The Role of 16S rRNA Gene Sequencing in Identification of Microorganisms Misidentified by Conventional Methods

PubMed Central

Petti, C. A.; Polage, C. R.; Schreckenberger, P.

2005-01-01

Traditional methods for microbial identification require the recognition of differences in morphology, growth, enzymatic activity, and metabolism to define genera and species. Full and partial 16S rRNA gene sequencing methods have emerged as useful tools for identifying phenotypically aberrant microorganisms. We report on three bacterial blood isolates from three different College of American Pathologists-certified laboratories that were referred to ARUP Laboratories for definitive identification. Because phenotypic identification suggested unusual organisms not typically associated with the submitted clinical diagnosis, consultation with the Medical Director was sought and further testing was performed including partial 16S rRNA gene sequencing. All three patients had endocarditis, and conventional methods identified isolates from patients A, B, and C as a Facklamia sp., Eubacterium tenue, and a Bifidobacterium sp. 16S rRNA gene sequencing identified the isolates as Enterococcus faecalis, Cardiobacterium valvarum, and Streptococcus mutans, respectively. We conclude that the initial identifications of these three isolates were erroneous, may have misled clinicians, and potentially impacted patient care. 16S rRNA gene sequencing is a more objective identification tool, unaffected by phenotypic variation or technologist bias, and has the potential to reduce laboratory errors. PMID:16333109

Unusual pattern of the first dorsal metacarpal artery.

PubMed

Bianchi, Homero; Saravia, Diego; Ottone, Nicolas Ernesto

2017-07-01

This report describes an unusual pattern of the first dorsal metacarpal artery (FDMA) regarding its course and termination. This FDMA had an abnormal course, passing deep to various anatomical elements related to the index finger, with unusual termination in the radial and ulnar proper palmar digital arteries feeding the second and third fingers, respectively. There is no mention of this anatomical variation in the literature. We report the possible embryological origin of this case and other variations related to the FDMA. This unusual pattern represents a new reason to consider anatomical knowledge important for surgeons whose procedures are in this area and to ensure an accurate diagnosis and safe treatment of pathologies that might engage this anatomical variation.

Parallel or convergent evolution in human population genomic data revealed by genotype networks.

PubMed

R Vahdati, Ali; Wagner, Andreas

2016-08-02

Genotype networks are representations of genetic variation data that are complementary to phylogenetic trees. A genotype network is a graph whose nodes are genotypes (DNA sequences) with the same broadly defined phenotype. Two nodes are connected if they differ in some minimal way, e.g., in a single nucleotide. We analyze human genome variation data from the 1,000 genomes project, and construct haploid genotype (haplotype) networks for 12,235 protein coding genes. The structure of these networks varies widely among genes, indicating different patterns of variation despite a shared evolutionary history. We focus on those genes whose genotype networks show many cycles, which can indicate homoplasy, i.e., parallel or convergent evolution, on the sequence level. For 42 genes, the observed number of cycles is so large that it cannot be explained by either chance homoplasy or recombination. When analyzing possible explanations, we discovered evidence for positive selection in 21 of these genes and, in addition, a potential role for constrained variation and purifying selection. Balancing selection plays at most a small role. The 42 genes with excess cycles are enriched in functions related to immunity and response to pathogens. Genotype networks are representations of genetic variation data that can help understand unusual patterns of genomic variation.

A Rare SNP Identified a TCP Transcription Factor Essential for Tendril Development in Cucumber.

PubMed

Wang, Shenhao; Yang, Xueyong; Xu, Mengnan; Lin, Xingzhong; Lin, Tao; Qi, Jianjian; Shao, Guangjin; Tian, Nana; Yang, Qing; Zhang, Zhonghua; Huang, Sanwen

2015-12-07

Rare genetic variants are abundant in genomes but less tractable in genome-wide association study. Here we exploit a strategy of rare variation mapping to discover a gene essential for tendril development in cucumber (Cucumis sativus L.). In a collection of >3000 lines, we discovered a unique tendril-less line that forms branches instead of tendrils and, therefore, loses its climbing ability. We hypothesized that this unusual phenotype was caused by a rare variation and subsequently identified the causative single nucleotide polymorphism. The affected gene TEN encodes a TCP transcription factor conserved within the cucurbits and is expressed specifically in tendrils, representing a new organ identity gene. The variation occurs within a protein motif unique to the cucurbits and impairs its function as a transcriptional activator. Analyses of transcriptomes from near-isogenic lines identified downstream genes required for the tendril's capability to sense and climb a support. This study provides an example to explore rare functional variants in plant genomes. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Unusual Phenotypic Features in a Patient with a Novel Splice Mutation in the GHRHR Gene

PubMed Central

Hilal, Latifa; Hajaji, Yassir; Vie-Luton, Marie-Pierre; Ajaltouni, Zeina; Benazzouz, Bouchra; Chana, Maha; Chraïbi, Adelmajid; Kadiri, Abdelkrim; Amselem, Serge; Sobrier, Marie-Laure

2008-01-01

Isolated growth hormone deficiency (IGHD) may be of genetic origin. One of the few genes involved in that condition encodes the growth hormone releasing hormone receptor (GHRHR) that, through its ligand (GHRH), plays a pivotal role in the GH synthesis and secretion by the pituitary. Our objective is to describe the phenotype of two siblings born to a consanguineous union presenting with short stature (IGHD) and Magnetic Resonance Imaging (MRI) abnormalities, and to identify the molecular basis of this condition. Our main outcome measures were clinical and endocrinological investigations, MRI of the pituitary region, study of the GHRHR gene sequence and transcripts. In both patients, the severe growth retardation (−5SD) was combined with anterior pituitary hypoplasia. In addition to these classical phenotypic features for IGHD, one of the patients had a Chiari I malformation, an arachnoid cyst, and a dysmorphic anterior pituitary. A homozygous sequence variation in the consensus donor splice site of intron 1 (IVS1 + 2T > G) of the GHRHR gene was identified in both patients. Using in vitro transcription assay, we showed that this mutation results in abnormal splicing of GHRHR transcripts. In this report, which broadens the phenotype associated with GHRHR defects, we discuss the possible role of the GHRHR in the proper development of extrapituitary structures, through a mechanism that could be direct or secondary to severe GH deficiency. PMID:18297129

Phenotypic variation in California populations of valley oak (Quercus lobata Née) sampled along elevational gradients

Treesearch

Ana L. Albarrán-Lara; Jessica W. Wright; Paul F. Gugger; Annette Delfino-Mix; Juan Manuel Peñaloza-Ramírez; Victoria L. Sork

2015-01-01

California oaks exhibit tremendous phenotypic variation throughout their range. This variation reflects phenotypic plasticity in tree response to local environmental conditions as well as genetic differences underlying those phenotypes. In this study, we analyze phenotypic variation in leaf traits for valley oak adults sampled along three elevational transects and in...

Clinical report of a 17q12 microdeletion with additionally unreported clinical features.

PubMed

Roberts, Jennifer L; Gandomi, Stephanie K; Parra, Melissa; Lu, Ira; Gau, Chia-Ling; Dasouki, Majed; Butler, Merlin G

2014-01-01

Copy number variations involving the 17q12 region have been associated with developmental and speech delay, autism, aggression, self-injury, biting and hitting, oppositional defiance, inappropriate language, and auditory hallucinations. We present a tall-appearing 17-year-old boy with marfanoid habitus, hypermobile joints, mild scoliosis, pectus deformity, widely spaced nipples, pes cavus, autism spectrum disorder, intellectual disability, and psychiatric manifestations including physical and verbal aggression, obsessive-compulsive behaviors, and oppositional defiance. An echocardiogram showed borderline increased aortic root size. An abdominal ultrasound revealed a small pancreas, mild splenomegaly with a 1.3 cm accessory splenule, and normal kidneys and liver. A testing panel for Marfan, aneurysm, and related disorders was negative. Subsequently, a 400 K array-based comparative genomic hybridization (aCGH) + SNP analysis was performed which identified a de novo suspected pathogenic deletion on chromosome 17q12 encompassing 28 genes. Despite the limited number of cases described in the literature with 17q12 rearrangements, our proband's phenotypic features both overlap and expand on previously reported cases. Since syndrome-specific DNA sequencing studies failed to provide an explanation for this patient's unusual habitus, we postulate that this case represents an expansion of the 17q12 microdeletion phenotype. Further analysis of the deleted interval is recommended for new genotype-phenotype correlations.

Molecular genetic anatomy of inter- and intraserotype variation in the human bacterial pathogen group A Streptococcus.

PubMed

Beres, Stephen B; Richter, Ellen W; Nagiec, Michal J; Sumby, Paul; Porcella, Stephen F; DeLeo, Frank R; Musser, James M

2006-05-02

In recent years we have studied the relationship between strain genotypes and patient phenotypes in group A Streptococcus (GAS), a model human bacterial pathogen that causes extensive morbidity and mortality worldwide. We have concentrated our efforts on serotype M3 organisms because these strains are common causes of pharyngeal and invasive infections, produce unusually severe invasive infections, and can exhibit epidemic behavior. Our studies have been hindered by the lack of genome-scale phylogenies of multiple GAS strains and whole-genome sequences of multiple serotype M3 strains recovered from individuals with defined clinical phenotypes. To remove some of these impediments, we sequenced to closure the genome of four additional GAS strains and conducted comparative genomic resequencing of 12 contemporary serotype M3 strains representing distinct genotypes and phenotypes. Serotype M3 strains are a single phylogenetic lineage. Strains from asymptomatic throat carriers were significantly less virulent for mice than sterile-site isolates and evolved to a less virulent phenotype by multiple genetic pathways. Strain persistence or extinction between epidemics was strongly associated with presence or absence, respectively, of the prophage encoding streptococcal pyrogenic exotoxin A. A serotype M3 clone significantly underrepresented among necrotizing fasciitis cases has a unique frameshift mutation that truncates MtsR, a transcriptional regulator controlling expression of genes encoding iron-acquisition proteins. Expression microarray analysis of this clone confirmed significant alteration in expression of genes encoding iron metabolism proteins. Our analysis provided unprecedented detail about the molecular anatomy of bacterial strain genotype-patient phenotype relationships.

Genetic Variation in the Nuclear and Organellar Genomes Modulates Stochastic Variation in the Metabolome, Growth, and Defense

PubMed Central

Joseph, Bindu; Corwin, Jason A.; Kliebenstein, Daniel J.

2015-01-01

Recent studies are starting to show that genetic control over stochastic variation is a key evolutionary solution of single celled organisms in the face of unpredictable environments. This has been expanded to show that genetic variation can alter stochastic variation in transcriptional processes within multi-cellular eukaryotes. However, little is known about how genetic diversity can control stochastic variation within more non-cell autonomous phenotypes. Using an Arabidopsis reciprocal RIL population, we showed that there is significant genetic diversity influencing stochastic variation in the plant metabolome, defense chemistry, and growth. This genetic diversity included loci specific for the stochastic variation of each phenotypic class that did not affect the other phenotypic classes or the average phenotype. This suggests that the organism's networks are established so that noise can exist in one phenotypic level like metabolism and not permeate up or down to different phenotypic levels. Further, the genomic variation within the plastid and mitochondria also had significant effects on the stochastic variation of all phenotypic classes. The genetic influence over stochastic variation within the metabolome was highly metabolite specific, with neighboring metabolites in the same metabolic pathway frequently showing different levels of noise. As expected from bet-hedging theory, there was more genetic diversity and a wider range of stochastic variation for defense chemistry than found for primary metabolism. Thus, it is possible to begin dissecting the stochastic variation of whole organismal phenotypes in multi-cellular organisms. Further, there are loci that modulate stochastic variation at different phenotypic levels. Finding the identity of these genes will be key to developing complete models linking genotype to phenotype. PMID:25569687

Genetic variation in the nuclear and organellar genomes modulates stochastic variation in the metabolome, growth, and defense.

PubMed

Joseph, Bindu; Corwin, Jason A; Kliebenstein, Daniel J

2015-01-01

Recent studies are starting to show that genetic control over stochastic variation is a key evolutionary solution of single celled organisms in the face of unpredictable environments. This has been expanded to show that genetic variation can alter stochastic variation in transcriptional processes within multi-cellular eukaryotes. However, little is known about how genetic diversity can control stochastic variation within more non-cell autonomous phenotypes. Using an Arabidopsis reciprocal RIL population, we showed that there is significant genetic diversity influencing stochastic variation in the plant metabolome, defense chemistry, and growth. This genetic diversity included loci specific for the stochastic variation of each phenotypic class that did not affect the other phenotypic classes or the average phenotype. This suggests that the organism's networks are established so that noise can exist in one phenotypic level like metabolism and not permeate up or down to different phenotypic levels. Further, the genomic variation within the plastid and mitochondria also had significant effects on the stochastic variation of all phenotypic classes. The genetic influence over stochastic variation within the metabolome was highly metabolite specific, with neighboring metabolites in the same metabolic pathway frequently showing different levels of noise. As expected from bet-hedging theory, there was more genetic diversity and a wider range of stochastic variation for defense chemistry than found for primary metabolism. Thus, it is possible to begin dissecting the stochastic variation of whole organismal phenotypes in multi-cellular organisms. Further, there are loci that modulate stochastic variation at different phenotypic levels. Finding the identity of these genes will be key to developing complete models linking genotype to phenotype.

Facial bone fragmentation in blind cavefish arises through two unusual ossification processes.

PubMed

Powers, Amanda K; Kaplan, Shane A; Boggs, Tyler E; Gross, Joshua B

2018-05-03

The precise mechanisms underlying cranial bone development, evolution and patterning remain incompletely characterised. This poses a challenge to understanding the etiologies of craniofacial malformations evolving in nature. Capitalising on natural variation, "evolutionary model systems" provide unique opportunities to identify underlying causes of aberrant phenotypes as a complement to studies in traditional systems. Mexican blind cavefish are a prime evolutionary model for cranial disorders since they frequently exhibit extreme alterations to the skull and lateral asymmetries. These aberrations occur in stark contrast to the normal cranial architectures of closely related surface-dwelling fish, providing a powerful comparative paradigm for understanding cranial bone formation. Using a longitudinal and in vivo analytical approach, we discovered two unusual ossification processes in cavefish that underlie the development of 'fragmented' and asymmetric cranial bones. The first mechanism involves the sporadic appearance of independent bony elements that fail to fuse together later in development. The second mechanism involves the "carving" of channels in the mature bone, a novel form of post-ossification remodeling. In the extreme cave environment, these novel mechanisms may have evolved to augment sensory input, and may indirectly result in a trade-off between sensory expansion and cranial bone development.

Developmental mechanisms underlying variation in craniofacial disease and evolution.

PubMed

Fish, Jennifer L

2016-07-15

Craniofacial disease phenotypes exhibit significant variation in penetrance and severity. Although many genetic contributions to phenotypic variation have been identified, genotype-phenotype correlations remain imprecise. Recent work in evolutionary developmental biology has exposed intriguing developmental mechanisms that potentially explain incongruities in genotype-phenotype relationships. This review focuses on two observations from work in comparative and experimental animal model systems that highlight how development structures variation. First, multiple genetic inputs converge on relatively few developmental processes. Investigation of when and how variation in developmental processes occurs may therefore help predict potential genetic interactions and phenotypic outcomes. Second, genetic mutation is typically associated with an increase in phenotypic variance. Several models outlining developmental mechanisms underlying mutational increases in phenotypic variance are discussed using Satb2-mediated variation in jaw size as an example. These data highlight development as a critical mediator of genotype-phenotype correlations. Future research in evolutionary developmental biology focusing on tissue-level processes may help elucidate the "black box" between genotype and phenotype, potentially leading to novel treatment, earlier diagnoses, and better clinical consultations for individuals affected by craniofacial anomalies. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome sequence of a serotype M3 strain of group A Streptococcus: phage-encoded toxins, the high-virulence phenotype, and clone emergence.

PubMed

Beres, Stephen B; Sylva, Gail L; Barbian, Kent D; Lei, Benfang; Hoff, Jessica S; Mammarella, Nicole D; Liu, Meng-Yao; Smoot, James C; Porcella, Stephen F; Parkins, Larye D; Campbell, David S; Smith, Todd M; McCormick, John K; Leung, Donald Y M; Schlievert, Patrick M; Musser, James M

2002-07-23

Genome sequences are available for many bacterial strains, but there has been little progress in using these data to understand the molecular basis of pathogen emergence and differences in strain virulence. Serotype M3 strains of group A Streptococcus (GAS) are a common cause of severe invasive infections with unusually high rates of morbidity and mortality. To gain insight into the molecular basis of this high-virulence phenotype, we sequenced the genome of strain MGAS315, an organism isolated from a patient with streptococcal toxic shock syndrome. The genome is composed of 1,900,521 bp, and it shares approximately 1.7 Mb of related genetic material with genomes of serotype M1 and M18 strains. Phage-like elements account for the great majority of variation in gene content relative to the sequenced M1 and M18 strains. Recombination produces chimeric phages and strains with previously uncharacterized arrays of virulence factor genes. Strain MGAS315 has phage genes that encode proteins likely to contribute to pathogenesis, such as streptococcal pyrogenic exotoxin A (SpeA) and SpeK, streptococcal superantigen (SSA), and a previously uncharacterized phospholipase A(2) (designated Sla). Infected humans had anti-SpeK, -SSA, and -Sla antibodies, indicating that these GAS proteins are made in vivo. SpeK and SSA were pyrogenic and toxic for rabbits. Serotype M3 strains with the phage-encoded speK and sla genes increased dramatically in frequency late in the 20th century, commensurate with the rise in invasive disease caused by M3 organisms. Taken together, the results show that phage-mediated recombination has played a critical role in the emergence of a new, unusually virulent clone of serotype M3 GAS.

Genome-scale investigation of phenotypically distinct but nearly clonal Trichoderma strains

PubMed Central

Weld, Richard J.; Cox, Murray P.; Bradshaw, Rosie E.; McLean, Kirstin L.; Stewart, Alison; Steyaert, Johanna M.

2016-01-01

Biological control agents (BCA) are beneficial organisms that are applied to protect plants from pests. Many fungi of the genus Trichoderma are successful BCAs but the underlying mechanisms are not yet fully understood. Trichoderma cf. atroviride strain LU132 is a remarkably effective BCA compared to T. cf. atroviride strain LU140 but these strains were found to be highly similar at the DNA sequence level. This unusual combination of phenotypic variability and high DNA sequence similarity between separately isolated strains prompted us to undertake a genome comparison study in order to identify DNA polymorphisms. We further investigated if the polymorphisms had functional effects on the phenotypes. The two strains were clearly identified as individuals, exhibiting different growth rates, conidiation and metabolism. Superior pathogen control demonstrated by LU132 depended on its faster growth, which is a prerequisite for successful distribution and competition. Genome sequencing identified only one non-synonymous single nucleotide polymorphism (SNP) between the strains. Based on this SNP, we successfully designed and validated an RFLP protocol that can be used to differentiate LU132 from LU140 and other Trichoderma strains. This SNP changed the amino acid sequence of SERF, encoded by the previously undescribed single copy gene “small EDRK-rich factor” (serf). A deletion of serf in the two strains did not lead to identical phenotypes, suggesting that, in addition to the single functional SNP between the nearly clonal Trichoderma cf. atroviride strains, other non-genomic factors contribute to their phenotypic variation. This finding is significant as it shows that genomics is an extremely useful but not exhaustive tool for the study of biocontrol complexity and for strain typing. PMID:27190719

Mega-evolutionary dynamics of the adaptive radiation of birds.

PubMed

Cooney, Christopher R; Bright, Jen A; Capp, Elliot J R; Chira, Angela M; Hughes, Emma C; Moody, Christopher J A; Nouri, Lara O; Varley, Zoë K; Thomas, Gavin H

2017-02-16

The origin and expansion of biological diversity is regulated by both developmental trajectories and limits on available ecological niches. As lineages diversify, an early and often rapid phase of species and trait proliferation gives way to evolutionary slow-downs as new species pack into ever more densely occupied regions of ecological niche space. Small clades such as Darwin's finches demonstrate that natural selection is the driving force of adaptive radiations, but how microevolutionary processes scale up to shape the expansion of phenotypic diversity over much longer evolutionary timescales is unclear. Here we address this problem on a global scale by analysing a crowdsourced dataset of three-dimensional scanned bill morphology from more than 2,000 species. We find that bill diversity expanded early in extant avian evolutionary history, before transitioning to a phase dominated by packing of morphological space. However, this early phenotypic diversification is decoupled from temporal variation in evolutionary rate: rates of bill evolution vary among lineages but are comparatively stable through time. We find that rare, but major, discontinuities in phenotype emerge from rapid increases in rate along single branches, sometimes leading to depauperate clades with unusual bill morphologies. Despite these jumps between groups, the major axes of within-group bill-shape evolution are remarkably consistent across birds. We reveal that macroevolutionary processes underlying global-scale adaptive radiations support Darwinian and Simpsonian ideas of microevolution within adaptive zones and accelerated evolution between distinct adaptive peaks.

The role of clinical pharmacology in molecular genetics

NASA Technical Reports Server (NTRS)

Robertson, D.

1997-01-01

PROBLEM: Discovering the causes of unusual phenotypes in human subjects is an important aspect of patient-oriented research. MATERIAL: The tools of clinical pharmacology are uniquely useful in addressing these problems. PATIENTS, SUBJECTS, OR CASE HISTORIES: We evaluated a 42-year-old patient with lifelong orthostatic hypotension and ptosis of the eyelids. He underwent a series of biochemical, physiological, and pharmacological tests outlined in this article. RESULTS: These studies indicated that sympathetic innervation was intact but that the sympathetic neurotransmitter was dopamine rather than norepinephrine. These results demonstrated that dopamine-beta-hydroxylase deficiency underlies the clinical abnormalities of this patient. CONCLUSION: In selected individuals with unusual phenotypes, the techniques of clinical chemistry and clinical pharmacology can define the nature of the defect at almost the resolution of the human genome.

Unusual Turner syndrome mosaic with a triple x cell line (47,X/49,XXX) in a western lowland gorilla (Gorilla gorilla gorilla).

PubMed

Bradford, Carol M; Tupa, Lynn; Wiese, Debbie; Hurley, Timothy J; Zimmerman, Ralph

2013-12-01

A 29-yr-old female western lowland gorilla (Gorilla gorilla gorilla) was evaluated for low fertility and a midterm abortion. Laboratory testing included karyotyping, which revealed an unusual mosaicism for Turner syndrome with Triple X (47,X/49,XXX). This appears to be the first report of Turner syndrome in a great ape. In humans, Turner syndrome occurs in approximately 1 in 3,000 females, with half of those monosomic for the X chromosome. A small proportion is mosaic for a triple X cell line (3-4%). In humans, Turner syndrome is associated with characteristic phenotype including short stature, obesity, a broad chest with widely spaced nipples, webbing of the neck, and anteverted ears. This individual gorilla is significantly shorter in stature than conspecifics and is obese despite normal caloric intake. Individuals with Turner syndrome should also be screened for common health issues, including congenital heart defects, obesity, kidney abnormalities, hypertension, hypothyroidism, and diabetes mellitus. Animals with decreased fertility, multiple miscarriages, fetal losses, unusual phenotypes, or a combination of these symptoms should be evaluated for genetic abnormalities.

Seed predators exert selection on the subindividual variation of seed size.

PubMed

Sobral, M; Guitián, J; Guitián, P; Larrinaga, A R

2014-07-01

Subindividual variation among repeated organs in plants constitutes an overlooked level of variation in phenotypic selection studies, despite being a major component of phenotypic variation. Animals that interact with plants could be selective agents on subindividual variation. This study examines selective pressures exerted during post-dispersal seed predation and germination on the subindividual variation of seed size in hawthorn (Crataegus monogyna). With a seed offering experiment and a germination test, we estimated phenotypic selection differentials for average and subindividual variation of seed size due to seed predation and germination. Seed size affects germination, growth rate and the probability of an individual seed of escaping predation. Longer seeds showed higher germination rates, but this did not result in significant selection on phenotypes of the maternal trees. On the other hand, seed predators avoided wider seeds, and by doing so exerted phenotypic selection on adult average and subindividual variation of seed size. The detected selection on subindividual variation suggests that the levels of phenotypic variation within individual plants may be, at least partly, the adaptive consequence of animal-mediated selection. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

Contextualizing Genetics for Regional Heart Failure Care

PubMed Central

Iyngkaran, Pupalan; Thomas, Merlin C.; Johnson, Renee; French, John; Ilton, Marcus; McDonald, Peter; Hare, David L.; Fatkin, Diane

2016-01-01

Congestive heart failure (CHF) is a chronic and often devastating cardiovascular disorder with no cure. There has been much advancement in the last two decades that has seen improvements in morbidity and mortality. Clinicians have also noted variations in the responses to therapies. More detailed observations also point to clusters of diseases, phenotypic groupings, unusual severity and the rates at which CHF occurs. Medical genetics is playing an increasingly important role in answering some of these observations. This developing field in many respects provides more information than is currently clinically applicable. This includes making sense of the established single gene mutations or uncommon private mutations. In this thematic series which discusses the many factors that could be relevant for CHF care, once established treatments are available in the communities; this section addresses a contextual role for medical genetics. PMID:27280306

Directional selection effects on patterns of phenotypic (co)variation in wild populations

PubMed Central

Patton, J. L.; Hubbe, A.; Marroig, G.

2016-01-01

Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. PMID:27881744

Rapid evolution of fire melanism in replicated populations of pygmy grasshoppers.

PubMed

Forsman, Anders; Karlsson, Magnus; Wennersten, Lena; Johansson, Jenny; Karpestam, Einat

2011-09-01

Evolutionary theory predicts an interactive process whereby spatiotemporal environmental heterogeneity will maintain genetic variation, while genetic and phenotypic diversity will buffer populations against stress and allow for fast adaptive evolution in rapidly changing environments. Here, we study color polymorphism patterns in pygmy grasshoppers (Tetrix subulata) and show that the frequency of the melanistic (black) color variant was higher in areas that had been ravaged by fires the previous year than in nonburned habitats, that, in burned areas, the frequency of melanistic grasshoppers dropped from ca. 50% one year after a fire to 30% after four years, and that the variation in frequencies of melanistic individuals among and within populations was genetically based on and represented evolutionary modifications. Dark coloration may confer a selective benefit mediated by enhanced camouflage in recently fire-ravaged areas characterized by blackened visual backgrounds before vegetation has recovered. These findings provide rare evidence for unusually large, extremely rapid adaptive contemporary evolution in replicated natural populations in response to divergent and fluctuating selection associated with spatiotemporal environmental changes. © 2011 The Author(s).

A powerful and flexible statistical framework for testing hypotheses of allele-specific gene expression from RNA-seq data

PubMed Central

Skelly, Daniel A.; Johansson, Marnie; Madeoy, Jennifer; Wakefield, Jon; Akey, Joshua M.

2011-01-01

Variation in gene expression is thought to make a significant contribution to phenotypic diversity among individuals within populations. Although high-throughput cDNA sequencing offers a unique opportunity to delineate the genome-wide architecture of regulatory variation, new statistical methods need to be developed to capitalize on the wealth of information contained in RNA-seq data sets. To this end, we developed a powerful and flexible hierarchical Bayesian model that combines information across loci to allow both global and locus-specific inferences about allele-specific expression (ASE). We applied our methodology to a large RNA-seq data set obtained in a diploid hybrid of two diverse Saccharomyces cerevisiae strains, as well as to RNA-seq data from an individual human genome. Our statistical framework accurately quantifies levels of ASE with specified false-discovery rates, achieving high reproducibility between independent sequencing platforms. We pinpoint loci that show unusual and biologically interesting patterns of ASE, including allele-specific alternative splicing and transcription termination sites. Our methodology provides a rigorous, quantitative, and high-resolution tool for profiling ASE across whole genomes. PMID:21873452

Complex small-molecule architectures regulate phenotypic plasticity in a nematode.

