-
Current Protocols Dec 2023Individuals of European descent have historically been the focus of genetic studies and possess relatively homogenous genomes. As a result, analytical methods have been...
Individuals of European descent have historically been the focus of genetic studies and possess relatively homogenous genomes. As a result, analytical methods have been developed and optimized with such genomes in mind. African-descent and Latino individuals generally possess genomes of greater architectural complexity due to mosaic genomic ancestry, which can extensively and intricately impact phenotypic expression. As such, genetic analyses of admixed individuals require that genetic admixture be quantified to accurately model the impact of genetic variation on phenotypic expression. In this overview, we explore how fundamental genetic concepts such as linkage disequilibrium and differential allele frequency interact with genetic admixture to uniquely influence phenotypes in admixed individuals. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
Topics: Humans; Gene Frequency; Genetics, Population; Linkage Disequilibrium; Phenotype; Genome, Human
PubMed: 38146906
DOI: 10.1002/cpz1.953 -
Neuropsychopharmacology : Official... Jan 2021The broad adoption and use of smartphones has led to fundamentally new opportunities for capturing social, behavioral, and cognitive phenotypes in free-living settings,... (Review)
Review
The broad adoption and use of smartphones has led to fundamentally new opportunities for capturing social, behavioral, and cognitive phenotypes in free-living settings, outside of research laboratories and clinics. Predicated on the use of existing personal devices rather than the introduction of additional instrumentation, smartphone-based digital phenotyping presents us with several opportunities and challenges in data collection and data analysis. These two aspects are strongly coupled, because decisions about what data to collect and how to collect it constrain what statistical analyses can be carried out, now and years later, and therefore ultimately determine what scientific, clinical, and public health questions may be asked and answered. Digital phenotyping combines the excitement of fast-paced technologies, smartphones, cloud computing and machine learning, with deep mathematical and statistical questions, and it does this in the service of a better understanding our own behavior in ways that are objective, scalable, and reproducible. We will discuss some fundamental aspects of collection and analysis of digital phenotyping data, which takes us on a brief tour of several important scientific and technological concepts, from the open-source paradigm to computational complexity, with some unexpected insights provided by fields as varied as zoology and quantum mechanics.
Topics: Data Collection; Machine Learning; Phenotype; Research Design; Smartphone
PubMed: 32679583
DOI: 10.1038/s41386-020-0771-3 -
Molecular Systems Biology Jun 2020Pooled genetic screening is a powerful method to systematically link genotype to phenotype and gain insights into biological processes, but applying it to visual...
Pooled genetic screening is a powerful method to systematically link genotype to phenotype and gain insights into biological processes, but applying it to visual phenotypes such as cell morphology or protein localization has remained a challenge. In their recent work, Fowler and colleagues (Hasle et al, 2020) describe an elegant approach for high-throughput cell sorting according to visual phenotypes based on selective photoconversion. This allows combining the advantages of high-content phenotyping by fluorescence microscopy with the efficiency of pooled screening to dissect complex phenotypes.
Topics: Genotype; Microscopy, Fluorescence; Phenotype
PubMed: 32543109
DOI: 10.15252/msb.20209640 -
Journal of Forensic and Legal Medicine May 2022Forensic DNA Phenotyping (FDP) has provided better understanding of various phenotypic features (e.g., height, skin colour, eye colour, structure and shape of scalp... (Review)
Review
INTRODUCTION
Forensic DNA Phenotyping (FDP) has provided better understanding of various phenotypic features (e.g., height, skin colour, eye colour, structure and shape of scalp hair, baldness, facial features etc.) and associated genetic variations. The current study was designed to investigate the genetic variants and their potential contribution towards accurate phenotype prediction systems. Short Tandem Repeat (STR) based DNA typing method can be uninformative or with little potential to solve a crime in absence of suspect DNA profile in the database. Forensic DNA Phenotyping (FDP), prediction of externally visible characteristics (EVCs) from the crime scene DNA would certainly provide a new dimension to personal identification. The aim of this review paper is to highlight the significance and future prospects of FDP.
RESULTS
A comprehensive literature review was conducted using PubMed and similar e-databases with keywords from two main components-phenotype and the associated genetic variants. To ensure a thorough literature review, searches were extended using the snowballing technique from reference lists. Key data extracted were type of study, sample characteristics (sample size, age, geographical location and ancestry), details of SNPs studied and prediction accuracies.
CONCLUSION
Phenotyping tools based on genotyping and statistical analysis for the prediction of human pigmentation are propitious in solving cold cases. This indicates the inevitability of future studies for the identification of new genetic markers for accurate prediction of phenotype or EVCs via genome-wide association study (GWAS) in diverse global populations.
