals especially in wheat is a main objective for plant breeders. One of the main constrains for improving this trait is the G × E interaction (GEI) which affects the ...performance of wheat genotypes in different environments. Selecting high yielding genotypes that can be used for a target set of environments is needed. Phenotypic selection can be misleading due to the environmental conditions. Incorporating information from phenotypic and genomic analyses can be useful in selecting the higher yielding genotypes for a group of environments.
A set of 270 F
wheat genotypes in the Nebraska winter wheat breeding program was tested for grain yield in nine environments. High genetic variation for grain yield was found among the genotypes. G × E interaction was also highly significant. The highest yielding genotype differed in each environment. The correlation for grain yield among the nine environments was low (0 to 0.43). Genome-wide association study revealed 70 marker traits association (MTAs) associated with increased grain yield. The analysis of linkage disequilibrium revealed 16 genomic regions with a highly significant linkage disequilibrium (LD). The candidate parents' genotypes for improving grain yield in a group of environments were selected based on three criteria; number of alleles associated with increased grain yield in each selected genotype, genetic distance among the selected genotypes, and number of different alleles between each two selected parents.
Although G × E interaction was present, the advances in DNA technology provided very useful tools and analyzes. Such features helped to genetically select the highest yielding genotypes that can be used to cross grain production in a group of environments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The discovery of the genetic cause of an inflammatory disorder shows that, in winnowing down candidate variants obtained by DNA sequencing screens, geneticists have been (so to speak) throwing the ...baby out with the bath water.
Large studies use genotype data to discover genetic contributions to complex traits and infer relationships between those traits. Co-incident geographical variation in genotypes and health traits can ...bias these analyses. Here we show that single genetic variants and genetic scores composed of multiple variants are associated with birth location within UK Biobank and that geographic structure in genotype data cannot be accounted for using routine adjustment for study centre and principal components derived from genotype data. We find that major health outcomes appear geographically structured and that coincident structure in health outcomes and genotype data can yield biased associations. Understanding and accounting for this phenomenon will be important when making inference from genotype data in large studies.
Genotype‐by‐environment interaction (GEI) is one of the major factors affecting the prediction accuracy of genomic selection (GS) models. Standard models have low power to model complex GEI, and they ...fail to predict phenotypes in unobserved environments. Here, we developed a novel prediction model that account for GEI, named 3GS, that combines genotype plus genotype × environment (GGE) analysis with GS. The model calculates the principal components (PCs) of the environmental phenotypes using GGE analysis and predict the performance of these PCs using standard GS models before converting the GEBVs of these PCs (pcGEBVs) back to the original phenotypes. We demonstrated three advantages of the new model. First, 3GS showed significantly higher prediction accuracy primarily for deviated environments that have low to negative correlations to other environments. Second, 3GS can predict new genotypes in unobserved environments with high accuracy. Third, the computational complexity of 3GS increases linearly with increasing the number of environments and the population size, unlike the standard models that exhibit exponential increase, making it hundreds of times faster than the standard models for large data sets. 3GS can improve prediction accuracy with minimal resources in modern breeding programmes in which massive populations get multi‐environment phenotypes with high‐throughput techniques.
We extended the genotype plus genotype by environment (GGE) model to incorporate genomic prediction. The new model, named 3GS, improved the accuracy and the computational efficiency of genomic prediction and had the ability to predict unobserved genotypes in unknown environments.
Abstract Dendranthema grandiflora is an important cut flower with high economic importance in the floriculture industry. Identification of stable and high yielding genotypes of Dendranthema ...grandiflora, hence becomes paramount for ensuring its year-round production. In this context, the genotype by environment interaction effects on 22 chrysanthemum hybrids across six test environments were investigated. The experiment was conducted using Randomized Complete Block Design with three replications for 6 years and data on various agro-morphological and yield-contributing traits were evaluated. Our analysis revealed significant mean sum of squares due to environmental, genotypic and genotype by environment interaction variations for all examined traits. A 2D GGE biplot constructed using first two principal components computed as 59.2% and 23.3% of the differences in genotype by environment interaction for flower yield per plant. The GGE biplot identified two top-performing genotypes, G2 and G5, while the AMMI model highlighted genotypes G17, G15, G6, G5, and G2 as the best performers. Genotype G17 ranked highest for multiple traits, while G2 displayed high mean flower yield as well as stability across all environments. According to AEC line, genotypes G2 and G5 exhibited exceptional stability, whereas genotypes G4, G18 and G19 demonstrated lower stability but maintained high average flower yields. Hence, our findings provide valuable insights into chrysanthemum hybrids that were not only best performing but also hold promise to meet the growers demand of the cut flower industry and can be recommended for large scale commercial cultivation.
In this article, an approach to measure fitness is proposed that considers fitness as a measure of competitive ability among phenotypes or genotypes. This approach is based on pairwise competition ...tests and is related to measures of "utility" in mathematical economics. Extending the results from utility theory it is possible to recover the classical Wrightian fitness measure without reference to models of population growth. A condition, quasi-BTL, similar to the Bradley-Terry-Luce condition of classical utility theory is shown to be necessary for the existence of frequency and context-independent fitness measures. Testing for violations of this quasi-BTL condition can be used to the detect genotype-by-genotype interactions and frequency-dependent fitness. A method for the detection of genotype by environment interactions is proposed that avoids potential scaling artifacts. Furthermore the measurement theoretical approach allows one to derive Wright's selection equation. This shows that classical selection equations are entirely general and exact. It is concluded that measurement theory is able to give definite answers to a number theoretical and practical questions. For instance, this theory identifies the correct scale for measuring gene interaction with respect to fitness and shows that different scales may lead to wrong conclusions.
Abstract
Aims
Truncating titin variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy (DCM). We aim to study clinical parameters and long-term outcomes related to the TTNtv ...genotype and determine the related molecular changes at tissue level in TTNtv DCM patients.
Methods and results
A total of 303 consecutive and extensively phenotyped DCM patients (including cardiac imaging, Holter monitoring, and endomyocardial biopsy) underwent DNA sequencing of 47 cardiomyopathy-associated genes including TTN, yielding 38 TTNtv positive (13%) patients. At long-term follow-up (median of 45 months, up to 12 years), TTNtv DCM patients had increased ventricular arrhythmias compared to other DCM, but a similar survival. Arrhythmias are especially prominent in TTNtv patients with an additional environmental trigger (i.e. virus infection, cardiac inflammation, systemic disease, toxic exposure). Importantly, cardiac mass is reduced in TTNtv patients, despite similar cardiac function and dimensions at cardiac magnetic resonance. These enhanced life-threatening arrhythmias and decreased cardiac mass in TTNtv DCM patients go along with significant cardiac energetic and matrix alterations. All components of the mitochondrial electron transport chain are significantly upregulated in TTNtv hearts at RNA-sequencing. Also, interstitial fibrosis was augmented in TTNtv patients at histological and transcript level.
Conclusion
Truncating titin variants lead to pronounced cardiac alterations in mitochondrial function, with increased interstitial fibrosis and reduced hypertrophy. Those structural and metabolic alterations in TTNtv hearts go along with increased ventricular arrhythmias at long-term follow-up, with a similar survival and overall cardiac function.
PDF