PubMed

Bose, Neelanjan; Ogawa, Akira; von Reuss, Stephan H; Yim, Joshua J; Ragsdale, Erik J; Sommer, Ralf J; Schroeder, Frank C

2012-12-07

Chemistry the worm's way: The nematode Pristionchus pacificus constructs elaborate small molecules from modified building blocks of primary metabolism, including an unusual xylopyranose-based nucleoside (see scheme). These compounds act as signaling molecules to control adult phenotypic plasticity and dauer development and provide examples of modular generation of structural diversity in metazoans. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Allelic and Phenotypic Heterogeneity in ABCA4 mutations

PubMed Central

Burke, Tomas R; Tsang, Stephen H

2011-01-01

Since the discovery of the ABCA4 gene as the cause of autosomal recessive Stargardt disease/fundus flavimaculatus much has been written of the phenotypic variability in ABCA4 retinopathy. In this review the authors discuss the findings seen on examination and the disease features detected using various clinical tests. Important differential diagnoses are presented and unusual presentations of ABCA4 disease highlighted. PMID:21510770

Growth retardation, intellectual disability, facial anomalies, cataract, thoracic hypoplasia and skeletal abnormalities: a novel phenotype

PubMed Central

Shah, Hitesh; Bens, Susanne; Caliebe, Almuth; Graham, John M.; Girisha, Katta Mohan

2012-01-01

We report a fourteen year old adolescent girl with growth deficiency, microcephaly, intellectual disability, distinctive dysmorphic features (bulbous nose with wide nasal base, hypotelorism, deeply set eyes, protruding cupped ears and thick lips), cataract, pigmentary retinopathy, hypoplastic thorax, kyphoscoliosis and unusual skeletal changes but without chromosomal imbalances detected by array-CGH who probably represents a novel phenotype. PMID:22987502

Variation in reproductive life history traits between two populations of Blackbanded Darters (Percina nigrofasciata)

USGS Publications Warehouse

Hughey, Myra C.; Heins, David C.; Jelks, Howard L.; Ory, Bridget A.; Jordan, Frank

2012-01-01

We examined the life history of Blackbanded Darters (Percina nigrofasciata) from two streams in the Choctawhatchee River drainage, Florida, over a three-year study period. Blackbanded Darters from Turkey Creek were longer than fish from Ten Mile Creek; however, size-adjusted clutch and egg sizes were similar between populations. Larger females produced larger clutches, whereas egg size did not vary with female body size. Seasonally, clutch sizes were greater in May than in August. When contrasted with previous studies of Blackbanded Darters in Alabama and Louisiana, the reproductive season of Blackbanded Darters in Florida was unusually long, ceasing for only a few months in late fall. The reproductive season was longer in Turkey Creek than in Ten Mile Creek. Differences in thermal regime among streams may explain differences in life history traits among local and distant populations of Blackbanded Darters. This research, alone and in combination with previous studies of this species, emphasizes two main points. First, it reaffirms that life history studies based on a single locality or conducted at a single point in time may fail to capture the full range of variation in life history traits. Second, it highlights the extensive phenotypic variation found in species with broad geographic ranges. Such species lend themselves to comparative and experimental research on patterns and causes of life history variation.

How can we estimate natural selection on endocrine traits? Lessons from evolutionary biology

PubMed Central

2016-01-01

An evolutionary perspective can enrich almost any endeavour in biology, providing a deeper understanding of the variation we see in nature. To this end, evolutionary endocrinologists seek to describe the fitness consequences of variation in endocrine traits. Much of the recent work in our field, however, follows a flawed approach to the study of how selection shapes endocrine traits. Briefly, this approach relies on among-individual correlations between endocrine phenotypes (often circulating hormone levels) and fitness metrics to estimate selection on those endocrine traits. Adaptive plasticity in both endocrine and fitness-related traits can drive these correlations, generating patterns that do not accurately reflect natural selection. We illustrate why this approach to studying selection on endocrine traits is problematic, referring to work from evolutionary biologists who, decades ago, described this problem as it relates to a variety of other plastic traits. We extend these arguments to evolutionary endocrinology, where the likelihood that this flaw generates bias in estimates of selection is unusually high due to the exceptional responsiveness of hormones to environmental conditions, and their function to induce adaptive life-history responses to environmental variation. We end with a review of productive approaches for investigating the fitness consequences of variation in endocrine traits that we expect will generate exciting advances in our understanding of endocrine system evolution. PMID:27881753

Directional selection effects on patterns of phenotypic (co)variation in wild populations.

PubMed

Assis, A P A; Patton, J L; Hubbe, A; Marroig, G

2016-11-30

Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. © 2016 The Author(s).

Unusual intraindividual variation of the nuclear 18S rRNA gene is widespread within the Acipenseridae.

PubMed

Krieger, Jeannette; Hett, Anne Kathrin; Fuerst, Paul A; Birstein, Vadim J; Ludwig, Arne

2006-01-01

Significant intraindividual variation in the sequence of the 18S rRNA gene is unusual in animal genomes. In a previous study, multiple 18S rRNA gene sequences were observed within individuals of eight species of sturgeon from North America but not in the North American paddlefish, Polyodon spathula, in two species of Polypterus (Polypterus delhezi and Polypterus senegalus), in other primitive fishes (Erpetoichthys calabaricus, Lepisosteus osseus, Amia calva) or in a lungfish (Protopterus sp.). These observations led to the hypothesis that this unusual genetic characteristic arose within the Acipenseriformes after the presumed divergence of the sturgeon and paddlefish families. In the present study, a survey of nearly all Eurasian acipenseriform species was conducted to examine 18S rDNA variation. Intraindividual variation was not found in the polyodontid species, the Chinese paddlefish, Psephurus gladius, but variation was detected in all Eurasian acipenserid species. The comparison of sequences from two major segments of the 18S rRNA gene and identification of sites where insertion/deletion events have occurred are placed in the context of evolutionary relationships within the Acipenseriformes and the evolution of rDNA variation in this group.

Coevolutionary dynamics of phenotypic diversity and contingent cooperation

PubMed Central

Wang, Long

2017-01-01

Phenotypic diversity is considered beneficial to the evolution of contingent cooperation, in which cooperators channel their help preferentially towards others of similar phenotypes. However, it remains largely unclear how phenotypic variation arises in the first place and thus leads to the construction of phenotypic complexity. Here we propose a mathematical model to study the coevolutionary dynamics of phenotypic diversity and contingent cooperation. Unlike previous models, our model does not assume any prescribed level of phenotypic diversity, but rather lets it be an evolvable trait. Each individual expresses one phenotype at a time and only the phenotypes expressed are visible to others. Moreover, individuals can differ in their potential of phenotypic variation, which is characterized by the number of distinct phenotypes they can randomly switch to. Each individual incurs a cost proportional to the number of potentially expressible phenotypes so as to retain phenotypic variation and expression. Our results show that phenotypic diversity coevolves with contingent cooperation under a wide range of conditions and that there exists an optimal level of phenotypic diversity best promoting contingent cooperation. It pays for contingent cooperators to elevate their potential of phenotypic variation, thereby increasing their opportunities of establishing cooperation via novel phenotypes, as these new phenotypes serve as secret tags that are difficult for defector to discover and chase after. We also find that evolved high levels of phenotypic diversity can occasionally collapse due to the invasion of defector mutants, suggesting that cooperation and phenotypic diversity can mutually reinforce each other. Thus, our results provide new insights into better understanding the coevolution of cooperation and phenotypic diversity. PMID:28141806

Phenotypic divergence despite low genetic differentiation in house sparrow populations.

PubMed

Ben Cohen, Shachar; Dor, Roi

2018-01-10

Studying patterns of phenotypic variation among populations can shed light on the drivers of evolutionary processes. The house sparrow (Passer domesticus) is one of the world's most ubiquitous bird species, as well as a successful invader. We investigated phenotypic variation in house sparrow populations across a climatic gradient and in relation to a possible scenario of an invasion. We measured variation in morphological, coloration, and behavioral traits (exploratory behavior and neophobia) and compared it to the neutral genetic variation. We found that sparrows were larger and darker in northern latitudes, in accordance with Bergmann's and Gloger's biogeographic rules. Morphology and behavior mostly differed between the southernmost populations and the other regions, supporting the possibility of an invasion. Genetic differentiation was low and diversity levels were similar across populations, indicating high gene flow. Nevertheless, the southernmost and northern populations differed genetically to some extent. Furthermore, genetic differentiation (F ST ) was lower in comparison to phenotypic variation (P ST ), indicating that the phenotypic variation is shaped by directional selection or by phenotypic plasticity. This study expands our knowledge on evolutionary mechanisms and biological invasions.

Mega-evolutionary dynamics of the adaptive radiation of birds

PubMed Central

Capp, Elliot J. R.; Chira, Angela M.; Hughes, Emma C.; Moody, Christopher J. A.; Nouri, Lara O.; Varley, Zoë K.; Thomas, Gavin H.

2017-01-01

The origin and expansion of biological diversity is regulated by both developmental trajectories1,2 and limits on available ecological niches3–7. As lineages diversify an early, often rapid, phase of species and trait proliferation gives way to evolutionary slowdowns as new species pack into ever more densely occupied regions of ecological niche space6,8. Small clades such as Darwin’s finches demonstrate that natural selection is the driving force of adaptive radiations, but how microevolutionary processes scale up to shape the expansion of phenotypic diversity over much longer evolutionary timescales is unclear9. Here we address this problem on a global scale by analysing a novel crowd-sourced dataset of 3D-scanned bill morphology from >2000 species. We find that bill diversity expanded early in extant avian evolutionary history before transitioning to a phase dominated by morphospace packing. However, this early phenotypic diversification is decoupled from temporal variation in evolutionary rate: rates of bill evolution vary among lineages but are comparatively stable through time. We find that rare but major discontinuities in phenotype emerge from rapid increases in rate along single branches, sometimes leading to depauperate clades with unusual bill morphologies. Despite these jumps between groups, the major axes of within-group bill shape evolution are remarkably consistent across birds. We reveal that macroevolutionary processes underlying global-scale adaptive radiations support Darwinian9 and Simpsonian4 ideas of microevolution within adaptive zones and accelerated evolution between distinct adaptive peaks. PMID:28146475

Multivariate Analysis of Genotype-Phenotype Association.

PubMed

Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

2016-04-01

With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map has important consequences for gene identification and may shed light on the evolvability of organisms. Copyright © 2016 by the Genetics Society of America.

The impact of nectar chemical features on phenotypic variation in two related nectar yeasts.

PubMed

Pozo, María I; Herrera, Carlos M; Van den Ende, Wim; Verstrepen, Kevin; Lievens, Bart; Jacquemyn, Hans

2015-06-01

Floral nectars become easily colonized by microbes, most often species of the ascomycetous yeast genus Metschnikowia. Although it is known that nectar composition can vary tremendously among plant species, most probably corresponding to the nutritional requirements of their main pollinators, far less is known about how variation in nectar chemistry affects intraspecific variation in nectarivorous yeasts. Because variation in nectar traits probably affects growth and abundance of nectar yeasts, nectar yeasts can be expected to display large phenotypic variation in order to cope with varying nectar conditions. To test this hypothesis, we related variation in the phenotypic landscape of a vast collection of nectar-living yeast isolates from two Metschnikowia species (M. reukaufii and M. gruessii) to nectar chemical traits using non-linear redundancy analyses. Nectar yeasts were collected from 19 plant species from different plant families to include as much variation in nectar chemical traits as possible. As expected, nectar yeasts displayed large variation in phenotypic traits, particularly in traits related to growth performance in carbon sources and inhibitors, which was significantly related to the host plant from which they were isolated. Total sugar concentration and relative fructose content significantly explained the observed variation in the phenotypic profile of the investigated yeast species, indicating that sugar concentration and composition are the key traits that affect phenotypic variation in nectarivorous yeasts. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Environmentally induced (co)variance in sperm and offspring phenotypes as a source of epigenetic effects.

PubMed

Marshall, Dustin J

2015-01-01

Traditionally, it has been assumed that sperm are a vehicle for genes and nothing more. As such, the only source of variance in offspring phenotype via the paternal line has been genetic effects. More recently, however, it has been shown that the phenotype or environment of fathers can affect the phenotype of offspring, challenging traditional theory with implications for evolution, ecology and human in vitro fertilisation. Here, I review sources of non-genetic variation in the sperm phenotype and evidence for co-variation between sperm and offspring phenotypes. I distinguish between two environmental sources of variation in sperm phenotype: the pre-release environment and the post-release environment. Pre-release, sperm phenotypes can vary within species according to male phenotype (e.g. body size) and according to local conditions such as the threat of sperm competition. Post-release, the physicochemical conditions that sperm experience, either when freely spawned or when released into the female reproductive tract, can further filter or modify sperm phenotypes. I find evidence that both pre- and post-release sperm environments can affect offspring phenotype; fertilisation is not a new beginning – rather, the experiences of sperm with the father and upon release can drive variation in the phenotype of the offspring. Interestingly, there was some evidence for co-variation between the stress resistance of sperm and the stress resistance of offspring, though more studies are needed to determine whether such effects are widespread. Overall, it appears that environmentally induced covariation between sperm and offspring phenotypes is non-negligible and further work is needed to determine their prevalence and strength. © 2015. Published by The Company of Biologists Ltd.

Third Prader-Willi syndrome phenotype due to maternal uniparental disomy 15 with mosaic trisomy 15.

PubMed

Olander, E; Stamberg, J; Steinberg, L; Wulfsberg, E A

2000-07-31

We report on a boy with mosaicism for trisomy 15 and Prader-Willi syndrome (PWS) due to maternal isodisomy for chromosome 15. His phenotype is consistent with PWS and trisomy 15 mosaicism. Although our patient is unusual in having maternal isodisomy rather than the more common maternal heterodisomy, we think that his more severe PWS phenotype is due to his trisomy 15 mosaicism rather than to homozygosity for deleterious chromosome 15 genes. We propose that individuals with PWS have one of three similar but distinctive phenotypes depending on the cause of their condition. Patients with paternal deletions have the typical PWS phenotype, patients with maternal UPD have a slightly milder phenotype with better cognitive function, and those with maternal UPD and mosaic trisomy 15 have the most severe phenotype with a high incidence of congenital heart disease. These phenotype-genotype differences are useful to guide the work-up of patients with suspected PWS and to provide prognostic counseling for families.

Unusual solar energetic proton fluxes at 1 AU within an interplanetary CME

NASA Astrophysics Data System (ADS)

Mulligan, T.; Blake, J. B.; Mewaldt, R. A.

In mid December 2006 several flares on the Sun occurred in rapid succession, spawning several CMEs and bathing the Earth in multiple solar energetic particle (SEP) events. One such SEP occurring on December 15th was observed at the Earth just as an interplanetary CME (ICME) from a previous flare on December 13th was transiting the Earth. Although solar wind observations during this time show typical energetic proton fluxes from the prior SEP and IP shock driven ahead of the ICME, as the ICME passes the Earth unusual energetic particle signatures are observed. Measurements from ACE, Wind, and STEREO show unusual proton flux variations at energies ranging from ~3 MeV up to greater than 70 MeV. Within the Earth’s magnetosphere Polar HIST also sees unusual proton flux variations at energies greater than 10 MeV while crossing open field lines in the southern polar cap. However, no such variation in the energetic proton flux is observed at the GOES 10 or GOES 11 spacecraft in geosynchronous orbit. Differential fluxes observed at GOES 12 in the 15-40 MeV energy range show some variation. However, the overall energetic particle signature within the ICME at GEO orbits remains unclear. This event illustrates the need for caution when using GEO data in statistical studies of SEP events and in interplanetary models of energetic particle transport to 1 AU.

Contemporary and historical evolutionary processes interact to shape patterns of within-lake phenotypic divergences in polyphenic pumpkinseed sunfish, Lepomis gibbosus.

PubMed

Weese, Dylan J; Ferguson, Moira M; Robinson, Beren W

2012-03-01

Historical and contemporary evolutionary processes can both contribute to patterns of phenotypic variation among populations of a species. Recent studies are revealing how interactions between historical and contemporary processes better explain observed patterns of phenotypic divergence than either process alone. Here, we investigate the roles of evolutionary history and adaptation to current environmental conditions in structuring phenotypic variation among polyphenic populations of sunfish inhabiting 12 postglacial lakes in eastern North America. The pumpkinseed sunfish polyphenism includes sympatric ecomorphs specialized for littoral or pelagic lake habitats. First, we use population genetic methods to test the evolutionary independence of within-lake phenotypic divergences of ecomorphs and to describe patterns of genetic structure among lake populations that clustered into three geographical groupings. We then used multivariate analysis of covariance (MANCOVA) to partition body shape variation (quantified with geometric morphometrics) among the effects of evolutionary history (reflecting phenotypic variation among genetic clusters), the shared phenotypic response of all populations to alternate habitats within lakes (reflecting adaptation to contemporary conditions), and unique phenotypic responses to habitats within lakes nested within genetic clusters. All effects had a significant influence on body form, but the effects of history and the interaction between history and contemporary habitat were larger than contemporary processes in structuring phenotypic variation. This highlights how divergence can be better understood against a known backdrop of evolutionary history.

Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation, cleft lip and cleft palate, cardiovascular abnormalities.

PubMed

Tonni, Gabriele; Lituania, Mario; Chitayat, David; Bonasoni, Maria Paola; Keating, Sarah; Thompson, Megan; Shannon, Patrick

2014-12-01

Trisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. The first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. Complete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy. Copyright © 2014. Published by Elsevier B.V.

Fitness consequences of maternal and embryonic responses to environmental variation: using reptiles as models for studies of developmental plasticity.

PubMed

Warner, Daniel A

2014-11-01

Environmental factors strongly influence phenotypic variation within populations. The environment contributes to this variation in two ways: (1) by acting as a determinant of phenotypic variation (i.e., plastic responses) and (2) as an agent of selection that "chooses" among existing phenotypes. Understanding how these two environmental forces contribute to phenotypic variation is a major goal in the field of evolutionary biology and a primary objective of my research program. The objective of this article is to provide a framework to guide studies of environmental sources of phenotypic variation (specifically, developmental plasticity and maternal effects, and their adaptive significance). Two case studies from my research on reptiles are used to illustrate the general approaches I have taken to address these conceptual topics. Some key points for advancing our understanding of environmental influences on phenotypic variation include (1) merging laboratory-based research that identifies specific environmental effects with field studies to validate ecological relevance; (2) using controlled experimental approaches that mimic complex environments found in nature; (3) integrating data across biological fields (e.g., genetics, morphology, physiology, behavior, and ecology) under an evolutionary framework to provide novel insights into the underlying mechanisms that generate phenotypic variation; (4) assessing fitness consequences using measurements of survival and/or reproductive success across ontogeny (from embryos to adults) and under multiple ecologically-meaningful contexts; and (5) quantifying the strength and form of natural selection in multiple populations over multiple periods of time to understand the spatial and temporal consistency of phenotypic selection. Research programs that focus on organisms that are amenable to these approaches will provide the most promise for advancing our understanding of the environmental factors that generate the remarkable phenotypic diversity observed within populations. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Functional genomics of physiological plasticity and local adaptation in killifish.

PubMed

Whitehead, Andrew; Galvez, Fernando; Zhang, Shujun; Williams, Larissa M; Oleksiak, Marjorie F

2011-01-01

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation.

Functional Genomics of Physiological Plasticity and Local Adaptation in Killifish

PubMed Central

Galvez, Fernando; Zhang, Shujun; Williams, Larissa M.; Oleksiak, Marjorie F.

2011-01-01

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of Fundulus occupy the continuum of osmotic habitats from freshwater to marine and populations within Fundulus heteroclitus span far greater variation in pollution tolerance than across all species of fish. Here, we explore how transcriptome regulation underpins extreme physiological plasticity on osmotic shock and how genomic and transcriptomic variation is associated with locally evolved pollution tolerance. We show that F. heteroclitus quickly acclimate to extreme osmotic shock by mounting a dramatic rapid transcriptomic response including an early crisis control phase followed by a tissue remodeling phase involving many regulatory pathways. We also show that convergent evolution of locally adapted pollution tolerance involves complex patterns of gene expression and genome sequence variation, which is confounded with body-weight dependence for some genes. Similarly, exploiting the natural phenotypic variation associated with other established and emerging model organisms is likely to greatly accelerate the pace of discovery of the genomic basis of phenotypic variation. PMID:20581107

Genotypic richness predicts phenotypic variation in an endangered clonal plant

PubMed Central

Sinclair, Elizabeth A.; Poore, Alistair G.B.; Bain, Keryn F.; Vergés, Adriana

2016-01-01

Declines in genetic diversity within a species can affect the stability and functioning of populations. The conservation of genetic diversity is thus a priority, especially for threatened or endangered species. The importance of genetic variation, however, is dependent on the degree to which it translates into phenotypic variation for traits that affect individual performance and ecological processes. This is especially important for predominantly clonal species, as no single clone is likely to maximise all aspects of performance. Here we show that intraspecific genotypic diversity as measured using microsatellites is a strong predictor of phenotypic variation in morphological traits and shoot productivity of the threatened, predominantly clonal seagrass Posidonia australis, on the east coast of Australia. Biomass and surface area variation was most strongly predicted by genotypic richness, while variation in leaf chemistry (phenolics and nitrogen) was unrelated to genotypic richness. Genotypic richness did not predict tissue loss to herbivores or epiphyte load, however we did find that increased herbivore damage was positively correlated with allelic richness. Although there was no clear relationship between higher primary productivity and genotypic richness, variation in shoot productivity within a meadow was significantly greater in more genotypically diverse meadows. The proportion of phenotypic variation explained by environmental conditions varied among different genotypes, and there was generally no variation in phenotypic traits among genotypes present in the same meadows. Our results show that genotypic richness as measured through the use of presumably neutral DNA markers does covary with phenotypic variation in functionally relevant traits such as leaf morphology and shoot productivity. The remarkably long lifespan of individual Posidonia plants suggests that plasticity within genotypes has played an important role in the longevity of the species. However, the strong link between genotypic and phenotypic variation suggests that a range of genotypes is still the best case scenario for adaptation to and recovery from predicted environmental change. PMID:26925313

Maxillary and Mandibular First Premolars Showing Three-Cusp Pattern: An Unusual Presentation

PubMed Central

Kotrashetti, Vijayalakshmi; Nayak, Aarati; Patil, Viraj; Kulkarni, Mayuri; Somannavar, Pradeep

2013-01-01

Dental anatomy is the study of morphology of various teeth in human dentitions. The application of dental anatomy in clinical practice is important, and dentist should have a thorough knowledge regarding the morphology of the teeth. At times as a result of genetic variation, environmental factors, diet of an individual and race, variations in the morphology of the teeth can be observed. These variations have been extensively studied by the researcher in the field of anthropology to define a particular race. The most commonly observed changes include peg-shaped laterals, shovel-shaped incisors, and extra cusp on molar. Common variations documented with regard to maxillary and mandibular first premolars are the variation in the number of roots. But the variations with respect to crown morphology are few. We report a first documented unusual presentation of maxillary and mandibular first premolars with three-cusps pattern in a female patient. PMID:23476817

Playing by the rules? Phenotypic adaptation to temperate environments in an American marsupial

PubMed Central

Harrigan, Ryan J.; Wayne, Robert K.

2018-01-01

Phenotypic variation along environmental gradients can provide evidence suggesting local adaptation has shaped observed morphological disparities. These differences, in traits such as body and extremity size, as well as skin and coat pigmentation, may affect the overall fitness of individuals in their environments. The Virginia opossum (Didelphis virginiana) is a marsupial that shows phenotypic variation across its range, one that has recently expanded into temperate environments. It is unknown, however, whether the variation observed in the species fits adaptive ecogeographic patterns, or if phenotypic change is associated with any environmental factors. Using phenotypic measurements of over 300 museum specimens of Virginia opossum, collected throughout its distribution range, we applied regression analysis to determine if phenotypes change along a latitudinal gradient. Then, using predictors from remote-sensing databases and a random forest algorithm, we tested environmental models to find the most important variables driving the phenotypic variation. We found that despite the recent expansion into temperate environments, the phenotypic variation in the Virginia opossum follows a latitudinal gradient fitting three adaptive ecogeographic patterns codified under Bergmann’s, Allen’s and Gloger’s rules. Temperature seasonality was an important predictor of body size variation, with larger opossums occurring at high latitudes with more seasonal environments. Annual mean temperature predicted important variation in extremity size, with smaller extremities found in northern populations. Finally, we found that precipitation and temperature seasonality as well as low temperatures were strong environmental predictors of skin and coat pigmentation variation; darker opossums are distributed at low latitudes in warmer environments with higher precipitation seasonality. These results indicate that the adaptive mechanisms underlying the variation in body size, extremity size and pigmentation are related to the resource seasonality, heat conservation, and pathogen-resistance hypotheses, respectively. Our findings suggest that marsupials may be highly susceptible to environmental changes, and in the case of the Virginia opossum, the drastic phenotypic evolution in northern populations may have arisen rapidly, facilitating the colonization of seasonal and colder habitats of temperate North America. PMID:29607255

Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures

PubMed Central

Barboza, L.L.; Campos, V.M.A.; Magalhães, L.A.G.; Paoli, F.; Fonseca, A.S.

2015-01-01

Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols. PMID:26445339

Reversion of mtDNA depletion in a patient with TK2 deficiency.

PubMed

Vilà, M R; Segovia-Silvestre, T; Gámez, J; Marina, A; Naini, A B; Meseguer, A; Lombès, A; Bonilla, E; DiMauro, S; Hirano, M; Andreu, A L

2003-04-08

Mutations in the thymidine kinase 2 (TK2) gene cause a myopathic form of the mitochondrial DNA depletion syndrome (MDS). Here, the authors report the unusual clinical, biochemical, and molecular findings in a 14-year-old patient in whom pathogenic mutations were identified in the TK2 gene. This report extends the phenotypic expression of primary TK2 deficiency and suggests that factors other than TK2 may modify expression of the clinical phenotype in patients with MDS syndrome.

Heritability and genetic covariation of sensitivity to PROP, SOA, quinine HCl, and caffeine.

PubMed

Hansen, Jonathan L; Reed, Danielle R; Wright, Margaret J; Martin, Nicholas G; Breslin, Paul A S

2006-06-01

The perceived bitterness intensity for bitter solutions of propylthiouracil (PROP), sucrose octa-acetate (SOA), quinine HCl and caffeine were examined in a genetically informative sample of 392 females and 313 males (mean age of 17.8 +/- 3.1 years), including 62 monozygotic and 131 dizygotic twin pairs and 237 sib pairs. Broad-sense heritabilities were estimated at 0.72, 0.28, 0.34, and 0.30 for PROP, SOA, quinine, and caffeine, respectively, for perceived intensity measures. Modeling showed 1) a group factor which explained a large amount of the genetic variation in SOA, quinine, and caffeine (22-28% phenotypic variation), 2) a factor responsible for all the genetic variation in PROP (72% phenotypic variation), which only accounted for 1% and 2% of the phenotypic variation in SOA and caffeine, respectively, and 3) a modest specific genetic factor for quinine (12% phenotypic variation). Unique environmental influences for all four compounds were due to a single factor responsible for 7-22% of phenotypic variation. The results suggest that the perception of PROP and the perception of SOA, quinine, and caffeine are influenced by two distinct sets of genes.

Heritability and Genetic Covariation of Sensitivity to PROP, SOA, Quinine HCl, and Caffeine

PubMed Central

Hansen, Jonathan L.; Reed, Danielle R.; Wright, Margaret J.; Martin, Nicholas G.; Breslin, Paul A. S.