Topics: Crime; DNA; Forensic Genetics; Genome-Wide Association Study; Humans; Phenotype; Polymorphism, Single Nucleotide
PubMed: 35427851
DOI: 10.1016/j.jflm.2022.102351 -
Biologie Aujourd'hui 2020Phenotypic plasticity describes the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. It has major... (Review)
Review
Phenotypic plasticity describes the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. It has major implications in agronomy, animal husbandry and medicine and is also thought to facilitate evolution. Phenotypic plasticity is widely observed in the wild. It is only relatively recently that the mechanisms involved in phenotypic plasticity have been analysed. Thanks to laboratory experiments we understand better how environmental conditions are involved in phenotypic variations. This article introduces major concepts from the phenotypic plasticity field, presents briefly mechanisms involved in phenotypic plasticity and discusses the links between phenotypic plasticity and evolution.
Topics: Adaptation, Physiological; Animals; Biological Evolution; Gene-Environment Interaction; Genetic Variation; Humans; Phenotype; Temperature
PubMed: 32773027
DOI: 10.1051/jbio/2020004 -
Journal of Experimental Botany May 2022Gas exchange techniques revolutionized plant research and advanced understanding, including associated fluxes and efficiencies, of photosynthesis, photorespiration, and... (Review)
Review
Gas exchange techniques revolutionized plant research and advanced understanding, including associated fluxes and efficiencies, of photosynthesis, photorespiration, and respiration of plants from cellular to ecosystem scales. These techniques remain the gold standard for inferring photosynthetic rates and underlying physiology/biochemistry, although their utility for high-throughput phenotyping (HTP) of photosynthesis is limited both by the number of gas exchange systems available and the number of personnel available to operate the equipment. Remote sensing techniques have long been used to assess ecosystem productivity at coarse spatial and temporal resolutions, and advances in sensor technology coupled with advanced statistical techniques are expanding remote sensing tools to finer spatial scales and increasing the number and complexity of phenotypes that can be extracted. In this review, we outline the photosynthetic phenotypes of interest to the plant science community and describe the advances in high-throughput techniques to characterize photosynthesis at spatial scales useful to infer treatment or genotypic variation in field-based experiments or breeding trials. We will accomplish this objective by presenting six lessons learned thus far through the development and application of proximal/remote sensing-based measurements and the accompanying statistical analyses. We will conclude by outlining what we perceive as the current limitations, bottlenecks, and opportunities facing HTP of photosynthesis.
Topics: Ecosystem; Genotype; Phenotype; Photosynthesis
PubMed: 35218184
DOI: 10.1093/jxb/erac077 -
Seminars in Respiratory and Critical... Aug 2021Bronchiectasis is a heterogenous disease with multiple etiologies and associated comorbidities. As bronchiectasis is a complex disease, it is unsound to think of it as a...
Bronchiectasis is a heterogenous disease with multiple etiologies and associated comorbidities. As bronchiectasis is a complex disease, it is unsound to think of it as a single disease particularly when the differing etiologies are likely to be driving bronchiectasis through initial divergent molecular pathways, known as endotypes, that phenotypically present as the same disease due to protracted airway inflammation, but revealing potential differing underlying mechanisms that may have disparity of drug responses. Improved understanding of the cellular immune, inflammatory, and microbiological milieu associated with clinical and radiological features of bronchiectasis has resulted in the recognition of important endotypes and phenotypes that will allow for personalized treatments to improve quality of life and outcomes of patients with bronchiectasis. Here we discuss clinical and radiological phenotypes, as well as emerging molecular endotypes that are possible treatable traits in bronchiectasis.
Topics: Bronchiectasis; Humans; Phenotype; Quality of Life; Radiography
PubMed: 34261179
DOI: 10.1055/s-0041-1730894 -
Current Protocols Feb 2023Platelets play key roles in hemostasis, immunity, and inflammation, and tests of platelet phenotype and function are useful in studies of disease biology and pathology....
Platelets play key roles in hemostasis, immunity, and inflammation, and tests of platelet phenotype and function are useful in studies of disease biology and pathology. Full spectrum flow cytometry offers distinct advantages over standard tests and enables the sensitive and simultaneous detection of many biomarkers. A typical assay provides a wealth of information on platelet biology and allows the assessment of in vivo activation and in vitro reactivity, as well as the discovery of novel phenotypes. Here, we describe the analysis of platelets by full spectrum flow cytometry and discuss a range of controls and methods for interpreting results. © 2023 Wiley Periodicals LLC. Basic Protocol: Platelet phenotyping by full spectrum flow cytometry Support Protocol 1: Spectral unmixing Support Protocol 2: Data preprocessing.
