Summary
The recent global obesity epidemic is attributed to major societal and environmental changes, such as excessive energy intake and sedentary lifestyle. However, exposure to ‘obesogenic’ ...environments does not necessarily result in obesity at the individual level, as 40–75% of body mass index variation in population is attributed to genetic differences. The thrifty genotype theory posits that genetic variants promoting efficient food sequestering and optimal deposition of fat during periods of food abundance were evolutionarily advantageous for the early hunter–gatherer and were positively selected. However, the thrifty genotype is likely too simplistic and fails to provide a justification for the complex distribution of obesity predisposing gene variants and for the broad range of body mass index observed in diverse ethnic groups. This review proposes that gene pleiotropy may better account for the variability in the distribution of obesity susceptibility alleles across modern populations. We outline the lazy‐thrifty versus peppy‐thrifty genotype hypothesis and detail the body of evidence in the literature in support of this novel concept. Future population genetics and mathematical modelling studies that account for pleiotropy may further improve our understanding of the evolutionary origins of the current obesity epidemic.
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.
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.
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
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.
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.
We introduce CellPhy, a maximum likelihood framework for inferring phylogenetic trees from somatic single-cell single-nucleotide variants. CellPhy leverages a finite-site Markov genotype model with ...16 diploid states and considers amplification error and allelic dropout. We implement CellPhy into RAxML-NG, a widely used phylogenetic inference package that provides statistical confidence measurements and scales well on large datasets with hundreds or thousands of cells. Comprehensive simulations suggest that CellPhy is more robust to single-cell genomics errors and outperforms state-of-the-art methods under realistic scenarios, both in accuracy and speed. CellPhy is freely available at https://github.com/amkozlov/cellphy .
Familial adenomatous polyposis (FAP) patients develop various life‐threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the ...localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype–phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high‐grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398–1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required.
Familial adenomatous polyposis patients develop various life‐threatening comorbidities in the gastrointestinal tract and other organs. This study clearly elucidated a genotype–phenotype correlation in the APC gene developing severe extracolonic phenotypes.
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.
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