2006-01-01

The perceived bitterness intensity for bitter solutions of propylthiouracil (PROP), sucrose octa-acetate (SOA), quinine HCl and caffeine were examined in a genetically informative sample of 392 females and 313 males (mean age of 17.8 ± 3.1 years), including 62 MZ and 131 DZ twin pairs and 237 sib pairs. Broad-sense heritabilities were estimated at 0.72, 0.28, 0.34, and 0.30 for PROP, SOA, quinine, and caffeine, respectively, for perceived intensity measures. Modeling showed 1) a group factor which explained a large amount of the genetic variation in SOA, quinine, and caffeine (22–28% phenotypic variation), 2) a factor responsible for all the genetic variation in PROP (72% phenotypic variation), which only accounted for 1% and 2% of the phenotypic variation in SOA and caffeine, respectively, and 3) a modest specific genetic factor for quinine (12% phenotypic variation). Unique environmental influences for all four compounds were due to a single factor responsible for 7–22% of phenotypic variation. The results suggest that the perception of PROP and the perception of SOA, quinine, and caffeine are influenced by two distinct sets of genes. PMID:16527870

Effects of a Transposable Element Insertion on Alcohol Dehydrogenase Expression in Drosophila Melanogaster

PubMed Central

Dunn, R. C.; Laurie, C. C.

1995-01-01

Variation in the DNA sequence and level of alcohol dehydrogenase (Adh) gene expression in Drosophila melanogaster have been studied to determine what types of DNA polymorphisms contribute to phenotypic variation in natural populations. The Adh gene, like many others, shows a high level of variability in both DNA sequence and quantitative level of expression. A number of transposable element insertions occur in the Adh region and one of these, a copia insertion in the 5' flanking region, is associated with unusually low Adh expression. To determine whether this insertion (called RI42) causes the low expression level, the insertion was excised from the cloned RI42 Adh gene and the effect was assessed by P-element transformation. Removal of this insertion causes a threefold increase in the level of ADH, clearly showing that it contributes to the naturally occurring variation in expression at this locus. Removal of all but one LTR also causes a threefold increase, indicating that the mechanism is not a simple sequence disruption. Furthermore, this copia insertion, which is located between the two Adh promoters and their upstream enhancer sequences, has differential effects on the levels of proximal and distal transcripts. Finally, a test for the possible modifying effects of two suppressor loci, su(w(a)) and su(f), on this insertional mutation was negative, in contrast to a previous report in the literature. PMID:7498745

Evolution in health and medicine Sackler colloquium: Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease.

PubMed

Feinberg, Andrew P; Irizarry, Rafael A

2010-01-26

Neo-Darwinian evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for evolutionary adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

Rodent model choice has major impact on variability of standard preclinical readouts associated with diabetes and obesity research

PubMed Central

Jensen, Victoria S; Porsgaard, Trine; Lykkesfeldt, Jens; Hvid, Henning

2016-01-01

Laboratory rodents are available as either genetically defined inbred strains or genetically undefined outbred stocks. As outbred rodents are generally thought to display a higher level of phenotypic variation compared to inbred strains, it has been argued that experimental studies should preferentially be performed by using inbred rodents. However, very few studies with adequate sample sizes have in fact compared phenotypic variation between inbred strains and outbred stocks of rodents and moreover, these studies have not reached consistent conclusions. The aim of the present study was to compare the phenotypic variation in commonly used experimental readouts within obesity and diabetes research, for four of the most frequently used mouse strains: inbred C57BL/6 and BALB/c and outbred NMRI and CD-1 mice. The variation for all readouts was examined by calculating the coefficient of variation (CV), i.e., the relative variation, including a 95% confidence interval for the CV. We observed that for the majority of the selected readouts, inbred and outbred mice showed comparable phenotypic variation. The observed variation appeared highly influenced by strain choice and type of readout, which suggests that these collectively would serve as more predictive of the phenotypic variation than the more general classification of mice as inbred or outbred based on genetic heterogeneity. PMID:27648148

Unusual clustering of coefficients of variation in published articles from a medical biochemistry department in India.

PubMed

Hudes, Mark L; McCann, Joyce C; Ames, Bruce N

2009-03-01

A simple statistical method is described to test whether data are consistent with minimum statistical variability expected in a biological experiment. The method is applied to data presented in data tables in a subset of 84 articles among more than 200 published by 3 investigators in a small medical biochemistry department at a major university in India and to 29 "control" articles selected by key word PubMed searches. Major conclusions include: 1) unusual clustering of coefficients of variation (CVs) was observed for data from the majority of articles analyzed that were published by the 3 investigators from 2000-2007; unusual clustering was not observed for data from any of their articles examined that were published between 1992 and 1999; and 2) among a group of 29 control articles retrieved by PubMed key word, title, or title/abstract searches, unusually clustered CVs were observed in 3 articles. Two of these articles were coauthored by 1 of the 3 investigators, and 1 was from the same university but a different department. We are unable to offer a statistical or biological explanation for the unusual clustering observed.

Maintenance of phenotypic variation: repeatibility, heritability, and size-dependent processes in a wild brook trout population

Treesearch

Benjamin H. Letcher; Jason A Coombs; Keith H. Nislow

2011-01-01

Phenotypic variation in body size can result from within-cohort variation in birth dates, among-individual growth variation and size-selective processes. We explore the relative effects of these processes on the maintenance of wide observed body size variation in stream-dwelling brook trout (Salvelinus fontinalis). Based on the analyses of multiple...

Unusual ionospheric variations before the strong Auckland Islands, New Zealand earthquake of 30th September, 2007

NASA Astrophysics Data System (ADS)

Ibanga, J. I.; Akpan, A. E.; George, N. J.; Ekanem, A. M.; George, A. M.

2018-06-01

Using the IAP experiment on board, the DEMETER and TEC from GPS data, unusual ionospheric variations have been observed some days before the 7.4 magnitude New Zealand earthquake. Both sets of data recorded perturbations 10 days before the earthquake at about the same time. The total ion density per centimeter cube (cm-3), recorded a variation of 6.94 while the differential total electron content (DTEC) in total electron content unit 1016 electron per metre square gave a value of 2.93TECU. The observed anomalies were screened for false alarm using the geomagnetic indices of Kernnifzer digit (Kp) and disturbance storm time (Dst.) It was however seen that the state of the ionosphere was geomagnetically quiet during this period; hence the observed variations were seismogenic.

Network Hubs Buffer Environmental Variation in Saccharomyces cerevisiae

PubMed Central

Levy, Sasha F; Siegal, Mark L

2008-01-01

Regulatory and developmental systems produce phenotypes that are robust to environmental and genetic variation. A gene product that normally contributes to this robustness is termed a phenotypic capacitor. When a phenotypic capacitor fails, for example when challenged by a harsh environment or mutation, the system becomes less robust and thus produces greater phenotypic variation. A functional phenotypic capacitor provides a mechanism by which hidden polymorphism can accumulate, whereas its failure provides a mechanism by which evolutionary change might be promoted. The primary example to date of a phenotypic capacitor is Hsp90, a molecular chaperone that targets a large set of signal transduction proteins. In both Drosophila and Arabidopsis, compromised Hsp90 function results in pleiotropic phenotypic effects dependent on the underlying genotype. For some traits, Hsp90 also appears to buffer stochastic variation, yet the relationship between environmental and genetic buffering remains an important unresolved question. We previously used simulations of knockout mutations in transcriptional networks to predict that many gene products would act as phenotypic capacitors. To test this prediction, we use high-throughput morphological phenotyping of individual yeast cells from single-gene deletion strains to identify gene products that buffer environmental variation in Saccharomyces cerevisiae. We find more than 300 gene products that, when absent, increase morphological variation. Overrepresented among these capacitors are gene products that control chromosome organization and DNA integrity, RNA elongation, protein modification, cell cycle, and response to stimuli such as stress. Capacitors have a high number of synthetic-lethal interactions but knockouts of these genes do not tend to cause severe decreases in growth rate. Each capacitor can be classified based on whether or not it is encoded by a gene with a paralog in the genome. Capacitors with a duplicate are highly connected in the protein–protein interaction network and show considerable divergence in expression from their paralogs. In contrast, capacitors encoded by singleton genes are part of highly interconnected protein clusters whose other members also tend to affect phenotypic variability or fitness. These results suggest that buffering and release of variation is a widespread phenomenon that is caused by incomplete functional redundancy at multiple levels in the genetic architecture. PMID:18986213

Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

PubMed

Andrews, Tallulah; Meader, Stephen; Vulto-van Silfhout, Anneke; Taylor, Avigail; Steinberg, Julia; Hehir-Kwa, Jayne; Pfundt, Rolph; de Leeuw, Nicole; de Vries, Bert B A; Webber, Caleb

2015-03-01

Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51%) groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i) this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii) that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

Behavioural Phenotype in Borjeson-Forssman-Lehmann Syndrome

ERIC Educational Resources Information Center

de Winter, C. F.; van Dijk, F.; Stolker, J. J.; Hennekam, R. C. M.

2009-01-01

Background: Borjeson-Forssman-Lehmann syndrome (BFLs) is an X-linked inherited disorder characterised by unusual facial features, abnormal fat distribution and intellectual disability. As many genetically determined disorders are characterised not only by physical features but also by specific behaviour, we studied whether a specific behavioural…

Quantitative genetics of circulating Hyaluronic Acid (HA) and its correlation with hand osteoarthritis and obesity-related phenotypes in a community-based sample.

PubMed

Prakash, Jai; Gabdulina, Gulzhan; Trofimov, Svetlana; Livshits, Gregory

2017-09-01

One of the potential molecular biomarkers of osteoarthritis (OA) is hyaluronic acid (HA). HA levels may be related to the severity and progression of OA. However, little is known about the contribution of major risk factors for osteoarthritis, e.g. obesity-related phenotypes and genetics to HA variation. To clarify the quantitative effect of these factors on HA. An ethnically homogeneous sample of 911 apparently healthy European-derived individuals, assessed for radiographic hand osteoarthritis (RHOA), HA, leptin, adiponectin, and several anthropometrical measures of obesity-related phenotypes was studied. Model-based quantitative genetic analysis was used to reveal genetic and shared environmental factors affecting the variation of the study's phenotypes. The HA levels significantly correlated with the age, RHOA, adiponectin, obesity-related phenotypes, and the waist-to-hip ratio. The putative genetic effects contributed significantly to the variation of HA (66.2 ± 9.3%) and they were also significant factors in the variations of all the other studied phenotypes, with the heritability estimate ranging between 0.122 ± 4.4% (WHR) and 45.7 ± 2.2% (joint space narrowing). This is the first study to report heritability estimates of HA variation and its correlation with obesity-related phenotypes, ADP and RHOA. However, the nature of genetic effects on HA and its correlation with other study phenotypes require further clarification.

Beyond Punnett Squares: Student Word Association and Explanations of Phenotypic Variation through an Integrative Quantitative Genetics Unit Investigating Anthocyanin Inheritance and Expression in "Brassica rapa" Fast Plants

ERIC Educational Resources Information Center

Batzli, Janet M.; Smith, Amber R.; Williams, Paul H.; McGee, Seth A.; Dosa, Katalin; Pfammatter, Jesse

2014-01-01

Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question "What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev)," we developed a 4-wk unit for an inquiry-based laboratory…

Ocular manifestations of branchio-oculo-facial syndrome: Report of a novel mutation and review of the literature

PubMed Central

Al-Dosari, M.S.; Almazyad, M.; Al-Ebdi, L.; Mohamed, J.Y.; Al-Dahmash, Saad; Al-Dhibi, Hassan; Al-Kahtani, Eman; Al-Turkmani, Shahira; Hall, B.D.

2010-01-01

Purpose To report unusual ocular manifestations of branchio-oculo-facial syndrome (BOFS) caused by a novel mutation in activating enhancer binding protein 2 alpha (TFAP2A). Methods Full ophthalmological evaluation and direct sequencing of TFAP2A. Results A 10-year-old girl with unusual ocular manifestations of BOFS such as elliptical shaped microcornea and a novel de novo TFAP2A mutation was identified. Conclusions This report expands the ocular phenotypic spectrum of BOFS and adds to the small number of reported TFAP2A mutations. PMID:20461149

Phenotypes in phylogeography: Species’ traits, environmental variation, and vertebrate diversification

PubMed Central

Bell, Rayna C.; Mason, Nicholas A.

2016-01-01

Almost 30 y ago, the field of intraspecific phylogeography laid the foundation for spatially explicit and genealogically informed studies of population divergence. With new methods and markers, the focus in phylogeography shifted to previously unrecognized geographic genetic variation, thus reducing the attention paid to phenotypic variation in those same diverging lineages. Although phenotypic differences among lineages once provided the main data for studies of evolutionary change, the mechanisms shaping phenotypic differentiation and their integration with intraspecific genetic structure have been underexplored in phylogeographic studies. However, phenotypes are targets of selection and play important roles in species performance, recognition, and diversification. Here, we focus on three questions. First, how can phenotypes elucidate mechanisms underlying concordant or idiosyncratic responses of vertebrate species evolving in shared landscapes? Second, what mechanisms underlie the concordance or discordance of phenotypic and phylogeographic differentiation? Third, how can phylogeography contribute to our understanding of functional phenotypic evolution? We demonstrate that the integration of phenotypic data extends the reach of phylogeography to explain the origin and maintenance of biodiversity. Finally, we stress the importance of natural history collections as sources of high-quality phenotypic data that span temporal and spatial axes. PMID:27432983

A survey of copy number variation in the porcine genome detected from whole-genome sequence

USDA-ARS?s Scientific Manuscript database

An important challenge to post-genomic biology is relating observed phenotypic variation to the underlying genotypic variation. Genome-wide association studies (GWAS) have made thousands of connections between single nucleotide polymorphisms (SNPs) and phenotypes, implicating regions of the genome t...

Naturally occurring variation in tadpole morphology and performance linked to predator regime

Treesearch

James B. Johnson; Daniel Saenz; Cory K. Adams; Toby J. Hibbitts

2015-01-01

Divergent natural selection drives a considerable amount of the phenotypic and genetic variation observed in natural populations. For example, variation in the predator community can generate conflicting selection on behavioral, life-history, morphological, and performance traits. Differences in predator regime can subsequently increase phenotypic and genetic...

A comparison of blood nitric oxide metabolites and hemoglobin functional properties among diving mammals.

PubMed

Fago, Angela; Parraga, Daniel Garcia; Petersen, Elin E; Kristensen, Niels; Giouri, Lea; Jensen, Frank B

2017-03-01

The ability of marine mammals to hunt prey at depth is known to rely on enhanced oxygen stores and on selective distribution of blood flow, but the molecular mechanisms regulating blood flow and oxygen transport remain unresolved. To investigate the molecular mechanisms that may be important in regulating blood flow, we measured concentration of nitrite and S-nitrosothiols (SNO), two metabolites of the vasodilator nitric oxide (NO), in the blood of 5 species of marine mammals differing in their dive duration: bottlenose dolphin, South American sea lion, harbor seal, walrus and beluga whale. We also examined oxygen affinity, sensitivity to 2,3-diphosphoglycerate (DPG) and nitrite reductase activity of the hemoglobin (Hb) to search for possible adaptive variations in these functional properties. We found levels of plasma and red blood cells nitrite similar to those reported for terrestrial mammals, but unusually high concentrations of red blood cell SNO in bottlenose dolphin, walrus and beluga whale, suggesting enhanced SNO-dependent signaling in these species. Purified Hbs showed similar functional properties in terms of oxygen affinity and sensitivity to DPG, indicating that reported large variations in blood oxygen affinity among diving mammals likely derive from phenotypic variations in red blood cell DPG levels. The nitrite reductase activities of the Hbs were overall slightly higher than that of human Hb, with the Hb of beluga whale, capable of longest dives, having the highest activity. Taken together, these results underscore adaptive variations in circulatory NO metabolism in diving mammals but not in the oxygenation properties of the Hb. Copyright © 2016 Elsevier Inc. All rights reserved.

Adaptive potential of genomic structural variation in human and mammalian evolution.

PubMed

Radke, David W; Lee, Charles

2015-09-01

Because phenotypic innovations must be genetically heritable for biological evolution to proceed, it is natural to consider new mutation events as well as standing genetic variation as sources for their birth. Previous research has identified a number of single-nucleotide polymorphisms that underlie a subset of adaptive traits in organisms. However, another well-known class of variation, genomic structural variation, could have even greater potential to produce adaptive phenotypes, due to the variety of possible types of alterations (deletions, insertions, duplications, among others) at different genomic positions and with variable lengths. It is from these dramatic genomic alterations, and selection on their phenotypic consequences, that adaptations leading to biological diversification could be derived. In this review, using studies in humans and other mammals, we highlight examples of how phenotypic variation from structural variants might become adaptive in populations and potentially enable biological diversification. Phenotypic change arising from structural variants will be described according to their immediate effect on organismal metabolic processes, immunological response and physical features. Study of population dynamics of segregating structural variation can therefore provide a window into understanding current and historical biological diversification. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Epistasis and Pleiotropy Affect the Modularity of the Genotype-Phenotype Map of Cross-Resistance in HIV-1.

PubMed

Polster, Robert; Petropoulos, Christos J; Bonhoeffer, Sebastian; Guillaume, Frédéric

2016-12-01

The genotype-phenotype (GP) map is a central concept in evolutionary biology as it describes the mapping of molecular genetic variation onto phenotypic trait variation. Our understanding of that mapping remains partial, especially when trying to link functional clustering of pleiotropic gene effects with patterns of phenotypic trait co-variation. Only on rare occasions have studies been able to fully explore that link and tend to show poor correspondence between modular structures within the GP map and among phenotypes. By dissecting the structure of the GP map of the replicative capacity of HIV-1 in 15 drug environments, we provide a detailed view of that mapping from mutational pleiotropic variation to phenotypic co-variation, including epistatic effects of a set of amino-acid substitutions in the reverse transcriptase and protease genes. We show that epistasis increases the pleiotropic degree of single mutations and provides modularity to the GP map of drug resistance in HIV-1. Moreover, modules of epistatic pleiotropic effects within the GP map match the phenotypic modules of correlated replicative capacity among drug classes. Epistasis thus increases the evolvability of cross-resistance in HIV by providing more drug- and class-specific pleiotropic profiles to the main effects of the mutations. We discuss the implications for the evolution of cross-resistance in HIV. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Female guppies agree to differ: phenotypic and genetic variation in mate-choice behavior and the consequences for sexual selection.

PubMed

Brooks, R; Endler, J A

2001-08-01

Variation among females in mate choice may influence evolution by sexual selection. The genetic basis of this variation is of interest because the elaboration of mating preferences requires additive genetic variation in these traits. Here we measure the repeatability and heritability of two components of female choosiness (responsiveness and discrimination) and of female preference functions for the multiple ornaments borne by male guppies (Poecilia reticulata). We show that there is significant repeatable variation in both components of choosiness and in some preference functions but not in others. There appear to be several male ornaments that females find uniformly attractive and others for which females differ in preference. One consequence is that there is no universally attractive male phenotype. Only responsiveness shows significant additive genetic variation. Variation in responsiveness appears to mask variation in discrimination and some preference functions and may be the most biologically relevant source of phenotypic and genetic variation in mate-choice behavior. To test the potential evolutionary importance of the phenotypic variation in mate choice that we report, we estimated the opportunity for and the intensity of sexual selection under models of mate choice that excluded and that incorporated individual female variation. We then compared these estimates with estimates based on measured mating success. Incorporating individual variation in mate choice generally did not predict the outcome of sexual selection any better than models that ignored such variation.

Identification of two novel mutations in the SLC45A2 gene in a Hungarian pedigree affected by unusual OCA type 4.

PubMed

Tóth, Lola; Fábos, Beáta; Farkas, Katalin; Sulák, Adrienn; Tripolszki, Kornélia; Széll, Márta; Nagy, Nikoletta

2017-03-15

Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities. OCA type IV (OCA4, OMIM 606574) develops due to homozygous or compound heterozygous mutations in the solute carrier family 45, member 2 (SLC45A2) gene. This gene encodes a membrane-associated transport protein, which regulates tyrosinase activity and, thus, melanin content by changing melanosomal pH and disrupting the incorporation of copper into tyrosinase. Here we report two Hungarian siblings affected by an unusual OCA4 phenotype. After genomic DNA was isolated from peripheral blood of the patients, the coding regions of the SLC45A2 gene were sequenced. In silico tools were applied to identify the functional impact of the newly detected mutations. Direct sequencing of the SLC45A2 gene revealed two novel, heterozygous mutations, one missense (c.1226G > A, p.Gly409Asp) and one nonsense (c.1459C > T, p.Gln437*), which were present in both patients, suggesting the mutations were compound heterozygous. In silico tools suggest that these variations are disease causing mutations. The newly identified mutations may affect the transmembrane domains of the protein, and could impair transport function, resulting in decreases in both melanosomal pH and tyrosinase activity. Our study provides expands on the mutation spectrum of the SLC45A2 gene and the genetic background of OCA4.

Interactions among Trypanosoma brucei RAD51 paralogues in DNA repair and antigenic variation

PubMed Central

Dobson, Rachel; Stockdale, Christopher; Lapsley, Craig; Wilkes, Jonathan; McCulloch, Richard

2011-01-01

Homologous recombination in Trypanosoma brucei is used for moving variant surface glycoprotein (VSG) genes into expression sites during immune evasion by antigenic variation. A major route for such VSG switching is gene conversion reactions in which RAD51, a universally conserved recombinase, catalyses homology-directed strand exchange. In any eukaryote, RAD51-directed strand exchange in vivo is mediated by further factors, including RAD51-related proteins termed Rad51 paralogues. These appear to be ubiquitously conserved, although their detailed roles in recombination remain unclear. In T. brucei, four putative RAD51 paralogue genes have been identified by sequence homology. Here we show that all four RAD51 paralogues act in DNA repair, recombination and RAD51 subnuclear dynamics, though not equivalently, while mutation of only one RAD51 paralogue gene significantly impedes VSG switching. We also show that the T. brucei RAD51 paralogues interact, and that the complexes they form may explain the distinct phenotypes of the mutants as well as observed expression interdependency. Finally, we document the Rad51 paralogues that are encoded by a wide range of protists, demonstrating that the Rad51 paralogue repertoire in T. brucei is unusually large among microbial eukaryotes and that one member of the protein family corresponds with a key, conserved eukaryotic Rad51 paralogue. PMID:21615552

The causes and ecological correlates of head scale asymmetry and fragmentation in a tropical snake.

PubMed

Brown, Gregory P; Madsen, Thomas; Dubey, Sylvain; Shine, Rick

2017-09-12

The challenge of identifying the proximate causes and ecological consequences of phenotypic variation can be facilitated by studying traits that are usually but not always bilaterally symmetrical; deviations from symmetry likely reflect disrupted embryogenesis. Based on a 19-year mark-recapture study of >1300 slatey-grey snakes (Stegonotus cucullatus) in tropical Australia, and incubation of >700 eggs, we document developmental and ecological correlates of two morphological traits: asymmetry and fragmentation of head scales. Asymmetry was directional (more scales on the left side) and was higher in individuals with lower heterozygosity, but was not heritable. In contrast, fragmentation was heritable and was higher in females than males. Both scale asymmetry and fragmentation were increased by rapid embryogenesis but were not affected by hydric conditions during incubation. Snakes with asymmetry and fragmentation exhibited slightly lower survival and increased (sex-specific) movements, and females with more scale fragmentation produced smaller eggs. Counterintuitively, snakes with more asymmetry had higher growth rates (possibly reflecting trade-offs with other traits), and snakes with more fragmentation had fewer parasites (possibly due to lower feeding rates). Our data paint an unusually detailed picture of the complex genetic and environmental factors that, by disrupting early embryonic development, generate variations in morphology that have detectable correlations with ecological performance.

The Convergent Evolution of Blue Iris Pigmentation in Primates Took Distinct Molecular Paths

PubMed Central

Meyer, Wynn K; Zhang, Sidi; Hayakawa, Sachiko; Imai, Hiroo; Przeworski, Molly

2013-01-01

How many distinct molecular paths lead to the same phenotype? One approach to this question has been to examine the genetic basis of convergent traits, which likely evolved repeatedly under a shared selective pressure. We investigated the convergent phenotype of blue iris pigmentation, which has arisen independently in four primate lineages: humans, blue-eyed black lemurs, Japanese macaques, and spider monkeys. Characterizing the phenotype across these species, we found that the variation within the blue-eyed subsets of each species occupies strongly overlapping regions of CIE L*a*b* color space. Yet whereas Japanese macaques and humans display continuous variation, the phenotypes of blue-eyed black lemurs and their sister species (whose irises are brown) occupy more clustered subspaces. Variation in an enhancer of OCA2 is primarily responsible for the phenotypic difference between humans with blue and brown irises. In the orthologous region, we found no variant that distinguishes the two lemur species or associates with quantitative phenotypic variation in Japanese macaques. Given the high similarity between the blue iris phenotypes in these species and that in humans, this finding implies that evolution has used different molecular paths to reach the same end. Am J Phys Anthropol 151:398–407, 2013.© 2013 Wiley Periodicals, Inc. PMID:23640739

Phenotypic variation among Phytophthora ramorum isolates from California and Oregon

Treesearch

Daniel Hüberli; Tamar Harnik; Matthew Meshriy; Lori Miles; Matteo Garbelotto

2006-01-01

To manage and control Phytophthora ramorum successfully, it is important to know the amount of phenotypic variation within a given pathogen population. Because the pathogen has only recently been described, there are few studies on morphological and pathological variation of isolates from the United States. One study has compared growth rate on agar...

Selection and phenotypic characterization of a core collection of Brachypodium distachyon inbred lines.

PubMed

Tyler, Ludmila; Fangel, Jonatan U; Fagerström, Alexandra Dotson; Steinwand, Michael A; Raab, Theodore K; Willats, William Gt; Vogel, John P

2014-01-14

The model grass Brachypodium distachyon is increasingly used to study various aspects of grass biology. A large and genotypically diverse collection of B. distachyon germplasm has been assembled by the research community. The natural variation in this collection can serve as a powerful experimental tool for many areas of inquiry, including investigating biomass traits. We surveyed the phenotypic diversity in a large collection of inbred lines and then selected a core collection of lines for more detailed analysis with an emphasis on traits relevant to the use of grasses as biofuel and grain crops. Phenotypic characters examined included plant height, growth habit, stem density, flowering time, and seed weight. We also surveyed differences in cell wall composition using near infrared spectroscopy (NIR) and comprehensive microarray polymer profiling (CoMPP). In all cases, we observed extensive natural variation including a two-fold variation in stem density, four-fold variation in ferulic acid bound to hemicellulose, and 1.7-fold variation in seed mass. These characterizations can provide the criteria for selecting diverse lines for future investigations of the genetic basis of the observed phenotypic variation.

Genome-wide DNA methylation alterations of Alternanthera philoxeroides in natural and manipulated habitats: implications for epigenetic regulation of rapid responses to environmental fluctuation and phenotypic variation.

PubMed

Gao, Lexuan; Geng, Yupeng; Li, Bo; Chen, Jiakuan; Yang, Ji

2010-11-01

Alternanthera philoxeroides (alligator weed) is an invasive weed that can colonize both aquatic and terrestrial habitats. Individuals growing in different habitats exhibit extensive phenotypic variation but little genetic differentiation in its introduced range. The mechanisms underpinning the wide range of phenotypic variation and rapid adaptation to novel and changing environments remain uncharacterized. In this study, we examined the epigenetic variation and its correlation with phenotypic variation in plants exposed to natural and manipulated environmental variability. Genome-wide methylation profiling using methylation-sensitive amplified fragment length polymorphism (MSAP) revealed considerable DNA methylation polymorphisms within and between natural populations. Plants of different source populations not only underwent significant morphological changes in common garden environments, but also underwent a genome-wide epigenetic reprogramming in response to different treatments. Methylation alterations associated with response to different water availability were detected in 78.2% (169/216) of common garden induced polymorphic sites, demonstrating the environmental sensitivity and flexibility of the epigenetic regulatory system. These data provide evidence of the correlation between epigenetic reprogramming and the reversible phenotypic response of alligator weed to particular environmental factors. © 2010 Blackwell Publishing Ltd.