Topics: Blood Platelets; Flow Cytometry; Hemostasis; Phenotype; Biomarkers
PubMed: 36779850
DOI: 10.1002/cpz1.687 -
Theoretical Population Biology Feb 2024Natural selection acts on phenotypes constructed over development, which raises the question of how development affects evolution. Classic evolutionary theory indicates...
Natural selection acts on phenotypes constructed over development, which raises the question of how development affects evolution. Classic evolutionary theory indicates that development affects evolution by modulating the genetic covariation upon which selection acts, thus affecting genetic constraints. However, whether genetic constraints are relative, thus diverting adaptation from the direction of steepest fitness ascent, or absolute, thus blocking adaptation in certain directions, remains uncertain. This limits understanding of long-term evolution of developmentally constructed phenotypes. Here we formulate a general, tractable mathematical framework that integrates age progression, explicit development (i.e., the construction of the phenotype across life subject to developmental constraints), and evolutionary dynamics, thus describing the evolutionary and developmental (evo-devo) dynamics. The framework yields simple equations that can be arranged in a layered structure that we call the evo-devo process, whereby five core elementary components generate all equations including those mechanistically describing genetic covariation and the evo-devo dynamics. The framework recovers evolutionary dynamic equations in gradient form and describes the evolution of genetic covariation from the evolution of genotype, phenotype, environment, and mutational covariation. This shows that genotypic and phenotypic evolution must be followed simultaneously to yield a dynamically sufficient description of long-term phenotypic evolution in gradient form, such that evolution described as the climbing of a fitness landscape occurs in "geno-phenotype" space. Genetic constraints in geno-phenotype space are necessarily absolute because the phenotype is related to the genotype by development. Thus, the long-term evolutionary dynamics of developed phenotypes is strongly non-standard: (1) evolutionary equilibria are either absent or infinite in number and depend on genetic covariation and hence on development; (2) developmental constraints determine the admissible evolutionary path and hence which evolutionary equilibria are admissible; and (3) evolutionary outcomes occur at admissible evolutionary equilibria, which do not generally occur at fitness landscape peaks in geno-phenotype space, but at peaks in the admissible evolutionary path where "total genotypic selection" vanishes if exogenous plastic response vanishes and mutational variation exists in all directions of genotype space. Hence, selection and development jointly define the evolutionary outcomes if absolute mutational constraints and exogenous plastic response are absent, rather than the outcomes being defined only by selection. Moreover, our framework provides formulas for the sensitivities of a recurrence and an alternative method to dynamic optimization (i.e., dynamic programming or optimal control) to identify evolutionary outcomes in models with developmentally dynamic traits. These results show that development has major evolutionary effects.
Topics: Biological Evolution; Phenotype; Genotype; Selection, Genetic; Mutation
PubMed: 38043588
DOI: 10.1016/j.tpb.2023.11.003 -
Revue Neurologique 2015The field of essential tremor (ET) genetics remains extremely challenging. The relative lack of progress in understanding the genetic etiology of ET, however, does not... (Review)
Review
The field of essential tremor (ET) genetics remains extremely challenging. The relative lack of progress in understanding the genetic etiology of ET, however, does not reflect the lack of a genetic contribution, but rather, the presence of substantial phenotypic and genotypic heterogeneity. A meticulous approach to phenotyping is important for genetic research in ET. The only tool for phenotyping is the clinical history and examination. There is currently no ET-specific serum or imaging biomarker or defining neuropathological feature (e.g., a protein aggregate specific to ET) that can be used for phenotyping, and there is considerable clinical overlap with other disorders such as Parkinson's disease (PD) and dystonia. These issues greatly complicate phenotyping; thus, in some studies, as many as 30-50% of cases labeled as "ET" have later been found to carry other diagnoses (e.g., dystonia, PD) rather than ET. A cursory approach to phenotyping (e.g., merely defining ET as an "action tremor") is likely a major issue in some family studies of ET, and this as well as lack of standardized phenotyping across studies and patient centers is likely to be a major contributor to the relative lack of success of genome wide association studies (GWAS). To dissect the genetic architecture of ET, whole genome sequencing (WGS) in carefully characterized and well-phenotyped discovery and replication datasets of large case-control and familial cohorts will likely be of value. This will allow specific hypotheses about the mode of inheritance and genetic architecture to be tested. There are a number of approaches that still remain unexplored in ET genetics, including the contribution of copy number variants (CNVs), 'uncommon' moderate effect alleles, 'rare' variant large effect alleles (including Mendelian and complex/polygenic modes of inheritance), de novo and gonadal mosaicism, epigenetic changes and non-coding variation. Using these approaches is likely to yield new ET genes.
Topics: Essential Tremor; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans
PubMed: 26003805
DOI: 10.1016/j.neurol.2015.02.015