Individuals in food webs: the relationships between trophic position, omnivory and among-individual diet variation.

PubMed

Svanbäck, Richard; Quevedo, Mario; Olsson, Jens; Eklöv, Peter

2015-05-01

Among-individual diet variation is common in natural populations and may occur at any trophic level within a food web. Yet, little is known about its variation among trophic levels and how such variation could affect phenotypic divergence within populations. In this study we investigate the relationships between trophic position (the population's range and average) and among-individual diet variation. We test for diet variation among individuals and across size classes of Eurasian perch (Perca fluviatilis), a widespread predatory freshwater fish that undergoes ontogenetic niche shifts. Second, we investigate among-individual diet variation within fish and invertebrate populations in two different lake communities using stable isotopes. Third, we test potential evolutionary implications of population trophic position by assessing the relationship between the proportion of piscivorous perch (populations of higher trophic position) and the degree of phenotypic divergence between littoral and pelagic perch sub-populations. We show that among-individual diet variation is highest at intermediate trophic positions, and that this high degree of among-individual variation likely causes an increase in the range of trophic positions among individuals. We also found that phenotypic divergence was negatively related to trophic position in a population. This study thus shows that trophic position is related to and may be important for among-individual diet variation as well as to phenotypic divergence within populations.

Spatial and temporal drivers of phenotypic diversity in polymorphic snakes.

PubMed

Cox, Christian L; Davis Rabosky, Alison R

2013-08-01

Color polymorphism in natural populations presents an ideal opportunity to study the evolutionary drivers of phenotypic diversity. Systems with striking spatial, temporal, and qualitative variation in color can be leveraged to study the mechanisms promoting the distribution of different types of variation in nature. We used the highly polymorphic ground snake (Sonora semiannulata), a putative coral snake mimic with both cryptic and conspicuous morphs, to compare patterns of neutral genetic variation and variation over space and time in color polymorphism to investigate the mechanistic drivers of phenotypic variation across scales. We found that strong selection promotes color polymorphism across spatial and temporal scales, with morph frequencies differing markedly between juvenile and adult age classes within a single population, oscillating over time within multiple populations, and varying drastically over the landscape despite minimal population genetic structure. However, we found no evidence that conspicuousness of morphs was related to which color pattern was favored by selection or to any geographic factors, including sympatry with coral snakes. We suggest that complex patterns of phenotypic variation in polymorphic systems may be a fundamental outcome of the conspicuousness of morphs and that explicit tests of temporal and geographic variation are critical to the interpretation of conspicuousness and mimicry.

Clinical Significance of an Unusual Variation

PubMed Central

Murugan, M. Senthil; Sudha, R.; Bhargavan, Rajesh

2016-01-01

The infrahyoid muscles are involved in vocalisation and swallowing; among these, the sternothyroid muscle is derived from the common primitive sheet. The improper differentiation of this muscle may therefore result in morphological variations. We report an unusual variation found during the dissection of a 65-year-old male cadaver at the Sri Manakula Vinayagar Medical College, Madagadipet, Pondicherry, India, in 2015. An anomalous belly of the right sternothyroid muscle was observed between the internal jugular (IJ) vein and the internal carotid artery with an additional insertion into the tympanic plate and petrous part of the temporal bone and the presence of a levator glandulae thyroideae muscle. The anomalous muscle may compress the IJ vein if it is related to the neurovascular structures of neck; hence, knowledge of variations of the infrahyoid muscles can aid in the evaluation of IJ vein compression among patients with idiopathic symptoms resulting from venous congestion. PMID:28003898

Morphological and Genetic Analysis of Four Color Morphs of Bean Leaf Beetle.

PubMed

Tiroesele, Bamphitlhi; Skoda, Steven R; Hunt, Thomas E; Lee, Donald J; Ullah, Muhammad Irfan; Molina-Ochoa, Jaime; Foster, John E

2018-03-01

Bean leaf beetle (BLB), Cerotoma trifurcata (Forster; Coleoptera: Chrysomelidae), exhibits considerable color variation but little is known about the underlying genetic structure and gene flow among color phenotypes. Genetic and morphological variation among four color phenotypes-green with spots (G+S), green without spots (G-S), red with spots (R+S) and red without spots (R-S)-were analyzed using amplified fragment length polymorphisms (AFLP) and morphometrics, respectively. AFLP generated 175 markers that showed ≥80% polymorphism. Analysis of molecular variance (AMOVA) indicated that genetic variation was greatest within phenotypes (82.6-84.0%); gene flow among the four phenotypes was relatively high (Nm = 3.82). The dendrogram and STRUCTURE analysis indicated some population divergence of G-S from the other phenotypes. Morphological parameters were similar among phenotypes except that R+S showed significant differences in weight and body-length. Canonical variables 1 and 2, based on average morphometric characters, accounted for 98% of the total variation; some divergence was indicated between G+S and R+S from each other and from the G-S/R-S BLB color morphs. The pattern of genetic variation indicated potential divergence of G-S and G+S from each other and from R-S and R+S. Although these results indicate that the four different color morphs are not genetically or reproductively isolated, there is some genetic differentiation/structure and morphological dissimilarity suggesting weak/incomplete isolation.

The genotype-phenotype map of an evolving digital organism.

PubMed

Fortuna, Miguel A; Zaman, Luis; Ofria, Charles; Wagner, Andreas

2017-02-01

To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable.

The genotype-phenotype map of an evolving digital organism

PubMed Central

Zaman, Luis; Wagner, Andreas

2017-01-01

To understand how evolving systems bring forth novel and useful phenotypes, it is essential to understand the relationship between genotypic and phenotypic change. Artificial evolving systems can help us understand whether the genotype-phenotype maps of natural evolving systems are highly unusual, and it may help create evolvable artificial systems. Here we characterize the genotype-phenotype map of digital organisms in Avida, a platform for digital evolution. We consider digital organisms from a vast space of 10141 genotypes (instruction sequences), which can form 512 different phenotypes. These phenotypes are distinguished by different Boolean logic functions they can compute, as well as by the complexity of these functions. We observe several properties with parallels in natural systems, such as connected genotype networks and asymmetric phenotypic transitions. The likely common cause is robustness to genotypic change. We describe an intriguing tension between phenotypic complexity and evolvability that may have implications for biological evolution. On the one hand, genotypic change is more likely to yield novel phenotypes in more complex organisms. On the other hand, the total number of novel phenotypes reachable through genotypic change is highest for organisms with simple phenotypes. Artificial evolving systems can help us study aspects of biological evolvability that are not accessible in vastly more complex natural systems. They can also help identify properties, such as robustness, that are required for both human-designed artificial systems and synthetic biological systems to be evolvable. PMID:28241039

Testing Peer Effects among College Students: Evidence from an Unusual Admission Policy Change in China

ERIC Educational Resources Information Center

Lu, Fangwen

2014-01-01

This paper studies a natural experiment due to an unusual change in the college admission policy at a Chinese university, which brought a large number of low-score students into several academic departments in the university. Exploiting large variations in peer characteristics and strong interactions among peer groups, the analysis finds that…

NAT2, meat consumption and colorectal cancer incidence: an ecological study among 27 countries.

PubMed

Ognjanovic, Simona; Yamamoto, Jennifer; Maskarinec, Gertraud; Le Marchand, Loïc

2006-11-01

The polymorphic gene NAT2 is a major determinant of N-acetyltransferase activity and, thus, may be responsible for differences in one's ability to bioactivate heterocyclic amines, a class of procarcinogens in cooked meat. An unusually marked geographic variation in enzyme activity has been described for NAT2. The present study re-examines the international direct correlation reported for meat intake and colorectal cancer (CRC) incidence, and evaluates the potential modifying effects of NAT2 phenotype and other lifestyle factors on this correlation. Country-specific CRC incidence data, per capita consumption data for meat and other dietary factors, prevalence of the rapid/intermediate NAT2 phenotype, and prevalence of smoking for 27 countries were used. Multiple linear regression models were fit and partial correlation coefficients (PCCs) were computed for men and women separately. Inclusion of the rapid/intermediate NAT2 phenotype with meat consumption improved the fit of the regression model for CRC incidence in both sexes (males-R (2) = 0.78, compared to 0.70 for meat alone; p for difference in model fit-0.009; females-R (2) = 0.76 compared to 0.69 for meat alone; p = 0.02). Vegetable consumption (inversely and in both sexes) and fish consumption (directly and in men only) were also weakly correlated with CRC, whereas smoking prevalence and alcohol consumption had no effects on the models. The PCC between NAT2 and CRC incidence was 0.46 in males and 0.48 in females when meat consumption was included in the model, compared to 0.14 and 0.15, respectively, when it was not. These data suggest that, in combination with meat intake, some proportion of the international variability in CRC incidence may be attributable to genetic susceptibility to heterocyclic amines, as determined by NAT2 genotype.

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

PubMed

Fishman, G A; Stone, E M; Grover, S; Derlacki, D J; Haines, H L; Hockey, R R

1999-04-01

To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

Adrenal insufficiency in a child with MELAS syndrome.

PubMed

Afroze, Bushra; Amjad, Nida; Ibrahim, Shahnaz H; Humayun, Khadija Nuzhat; Yakob, Yusnita

2014-11-01

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) are established subgroups of mitochondrial encephalomyopathy. m.3243A>G a common point mutation is detected in tRNA in majority of patients with MELAS phenotype whereas m.8344A>G point mutation in tRNA is observed, in MERRF phenotype. Adrenal insufficiency has not been reported in mitochondrial disease, except in Kearns-Sayre Syndrome (KSS), which is a mitochondrial deletion syndrome. We report an unusual presentation in a five year old boy who presented with clinical phenotype of MELAS and was found to have m.8344A>G mutation in tRNA. Addison disease was identified due to hyperpigmentation of lips and gums present from early childhood. This is the first report describing adrenal insufficiency in a child with MELAS phenotype. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Endochondral gigantism: a newly recognized skeletal dysplasia with pre- and postnatal overgrowth and endocrine abnormalities.

PubMed

Schmidt, Heinrich; Kammer, Birgit; Grasser, Monika; Enders, Angelika; Rost, Imma; Kiess, Wieland

2007-08-15

We report on a 3-year-old male, born at 34 weeks of gestation, with marked pre- and postnatal overgrowth, birth weight of 6,600 g, length of 61 cm, and head circumference of 38.5 cm. A striking phenotype was recorded at birth, which became more evident during the follow-up period. He had macrobrachycephaly, facial abnormalities, small thoracic cage, long trunk, deformed spine, rhizomelia, large hands and feets, absent subcutaneous fat, small umbilical hernia, inguinal hernias, and large joints with mild contractures. Hypoglycemic episodes and obstructive apnea complicated the neonatal period. During follow-up, overgrowth continued with a height of 146 cm (+11.65 SDS) and a weight of 39 kg (BMI 18.3 kg/m(2)) at 3.5 years. Endocrinological work-up disclosed extremely low levels of growth hormone, insulin-like growth factors, and insulin. What makes our patient unique is the association of marked prenatal overgrowth; unusual phenotype; skeletal dysplasia caused by accelerated endochondral ossification resulting in cartilage hyperplasia of the skull base and spine, and postnatal gigantism; and complete absence of subcutaneous fat. Other well-known overgrowth syndromes were excluded. We hypothesize that autocrine/paracrine growth factors could be the cause of excessive endochondral ossification. Alternately, activating mutations in transcription factors involved in both growth and endocrine/metabolic homeostasis could be responsible for this unusual phenotype. (c) 2007 Wiley-Liss, Inc.

Hsp90 and environmental stress transform the adaptive value of natural genetic variation.

PubMed

Jarosz, Daniel F; Lindquist, Susan

2010-12-24

How can species remain unaltered for long periods yet also undergo rapid diversification? By linking genetic variation to phenotypic variation via environmental stress, the Hsp90 protein-folding reservoir might promote both stasis and change. However, the nature and adaptive value of Hsp90-contingent traits remain uncertain. In ecologically and genetically diverse yeasts, we find such traits to be both common and frequently adaptive. Most are based on preexisting variation, with causative polymorphisms occurring in coding and regulatory sequences alike. A common temperature stress alters phenotypes similarly. Both selective inhibition of Hsp90 and temperature stress increase correlations between genotype and phenotype. This system broadly determines the adaptive value of standing genetic variation and, in so doing, has influenced the evolution of current genomes.

Brief Report: Autism-Like Traits Are Associated with Enhanced Ability to Disembed Visual Forms

ERIC Educational Resources Information Center

Sabatino DiCriscio, Antoinette; Troiani, Vanessa

2017-01-01

Atypical visual perceptual skills are thought to underlie unusual visual attention in autism spectrum disorders. We assessed whether individual differences in visual processing skills scaled with quantitative traits associated with the broader autism phenotype (BAP). Visual perception was assessed using the Figure-ground subtest of the Test of…

A quantitative analysis of phenotypic variations of Metrosideros polymorpha within and across populations along environmental gradients on Mauna Loa, Hawaii.

PubMed

Tsujii, Yuki; Onoda, Yusuke; Izuno, Ayako; Isagi, Yuji; Kitayama, Kanehiro

2016-04-01

Metrosideros polymorpha, a dominant tree species in the Hawaiian Islands, shows an extreme phenotypic polymorphism both across gradients of climatic/edaphic conditions and within populations, making it a potentially useful model species for evolutionary study. In order to understand how the phenotypic diversity is maintained within populations as well as across populations, we examined the diversities of several leaf and stem functional traits across five elevations and two soil substrates on the volcanic mountain of Mauna Loa, on the island of Hawaii. Leaf dry mass per area (LMA), a key leaf functional trait, was particularly focused on and analyzed in relation to its underlying components-namely, tissue LMA and trichome LMA (LMA = tissue LMA + trichome LMA). Across populations, tissue LMA increased linearly with elevation while trichome LMA showed unimodal patterns with elevation, which were better correlated with temperature and rainfall, respectively. Substantial phenotypic variations were also found within populations. Interestingly, the variations of tissue LMA were often negatively correlated to trichome LMA within populations, which contrasts with the cross-populations pattern, where a strong positive correlation between tissue LMA and trichome LMA was found. This suggests that phenotypic variations within populations were substantially influenced by local ecological processes. Soil depth (an indicator of local water availability) and tree size (an indicator of colonized timing) modestly explained the within-population variations, implying other local environmental factors and/or random processes are also important in local phenotypic diversity. This study provides an insight about how phenotypic diversity of plant species is maintained from local to landscape levels.

Proanthocyanidin profile of cowpea (Vigna unguiculata) reveals catechin-O-glucoside as the dominant compound.

PubMed

Ojwang, Leonnard O; Yang, Liyi; Dykes, Linda; Awika, Joseph

2013-08-15

Proanthocyanidin (PA) profile and content can have important nutritional and health implications on plant foods. Six diverse cowpea phenotypes (black, red, green, white, light-brown and golden-brown) were investigated for PA composition using normal-phase HPLC and reversed-phase UPLC-TQD-MS. Catechin and (epi)afzelechin were the major flavan-3-ol units. Unusual composition was observed in all cowpea phenotypes with significant degrees of glycosylation in the monomers and dimers. The PA content of cowpea (dry basis) ranged between 2.2 and 6.3 mg/g. Monomeric flavan-3-ols were the largest group of PA (36-69%) in cowpea, with catechin-7-O-glucoside accounting for most (about 88%) of the monomers. The oligomers with degree of polymerization (DP) 2-4 ranged from 0.41 to 1.3 mg/g (15-20%), whereas DP>10 polymers accounted for only 13.5% of PA. Future studies that highlight the impact of the unusual cowpea PA profile on nutritional and bioactive properties of this important legume are warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ullrich-Turner phenotype with unusual manifestation in a patient with mosaicism 45,X/47,XX,+18

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franceschini, P.; Guala, A.; Camerano, P.

1996-03-01

We report on a girl with Ullrich-Turner phenotype and 45,X/47,XX,+18 chromosomal mosaicism. Only two other patients with similar mosaicism have been reported, both girls with XY sex chromosome constitution. The face of the patient was highly asymmetric, the right side being almost normal, the left showing a typical Ullrich-Turner syndrome appearance. This clinical impression was strengthened by photographic doubling of both hemifaces. The patient had normal intelligence and did not show any stigmata of trisomy 18. 13 refs., 2 figs., 1 tab.

Hemiclonal analysis of interacting phenotypes in male and female Drosophila melanogaster

PubMed Central

2014-01-01

Background Identifying the sources of variation in mating interactions between males and females is important because this variation influences the strength and/or the direction of sexual selection that populations experience. While the origins and effects of variation in male attractiveness and ornamentation have received much scrutiny, the causes and consequences of intraspecific variation in females have been relatively overlooked. We used cytogenetic cloning techniques developed for Drosophila melanogaster to create “hemiclonal” males and females with whom we directly observed sexual interaction between individuals of different known genetic backgrounds and measured subsequent reproductive outcomes. Using this approach, we were able to quantify the genetic contribution of each mate to the observed phenotypic variation in biologically important traits including mating speed, copulation duration, and subsequent offspring production, as well as measure the magnitude and direction of intersexual genetic correlation between female choosiness and male attractiveness. Results We found significant additive genetic variation contributing to mating speed that can be attributed to male genetic identity, female genetic identity, but not their interaction. Furthermore we found that phenotypic variation in copulation duration had a significant male-associated genetic component. Female genetic identity and the interaction between male and female genetic identity accounted for a substantial amount of the observed phenotypic variation in egg size. Although previous research predicts a trade-off between egg size and fecundity, this was not evident in our results. We found a strong negative genetic correlation between female choosiness and male attractiveness, a result that suggests a potentially important role for sexually antagonistic alleles in sexual selection processes in our population. Conclusion These results further our understanding of sexual selection because they identify that genetic identity plays a significant role in phenotypic variation in female behaviour and fecundity. This variation may be potentially due to ongoing sexual conflict found between the sexes for interacting phenotypes. Our unexpected observation of a negative correlation between female choosiness and male attractiveness highlights the need for more explicit theoretical models of genetic covariance to investigate the coevolution of female choosiness and male attractiveness. PMID:24884361

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

PubMed Central

Weaver, Cole A.; Miller, Steven F.; da Fontoura, Clarissa S. G.; Wehby, George L.; Amendt, Brad A.; Holton, Nathan E.; Allareddy, Veeratrishul; Southard, Thomas E.; Moreno Uribe, Lina M.

2017-01-01

Introduction Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes, DUSP6, ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Methods Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Results Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P < 0.05) were identified with PITX2, SNAI3, 11q22.2-q22.3, 4p16.1, ISL1, and FGF8. Principal component analysis for asymmetric variations identified 4 components that explained 51% of the total variations and captured left-to-right discrepancies resulting in midline deviations, unilateral crossbites, and ectopic eruptions. Suggestive associations were found with TBX1 AJUBA, SNAI3 SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P <0.00022). Suggestive associations were found for centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. Conclusions Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified. PMID:28257739

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

DOE PAGES

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.; ...

2016-07-11

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho-physiological traits was explored and showed chlorogenic and shikimic acid to be associated with photosynthesis, early plant growth and final biomass measures in sorghum. In conclusion, taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture.« less

Non-targeted Metabolomics in Diverse Sorghum Breeding Lines Indicates Primary and Secondary Metabolite Profiles Are Associated with Plant Biomass Accumulation and Photosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, Marie F.; Heuberger, Adam L.; Kirkwood, Jay S.

Metabolomics is an emerging method to improve our understanding of how genetic diversity affects phenotypic variation in plants. Recent studies have demonstrated that genotype has a major influence on biochemical variation in several types of plant tissues, however, the association between metabolic variation and variation in morphological and physiological traits is largely unknown. Sorghum bicolor (L.) is an important food and fuel crop with extensive genetic and phenotypic variation. Sorghum lines have been bred for differing phenotypes beneficial for production of grain (food), stem sugar (food, fuel), and cellulosic biomass (forage, fuel), and these varying phenotypes are the end productsmore » of innate metabolic programming which determines how carbon is allocated during plant growth and development. Further, sorghum has been adapted among highly diverse environments. Because of this geographic and phenotypic variation, the sorghum metabolome is expected to be highly divergent; however, metabolite variation in sorghum has not been characterized. Here, we utilize a phenotypically diverse panel of sorghum breeding lines to identify associations between leaf metabolites and morpho-physiological traits. The panel (11 lines) exhibited significant variation for 21 morpho-physiological traits, as well as broader trends in variation by sorghum type (grain vs. biomass types). Variation was also observed for cell wall constituents (glucan, xylan, lignin, ash). Non-targeted metabolomics analysis of leaf tissue showed that 956 of 1181 metabolites varied among the lines (81%, ANOVA, FDR adjusted p < 0.05). Both univariate and multivariate analyses determined relationships between metabolites and morpho-physiological traits, and 384 metabolites correlated with at least one trait (32%, p < 0.05), including many secondary metabolites such as glycosylated flavonoids and chlorogenic acids. The use of metabolomics to explain relationships between two or more morpho-physiological traits was explored and showed chlorogenic and shikimic acid to be associated with photosynthesis, early plant growth and final biomass measures in sorghum. In conclusion, taken together, this study demonstrates the integration of metabolomics with morpho-physiological datasets to elucidate links between plant metabolism, growth, and architecture.« less

Abundant raw material for cis-regulatory evolution in humans

NASA Technical Reports Server (NTRS)

Rockman, Matthew V.; Wray, Gregory A.

2002-01-01

Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.

Effects of environmental disturbance on phenotypic variation: an integrated assessment of canalization, developmental stability, modularity, and allometry in lizard head shape.

PubMed

Lazić, Marko M; Carretero, Miguel A; Crnobrnja-Isailović, Jelka; Kaliontzopoulou, Antigoni

2015-01-01

When populations experience suboptimal conditions, the mechanisms involved in the regulation of phenotypic variation can be challenged, resulting in increased phenotypic variance. This kind of disturbance can be diagnosed by using morphometric tools to study morphological patterns at different hierarchical levels and evaluate canalization, developmental stability, integration, modularity, and allometry. We assess the effect of urbanization on phenotypic variation in the common wall lizard (Podarcis muralis) by using geometric morphometrics to assess disturbance to head shape development. The head shapes of urban lizards were more variable and less symmetric, suggesting that urban living is more likely to disturb development. Head shape variation was congruent within and across individuals, which indicated that canalization and developmental stability are two related phenomena in these organisms. Furthermore, urban lizards exhibited smaller mean head sizes, divergent size-shape allometries, and increased deviation from within-group allometric lines. This suggests that mechanisms regulating head shape allometry may also be disrupted. The integrated evaluation of several measures of developmental instability at different hierarchical levels, which provided in this case congruent results, can be a powerful methodological guide for future studies, as it enhances the detection of environmental disturbances on phenotypic variation and aids biological interpretation of the results.

Natural polyploidy in Vanilla planifolia (Orchidaceae).

PubMed

Bory, Séverine; Catrice, Olivier; Brown, Spencer; Leitch, Ilia J; Gigant, Rodolphe; Chiroleu, Frédéric; Grisoni, Michel; Duval, Marie-France; Besse, Pascale

2008-10-01

Vanilla planifolia accessions cultivated in Reunion Island display important phenotypic variation, but little genetic diversity is demonstrated by AFLP and SSR markers. This study, based on analyses of flow cytometry data, Feulgen microdensitometry data, chromosome counts, and stomatal length measurements, was performed to determine whether polyploidy could be responsible for some of the intraspecific phenotypic variation observed. Vanilla planifolia exhibited an important variation in somatic chromosome number in root cells, as well as endoreplication as revealed by flow cytometry. Nevertheless, the 2C-values of the 50 accessions studied segregated into three distinct groups averaging 5.03 pg (for most accessions), 7.67 pg (for the 'Stérile' phenotypes), and 10.00 pg (for the 'Grosse Vanille' phenotypes). For the three groups, chromosome numbers varied from 16 to 32, 16 to 38, and 22 to 54 chromosomes per cell, respectively. The stomatal length showed a significant variation from 37.75 microm to 48.25 microm. Given that 2C-values, mean chromosome numbers, and stomatal lengths were positively correlated and that 'Stérile' and 'Grosse Vanille' accessions were indistinguishable from 'Classique' accessions using molecular markers, the occurrence of recent autotriploid and autotetraploid types in Reunion Island is supported. This is the first report showing evidence of a recent autopolyploidy in V. planifolia contributing to the phenotypic variation observed in this species.

Dominant Epistasis Between Two Quantitative Trait Loci Governing Sporulation Efficiency in Yeast Saccharomyces cerevisiae

PubMed Central

Bergman, Juraj; Mitrikeski, Petar T.

2015-01-01

Summary Sporulation efficiency in the yeast Saccharomyces cerevisiae is a well-established model for studying quantitative traits. A variety of genes and nucleotides causing different sporulation efficiencies in laboratory, as well as in wild strains, has already been extensively characterised (mainly by reciprocal hemizygosity analysis and nucleotide exchange methods). We applied a different strategy in order to analyze the variation in sporulation efficiency of laboratory yeast strains. Coupling classical quantitative genetic analysis with simulations of phenotypic distributions (a method we call phenotype modelling) enabled us to obtain a detailed picture of the quantitative trait loci (QTLs) relationships underlying the phenotypic variation of this trait. Using this approach, we were able to uncover a dominant epistatic inheritance of loci governing the phenotype. Moreover, a molecular analysis of known causative quantitative trait genes and nucleotides allowed for the detection of novel alleles, potentially responsible for the observed phenotypic variation. Based on the molecular data, we hypothesise that the observed dominant epistatic relationship could be caused by the interaction of multiple quantitative trait nucleotides distributed across a 60--kb QTL region located on chromosome XIV and the RME1 locus on chromosome VII. Furthermore, we propose a model of molecular pathways which possibly underlie the phenotypic variation of this trait. PMID:27904371

Examination of Clock and Adcyap1 gene variation in a neotropical migratory passerine

PubMed Central

Bridge, Eli S.; Ross, Jeremy D.; Shipley, J. Ryan; Kelly, Jeffrey F.

2018-01-01

Complex behavioral traits, such as those making up a migratory phenotype, are regulated by multiple environmental factors and multiple genes. We investigated possible relationships between microsatellite variation at two candidate genes implicated in the control of migratory behavior, Clock and Adcyap1, and several aspects of migratory life-history and evolutionary divergence in the Painted Bunting (Passerina ciris), a species that shows wide variation in migratory and molting strategies across a disjunct distribution. We focused on Clock and Adcyap1 microsatellite variation across three Painted Bunting populations in Oklahoma, Louisiana, and North Carolina, and for the Oklahoma breeding population we used published migration tracking data on adult males to explore phenotypic variation in individual migratory behavior. We found no correlation between microsatellite allele size within either Clock and Adcyap1 relative to the initiation or duration of fall migration in adult males breeding in Oklahoma. We also show the lack of significant correlations with aspects of the migratory phenotype for the Louisiana population. Our research highlights the limitations of studying microsatellite allelic mutations that are of undetermined functional influence relative to complex behavioral phenotypes. PMID:29324772

Brief Report: Autism-like Traits are Associated With Enhanced Ability to Disembed Visual Forms.

PubMed

Sabatino DiCriscio, Antoinette; Troiani, Vanessa

2017-05-01

Atypical visual perceptual skills are thought to underlie unusual visual attention in autism spectrum disorders. We assessed whether individual differences in visual processing skills scaled with quantitative traits associated with the broader autism phenotype (BAP). Visual perception was assessed using the Figure-ground subtest of the Test of visual perceptual skills-3rd Edition (TVPS). In a large adult cohort (n = 209), TVPS-Figure Ground scores were positively correlated with autistic-like social features as assessed by the Broader autism phenotype questionnaire. This relationship was gender-specific, with males showing a correspondence between visual perceptual skills and autistic-like traits. This work supports the link between atypical visual perception and autism and highlights the importance in characterizing meaningful individual differences in clinically relevant behavioral phenotypes.

Sources of floral scent variation

PubMed Central

Raguso, Robert A; Ashman, Tia-Lynn

2009-01-01

Studies of floral scent generally assume that genetic adaptation due to pollinator-mediated natural selection explains a significant amount of phenotypic variance, ignoring the potential for phenotypic plasticity in this trait. In this paper, we assess this latter possibility, looking first at previous studies of floral scent variation in relation to abiotic environmental factors. We then present data from our own research that suggests among-population floral scent variation is determined, in part, by environmental conditions and thus displays phenotypic plasticity. Such an outcome has strong ramifications for the study of floral scent variation; we conclude by presenting some fundamental questions that should lead to greater insight into our understanding of the evolution of this trait, which is important to plant-animal interactions. PMID:19649189

Association of genetic and phenotypic variability with geography and climate in three southern California oaks.

PubMed

Riordan, Erin C; Gugger, Paul F; Ortego, Joaquín; Smith, Carrie; Gaddis, Keith; Thompson, Pam; Sork, Victoria L

2016-01-01

Geography and climate shape the distribution of organisms, their genotypes, and their phenotypes. To understand historical and future evolutionary and ecological responses to climate, we compared the association of geography and climate of three oak species (Quercus engelmannii, Quercus berberidifolia, and Quercus cornelius-mulleri) in an environmentally heterogeneous region of southern California at three organizational levels: regional species distributions, genetic variation, and phenotypic variation. We identified climatic variables influencing regional distribution patterns using species distribution models (SDMs), and then tested whether those individual variables are important in shaping genetic (microsatellite) and phenotypic (leaf morphology) variation. We estimated the relative contributions of geography and climate using multivariate redundancy analyses (RDA) with variance partitioning. The modeled distribution of each species was influenced by climate differently. Our analysis of genetic variation using RDA identified small but significant associations between genetic variation with climate and geography in Q. engelmannii and Q. cornelius-mulleri, but not in Q. berberidifolia, and climate explained more of the variation. Our analysis of phenotypic variation in Q. engelmannii indicated that climate had more impact than geography, but not in Q. berberidifolia. Throughout our analyses, we did not find a consistent pattern in effects of individual climatic variables. Our comparative analysis illustrates that climate influences tree response at all organizational levels, but the important climate factors vary depending on the level and on the species. Because of these species-specific and level-specific responses, today's sympatric species are unlikely to have similar distributions in the future. © 2016 Botanical Society of America.

Random phenotypic variation of yeast (Saccharomyces cerevisiae) single-gene knockouts fits a double pareto-lognormal distribution.

PubMed

Graham, John H; Robb, Daniel T; Poe, Amy R

2012-01-01

Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-free topology of gene regulatory, metabolic, and protein-protein interaction networks. If this hypothesis is true, then the phenotypic response to the perturbation of particular nodes in such a network should be proportional to the number of links those nodes make with neighboring nodes. This suggests a probability distribution approximating an inverse power-law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellular processes are essential to normal development. Consequently, a more realistic distribution should have a y-intercept close to zero in the lower tail, a mode greater than zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN) distribution is an ideal candidate distribution. It consists of a mixture of a lognormal body and upper and lower power-law tails. If our assumptions are true, the DPLN distribution should provide a better fit to random phenotypic variation in a large series of single-gene knockout lines than other skewed or symmetrical distributions. We fit a large published data set of single-gene knockout lines in Saccharomyces cerevisiae to seven different probability distributions: DPLN, right Pareto-lognormal (RPLN), left Pareto-lognormal (LPLN), normal, lognormal, exponential, and Pareto. The best model was judged by the Akaike Information Criterion (AIC). Phenotypic variation among gene knockouts in S. cerevisiae fits a double Pareto-lognormal (DPLN) distribution better than any of the alternative distributions, including the right Pareto-lognormal and lognormal distributions. A DPLN distribution is consistent with the hypothesis that developmental stability is mediated, in part, by distributed robustness, the resilience of gene regulatory, metabolic, and protein-protein interaction networks. Alternatively, multiplicative cell growth, and the mixing of lognormal distributions having different variances, may generate a DPLN distribution.

Linking genotype to phenotype in a changing ocean: inferring the genomic architecture of a blue mussel stress response with genome-wide association.

PubMed

Kingston, S E; Martino, P; Melendy, M; Reed, F A; Carlon, D B

2018-03-01

A key component to understanding the evolutionary response to a changing climate is linking underlying genetic variation to phenotypic variation in stress response. Here, we use a genome-wide association approach (GWAS) to understand the genetic architecture of calcification rates under simulated climate stress. We take advantage of the genomic gradient across the blue mussel hybrid zone (Mytilus edulis and Mytilus trossulus) in the Gulf of Maine (GOM) to link genetic variation with variance in calcification rates in response to simulated climate change. Falling calcium carbonate saturation states are predicted to negatively impact many marine organisms that build calcium carbonate shells - like blue mussels. We sampled wild mussels and measured net calcification phenotypes after exposing mussels to a 'climate change' common garden, where we raised temperature by 3°C, decreased pH by 0.2 units and limited food supply by filtering out planktonic particles >5 μm, compared to ambient GOM conditions in the summer. This climate change exposure greatly increased phenotypic variation in net calcification rates compared to ambient conditions. We then used regression models to link the phenotypic variation with over 170 000 single nucleotide polymorphism loci (SNPs) generated by genotype by sequencing to identify genomic locations associated with calcification phenotype, and estimate heritability and architecture of the trait. We identified at least one of potentially 2-10 genomic regions responsible for 30% of the phenotypic variation in calcification rates that are potential targets of natural selection by climate change. Our simulations suggest a power of 13.7% with our study's average effective sample size of 118 individuals and rare alleles, but a power of >90% when effective sample size is 900. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Autozygome Sequencing Expands the Horizon of Human Knockout Research and Provides Novel Insights into Human Phenotypic Variation

PubMed Central

Anazi, Shamsa; Alshamekh, Shomoukh; Alkuraya, Fowzan S.

2013-01-01

The use of autozygosity as a mapping tool in the search for autosomal recessive disease genes is well established. We hypothesized that autozygosity not only unmasks the recessiveness of disease causing variants, but can also reveal natural knockouts of genes with less obvious phenotypic consequences. To test this hypothesis, we exome sequenced 77 well phenotyped individuals born to first cousin parents in search of genes that are biallelically inactivated. Using a very conservative estimate, we show that each of these individuals carries biallelic inactivation of 22.8 genes on average. For many of the 169 genes that appear to be biallelically inactivated, available data support involvement in modulating metabolism, immunity, perception, external appearance and other phenotypic aspects, and appear therefore to contribute to human phenotypic variation. Other genes with biallelic inactivation may contribute in yet unknown mechanisms or may be on their way to conversion into pseudogenes due to true recent dispensability. We conclude that sequencing the autozygome is an efficient way to map the contribution of genes to human phenotypic variation that goes beyond the classical definition of disease. PMID:24367280

Clinical commentary on "Paroxysmal kinesigenic dyskinesia-like phenotype in multiple sclerosis" and "Secondary paroxysmal dyskinesia in multiple sclerosis: Clinical-radiological features and treatment. Case report of seven patients".

PubMed

Pareés, Isabel

2017-11-01

This clinical commentary discusses the phenomenology and treatment of paroxysmal dyskinesia in patients with multiple sclerosis. It calls for a consensus on the definition as well as for larger studies to better understand this unusual clinical association.

Assessing the complex architecture of polygenic traits in diverged yeast populations.

PubMed

Cubillos, Francisco A; Billi, Eleonora; Zörgö, Enikö; Parts, Leopold; Fargier, Patrick; Omholt, Stig; Blomberg, Anders; Warringer, Jonas; Louis, Edward J; Liti, Gianni

2011-04-01

Phenotypic variation arising from populations adapting to different niches has a complex underlying genetic architecture. A major challenge in modern biology is to identify the causative variants driving phenotypic variation. Recently, the baker's yeast, Saccharomyces cerevisiae has emerged as a powerful model for dissecting complex traits. However, past studies using a laboratory strain were unable to reveal the complete architecture of polygenic traits. Here, we present a linkage study using 576 recombinant strains obtained from crosses of isolates representative of the major lineages. The meiotic recombinational landscape appears largely conserved between populations; however, strain-specific hotspots were also detected. Quantitative measurements of growth in 23 distinct ecologically relevant environments show that our recombinant population recapitulates most of the standing phenotypic variation described in the species. Linkage analysis detected an average of 6.3 distinct QTLs for each condition tested in all crosses, explaining on average 39% of the phenotypic variation. The QTLs detected are not constrained to a small number of loci, and the majority are specific to a single cross-combination and to a specific environment. Moreover, crosses between strains of similar phenotypes generate greater variation in the offspring, suggesting the presence of many antagonistic alleles and epistatic interactions. We found that subtelomeric regions play a key role in defining individual quantitative variation, emphasizing the importance of the adaptive nature of these regions in natural populations. This set of recombinant strains is a powerful tool for investigating the complex architecture of polygenic traits. © 2011 Blackwell Publishing Ltd.

Phenotypic Evolution With and Beyond Genome Evolution.

PubMed

Félix, M-A

2016-01-01

DNA does not make phenotypes on its own. In this volume entitled "Genes and Phenotypic Evolution," the present review draws the attention on the process of phenotype construction-including development of multicellular organisms-and the multiple interactions and feedbacks between DNA, organism, and environment at various levels and timescales in the evolutionary process. First, during the construction of an individual's phenotype, DNA is recruited as a template for building blocks within the cellular context and may in addition be involved in dynamical feedback loops that depend on the environmental and organismal context. Second, in the production of phenotypic variation among individuals, stochastic, environmental, genetic, and parental sources of variation act jointly. While in controlled laboratory settings, various genetic and environmental factors can be tested one at a time or in various combinations, they cannot be separated in natural populations because the environment is not controlled and the genotype can rarely be replicated. Third, along generations, genotype and environment each have specific properties concerning the origin of their variation, the hereditary transmission of this variation, and the evolutionary feedbacks. Natural selection acts as a feedback from phenotype and environment to genotype. This review integrates recent results and concrete examples that illustrate these three points. Although some themes are shared with recent calls and claims to a new conceptual framework in evolutionary biology, the viewpoint presented here only means to add flesh to the standard evolutionary synthesis. © 2016 Elsevier Inc. All rights reserved.

Environmental Epigenetics and a Unified Theory of the Molecular Aspects of Evolution: A Neo-Lamarckian Concept that Facilitates Neo-Darwinian Evolution.

PubMed

Skinner, Michael K

2015-04-26

Environment has a critical role in the natural selection process for Darwinian evolution. The primary molecular component currently considered for neo-Darwinian evolution involves genetic alterations and random mutations that generate the phenotypic variation required for natural selection to act. The vast majority of environmental factors cannot directly alter DNA sequence. Epigenetic mechanisms directly regulate genetic processes and can be dramatically altered by environmental factors. Therefore, environmental epigenetics provides a molecular mechanism to directly alter phenotypic variation generationally. Lamarck proposed in 1802 the concept that environment can directly alter phenotype in a heritable manner. Environmental epigenetics and epigenetic transgenerational inheritance provide molecular mechanisms for this process. Therefore, environment can on a molecular level influence the phenotypic variation directly. The ability of environmental epigenetics to alter phenotypic and genotypic variation directly can significantly impact natural selection. Neo-Lamarckian concept can facilitate neo-Darwinian evolution. A unified theory of evolution is presented to describe the integration of environmental epigenetic and genetic aspects of evolution. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Thermoluminescence of Antarctic meteorites: A rapid screening technique for terrestrial age estimation, pairing studies and identification of specimens with unusual prefall histories

NASA Technical Reports Server (NTRS)

Sutton, S. R.; Walker, R. M.

1986-01-01

Thermoluminescence (TL) is a promising technique for rapid screening of the large numbers of Antarctic meteorites, permitting identification of interesting specimens that can then be studied in detail by other, more definite techniques. Specifically, TL permits determination of rough terrestrial age, identification of potential paired groups and location of specimens with unusual pre-fall histories. Meteorites with long terrestrial ages are particularly valuable for studying transport and weathering mechanisms. Pairing studies are possible because TL variations among meteorites are large compared to variations within individual objects, especially for natural TL. Available TL data for several L3 fragments, three of which were paired by other techniques, are presented as an example of the use of TL parameters in pairing studies. Additional TL measurements, specifically a blind test, are recommended to satisfactorily establish the reliability of this pairing property. The TL measurements also identify fragments with unusual pre-fall histories, such an near-Sun orbits.

Common genetic variation drives molecular heterogeneity in human iPSCs.

PubMed

Kilpinen, Helena; Goncalves, Angela; Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard; Stegle, Oliver; Gaffney, Daniel J

2017-06-15

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

Common genetic variation drives molecular heterogeneity in human iPSCs

PubMed Central

Leha, Andreas; Afzal, Vackar; Alasoo, Kaur; Ashford, Sofie; Bala, Sendu; Bensaddek, Dalila; Casale, Francesco Paolo; Culley, Oliver J; Danecek, Petr; Faulconbridge, Adam; Harrison, Peter W; Kathuria, Annie; McCarthy, Davis; McCarthy, Shane A; Meleckyte, Ruta; Memari, Yasin; Moens, Nathalie; Soares, Filipa; Mann, Alice; Streeter, Ian; Agu, Chukwuma A; Alderton, Alex; Nelson, Rachel; Harper, Sarah; Patel, Minal; White, Alistair; Patel, Sharad R; Clarke, Laura; Halai, Reena; Kirton, Christopher M; Kolb-Kokocinski, Anja; Beales, Philip; Birney, Ewan; Danovi, Davide; Lamond, Angus I; Ouwehand, Willem H; Vallier, Ludovic; Watt, Fiona M; Durbin, Richard

2017-01-01

Induced pluripotent stem cell (iPSC) technology has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterisation of many existing iPSC lines limits their potential use for research and therapy. Here, we describe the systematic generation, genotyping and phenotyping of 711 iPSC lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative (HipSci: http://www.hipsci.org). Our study outlines the major sources of genetic and phenotypic variation in iPSCs and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5-46% of the variation in different iPSC phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of rare, genomic copy number mutations that are repeatedly observed in iPSC reprogramming and present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells. PMID:28489815

Variation and Functional Impact of Neanderthal Ancestry in Western Asia

PubMed Central

Taskent, Recep Ozgur; Alioglu, Nursen Duha; Fer, Evrim

2017-01-01

Abstract Neanderthals contributed genetic material to modern humans via multiple admixture events. Initial admixture events presumably occurred in Western Asia shortly after humans migrated out of Africa. Despite being a focal point of admixture, earlier studies indicate lower Neanderthal introgression rates in some Western Asian populations as compared with other Eurasian populations. To better understand the genome-wide and phenotypic impact of Neanderthal introgression in the region, we sequenced whole genomes of nine present-day Europeans, Africans, and the Western Asian Druze at high depth, and analyzed available whole genome data from various other populations, including 16 genomes from present-day Turkey. Our results confirmed previous observations that contemporary Western Asian populations, on an average, have lower levels of Neanderthal-introgressed DNA relative to other Eurasian populations. Modern Western Asians also show comparatively high variability in Neanderthal ancestry, which may be attributed to the complex demographic history of the region. We further replicated the previously described depletion of putatively functional sequences among Neanderthal-introgressed haplotypes. Still, we find dozens of common Neanderthal-introgressed haplotypes in the Turkish sample associated with human phenotypes, including anthropometric and metabolic traits, as well as the immune response. One of these haplotypes is unusually long and harbors variants that affect the expression of members of the CCR gene family and are associated with celiac disease. Overall, our results paint a complex first picture of the genomic impact of Neanderthal introgression in the Western Asian populations. PMID:29040546

Significant genetic and phenotypic changes arising from clonal growth of a single spore of an arbuscular mycorrhizal fungus over multiple generations.

PubMed

Ehinger, Martine O; Croll, Daniel; Koch, Alexander M; Sanders, Ian R

2012-11-01

Arbuscular mycorrhizal fungi (AMF) are highly successful plant symbionts. They reproduce clonally producing multinucleate spores. It has been suggested that some AMF harbor genetically different nuclei. However, recent advances in sequencing the Glomus irregulare genome have indicated very low within-fungus polymorphism. We tested the null hypothesis that, with no genetic differences among nuclei, no significant genetic or phenotypic variation would occur among clonal single spore lines generated from one initial AMF spore. Furthermore, no additional variation would be expected in the following generations of single spore lines. Genetic diversity contained in one initial spore repeatedly gave rise to genetically different variants of the fungus with novel phenotypes. The genetic changes represented quantitative changes in allele frequencies, most probably as a result of changes in the frequency of genetic variation partitioned on different nuclei. The genetic and phenotypic variation is remarkable, given that it arose repeatedly from one clonal individual. Our results highlight the dynamic nature of AMF genetics. Even though within-fungus genetic variation is low, some is probably partitioned among nuclei and potentially causes changes in the phenotype. Our results are important for understanding AMF genetics, as well as for researchers and biotechnologists hoping to use AMF genetic diversity for the improvement of AMF inoculum. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.

PubMed

Yadav, Anupama; Dhole, Kaustubh; Sinha, Himanshu

2016-12-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.

Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits

PubMed Central

Yadav, Anupama; Dhole, Kaustubh

2016-01-01

Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets. PMID:28172852

A Finite Mixture Method for Outlier Detection and Robustness in Meta-Analysis

ERIC Educational Resources Information Center

Beath, Ken J.

2014-01-01

When performing a meta-analysis unexplained variation above that predicted by within study variation is usually modeled by a random effect. However, in some cases, this is not sufficient to explain all the variation because of outlier or unusual studies. A previously described method is to define an outlier as a study requiring a higher random…

A case of modular phenotypic plasticity in the depth gradient for the gorgonian coral Antillogorgia bipinnata (Cnidaria: Octocorallia).

PubMed

Calixto-Botía, Iván; Sánchez, Juan A

2017-02-17

Phenotypic plasticity, as a phenotypic response induced by the environment, has been proposed as a key factor in the evolutionary history of corals. A significant number of octocoral species show high phenotypic variation, exhibiting a strong overlap in intra- and inter-specific morphologic variation. This is the case of the gorgonian octocoral Antillogorgia bipinnata (Verrill 1864), which shows three polyphyletic morphotypes along a bathymetric gradient. This research tested the phenotypic plasticity of modular traits in A. bipinnata with a reciprocal transplant experiment involving 256 explants from two morphotypes in two locations and at two depths. Vertical and horizontal length and number of new branches were compared 13 weeks following transplant. The data were analysed with a linear mixed-effects model and a graphic approach by reaction norms. At the end of the experiment, 91.8% of explants survived. Lower vertical and horizontal growth rates and lower branch promotion were found for deep environments compared to shallow environments. The overall variation behaved similarly to the performance of native transplants. In particular, promotion of new branches showed variance mainly due to a phenotypic plastic effect. Globally, environmental and genotypic effects explain the variation of the assessed traits. Survival rates besides plastic responses suggest an intermediate scenario between adaptive plasticity and local adaptation that may drive a potential process of adaptive divergence along depth cline in A. bipinnata.

Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions?

PubMed Central

Hall, F. Scott; Perona, Maria T. G.

2012-01-01

This review addresses the recent convergence of our long-standing knowledge of the regulation of behavioral phenotypes by developmental experience with recent advances in our understanding of mechanisms regulating gene expression. This review supports a particular perspective on the developmental regulation of behavioral phenotypes: That the role of common developmental experiences (e.g. maternal interactions, peer interactions, exposure to a complex environment, etc.) is to fit individuals to the circumstances of their lives within bounds determined by long-standing (evolutionary) mechanisms that have shaped responses to critical and fundamental types of experience via those aspects of gene structure that regulate gene expression. The phenotype of a given species is not absolute for a given genotype but rather variable within bounds that are determined by mechanisms regulated by experience (e.g. epigenetic mechanisms). This phenotypic variation is not necessarily random, or evenly distributed along a continuum of description or measurement, but often highly disjointed, producing distinct, even opposing, phenotypes. The potentiality for these varying phenotypes is itself the product of evolution, the potential for alternative phenotypes itself conveying evolutionary advantage. Examples of such phenotypic variation, resulting from environmental or experiential influences, have a long history of study in neurobiology, and a number of these will be discussed in this review: neurodevelopmental experiences that produce phenotypic variation in visual perception, cognitive function, and emotional behavior. Although other examples will be discussed, particular emphasis will be made on the role of social behavior on neurodevelopment and phenotypic determination. It will be argued that an important purpose of some aspects of social behavior is regulation of neurobehavioral phenotypes by experience via genetic regulatory mechanisms. PMID:22643448

Ecophenotypic Variation and Developmental Instability in the Late Cretaceous Echinoid Micraster brevis (Irregularia; Spatangoida)

PubMed Central

Schlüter, Nils

2016-01-01

The Late Cretaceous echinoid genus Micraster (irregular echinoids, Spatangoida) is one of the most famous examples of a continuous evolutionary lineage in invertebrate palaeontology. The influence of the environment on the phenotype, however, was not tested so far. This study analyses differences in phenotypical variations within three populations of Micraster (Gibbaster) brevis from the early Coniacian, two from the Münsterland Cretaceous Basin (Germany) and one from the North Cantabrian Basin (Spain). The environments of the Spanish and the German sites differed by their sedimentary characteristics, which are generally a crucial factor for morphological adaptations in echinoids. Most of the major phenotypical variations (position of the ambitus, periproct and development of the subanal fasciole) among the populations can be linked to differences in their host sediments. These phenotypic variations are presumed to be an expression of phenotpic plasticiy, which has not been considered in Micraster in previous studies. Two populations (Erwitte area, Germany; Liencres area, Spain) were tested for stochastic variation (fluctuating asymmetry) due to developmental instability, which was present in all studied traits. However, differences in the amount of fluctuating asymmetry between both populations were recognised only in one trait (amount of pore pairs in the anterior paired petals). The results strengthen previous assumptions on ecophenotypic variations in Micraster. PMID:26849648

Genetic Modifiers of Sickle Cell Disease

PubMed Central

Steinberg, Martin H.; Sebastiani, Paola

2015-01-01

Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident ∝ thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new “druggable” pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease. PMID:22641398

Clinical and Molecular Aspects of an Informative Family with Neurofibromatosis Type 1 and Noonan Phenotype

PubMed Central

Stevenson, David A.; Viskochil, David H.; Rope, Alan F.; Carey, John C.

2011-01-01

NF-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndromes, which are separate syndromes. Potential etiologies of NF-Noonan syndrome include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS. PMID:16542390

Phenotypic expression of partial AZFc deletions is independent of the variations in DAZL and BOULE in a Han population.

PubMed

Chen, Pu; Ma, Mingyi; Li, Lei; Zhang, Sizhong; Su, Dan; Ma, Yongxin; Liu, Yunqiang; Tao, Dachang; Lin, Li; Yang, Yuan

2010-01-01

DAZ on the Y chromosome and 2 autosomal ancestral genes DAZL and BOULE are suggested to represent functional conservation in spermatogenesis. The partial AZFc deletion, a common mutation of the Y chromosome, always involves 2 DAZ copies and represents a different spermatogenic phenotype in the populations studied. To investigate whether the variations in DAZL and BOULE influence partial AZFc deletion phenotype, the genotyping of 15 loci variations, including 4 known mutations and 11 single-nucleotide polymorphisms (SNPs), was carried out in 157 azoo-/oligzoospermic men and 57 normozoospermic men, both groups with partial AZFc deletions. The frequencies of the alleles, genotypes, and haplotypes of the variations were compared between the 2 groups. As a result, for 9 exonic variations in DAZL and BOULE, only T12A was observed in both groups with similar frequency, and I71V was identified in an azoospermic man with b2/b3 deletion, whereas the rest were absent in the population. The distribution of DAZL haplotypes from 4 variations, including T12A, and of BOULE haplotypes from 2 SNPs was similar between men with normozoospermia and spermatogenic failure. Our findings indicate that the contribution of DAZL and BOULE variations to spermatogenic impairment in men with the DAZ defect is greatly limited, suggesting that expression of spermatogenic phenotypes of partial AZFc deletions is independent of the variations in DAZL and BOULE in the Han population.

Hsp90: A Global Regulator of the Genotype-to-Phenotype Map in Cancers.

PubMed

Jarosz, Daniel

2016-01-01

Cancer cells have the unusual capacity to limit the cost of the mutation load that they harbor and simultaneously harness its evolutionary potential. This property fuels drug resistance, a key failure mode in oncogene-directed therapy. However, the factors that regulate this capacity might also provide an Achilles' heel that could be exploited therapeutically. Recently, insight has come from a seemingly distant field: protein folding. It is now clear that protein homeostasis broadly supports malignancy and fuels the rapid evolution of drug resistance. Among protein homeostatic mechanisms that influence cancer biology, the essential ATP-driven molecular chaperone heat-shock protein 90 (Hsp90) is especially important. Hsp90 catalyzes folding of many proteins that regulate growth and development. These "client" kinases, transcription factors, and ubiquitin ligases often play critical roles in human disease, especially cancer. Studies in a wide range of systems-from single-celled organisms to human tumor samples-suggest that Hsp90 can broadly reshape the map between genotype and phenotype, acting as a "capacitor" and "potentiator" of genetic variation. Indeed, it has likely done so to such a degree that it has left an impress on diverse genome sequences. Hsp90 can constitute as much as 5% of total protein in transformed cells and increased levels of heat-shock activation correlate with poor prognosis in breast cancer. These findings and others have motivated a flurry of interest in Hsp90 inhibitors as cancer therapeutics, which have met with rather limited success as single agents, but may eventually prove invaluable in limiting the emergence of resistance to other chemotherapeutics, both genotoxic and molecularly targeted. Here, we provide an overview of Hsp90 function, review its relationship to genetic variation and the evolution of new traits, and discuss the importance of these findings for cancer biology and future efforts to drug this pathway. © 2016 Elsevier Inc. All rights reserved.

The Evolution of Phenotypic Switching in Subdivided Populations

PubMed Central

Carja, Oana; Liberman, Uri; Feldman, Marcus W.

2014-01-01

Stochastic switching is an example of phenotypic bet hedging, where offspring can express a phenotype different from that of their parents. Phenotypic switching is well documented in viruses, yeast, and bacteria and has been extensively studied when the selection pressures vary through time. However, there has been little work on the evolution of phenotypic switching under both spatially and temporally fluctuating selection pressures. Here we use a population genetic model to explore the interaction of temporal and spatial variation in determining the evolutionary dynamics of phenotypic switching. We find that the stable switching rate is mainly determined by the rate of environmental change and the migration rate. This stable rate is also a decreasing function of the recombination rate, although this is a weaker effect than those of either the period of environmental change or the migration rate. This study highlights the interplay of spatial and temporal environmental variability, offering new insights into how migration can influence the evolution of phenotypic switching rates, mutation rates, or other sources of phenotypic variation. PMID:24496012

Contrasting modes and tempos of venom expression evolution in two snake species.

PubMed

Margres, Mark J; McGivern, James J; Seavy, Margaret; Wray, Kenneth P; Facente, Jack; Rokyta, Darin R

2015-01-01

Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process and thus the genetic basis of adaptive evolution requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom gland toward toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait but also have extensive conservation and biomedical implications. C. adamanteus is currently a candidate for federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species. Copyright © 2015 by the Genetics Society of America.

Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases.

PubMed

Bueno, Anibal; Rodríguez-López, Rocío; Reyes-Palomares, Armando; Rojano, Elena; Corpas, Manuel; Nevado, Julián; Lapunzina, Pablo; Sánchez-Jiménez, Francisca; Ranea, Juan A G

2018-06-26

Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8-9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype-phenotype relationships. We aimed to improve the identification of statistically consistent genotype-phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype-patient-genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes.

Pulmonary phenotypes associated with genetic variation in telomere-related genes.

PubMed

Hoffman, Thijs W; van Moorsel, Coline H M; Borie, Raphael; Crestani, Bruno

2018-05-01

Genomic mutations in telomere-related genes have been recognized as a cause of familial forms of idiopathic pulmonary fibrosis (IPF). However, it has become increasingly clear that telomere syndromes and telomere shortening are associated with various types of pulmonary disease. Additionally, it was found that also single nucleotide polymorphisms (SNPs) in telomere-related genes are risk factors for the development of pulmonary disease. This review focuses on recent updates on pulmonary phenotypes associated with genetic variation in telomere-related genes. Genomic mutations in seven telomere-related genes cause pulmonary disease. Pulmonary phenotypes associated with these mutations range from many forms of pulmonary fibrosis to emphysema and pulmonary vascular disease. Telomere-related mutations account for up to 10% of sporadic IPF, 25% of familial IPF, 10% of connective-tissue disease-associated interstitial lung disease, and 1% of COPD. Mixed disease forms have also been found. Furthermore, SNPs in TERT, TERC, OBFC1, and RTEL1, as well as short telomere length, have been associated with several pulmonary diseases. Treatment of pulmonary disease caused by telomere-related gene variation is currently based on disease diagnosis and not on the underlying cause. Pulmonary phenotypes found in carriers of telomere-related gene mutations and SNPs are primarily pulmonary fibrosis, sometimes emphysema and rarely pulmonary vascular disease. Genotype-phenotype relations are weak, suggesting that environmental factors and genetic background of patients determine disease phenotypes to a large degree. A disease model is presented wherever genomic variation in telomere-related genes cause specific pulmonary disease phenotypes whenever triggered by environmental exposure, comorbidity, or unknown factors.

Airway Autoimmune Inflammatory Response (AAIR) Syndrome: An Asthma-Autoimmune Overlap Disorder?

PubMed

Spencer, Chantal Y; Millman, Jennifer; Veiga, Keila; Vicencio, Alfin G

2018-02-15

Asthma encompasses numerous phenotypes that may require alternate approaches to diagnosis and therapy, particularly for patients whose symptoms remain poorly controlled despite escalating treatment. We describe 3 patients with apparent asthma who demonstrated unusual findings on cryobiopsy by flexible bronchoscopy and responded to therapy directed against autoimmune disease. Copyright © 2018 by the American Academy of Pediatrics.

Unusual presentation of childhood Systemic Lupus Erythematosus

PubMed Central

Kumar, Sathish; Agarwal, Indira

2007-01-01

Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone. PMID:18028550

Water Intake and Risk of Hyponatraemia in Prader-Willi Syndrome

ERIC Educational Resources Information Center

Akefeldt, A.

2009-01-01

Background and Methods: Unusual water intake and drinking behaviour has occasionally been observed in individuals with Prader-Willi syndrome (PWS). The aim of this study is to explore whether this observation is a part of the PWS phenotype and what the consequences may be. The parents of 51 individuals with PWS (age range 2-40 years) were asked by…

The Larson Blue coat color phenotype in Holsteins: Characteristics and effects on body temperature regulation and production in lactating cows in a hot climate.

PubMed

Dikmen, S; Dahl, G E; Cole, J B; Null, D J; Hansen, P J

2017-03-01

Here we report a previously undescribed coat color phenotype in Holstein cattle. Larson Blue Holsteins, located on a dairy in south Florida, exhibit a coloration pattern that is similar to that of black and white or red and white Holsteins except that, instead of being black or red, darker regions of the body vary in color from gray to taupe. The Larson Blue phenotype was readily apparent in young calves. The phenotype is not due to inheritance of known mutations causing coat color variation in cattle, including dominant red, Telstar, silver color dilutor, or Dun color. Three variants with moderate effects on the () gene were identified in 2 Larson blue cows. Despite being lighter in color, there was no difference in daily variation in vaginal temperature between Larson Blue and other Holsteins when recorded during the summer for cows housed in free-stall barns with shade, fans, and sprinklers. Similarly, there was no effect of the Larson Blue phenotype on seasonal variation in milk yield. Therefore, the phenotype confers no advantage in terms of response to heat stress when cattle are housed in facilities with extensive cooling.

Clan-structured migration and phenotypic differentiation in the Jirels of Nepal.

PubMed

Williams-Blangero, S

1989-04-01

This paper examines the impact of clan-structured migration on the between-village differentiation of the Jirels, a tribal population of eastern Nepal. The Jirel population is geographically restricted to nine villages, all of which were sampled to some extent for this study. Data on five head measurements, stature, and digital ridge counts are utilized to illustrate the patterns of phenotypic variation. Multivariate statistical techniques are used to assess the extent to which clan membership and associated patterns of marital exchange influence the population structure of the Jirels. The phenotypic characteristics of randomly generated migrant sets are compared to those of the observed clan-structured sets, demonstrating the clan-related phenotypic nonrandomness of migrants. The results indicate that clan-structured migration may significantly influence the amount of between-village variation. Clan structure may be a significant factor in determining patterns of variation and should not be ignored in studies of microdifferentiation in tribal populations.

Biological monitoring of environmental quality: The use of developmental instability

USGS Publications Warehouse

Freeman, D.C.; Emlen, J.M.; Graham, J.H.; Hough, R. A.; Bannon, T.A.

1994-01-01

Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-free topology of gene regulatory, metabolic, and protein-protein interaction networks. If this hypothesis is true, then the phenotypic response to the perturbation of particular nodes in such a network should be proportional to the number of links those nodes make with neighboring nodes. This suggests a probability distribution approximating an inverse power-law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellular processes are essential to normal development. Consequently, a more realistic distribution should have a y-intercept close to zero in the lower tail, a mode greater than zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN) distribution is an ideal candidate distribution. It consists of a mixture of a lognormal body and upper and lower power-law tails.

Holistic and component plant phenotyping using temporal image sequence.

PubMed

Das Choudhury, Sruti; Bashyam, Srinidhi; Qiu, Yumou; Samal, Ashok; Awada, Tala

2018-01-01

Image-based plant phenotyping facilitates the extraction of traits noninvasively by analyzing large number of plants in a relatively short period of time. It has the potential to compute advanced phenotypes by considering the whole plant as a single object (holistic phenotypes) or as individual components, i.e., leaves and the stem (component phenotypes), to investigate the biophysical characteristics of the plants. The emergence timing, total number of leaves present at any point of time and the growth of individual leaves during vegetative stage life cycle of the maize plants are significant phenotypic expressions that best contribute to assess the plant vigor. However, image-based automated solution to this novel problem is yet to be explored. A set of new holistic and component phenotypes are introduced in this paper. To compute the component phenotypes, it is essential to detect the individual leaves and the stem. Thus, the paper introduces a novel method to reliably detect the leaves and the stem of the maize plants by analyzing 2-dimensional visible light image sequences captured from the side using a graph based approach. The total number of leaves are counted and the length of each leaf is measured for all images in the sequence to monitor leaf growth. To evaluate the performance of the proposed algorithm, we introduce University of Nebraska-Lincoln Component Plant Phenotyping Dataset (UNL-CPPD) and provide ground truth to facilitate new algorithm development and uniform comparison. The temporal variation of the component phenotypes regulated by genotypes and environment (i.e., greenhouse) are experimentally demonstrated for the maize plants on UNL-CPPD. Statistical models are applied to analyze the greenhouse environment impact and demonstrate the genetic regulation of the temporal variation of the holistic phenotypes on the public dataset called Panicoid Phenomap-1. The central contribution of the paper is a novel computer vision based algorithm for automated detection of individual leaves and the stem to compute new component phenotypes along with a public release of a benchmark dataset, i.e., UNL-CPPD. Detailed experimental analyses are performed to demonstrate the temporal variation of the holistic and component phenotypes in maize regulated by environment and genetic variation with a discussion on their significance in the context of plant science.

The relative contribution of drift and selection to phenotypic divergence: A test case using the horseshoe bats Rhinolophus simulator and Rhinolophus swinnyi.

PubMed

Mutumi, Gregory L; Jacobs, David S; Winker, Henning

2017-06-01

Natural selection and drift can act on populations individually, simultaneously or in tandem and our understanding of phenotypic divergence depends on our ability to recognize the contribution of each. According to the quantitative theory of evolution, if an organism has diversified through neutral evolutionary processes (mutation and drift), variation of phenotypic characteristics between different geographic localities ( B ) should be directly proportional to the variation within localities ( W ), that is, B  ∝  W . Significant deviations from this null model imply that non-neutral forces such as natural selection are acting on a phenotype. We investigated the relative contributions of drift and selection to intraspecific diversity using southern African horseshoe bats as a test case. We characterized phenotypic diversity across the distributional range of Rhinolophus simulator ( n =  101) and Rhinolophus swinnyi ( n =  125) using several traits associated with flight and echolocation. Our results suggest that geographic variation in both species was predominantly caused by disruptive natural selection ( B was not directly proportional to W ). Evidence for correlated selection (co-selection) among traits further confirmed that our results were not compatible with drift. Selection rather than drift is likely the predominant evolutionary process shaping intraspecific variation in traits that strongly impact fitness.

Bergmann's rule is maintained during a rapid range expansion in a damselfly.

PubMed

Hassall, Christopher; Keat, Simon; Thompson, David J; Watts, Phillip C

2014-02-01

Climate-induced range shifts result in the movement of a sample of genotypes from source populations to new regions. The phenotypic consequences of those shifts depend upon the sample characteristics of the dispersive genotypes, which may act to either constrain or promote phenotypic divergence, and the degree to which plasticity influences the genotype-environment interaction. We sampled populations of the damselfly Erythromma viridulum from northern Europe to quantify the phenotypic (latitude-body size relationship based on seven morphological traits) and genetic (variation at microsatellite loci) patterns that occur during a range expansion itself. We find a weak spatial genetic structure that is indicative of high gene flow during a rapid range expansion. Despite the potentially homogenizing effect of high gene flow, however, there is extensive phenotypic variation among samples along the invasion route that manifests as a strong, positive correlation between latitude and body size consistent with Bergmann's rule. This positive correlation cannot be explained by variation in the length of larval development (voltinism). While the adaptive significance of latitudinal variation in body size remains obscure, geographical patterns in body size in odonates are apparently underpinned by phenotypic plasticity and this permits a response to one or more environmental correlates of latitude during a range expansion. © 2013 John Wiley & Sons Ltd.

Phenotypic plasticity of winter wheat heading date and grain yield across the U.S. Great Plains

USDA-ARS?s Scientific Manuscript database

Phenotypic plasticity describes the range of phenotypes produced by a single genotype under varying environmental conditions. We evaluated the extent of phenotypic variation and plasticity in thermal time to heading and grain yield in 299 hard winter wheat (Triticum aestivum L.) genotypes representa...

Estimation Of The Proportion Of Variation Accounted For By DNA Tests. II: Phenotypic Variance

USDA-ARS?s Scientific Manuscript database

The proportion of phenotypic variation accounted for (Rp2) is an important characteristic of a DNA test. Therefore, several estimators of this quantity were evaluated by simulation of 500 replicates of a population of 1000 progeny of 100 sires (3 levels of narrow sense heritability and 4 levels of ...

Molecular mechanisms of epigenetic variation in plants.

PubMed

Fujimoto, Ryo; Sasaki, Taku; Ishikawa, Ryo; Osabe, Kenji; Kawanabe, Takahiro; Dennis, Elizabeth S

2012-01-01

Natural variation is defined as the phenotypic variation caused by spontaneous mutations. In general, mutations are associated with changes of nucleotide sequence, and many mutations in genes that can cause changes in plant development have been identified. Epigenetic change, which does not involve alteration to the nucleotide sequence, can also cause changes in gene activity by changing the structure of chromatin through DNA methylation or histone modifications. Now there is evidence based on induced or spontaneous mutants that epigenetic changes can cause altering plant phenotypes. Epigenetic changes have occurred frequently in plants, and some are heritable or metastable causing variation in epigenetic status within or between species. Therefore, heritable epigenetic variation as well as genetic variation has the potential to drive natural variation.

Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces cerevisiae.

PubMed

Hu, X H; Wang, M H; Tan, T; Li, J R; Yang, H; Leach, L; Zhang, R M; Luo, Z W

2007-03-01

Uncovering genetic control of variation in ethanol tolerance in natural populations of yeast Saccharomyces cerevisiae is essential for understanding the evolution of fermentation, the dominant lifestyle of the species, and for improving efficiency of selection for strains with high ethanol tolerance, a character of great economic value for the brewing and biofuel industries. To date, as many as 251 genes have been predicted to be involved in influencing this character. Candidacy of these genes was determined from a tested phenotypic effect following gene knockout, from an induced change in gene function under an ethanol stress condition, or by mutagenesis. This article represents the first genomics approach for dissecting genetic variation in ethanol tolerance between two yeast strains with a highly divergent trait phenotype. We developed a simple but reliable experimental protocol for scoring the phenotype and a set of STR/SNP markers evenly covering the whole genome. We created a mapping population comprising 319 segregants from crossing the parental strains. On the basis of the data sets, we find that the tolerance trait has a high heritability and that additive genetic variance dominates genetic variation of the trait. Segregation at five QTL detected has explained approximately 50% of phenotypic variation; in particular, the major QTL mapped on yeast chromosome 9 has accounted for a quarter of the phenotypic variation. We integrated the QTL analysis with the predicted candidacy of ethanol resistance genes and found that only a few of these candidates fall in the QTL regions.

The Stochastic Evolutionary Game for a Population of Biological Networks Under Natural Selection

PubMed Central

Chen, Bor-Sen; Ho, Shih-Ju

2014-01-01

In this study, a population of evolutionary biological networks is described by a stochastic dynamic system with intrinsic random parameter fluctuations due to genetic variations and external disturbances caused by environmental changes in the evolutionary process. Since information on environmental changes is unavailable and their occurrence is unpredictable, they can be considered as a game player with the potential to destroy phenotypic stability. The biological network needs to develop an evolutionary strategy to improve phenotypic stability as much as possible, so it can be considered as another game player in the evolutionary process, ie, a stochastic Nash game of minimizing the maximum network evolution level caused by the worst environmental disturbances. Based on the nonlinear stochastic evolutionary game strategy, we find that some genetic variations can be used in natural selection to construct negative feedback loops, efficiently improving network robustness. This provides larger genetic robustness as a buffer against neutral genetic variations, as well as larger environmental robustness to resist environmental disturbances and maintain a network phenotypic traits in the evolutionary process. In this situation, the robust phenotypic traits of stochastic biological networks can be more frequently selected by natural selection in evolution. However, if the harbored neutral genetic variations are accumulated to a sufficiently large degree, and environmental disturbances are strong enough that the network robustness can no longer confer enough genetic robustness and environmental robustness, then the phenotype robustness might break down. In this case, a network phenotypic trait may be pushed from one equilibrium point to another, changing the phenotypic trait and starting a new phase of network evolution through the hidden neutral genetic variations harbored in network robustness by adaptive evolution. Further, the proposed evolutionary game is extended to an n-tuple evolutionary game of stochastic biological networks with m players (competitive populations) and k environmental dynamics. PMID:24558296

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

PubMed

Bidwell, L C; McGeary, J E; Gray, J C; Palmer, R H C; Knopik, V S; MacKillop, J

2015-11-01

Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking. Copyright © 2015 Elsevier Inc. All rights reserved.

Correlational selection on personality and social plasticity: morphology and social context determine behavioural effects on mating success.

PubMed

Montiglio, Pierre-Olivier; Wey, Tina W; Chang, Ann T; Fogarty, Sean; Sih, Andrew

2017-03-01

Despite a central line of research aimed at quantifying relationships between mating success and sexually dimorphic traits (e.g., ornaments), individual variation in sexually selected traits often explains only a modest portion of the variation in mating success. Another line of research suggests that a significant portion of the variation in mating success observed in animal populations could be explained by correlational selection, where the fitness advantage of a given trait depends on other components of an individual's phenotype and/or its environment. We tested the hypothesis that interactions between multiple traits within an individual (phenotype dependence) or between an individual's phenotype and its social environment (context dependence) can select for individual differences in behaviour (i.e., personality) and social plasticity. To quantify the importance of phenotype- and context-dependent selection on mating success, we repeatedly measured the behaviour, social environment and mating success of about 300 male stream water striders, Aquarius remigis. Rather than explaining individual differences in long-term mating success, we instead quantified how the combination of a male's phenotype interacted with the immediate social context to explain variation in hour-by-hour mating decisions. We suggest that this analysis captures more of the mechanisms leading to differences in mating success. Males differed consistently in activity, aggressiveness and social plasticity. The mating advantage of these behavioural traits depended on male morphology and varied with the number of rival males in the pool, suggesting mechanisms selecting for consistent differences in behaviour and social plasticity. Accounting for phenotype and context dependence improved the amount of variation in male mating success we explained statistically by 30-274%. Our analysis of the determinants of male mating success provides important insights into the evolutionary forces that shape phenotypic variation. In particular, our results suggest that sexual selection is likely to favour individual differences in behaviour, social plasticity (i.e., individuals adjusting their behaviour), niche preference (i.e., individuals dispersing to particular social conditions) or social niche construction (i.e., individuals modifying the social environment). The true effect of sexual traits can only be understood in interaction with the individual's phenotype and environment. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Quantitative genetics of plumage color: lifetime effects of early nest environment on a colorful sexual signal

PubMed Central

Hubbard, Joanna K; Jenkins, Brittany R; Safran, Rebecca J

2015-01-01

Phenotypic differences among individuals are often linked to differential survival and mating success. Quantifying the relative influence of genetic and environmental variation on phenotype allows evolutionary biologists to make predictions about the potential for a given trait to respond to selection and various aspects of environmental variation. In particular, the environment individuals experience during early development can have lasting effects on phenotype later in life. Here, we used a natural full-sib/half-sib design as well as within-individual longitudinal analyses to examine genetic and various environmental influences on plumage color. We find that variation in melanin-based plumage color – a trait known to influence mating success in adult North American barn swallows (Hirundo rustica erythrogaster) – is influenced by both genetics and aspects of the developmental environment, including variation due to the maternal phenotype and the nest environment. Within individuals, nestling color is predictive of adult color. Accordingly, these early environmental influences are relevant to the sexually selected plumage color variation in adults. Early environmental conditions appear to have important lifelong implications for individual reproductive performance through sexual signal development in barn swallows. Our results indicate that feather color variation conveys information about developmental conditions and maternal care alleles to potential mates in North American barn swallows. Melanin-based colors are used for sexual signaling in many organisms, and our study suggests that these signals may be more sensitive to environmental variation than previously thought. PMID:26380676

Relationship between the species-representative phenotype and intraspecific variation in Ranunculaceae floral organ and Asteraceae flower numbers.

PubMed

Kitazawa, Miho S; Fujimoto, Koichi

2016-04-01

Phenotypic variation in floral morphologies contributes to speciation by testing various morphologies that might have higher adaptivity, leading eventually to phylogenetic diversity. Species diversity has been recognized, however, by modal morphologies where the variation is averaged out, so little is known about the relationship between the variation and the diversity. We analysed quantitatively the intraspecific variation of the organ numbers within flowers of Ranunculaceae, a family which branched near the monocot-eudicot separation, and the numbers of flowers within the capitula of Asteraceae, one of the most diverse families of eudicots. We used four elementary statistical quantities: mean, standard deviation (s.d.), degree of symmetry (skewness) and steepness (kurtosis). While these four quantities vary among populations, we found a common relationship between s.d. and the mean number of petals and sepals in Ranunculaceae and number of flowers per capitulum in Asteraceae. The s.d. is equal to the square root of the difference between the mean and specific number, showing robustness: for example, 3 in Ficaria sepals, 5 in Ranunculus petals and Anemone tepals, and 13 in Farfugium ray florets. This square-root relationship was not applicable to Eranthis petals which show little correlation between the s.d. and mean, and the stamens and carpels of Ranunculaceae whose s.d. is proportional to the mean. The specific values found in the square-root relationship provide a novel way to find the species-representative phenotype among varied morphologies. The representative phenotype is, in most cases, unique to the species or genus level, despite intraspecific differences of average phenotype among populations. The type of variation shown by the statistical quantities indicates not only the robustness of the morphologies but also how flowering plants changed during evolution among representative phenotypes that eventually led to phylogenetic diversification. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Relationship between the species-representative phenotype and intraspecific variation in Ranunculaceae floral organ and Asteraceae flower numbers

PubMed Central

Kitazawa, Miho S.; Fujimoto, Koichi

2016-01-01

Background and Aims Phenotypic variation in floral morphologies contributes to speciation by testing various morphologies that might have higher adaptivity, leading eventually to phylogenetic diversity. Species diversity has been recognized, however, by modal morphologies where the variation is averaged out, so little is known about the relationship between the variation and the diversity. Methods We analysed quantitatively the intraspecific variation of the organ numbers within flowers of Ranunculaceae, a family which branched near the monocot–eudicot separation, and the numbers of flowers within the capitula of Asteraceae, one of the most diverse families of eudicots. We used four elementary statistical quantities: mean, standard deviation (s.d.), degree of symmetry (skewness) and steepness (kurtosis). Key Results While these four quantities vary among populations, we found a common relationship between s.d. and the mean number of petals and sepals in Ranunculaceae and number of flowers per capitulum in Asteraceae. The s.d. is equal to the square root of the difference between the mean and specific number, showing robustness: for example, 3 in Ficaria sepals, 5 in Ranunculus petals and Anemone tepals, and 13 in Farfugium ray florets. This square-root relationship was not applicable to Eranthis petals which show little correlation between the s.d. and mean, and the stamens and carpels of Ranunculaceae whose s.d. is proportional to the mean. The specific values found in the square-root relationship provide a novel way to find the species-representative phenotype among varied morphologies. Conclusions The representative phenotype is, in most cases, unique to the species or genus level, despite intraspecific differences of average phenotype among populations. The type of variation shown by the statistical quantities indicates not only the robustness of the morphologies but also how flowering plants changed during evolution among representative phenotypes that eventually led to phylogenetic diversification. PMID:27052344

Short-range phenotypic divergence among genetically distinct parapatric populations of an Australian funnel-web spider.

PubMed

Wong, Mark K L; Woodman, James D; Rowell, David M

2017-07-01

Speciation involves divergence at genetic and phenotypic levels. Where substantial genetic differentiation exists among populations, examining variation in multiple phenotypic characters may elucidate the mechanisms by which divergence and speciation unfold. Previous work on the Australian funnel-web spider Atrax sutherlandi Gray (2010; Records of the Australian Museum 62 , 285-392; Mygalomorphae: Hexathelidae: Atracinae) has revealed a marked genetic structure along a 110-kilometer transect, with six genetically distinct, parapatric populations attributable to past glacial cycles. In the present study, we explore variation in three classes of phenotypic characters (metabolic rate, water loss, and morphological traits) within the context of this phylogeographic structuring. Variation in metabolic and water loss rates shows no detectable association with genetic structure; the little variation observed in these rates may be due to the spiders' behavioral adaptations (i.e., burrowing), which buffer the effects of climatic gradients across the landscape. However, of 17 morphological traits measured, 10 show significant variation among genetic populations, in a disjunct manner that is clearly not latitudinal. Moreover, patterns of variation observed for morphological traits serving different organismic functions (e.g., prey capture, burrowing, and locomotion) are dissimilar. In contrast, a previous study of an ecologically similar sympatric spider with little genetic structure indicated a strong latitudinal response in 10 traits over the same range. The congruence of morphological variation with deep phylogeographic structure in Tallaganda's A. sutherlandi populations, as well as the inconsistent patterns of variation across separate functional traits, suggest that the spiders are likely in early stages of speciation, with parapatric populations independently responding to local selective forces.

High level of molecular and phenotypic biodiversity in Jatropha curcas from Central America compared to Africa, Asia and South America

PubMed Central

2014-01-01

Background The main bottleneck to elevate jatropha (Jatropha curcas L.) from a wild species to a profitable biodiesel crop is the low genetic and phenotypic variation found in different regions of the world, hampering efficient plant breeding for productivity traits. In this study, 182 accessions from Asia (91), Africa (35), South America (9) and Central America (47) were evaluated at genetic and phenotypic level to find genetic variation and important traits for oilseed production. Results Genetic variation was assessed with SSR (Simple Sequence Repeat), TRAP (Target Region Amplification Polymorphism) and AFLP (Amplified fragment length polymorphism) techniques. Phenotypic variation included seed morphological characteristics, seed oil content and fatty acid composition and early growth traits. Jaccard’s similarity and cluster analysis by UPGM (Unweighted Paired Group Method) with arithmetic mean and PCA (Principle Component Analysis) indicated higher variability in Central American accessions compared to Asian, African and South American accessions. Polymorphism Information Content (PIC) values ranged from 0 to 0.65. In the set of Central American accessions. PIC values were higher than in other regions. Accessions from the Central American population contain alleles that were not found in the accessions from other populations. Analysis of Molecular Variance (AMOVA; P < 0.0001) indicated high genetic variation within regions (81.7%) and low variation across regions (18.3%). A high level of genetic variation was found on early growth traits and on components of the relative growth rate (specific leaf area, leaf weight, leaf weight ratio and net assimilation rate) as indicated by significant differences between accessions and by the high heritability values (50–88%). The fatty acid composition of jatropha oil significantly differed (P < 0.05) between regions. Conclusions The pool of Central American accessions showed very large genetic variation as assessed by DNA-marker variation compared to accessions from other regions. Central American accessions also showed the highest phenotypic variation and should be considered as the most important source for plant breeding. Some variation in early growth traits was found within a group of accessions from Asia and Africa, while these accessions did not differ in a single DNA-marker, possibly indicating epigenetic variation. PMID:24666927

Causal Genetic Variation Underlying Metabolome Differences.

PubMed

Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

2017-08-01

An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

Genome-wide association mapping and agronomic impact of cowpea root architecture.

PubMed

Burridge, James D; Schneider, Hannah M; Huynh, Bao-Lam; Roberts, Philip A; Bucksch, Alexander; Lynch, Jonathan P

2017-02-01

Genetic analysis of data produced by novel root phenotyping tools was used to establish relationships between cowpea root traits and performance indicators as well between root traits and Striga tolerance. Selection and breeding for better root phenotypes can improve acquisition of soil resources and hence crop production in marginal environments. We hypothesized that biologically relevant variation is measurable in cowpea root architecture. This study implemented manual phenotyping (shovelomics) and automated image phenotyping (DIRT) on a 189-entry diversity panel of cowpea to reveal biologically important variation and genome regions affecting root architecture phenes. Significant variation in root phenes was found and relatively high heritabilities were detected for root traits assessed manually (0.4 for nodulation and 0.8 for number of larger laterals) as well as repeatability traits phenotyped via DIRT (0.5 for a measure of root width and 0.3 for a measure of root tips). Genome-wide association study identified 11 significant quantitative trait loci (QTL) from manually scored root architecture traits and 21 QTL from root architecture traits phenotyped by DIRT image analysis. Subsequent comparisons of results from this root study with other field studies revealed QTL co-localizations between root traits and performance indicators including seed weight per plant, pod number, and Striga (Striga gesnerioides) tolerance. The data suggest selection for root phenotypes could be employed by breeding programs to improve production in multiple constraint environments.

Local adaptation within a hybrid species

PubMed Central

Eroukhmanoff, F; Hermansen, J S; Bailey, R I; Sæther, S A; Sætre, G-P

2013-01-01

Ecological divergence among populations may be strongly influenced by their genetic background. For instance, genetic admixture through introgressive hybridization or hybrid speciation is likely to affect the genetic variation and evolvability of phenotypic traits. We studied geographic variation in two beak dimensions and three other phenotypic traits of the Italian sparrow (Passer italiae), a young hybrid species formed through interbreeding between house sparrows (P. domesticus) and Spanish sparrows (P. hispaniolensis). We found that beak morphology was strongly influenced by precipitation regimes and that it appeared to be the target of divergent selection within Italian sparrows. Interestingly, however, the degree of parental genetic contribution in the hybrid species had no effect on phenotypic beak variation. Moreover, beak height divergence may mediate genetic differentiation between populations, consistent with isolation-by-adaptation within this hybrid species. The study illustrates how hybrid species may be relatively unconstrained by their admixed genetic background, allowing them to adapt rapidly to environmental variation. PMID:23695379

Phenotypic variation and identification of quantitative trait loci for ozone injury in a Fiskeby III x Mandarin (Ottawa) soybean population

USDA-ARS?s Scientific Manuscript database

Ground-level ozone reduces yield in crops such as soybean (Glycine max (L.) Merr.). Phenotypic variation has been observed for this trait in multiple species; however, breeding for ozone tolerance has been limited. A recombinant inbred population was developed from soybean genotypes differing in tol...

Characterization of phenotypic variation for dermo resistance among selectively-bred families of the Eastern oyster, Crassostrea virginica

USDA-ARS?s Scientific Manuscript database

Dermo disease impacts nearly every region where oysters are cultured in the Eastern U.S. and is a significant concern to industry stakeholders. Efforts to breed for Dermo resistance in the Eastern Oyster have had modest success, yet the range of existing phenotypic variation with respect to Dermo r...

Assessing the extent of phenotypic variation for dermo resistance among selectively-bred families of the Eastern Oyster, Crassostrea virginica

USDA-ARS?s Scientific Manuscript database

Dermo disease impacts nearly every region where oysters are cultured in the Eastern U.S. and is a significant concern to industry stakeholders. Efforts to breed for Dermo resistance in the Eastern Oyster have had modest success, yet the range of existing phenotypic variation with respect to Dermo ...

Spatial variation in effects of temperature on Phenotypic characteristics of Phytophthora ramorum isolates from eastern Sonoma county

Treesearch

Valerie Sherron; Nathan E. Rank; Michael Cohen; Brian L. Anacker; Ross K. Meentemeyer

2008-01-01

Quantifying the growth rates of plant pathogens in the laboratory can be useful for predicting rates of disease spread and impact in nature. The purpose of this study was to examine phenotypic variation among isolates of Phytophthora ramorum collected from a foliar host plant species, Umbellularia californica (California bay laurel...

Maxillary molars with morphologic variations of the palatal root canals: a report of four cases.

PubMed

Holderrieth, Silke; Gernhardt, Christian Ralf

2009-07-01

The purpose of this article was to show the importance of the knowledge of the anatomy of root canals. Unusual root and root canal morphologies associated with both buccal roots of upper molars have been recorded in several studies in the literature. However, scientific information focusing on variations of the palatal root is rare. In this report, four cases are presented involving the root canal treatment of maxillary first and second molars with unusual morphologic configurations of the palatal root canals. During root canal treatment, type IV and V configurations as defined by Vertucci of the palatal canals of two first and two second maxillary molars were identified. After mechanical instrumentation, the canals were obturated. Radiologic and clinical re-evaluation showed no signs of inflammation. This report describes and discusses the possibility of different root and canal variations of the maxillary molars from a clinical point of view. Anatomic variations can occur in any tooth, and palatal roots of maxillary first and second molars are no exception. Therefore, careful examination of radiographs and internal anatomy of teeth is essential.

Extensive genetic and DNA methylation variation contribute to heterosis in triploid loquat hybrids.

PubMed

Liu, Chao; Wang, Mingbo; Wang, Lingli; Guo, Qigao; Liang, Guolu

2018-04-24

We aim to overcome the unclear origin of the loquat and elucidate the heterosis mechanism of the triploid loquat. Here we investigated the genetic and epigenetic variations between the triploid plant and its parental lines using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified fragment length polymorphism (MSAP) analyses. We show that in addition to genetic variations, extensive DNA methylation variation occurred during the formation process of triploid loquat, with the triploid hybrid having increased DNA methylation compared to the parents. Furthermore, a correlation existed between genetic variation and DNA methylation remodeling, suggesting that genome instability may lead to DNA methylation variation or vice versa. Sequence analysis of the MSAP bands revealed that over 53% of them overlap with protein-coding genes, which may indicate a functional role of the differential DNA methylation in gene regulation and hence heterosis phenotypes. Consistent with this, the genetic and epigenetic alterations were associated closely to the heterosis phenotypes of triploid loquat, and this association varied for different traits. Our results suggested that the formation of triploid is accompanied by extensive genetic and DNA methylation variation, and these changes contribute to the heterosis phenotypes of the triploid loquats from the two cross lines.

Epidemiology and genetics of FTD: a door-to-door survey in Southern Italy

PubMed Central

Colao, Rosanna; Puccio, Gianfranco; Curcio, Sabrina AM; Mirabelli, Maria; Maletta, Raffaele; Anfossi, Maria; Gallo, Maura; Geracitano, Silvana; Conidi, Maria Elena; Di Lorenzo, Raffale; Clodomiro, Alessandra; Cupidi, Chiara; Marzano, Sandra; Comito, Francesco; Valenti, Vincenzo; Zirilli, Maria Angela; Ghani, Mahdi; Xi, Zhengrui; Sato, Christine; Moreno, Danielle; Borelli, Annelisa; Leone, Rosa Anna; St George-Hyslop, Peter; Rogaeva, Ekaterina; Bruni, Amalia C.

2016-01-01

Objectives To estimate FTD prevalence, identify FTD-related mutations, correlate FTD phenotype with mutations in a Southern Italian population. Methods Study population consisting of subjects ≥50 years of age residing in the Community of Biv. on January 1, 2004. Door-to-door two-phase design. Genetic and biochemical analyses were done on samples collected from 32 patients. Results Prevalence rates were 0.6 for AD, 0.4 for VD, 3.5 for FTD, 0.2 for Parkinson Dementia and 1.2 for unspecified dementia. Three GRN (one known and two novel) mutations with reduced plasma protein levels were found associated to three distinct phenotypes (behavioural, affective and delirious type). Conclusions We report an unusually high FTD prevalence in the investigated population, but a low prevalence of AD. We confirm the heterogeneity of FTD phenotype associated with different GRN mutations. PMID:22819134

Adult presentation of Bartter syndrome type IV with erythrocytosis.

PubMed

Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz

2015-01-01

Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis.

Natural Variation of Model Mutant Phenotypes in Ciona intestinalis

PubMed Central

Brown, Euan R.; Leccia, Nicola I.; Squarzoni, Paola; Tarallo, Raffaella; Alfano, Christian; Caputi, Luigi; D'Ambrosio, Palmira; Daniele, Paola; D'Aniello, Enrico; D'Aniello, Salvatore; Maiella, Sylvie; Miraglia, Valentina; Russo, Monia Teresa; Sorrenti, Gerarda; Branno, Margherita; Cariello, Lucio; Cirino, Paola; Locascio, Annamaria; Spagnuolo, Antonietta; Zanetti, Laura; Ristoratore, Filomena

2008-01-01

Background The study of ascidians (Chordata, Tunicata) has made a considerable contribution to our understanding of the origin and evolution of basal chordates. To provide further information to support forward genetics in Ciona intestinalis, we used a combination of natural variation and neutral population genetics as an approach for the systematic identification of new mutations. In addition to the significance of developmental variation for phenotype-driven studies, this approach can encompass important implications in evolutionary and population biology. Methodology/Principal Findings Here, we report a preliminary survey for naturally occurring mutations in three geographically interconnected populations of C. intestinalis. The influence of historical, geographical and environmental factors on the distribution of abnormal phenotypes was assessed by means of 12 microsatellites. We identified 37 possible mutant loci with stereotyped defects in embryonic development that segregate in a way typical of recessive alleles. Local populations were found to differ in genetic organization and frequency distribution of phenotypic classes. Conclusions/Significance Natural genetic polymorphism of C. intestinalis constitutes a valuable source of phenotypes for studying embryonic development in ascidians. Correlating genetic structure and the occurrence of abnormal phenotypes is a crucial focus for understanding the selective forces that shape natural finite populations, and may provide insights of great importance into the evolutionary mechanisms that generate animal diversity. PMID:18523552

Morphological divergence and flow-induced phenotypic plasticity in a native fish from anthropogenically altered stream habitats.

PubMed

Franssen, Nathan R; Stewart, Laura K; Schaefer, Jacob F

2013-11-01

Understanding population-level responses to human-induced changes to habitats can elucidate the evolutionary consequences of rapid habitat alteration. Reservoirs constructed on streams expose stream fishes to novel selective pressures in these habitats. Assessing the drivers of trait divergence facilitated by these habitats will help identify evolutionary and ecological consequences of reservoir habitats. We tested for morphological divergence in a stream fish that occupies both stream and reservoir habitats. To assess contributions of genetic-level differences and phenotypic plasticity induced by flow variation, we spawned and reared individuals from both habitats types in flow and no flow conditions. Body shape significantly and consistently diverged in reservoir habitats compared with streams; individuals from reservoirs were shallower bodied with smaller heads compared with individuals from streams. Significant population-level differences in morphology persisted in offspring but morphological variation compared with field-collected individuals was limited to the head region. Populations demonstrated dissimilar flow-induced phenotypic plasticity when reared under flow, but phenotypic plasticity in response to flow variation was an unlikely explanation for observed phenotypic divergence in the field. Our results, together with previous investigations, suggest the environmental conditions currently thought to drive morphological change in reservoirs (i.e., predation and flow regimes) may not be the sole drivers of phenotypic change.

First report of an unusual novel double mutation affecting the transcription repression domain of MeCP2 and causing a severe phenotype of Rett syndrome: Molecular analyses and computational investigation.

PubMed

Ghorbel, Rania; Ghorbel, Raouia; Rouissi, Aida; Fendri-Kriaa, Nourhene; Ben Salah, Ghada; Belguith, Neila; Ammar-Keskes, Leila; Gouider-Khouja, Neziha; Fakhfakh, Faiza

2018-02-26

Rett syndrome is an X-linked neurodevelopmental disorder that develops a profound intellectual and motor disability and affects 1 from 10 000 to 15 000 live female births. This disease is characterized by a period of apparently normal development until 6-18 months of age when motor and communication abilities regress which is caused by mutations occurred in the X-linked MECP2 gene, encoding the methyl-CpG binding protein 2. This research study reports a molecular analysis via an exhaustive gene sequencing which reveals an unusual novel double mutation (c.695 G > T; c.880C > T) located in a highly conserved region in MECP2 gene affecting the transcription repression domain (TRD) of MeCP2 protein and leading for the first time to a severe phenotype of Rett syndrome. Moreover, a computational investigation of MECP2 mutations demonstrates that the novel mutation c.695 G > T is highly deleterious which affects the MeCP2 protein showing also an adverse impact on MECP2 gene expression and resulting in an affected folding and decreased stability of MECP2 structures. Thus, the altered TRD domain engenders a disrupted process of MECP2 functions. Therefore, this is the first study which highlights a novel double mutation among the transcription repression domain (TRD) of MeCP2 protein in Rett patient with a severe clinical phenotype in North Africa region. Copyright © 2018 Elsevier Inc. All rights reserved.

The Varied Variability of PKS 0736+017

NASA Astrophysics Data System (ADS)

Clements, S. D.; Cubides, L. A.; Greiwe, C. L.; Habermas, K. S.; Jenks, A. K.; Long, A. M.; Patel, J. A.; Torres, Y. V.

2003-05-01

The flat spectrum radio quasar PKS 0736+017 has been an exciting observing target, exhibiting diverse optical variability behaviors and even sharing its field one evening with a minor planet. The behavior of PKS 0736+017 has included persistently faint and quiescent periods, episodes of quasi-periodic microvariability, dramatic flaring events, and periods of unusual oscillations. These assorted behaviors are examined, with particular emphasis on the quasi-periodic variations and unusual oscillations that accompanied a dramatic flare.

Fluctuating selection across years and phenotypic variation in food-deceptive orchids.

PubMed

Scopece, Giovanni; Juillet, Nicolas; Lexer, Christian; Cozzolino, Salvatore

2017-01-01

Nectarless flowers that deceive pollinators offer an opportunity to study asymmetric plant-insect interactions. Orchids are a widely used model for studying these interactions because they encompass several thousand species adopting deceptive pollination systems. High levels of intra-specific phenotypic variation have been reported in deceptive orchids, suggesting a reduced consistency of pollinator-mediated selection on their floral traits. Nevertheless, several studies report on widespread directional selection mediated by pollinators even in these deceptive orchids. In this study we test the hypothesis that the observed selection can fluctuate across years in strength and direction thus likely contributing to the phenotypic variability of this orchid group. We performed a three-year study estimating selection differentials and selection gradients for nine phenotypic traits involved in insect attraction in two Mediterranean orchid species, namely Orchis mascula and O. pauciflora , both relying on a well-described food-deceptive pollination strategy. We found weak directional selection and marginally significant selection gradients in the two investigated species with significant intra-specific differences in selection differentials across years. Our data do not link this variation with a specific environmental cause, but our results suggest that pollinator-mediated selection in food-deceptive orchids can change in strength and in direction over time. In perennial plants, such as orchids, different selection differentials in the same populations in different flowering seasons can contribute to the maintenance of phenotypic variation often reported in deceptive orchids.

MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.

PubMed

Townend, Gillian S; Ehrhart, Friederike; van Kranen, Henk J; Wilkinson, Mark; Jacobsen, Annika; Roos, Marco; Willighagen, Egon L; van Enckevort, David; Evelo, Chris T; Curfs, Leopold M G

2018-04-27

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data. © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.

Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

PubMed

Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

2014-02-15

The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.

The ecology of an adaptive radiation of three-spined stickleback from North Uist, Scotland.

PubMed

Magalhaes, Isabel S; D'Agostino, Daniele; Hohenlohe, Paul A; MacColl, Andrew D C

2016-09-01

There has been a large focus on the genetics of traits involved in adaptation, but knowledge of the environmental variables leading to adaptive changes is surprisingly poor. Combined use of environmental data with morphological and genomic data should allow us to understand the extent to which patterns of phenotypic and genetic diversity within a species can be explained by the structure of the environment. Here, we analyse the variation of populations of three-spined stickleback from 27 freshwater lakes on North Uist, Scotland, that vary greatly in their environment, to understand how environmental and genetic constraints contribute to phenotypic divergence. We collected 35 individuals per population and 30 abiotic and biotic environmental parameters to characterize variation across lakes and analyse phenotype-environment associations. Additionally, we used RAD sequencing to estimate the genetic relationships among a subset of these populations. We found a large amount of phenotypic variation among populations, most prominently in armour and spine traits. Despite large variation in the abiotic environment, namely in ion composition, depth and dissolved organic Carbon, more phenotypic variation was explained by the biotic variables (presence of predators and density of predator and competitors), than by associated abiotic variables. Genetic structure among populations was partly geographic, with closer populations being more similar. Altogether, our results suggest that differences in body shape among stickleback populations are the result of both canalized genetic and plastic responses to environmental factors, which shape fish morphology in a predictable direction regardless of their genetic starting point. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Phenotypic variation and covariation indicate high evolvability of acoustic communication in crickets.

PubMed

Blankers, T; Lübke, A K; Hennig, R M

2015-09-01

Studying the genetic architecture of sexual traits provides insight into the rate and direction at which traits can respond to selection. Traits associated with few loci and limited genetic and phenotypic constraints tend to evolve at high rates typically observed for secondary sexual characters. Here, we examined the genetic architecture of song traits and female song preferences in the field crickets Gryllus rubens and Gryllus texensis. Song and preference data were collected from both species and interspecific F1 and F2 hybrids. We first analysed phenotypic variation to examine interspecific differentiation and trait distributions in parental and hybrid generations. Then, the relative contribution of additive and additive-dominance variation was estimated. Finally, phenotypic variance-covariance (P) matrices were estimated to evaluate the multivariate phenotype available for selection. Song traits and preferences had unimodal trait distributions, and hybrid offspring were intermediate with respect to the parents. We uncovered additive and dominance variation in song traits and preferences. For two song traits, we found evidence for X-linked inheritance. On the one hand, the observed genetic architecture does not suggest rapid divergence, although sex linkage may have allowed for somewhat higher evolutionary rates. On the other hand, P matrices revealed that multivariate variation in song traits aligned with major dimensions in song preferences, suggesting a strong selection response. We also found strong covariance between the main traits that are sexually selected and traits that are not directly selected by females, providing an explanation for the striking multivariate divergence in male calling songs despite limited divergence in female preferences. © 2015 European Society For Evolutionary Biology.

Consistent individual differences in the social phenotypes of wild great tits, Parus major

PubMed Central

Aplin, L.M.; Firth, J.A.; Farine, D.R.; Voelkl, B.; Crates, R.A.; Culina, A.; Garroway, C.J.; Hinde, C.A.; Kidd, L.R.; Psorakis, I.; Milligan, N.D.; Radersma, R.; Verhelst, B.L.; Sheldon, B.C.

2015-01-01

Despite growing interest in animal social networks, surprisingly little is known about whether individuals are consistent in their social network characteristics. Networks are rarely repeatedly sampled; yet an assumption of individual consistency in social behaviour is often made when drawing conclusions about the consequences of social processes and structure. A characterization of such social phenotypes is therefore vital to understanding the significance of social network structure for individual fitness outcomes, and for understanding the evolution and ecology of individual variation in social behaviour more broadly. Here, we measured foraging associations over three winters in a large PIT-tagged population of great tits, and used a range of social network metrics to quantify individual variation in social behaviour. We then examined repeatability in social behaviour over both short (week to week) and long (year to year) timescales, and investigated variation in repeatability across age and sex classes. Social behaviours were significantly repeatable across all timescales, with the highest repeatability observed in group size choice and unweighted degree, a measure of gregariousness. By conducting randomizations to control for the spatial and temporal distribution of individuals, we further show that differences in social phenotypes were not solely explained by within-population variation in local densities, but also reflected fine-scale variation in social decision making. Our results provide rare evidence of stable social phenotypes in a wild population of animals. Such stable social phenotypes can be targets of selection and may have important fitness consequences, both for individuals and for their social-foraging associates. PMID:26512142

Probing the Reproducibility of Leaf Growth and Molecular Phenotypes: A Comparison of Three Arabidopsis Accessions Cultivated in Ten Laboratories1[W

PubMed Central

Massonnet, Catherine; Vile, Denis; Fabre, Juliette; Hannah, Matthew A.; Caldana, Camila; Lisec, Jan; Beemster, Gerrit T.S.; Meyer, Rhonda C.; Messerli, Gaëlle; Gronlund, Jesper T.; Perkovic, Josip; Wigmore, Emma; May, Sean; Bevan, Michael W.; Meyer, Christian; Rubio-Díaz, Silvia; Weigel, Detlef; Micol, José Luis; Buchanan-Wollaston, Vicky; Fiorani, Fabio; Walsh, Sean; Rinn, Bernd; Gruissem, Wilhelm; Hilson, Pierre; Hennig, Lars; Willmitzer, Lothar; Granier, Christine

2010-01-01

A major goal of the life sciences is to understand how molecular processes control phenotypes. Because understanding biological systems relies on the work of multiple laboratories, biologists implicitly assume that organisms with the same genotype will display similar phenotypes when grown in comparable conditions. We investigated to what extent this holds true for leaf growth variables and metabolite and transcriptome profiles of three Arabidopsis (Arabidopsis thaliana) genotypes grown in 10 laboratories using a standardized and detailed protocol. A core group of four laboratories generated similar leaf growth phenotypes, demonstrating that standardization is possible. But some laboratories presented significant differences in some leaf growth variables, sometimes changing the genotype ranking. Metabolite profiles derived from the same leaf displayed a strong genotype × environment (laboratory) component. Genotypes could be separated on the basis of their metabolic signature, but only when the analysis was limited to samples derived from one laboratory. Transcriptome data revealed considerable plant-to-plant variation, but the standardization ensured that interlaboratory variation was not considerably larger than intralaboratory variation. The different impacts of the standardization on phenotypes and molecular profiles could result from differences of temporal scale between processes involved at these organizational levels. Our findings underscore the challenge of describing, monitoring, and precisely controlling environmental conditions but also demonstrate that dedicated efforts can result in reproducible data across multiple laboratories. Finally, our comparative analysis revealed that small variations in growing conditions (light quality principally) and handling of plants can account for significant differences in phenotypes and molecular profiles obtained in independent laboratories. PMID:20200072

Limited phenotypic variation of hypocalcified amelogenesis imperfecta in a Danish five-generation family with a novel FAM83H nonsense mutation.

PubMed

Haubek, Dorte; Gjørup, Hans; Jensen, Lillian G; Juncker, Inger; Nyegaard, Mette; Børglum, Anders D; Poulsen, Sven; Hertz, Jens M

2011-11-01

BACKGROUND.  Autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI) is a disease with severe dental manifestations. OBJECTIVES.  The aims were by means of a genome-wide linkage scan to search for the gene underlying the ADHCAI phenotype in a Danish five-generation family and to study the phenotypic variation of the enamel in affected family members. RESULTS.  Significant linkage was found to a locus at chromosome 8q24.3 comprising the gene FAM83H identified to be responsible for ADHCAI in other families. Subsequent sequencing of FAM83H in affected family members revealed a novel nonsense mutation, p.Y302X. Limited phenotypic variation was found among affected family members with loss of translucency and discoloration of the enamel. Extensive posteruptive loss of enamel was found in all teeth of affected subjects. The tip of the cusps on the premolars and molars and a zone along the gingival margin seemed resistant to posteruptive loss of enamel. We have screened FAM83H in another five unrelated Danish patients with a phenotype of ADHCAI similar to that in the five-generation family, and identified a de novo FAM83H nonsense mutation, p.Q452X in one of these patients. CONCLUSION.  We have identified a FAM83H mutation in two of six unrelated families with ADHCAI and found limited phenotypic variation of the enamel in these patients. © 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.

Double-strand break repair processes drive evolution of the mitochondrial genome in Arabidopsis.

PubMed

Davila, Jaime I; Arrieta-Montiel, Maria P; Wamboldt, Yashitola; Cao, Jun; Hagmann, Joerg; Shedge, Vikas; Xu, Ying-Zhi; Weigel, Detlef; Mackenzie, Sally A

2011-09-27

The mitochondrial genome of higher plants is unusually dynamic, with recombination and nonhomologous end-joining (NHEJ) activities producing variability in size and organization. Plant mitochondrial DNA also generally displays much lower nucleotide substitution rates than mammalian or yeast systems. Arabidopsis displays these features and expedites characterization of the mitochondrial recombination surveillance gene MSH1 (MutS 1 homolog), lending itself to detailed study of de novo mitochondrial genome activity. In the present study, we investigated the underlying basis for unusual plant features as they contribute to rapid mitochondrial genome evolution. We obtained evidence of double-strand break (DSB) repair, including NHEJ, sequence deletions and mitochondrial asymmetric recombination activity in Arabidopsis wild-type and msh1 mutants on the basis of data generated by Illumina deep sequencing and confirmed by DNA gel blot analysis. On a larger scale, with mitochondrial comparisons across 72 Arabidopsis ecotypes, similar evidence of DSB repair activity differentiated ecotypes. Forty-seven repeat pairs were active in DNA exchange in the msh1 mutant. Recombination sites showed asymmetrical DNA exchange within lengths of 50- to 556-bp sharing sequence identity as low as 85%. De novo asymmetrical recombination involved heteroduplex formation, gene conversion and mismatch repair activities. Substoichiometric shifting by asymmetrical exchange created the appearance of rapid sequence gain and loss in association with particular repeat classes. Extensive mitochondrial genomic variation within a single plant species derives largely from DSB activity and its repair. Observed gene conversion and mismatch repair activity contribute to the low nucleotide substitution rates seen in these genomes. On a phenotypic level, these patterns of rearrangement likely contribute to the reproductive versatility of higher plants.

Genetic Architecture of Nest Building in Mice LG/J × SM/J

PubMed Central

Sauce, Bruno; de Brito, Reinaldo Alves; Peripato, Andrea Cristina

2012-01-01

Maternal care is critical to offspring growth and survival, which is greatly improved by building an effective nest. Some suggest that genetic variation and underlying genetic effects differ between fitness-related traits and other phenotypes. We investigated the genetic architecture of a fitness-related trait, nest building, in F2 female mice intercrossed from inbred strains SM/J and LG/J using a QTL analysis for six related nest phenotypes (Presence and Structure pre- and postpartum, prepartum Material Used and postpartum Temperature). We found 15 direct-effect QTLs explaining from 4 to 13% of the phenotypic variation in nest building, mostly with non-additive effect. Epistatic analyses revealed 71 significant epistatic interactions which together explain from 28.4 to 75.5% of the variation, indicating an important role for epistasis in the adaptive process of nest building behavior in mice. Our results suggest a genetic architecture with small direct effects and a larger number of epistatic interactions as expected for fitness-related phenotypes. PMID:22654894

Proteome-wide association studies identify biochemical modules associated with a wing-size phenotype in Drosophila melanogaster.

PubMed

Okada, Hirokazu; Ebhardt, H Alexander; Vonesch, Sibylle Chantal; Aebersold, Ruedi; Hafen, Ernst

2016-09-01

The manner by which genetic diversity within a population generates individual phenotypes is a fundamental question of biology. To advance the understanding of the genotype-phenotype relationships towards the level of biochemical processes, we perform a proteome-wide association study (PWAS) of a complex quantitative phenotype. We quantify the variation of wing imaginal disc proteomes in Drosophila genetic reference panel (DGRP) lines using SWATH mass spectrometry. In spite of the very large genetic variation (1/36 bp) between the lines, proteome variability is surprisingly small, indicating strong molecular resilience of protein expression patterns. Proteins associated with adult wing size form tight co-variation clusters that are enriched in fundamental biochemical processes. Wing size correlates with some basic metabolic functions, positively with glucose metabolism but negatively with mitochondrial respiration and not with ribosome biogenesis. Our study highlights the power of PWAS to filter functional variants from the large genetic variability in natural populations.

Neuroendocrinology of Sexual Plasticity in Teleost Fishes

PubMed Central

Godwin, John

2010-01-01

The study of sex differences has produced major insights into the organization of animal phenotypes and the regulatory mechanisms generating phenotypic variation from similar genetic templates. Teleost fishes display the greatest diversity of sexual expression among vertebrate animals. This diversity appears to arise from diversity in the timing of sex determination and less functional interdependence among the components of sexuality relative to tetrapod vertebrates. Teleost model systems therefore provide powerful models for understanding gonadal and non-gonadal influences on behavioral and physiological variation. This review addresses socially controlled sex change and alternate male phenotypes in fishes. These sexual patterns are informative natural experiments that illustrate how variation in conserved neuroendocrine pathways can give rise to a wide range of reproductive adaptations. Key regulatory factors underlying sex change and alternative male phenotypes that have been identified to date include steroid hormones and the neuropeptides GnRH and arginine vasotocin, but genomic approaches are now implicating a diversity of other influences as well. PMID:20176046

The evolution of phenotypic correlations and ‘developmental memory’

PubMed Central

Watson, Richard A.; Wagner, Günter P.; Pavlicev, Mihaela; Weinreich, Daniel M.; Mills, Rob

2014-01-01

Development introduces structured correlations among traits that may constrain or bias the distribution of phenotypes produced. Moreover, when suitable heritable variation exists, natural selection may alter such constraints and correlations, affecting the phenotypic variation available to subsequent selection. However, exactly how the distribution of phenotypes produced by complex developmental systems can be shaped by past selective environments is poorly understood. Here we investigate the evolution of a network of recurrent non-linear ontogenetic interactions, such as a gene regulation network, in various selective scenarios. We find that evolved networks of this type can exhibit several phenomena that are familiar in cognitive learning systems. These include formation of a distributed associative memory that can ‘store’ and ‘recall’ multiple phenotypes that have been selected in the past, recreate complete adult phenotypic patterns accurately from partial or corrupted embryonic phenotypes, and ‘generalise’ (by exploiting evolved developmental modules) to produce new combinations of phenotypic features. We show that these surprising behaviours follow from an equivalence between the action of natural selection on phenotypic correlations and associative learning, well-understood in the context of neural networks. This helps to explain how development facilitates the evolution of high-fitness phenotypes and how this ability changes over evolutionary time. PMID:24351058

A previously unreported association between Nance-Horan syndrome and spontaneous dental abscesses.

PubMed

Hibbert, Sally

2005-02-01

Atypical dentofacial structures may be the first indicator of other anomalies linked to a syndrome. This case describes the management of a 9-year-old girl referred for the routine management of supernumerary teeth. The anomalous form of her teeth, together with multiple supernumerary units and a history of congenital cataracts, were suggestive of a diagnosis of Nance-Horan syndrome. This is an X-linked disorder, in which females usually demonstrate mild expression; this case was unusual in respect to the marked phenotype expressed. Unusually, the girl developed 2 spontaneous abscesses of her noncarious upper incisor teeth; a feature never previously described in this syndrome. This report details the patient's dental management and discusses the possible pathogenesis of the dental abscesses, together with the genetic implications of this syndrome.

Dissection of complex adult traits in a mouse synthetic population.

PubMed

Burke, David T; Kozloff, Kenneth M; Chen, Shu; West, Joshua L; Wilkowski, Jodi M; Goldstein, Steven A; Miller, Richard A; Galecki, Andrzej T

2012-08-01

Finding the causative genetic variations that underlie complex adult traits is a significant experimental challenge. The unbiased search strategy of genome-wide association (GWAS) has been used extensively in recent human population studies. These efforts, however, typically find only a minor fraction of the genetic loci that are predicted to affect variation. As an experimental model for the analysis of adult polygenic traits, we measured a mouse population for multiple phenotypes and conducted a genome-wide search for effector loci. Complex adult phenotypes, related to body size and bone structure, were measured as component phenotypes, and each subphenotype was associated with a genomic spectrum of candidate effector loci. The strategy successfully detected several loci for the phenotypes, at genome-wide significance, using a single, modest-sized population (N = 505). The effector loci each explain 2%-10% of the measured trait variation and, taken together, the loci can account for over 25% of a trait's total population variation. A replicate population (N = 378) was used to confirm initially observed loci for one trait (femur length), and, when the two groups were merged, the combined population demonstrated increased power to detect loci. In contrast to human population studies, our mouse genome-wide searches find loci that individually explain a larger fraction of the observed variation. Also, the additive effects of our detected mouse loci more closely match the predicted genetic component of variation. The genetic loci discovered are logical candidates for components of the genetic networks having evolutionary conservation with human biology.

Variation and Functional Impact of Neanderthal Ancestry in Western Asia.

PubMed

Taskent, Recep Ozgur; Alioglu, Nursen Duha; Fer, Evrim; Melike Donertas, Handan; Somel, Mehmet; Gokcumen, Omer

2017-12-01

Neanderthals contributed genetic material to modern humans via multiple admixture events. Initial admixture events presumably occurred in Western Asia shortly after humans migrated out of Africa. Despite being a focal point of admixture, earlier studies indicate lower Neanderthal introgression rates in some Western Asian populations as compared with other Eurasian populations. To better understand the genome-wide and phenotypic impact of Neanderthal introgression in the region, we sequenced whole genomes of nine present-day Europeans, Africans, and the Western Asian Druze at high depth, and analyzed available whole genome data from various other populations, including 16 genomes from present-day Turkey. Our results confirmed previous observations that contemporary Western Asian populations, on an average, have lower levels of Neanderthal-introgressed DNA relative to other Eurasian populations. Modern Western Asians also show comparatively high variability in Neanderthal ancestry, which may be attributed to the complex demographic history of the region. We further replicated the previously described depletion of putatively functional sequences among Neanderthal-introgressed haplotypes. Still, we find dozens of common Neanderthal-introgressed haplotypes in the Turkish sample associated with human phenotypes, including anthropometric and metabolic traits, as well as the immune response. One of these haplotypes is unusually long and harbors variants that affect the expression of members of the CCR gene family and are associated with celiac disease. Overall, our results paint a complex first picture of the genomic impact of Neanderthal introgression in the Western Asian populations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

MALDI-TOF mass spectrometry proteomic phenotyping of clinically relevant fungi.

PubMed

Putignani, Lorenza; Del Chierico, Federica; Onori, Manuela; Mancinelli, Livia; Argentieri, Marta; Bernaschi, Paola; Coltella, Luana; Lucignano, Barbara; Pansani, Laura; Ranno, Stefania; Russo, Cristina; Urbani, Andrea; Federici, Giorgio; Menichella, Donato

2011-03-01

Proteomics is particularly suitable for characterising human pathogens with high life cycle complexity, such as fungi. Protein content and expression levels may be affected by growth states and life cycle morphs and correlate to species and strain variation. Identification and typing of fungi by conventional methods are often difficult, time-consuming and frequently, for unusual species, inconclusive. Proteomic phenotypes from MALDI-TOF MS were employed as analytical and typing expression profiling of yeast, yeast-like species and strain variants in order to achieve a microbial proteomics population study. Spectra from 303 clinical isolates were generated and processed by standard pattern matching with a MALDI-TOF Biotyper (MT). Identifications (IDs) were compared to a reference biochemical-based system (Vitek-2) and, when discordant, MT IDs were verified with genotyping IDs, obtained by sequencing the 25-28S rRNA hypervariable D2 region. Spectra were converted into virtual gel-like formats, and hierarchical clustering analysis was performed for 274 Candida profiles to investigate species and strain typing correlation. MT provided 257/303 IDs consistent with Vitek-2 ones. However, amongst 26/303 discordant MT IDs, only 5 appeared "true". No MT identification was achieved for 20/303 isolates for incompleteness of database species variants. Candida spectra clustering agreed with identified species and topology of Candida albicans and Candida parapsilosis specific dendrograms. MT IDs show a high analytical performance and profiling heterogeneity which seems to complement or even outclass existing typing tools. This variability reflects the high biological complexity of yeasts and may be properly exploited to provide epidemiological tracing and infection dispersion patterns.

Evolutionary genetics of maternal effects

PubMed Central

Wolf, Jason B.; Wade, Michael J.

2016-01-01

Maternal genetic effects (MGEs), where genes expressed by mothers affect the phenotype of their offspring, are important sources of phenotypic diversity in a myriad of organisms. We use a single‐locus model to examine how MGEs contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations. We elucidate the influence of MGEs by examining the offspring genotype‐phenotype relationship, which determines how MGEs affect evolutionary dynamics in response to selection on offspring phenotypes. This approach reveals important results that are not apparent from classic quantitative genetic treatments of MGEs. We show that additive and dominance MGEs make different contributions to evolutionary dynamics and patterns of variation, which are differentially affected by inbreeding. Dominance MGEs make the offspring genotype‐phenotype relationship frequency dependent, resulting in the appearance of negative frequency‐dependent selection, while additive MGEs contribute a component of parent‐of‐origin dependent variation. Inbreeding amplifies the contribution of MGEs to the additive genetic variance and, therefore enhances their evolutionary response. Considering evolutionary dynamics of allele frequency change on an adaptive landscape, we show that this landscape differs from the mean fitness surface, and therefore, under some condition, fitness peaks can exist but not be “available” to the evolving population. PMID:26969266

Development of resources and tools for mapping genetic sources of phenotypic variation

USDA-ARS?s Scientific Manuscript database

Commercial and experimental genetic resources were established and investigated for a range of reproductive and disease susceptibility phenotypes. The phenotyping efforts were accompanied with RNA and whole genome sequencing and novel assemblies of the swine genome. The efforts were complemented wit...

Why the short face? Developmental disintegration of the neurocranium drives convergent evolution in neotropical electric fishes.

PubMed

Evans, Kory M; Waltz, Brandon; Tagliacollo, Victor; Chakrabarty, Prosanta; Albert, James S

2017-03-01

Convergent evolution is widely viewed as strong evidence for the influence of natural selection on the origin of phenotypic design. However, the emerging evo-devo synthesis has highlighted other processes that may bias and direct phenotypic evolution in the presence of environmental and genetic variation. Developmental biases on the production of phenotypic variation may channel the evolution of convergent forms by limiting the range of phenotypes produced during ontogeny. Here, we study the evolution and convergence of brachycephalic and dolichocephalic skull shapes among 133 species of Neotropical electric fishes (Gymnotiformes: Teleostei) and identify potential developmental biases on phenotypic evolution. We plot the ontogenetic trajectories of neurocranial phenotypes in 17 species and document developmental modularity between the face and braincase regions of the skull. We recover a significant relationship between developmental covariation and relative skull length and a significant relationship between developmental covariation and ontogenetic disparity. We demonstrate that modularity and integration bias the production of phenotypes along the brachycephalic and dolichocephalic skull axis and contribute to multiple, independent evolutionary transformations to highly brachycephalic and dolichocephalic skull morphologies.

Embouchure dystonia--Portrait of a task-specific cranial dystonia.

PubMed

Frucht, Steven J

2009-09-15

Focal task-specific dystonia (FTSD) is an unusual disorder of motor control, which typically affects the hand but may also involve the face, jaw, and tongue. We report 89 musicians with dystonia of the embouchure (ED), the muscles of the lower face, jaw, and tongue used to control the flow of air into the mouthpiece of a woodwind or brass instrument. Symptoms of ED began at an average age of 36, were typically painless and only rarely were preceded by trauma. Specific musical techniques commonly triggered dystonia, often in one instrumental register. Task-specific embouchure tremor and lip-pulling ED phenotypes were common among high-register brass players (trumpet and French horn), whereas lip-locking occurred exclusively in low-register brass players (trombone and tuba). Jaw and tongue ED phenotypes occurred predominantly in woodwind players, and once present, frequently spread to speaking or eating. Six percent of all ED patients had coincident writer's cramp, suggesting a possible genetic predisposition to develop dystonia. We assessed two-point sensory discrimination in the upper lip, lower lip, and hand in ED patients, normal musicians, and nonmusician age-matched controls--there were no differences between groups. Once present, symptoms of ED did not remit and often disrupted careers and livelihoods. Better treatments are urgently needed for this unusual disorder of oral motor control.

Characterization of Genome-Wide Variation in Four-Row Wax, a Waxy Maize Landrace with a Reduced Kernel Row Phenotype

PubMed Central

Liu, Hanmei; Wang, Xuewen; Wei, Bin; Wang, Yongbin; Liu, Yinghong; Zhang, Junjie; Hu, Yufeng; Yu, Guowu; Li, Jian; Xu, Zhanbin; Huang, Yubi

2016-01-01

In southwest China, some maize landraces have long been isolated geographically, and have phenotypes that differ from those of widely grown cultivars. These landraces may harbor rich genetic variation responsible for those phenotypes. Four-row Wax is one such landrace, with four rows of kernels on the cob. We resequenced the genome of Four-row Wax, obtaining 50.46 Gb sequence at 21.87× coverage, then identified and characterized 3,252,194 SNPs, 213,181 short InDels (1–5 bp) and 39,631 structural variations (greater than 5 bp). Of those, 312,511 (9.6%) SNPs were novel compared to the most detailed haplotype map (HapMap) SNP database of maize. Characterization of variations in reported kernel row number (KRN) related genes and KRN QTL regions revealed potential causal mutations in fea2, td1, kn1, and te1. Genome-wide comparisons revealed abundant genetic variations in Four-row Wax, which may be associated with environmental adaptation. The sequence and SNP variations described here enrich genetic resources of maize, and provide guidance into study of seed numbers for crop yield improvement. PMID:27242868

Comparative epigenetic and genetic spatial structure of the perennial herb Helleborus foetidus: Isolation by environment, isolation by distance, and functional trait divergence.

PubMed

Herrera, Carlos M; Medrano, Mónica; Bazaga, Pilar

2017-08-16

Epigenetic variation can play a role in local adaptation; thus, there should be associations among epigenetic variation, environmental variation, and functional trait variation across populations. This study examines these relationships in the perennial herb Helleborus foetidus (Ranunculaceae). Plants from 10 subpopulations were characterized genetically (AFLP, SSR markers), epigenetically (MSAP markers), and phenotypically (20 functional traits). Habitats were characterized using six environmental variables. Isolation-by-distance (IBD) and isolation-by-environment (IBE) patterns of genetic and epigenetic divergence were assessed, as was the comparative explanatory value of geographical and environmental distance as predictors of epigenetic, genetic, and functional differentiation. Subpopulations were differentiated genetically, epigenetically, and phenotypically. Genetic differentiation was best explained by geographical distance, while epigenetic differentiation was best explained by environmental distance. Divergence in functional traits was correlated with environmental and epigenetic distances, but not with geographical and genetic distances. Results are compatible with the hypothesis that epigenetic IBE and functional divergence reflected responses to environmental variation. Spatial analyses simultaneously considering epigenetic, genetic, phenotypic and environmental information provide a useful tool to evaluate the role of environmental features as drivers of natural epigenetic variation between populations. © 2017 Botanical Society of America.

Intra and Interspecific Variations of Gene Expression Levels in Yeast Are Largely Neutral: (Nei Lecture, SMBE 2016, Gold Coast).

PubMed

Yang, Jian-Rong; Maclean, Calum J; Park, Chungoo; Zhao, Huabin; Zhang, Jianzhi

2017-09-01

It is commonly, although not universally, accepted that most intra and interspecific genome sequence variations are more or less neutral, whereas a large fraction of organism-level phenotypic variations are adaptive. Gene expression levels are molecular phenotypes that bridge the gap between genotypes and corresponding organism-level phenotypes. Yet, it is unknown whether natural variations in gene expression levels are mostly neutral or adaptive. Here we address this fundamental question by genome-wide profiling and comparison of gene expression levels in nine yeast strains belonging to three closely related Saccharomyces species and originating from five different ecological environments. We find that the transcriptome-based clustering of the nine strains approximates the genome sequence-based phylogeny irrespective of their ecological environments. Remarkably, only ∼0.5% of genes exhibit similar expression levels among strains from a common ecological environment, no greater than that among strains with comparable phylogenetic relationships but different environments. These and other observations strongly suggest that most intra and interspecific variations in yeast gene expression levels result from the accumulation of random mutations rather than environmental adaptations. This finding has profound implications for understanding the driving force of gene expression evolution, genetic basis of phenotypic adaptation, and general role of stochasticity in evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy.

PubMed

Heinig, Matthias; Adriaens, Michiel E; Schafer, Sebastian; van Deutekom, Hanneke W M; Lodder, Elisabeth M; Ware, James S; Schneider, Valentin; Felkin, Leanne E; Creemers, Esther E; Meder, Benjamin; Katus, Hugo A; Rühle, Frank; Stoll, Monika; Cambien, François; Villard, Eric; Charron, Philippe; Varro, Andras; Bishopric, Nanette H; George, Alfred L; Dos Remedios, Cristobal; Moreno-Moral, Aida; Pesce, Francesco; Bauerfeind, Anja; Rüschendorf, Franz; Rintisch, Carola; Petretto, Enrico; Barton, Paul J; Cook, Stuart A; Pinto, Yigal M; Bezzina, Connie R; Hubner, Norbert

2017-09-14

Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics.

Translation of Genotype to Phenotype by a Hierarchy of Cell Subsystems.

PubMed

Yu, Michael Ku; Kramer, Michael; Dutkowski, Janusz; Srivas, Rohith; Licon, Katherine; Kreisberg, Jason; Ng, Cherie T; Krogan, Nevan; Sharan, Roded; Ideker, Trey

2016-02-24

Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology's hierarchical structure, we organize genotype data into an "ontotype," that is, a hierarchy of perturbations representing the effects of genetic variation at multiple cellular scales. The ontotype is then interpreted using logical rules generated by machine learning to predict phenotype. This approach substantially outperforms previous, non-hierarchical methods for translating yeast genotype to cell growth phenotype, and it accurately predicts the growth outcomes of two new screens of 2,503 double gene knockouts impacting DNA repair or nuclear lumen. Ontotypes also generalize to larger knockout combinations, setting the stage for interpreting the complex genetics of disease.

Puncture-and-Pull Biomechanics in the Teeth of Predatory Coelurosaurian Dinosaurs.

PubMed

Torices, Angelica; Wilkinson, Ryan; Arbour, Victoria M; Ruiz-Omeñaca, Jose Ignacio; Currie, Philip J

2018-05-07

The teeth of putatively carnivorous dinosaurs are often blade-shaped with well-defined serrated cutting edges (Figure 1). These ziphodont teeth are often easily differentiated based on the morphology and density of the denticles [1, 2]. A tearing function has been proposed for theropod denticles in general [3], but the functional significance of denticle phenotypic variation has received less attention. In particular, the unusual hooked denticles found in troodontids suggest a different feeding strategy or diet compared to other small theropods. We used a two-pronged approach to investigate the function of denticle shape variation across theropods with both congruent body shapes and sizes (e.g., dromaeosaurids versus troodontids) and highly disparate body shapes and sizes (e.g., troodontids versus tyrannosaurids), using microwear and finite element analyses (Figure 1). We found that many toothed coelurosaurian theropods employed a puncture-and-pull feeding movement, in which parallel scratches form while biting down into prey and oblique scratches form as the head is pulled backward with the jaws closed. In finite element simulations, theropod teeth had the lowest stresses when bite forces were aligned with the oblique family of microwear scratches. Different denticle morphologies performed differently under a variety of simulated biting angles: Dromaeosaurus and Saurornitholestes were well-adapted for handling struggling prey, whereas troodontid teeth were more likely to fail at non-optimal bite angles. Troodontids may have favored softer, smaller, or immobile prey. Copyright © 2018 Elsevier Ltd. All rights reserved.

Unusual structural transition of antimicrobial VP1 peptide.

PubMed

Shanmugam, Ganesh; Phambu, Nsoki; Polavarapu, Prasad L

2011-05-01

VP1 peptide, an active domain of m-calpain enzyme with antimicrobial activity is found to undergo an unusual conformational transition in trifluoroethanol (TFE) solvent. The nature of, and time dependent variations in, circular dichroism associated with the amide I vibrations, suggest that VP1 undergoes self-aggregation forming anti-parallel β-sheet structure in TFE. Transmission electron micrograph (TEM) images revealed that β-sheet aggregates formed by VP1 possess fibril-like assemblies. Copyright © 2011 Elsevier B.V. All rights reserved.

[A mandibular second molar with three mesial roots: report of one case].

PubMed

Zhang, Ping

2010-02-01

A case of unusual root canal morphology was presented to demonstrate anatomic variations in mandibular second molars. This case report presented the endodontic therapy of a mandibular second molar with three canals in the mesial root. A mesial middle canal was found between the mesiobuccal and mesiolingual canals. This report indicated the importance of looking for additional canals and unusual canal morphology, because knowledge of their existence might occasionally enable clinicians to treat a case successfully that otherwise to fail.

Phenotypic variation among trees in a population of a Pistacia atlantica X P. integerrima cross sold as UCB-1 rootstock for grafting P. vera (pistachio) cultivars

USDA-ARS?s Scientific Manuscript database

UCB-1 is widely used in California as a pistachio rootstock because of its Verticillium resistance, salt and cold tolerance, and vigor. It can grow in most locations in California. However, significant variation exists in the phenotypic performance of trees grafted to seedling UCB-1 rootstocks. In J...

Testing whether macroevolution follows microevolution: Are colour differences among swans (Cygnus) attributable to variation at the MC1R locus?

PubMed Central

2008-01-01

Background The MC1R (melanocortin-1 receptor) locus underlies intraspecific variation in melanin-based dark plumage coloration in several unrelated birds with plumage polymorphisms. There is far less evidence for functional variants of MC1R being involved in interspecific variation, in which spurious genotype-phenotype associations arising through population history are a far greater problem than in intraspecific studies. We investigated the relationship between MC1R variation and plumage coloration in swans (Cygnus), which show extreme variation in melanic plumage phenotypes among species (white to black). Results The two species with melanic plumage, C. atratus and C. melanocoryphus (black and black-necked swans respectively), both have amino acid changes at important functional sites in MC1R that are consistent with increased MC1R activity and melanism. Reconstruction of MC1R evolution over a newly generated independent molecular phylogeny of Cygnus and related genera shows that these putative melanizing mutations were independently derived in the two melanic lineages. However, interpretation is complicated by the fact that one of the outgroup genera, Coscoroba, also has a putative melanizing mutation at MC1R that has arisen independently but has nearly pure white plumage. Epistasis at other loci seems the most likely explanation for this discrepancy. Unexpectedly, the phylogeny shows that the genus Cygnus may not be monophyletic, with C. melanocoryphus placed as a sister group to true geese (Anser), but further data will be needed to confirm this. Conclusion Our study highlights the difficulty of extrapolating from intraspecific studies to understand the genetic basis of interspecific adaptive phenotypic evolution, even with a gene whose structure-function relationships are as well understood as MC1R as confounding variation make clear genotype/phenotype associations difficult at the macroevolutionary scale. However, the identification of substitutions in the black and black-necked swan that are known to be associated with melanic phenotypes, suggests Cygnus may be another example where there appears to be convergent evolution at MC1R. This study therefore provides a novel example where previously described intraspecific genotype/phenotype associations occur at the macroevolutionary level. PMID:18789136

Testing whether macroevolution follows microevolution: are colour differences among swans (Cygnus) attributable to variation at the MCIR locus?

PubMed

Pointer, Marie A; Mundy, Nicholas I

2008-09-12

The MC1R (melanocortin-1 receptor) locus underlies intraspecific variation in melanin-based dark plumage coloration in several unrelated birds with plumage polymorphisms. There is far less evidence for functional variants of MC1R being involved in interspecific variation, in which spurious genotype-phenotype associations arising through population history are a far greater problem than in intraspecific studies. We investigated the relationship between MC1R variation and plumage coloration in swans (Cygnus), which show extreme variation in melanic plumage phenotypes among species (white to black). The two species with melanic plumage, C. atratus and C. melanocoryphus (black and black-necked swans respectively), both have amino acid changes at important functional sites in MC1R that are consistent with increased MC1R activity and melanism. Reconstruction of MC1R evolution over a newly generated independent molecular phylogeny of Cygnus and related genera shows that these putative melanizing mutations were independently derived in the two melanic lineages. However, interpretation is complicated by the fact that one of the outgroup genera, Coscoroba, also has a putative melanizing mutation at MC1R that has arisen independently but has nearly pure white plumage. Epistasis at other loci seems the most likely explanation for this discrepancy. Unexpectedly, the phylogeny shows that the genus Cygnus may not be monophyletic, with C. melanocoryphus placed as a sister group to true geese (Anser), but further data will be needed to confirm this. Our study highlights the difficulty of extrapolating from intraspecific studies to understand the genetic basis of interspecific adaptive phenotypic evolution, even with a gene whose structure-function relationships are as well understood as MC1R as confounding variation make clear genotype/phenotype associations difficult at the macroevolutionary scale. However, the identification of substitutions in the black and black-necked swan that are known to be associated with melanic phenotypes, suggests Cygnus may be another example where there appears to be convergent evolution at MC1R. This study therefore provides a novel example where previously described intraspecific genotype/phenotype associations occur at the macroevolutionary level.

'Junk' DNA and long-term phenotypic evolution in Silene section Elisanthe (Caryophyllaceae).

PubMed Central

Meagher, Thomas R; Costich, Denise E

2004-01-01

Nuclear DNA content variation over orders of magnitude across species has been attributed to 'junk' repetitive DNA with limited adaptive significance. By contrast, our previous work on Silene latifolia showed that DNA content is negatively correlated with flower size, a character of clear adaptive relevance. The present paper explores this relationship in a broader phylogenetic context to investigate the long-term evolutionary impacts of DNA content variation. The relationship between nuclear DNA content and phenotype variation was determined for four closely related species of Silene section Elisanthe (Caryophyllaceae). In addition to a consistent sexual dimorphism in DNA content across all of the species, we found DNA content variation among populations within, as well as among, species. We also found a general trend towards a negative correlation between DNA content and flower and leaf size over all four species, within males and females as well as overall. These results indicate that repetitive DNA may play a role in long-term phenotypic evolution. PMID:15801614

The evolution of trade-offs: testing predictions on response to selection and environmental variation.

PubMed

Roff, Derek A; Mostowy, Serge; Fairbairn, Daphne J

2002-01-01

The concept of phenotypic trade-offs is a central element in evolutionary theory. In general, phenotypic models assume a fixed trade-off function, whereas quantitative genetic theory predicts that the trade-off function will change as a result of selection. For a linear trade-off function selection will readily change the intercept but will have to be relatively stronger to change the slope. We test these predictions by examining the trade-off between fecundity and flight capability, as measured by dorso-longitudinal muscle mass, in four different populations of the sand cricket, Gryllus firmus. Three populations were recently derived from the wild, and the fourth had been in the laboratory for 19 years. We hypothesized that the laboratory population had most likely undergone more and different selection from the three wild populations and therefore should differ from these in respect to both slope and intercept. Because of geographic variation in selection, we predicted a general difference in intercept among the four populations. We further tested the hypothesis that this intercept will be correlated with proportion macropterous and that this relationship will itself vary with environmental conditions experienced during both the nymphal and adult period. Observed variation in the phenotypic trade-off was consistent with the predictions of the quantitative genetic model. These results point to the importance of modeling trade-offs as dynamic rather than static relationships. We discuss how phenotypic models can incorporate such variation. The phenotypic trade-off between fecundity and dorso-longitudinal muscle mass is determined in part by variation in body size, illustrating the necessity of considering trade-offs to be multi factorial rather than simply bivariate relationships.

Heritability and phenotypic variation of canine hip dysplasia radiographic traits in a cohort of Australian German shepherd dogs.

PubMed

Wilson, Bethany J; Nicholas, Frank W; James, John W; Wade, Claire M; Tammen, Imke; Raadsma, Herman W; Castle, Kao; Thomson, Peter C

2012-01-01

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14-0.24 (ordinal models), 0.14-0.25 (linear models) and 0.12-0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30 ± 0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals.

Adult presentation of Bartter syndrome type IV with erythrocytosis

PubMed Central

Heilberg, Ita Pfeferman; Tótoli, Cláudia; Calado, Joaquim Tomaz

2015-01-01

Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis. PMID:26537508

Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2.

PubMed

Witting, N; Duno, M; Vissing, J

2013-01-01

Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site. Copyright © 2012 Elsevier B.V. All rights reserved.

Phenotypic variation and fitness in a metapopulation of tubeworms (Ridgeia piscesae Jones) at hydrothermal vents.

PubMed

Tunnicliffe, Verena; St Germain, Candice; Hilário, Ana

2014-01-01

We examine the nature of variation in a hot vent tubeworm, Ridgeia piscesae, to determine how phenotypes are maintained and how reproductive potential is dictated by habitat. This foundation species at northeast Pacific hydrothermal sites occupies a wide habitat range in a highly heterogeneous environment. Where fluids supply high levels of dissolved sulphide for symbionts, the worm grows rapidly in a "short-fat" phenotype characterized by lush gill plumes; when plumes are healthy, sperm package capture is higher. This form can mature within months and has a high fecundity with continuous gamete output and a lifespan of about three years in unstable conditions. Other phenotypes occupy low fluid flux habitats that are more stable and individuals grow very slowly; however, they have low reproductive readiness that is hampered further by small, predator cropped branchiae, thus reducing fertilization and metabolite uptake. Although only the largest worms were measured, only 17% of low flux worms were reproductively competent compared to 91% of high flux worms. A model of reproductive readiness illustrates that tube diameter is a good predictor of reproductive output and that few low flux worms reached critical reproductive size. We postulate that most of the propagules for the vent fields originate from the larger tubeworms that live in small, unstable habitat patches. The large expanses of worms in more stable low flux habitat sustain a small, but long-term, reproductive output. Phenotypic variation is an adaptation that fosters both morphological and physiological responses to differences in chemical milieu and predator pressure. This foundation species forms a metapopulation with variable growth characteristics in a heterogeneous environment where a strategy of phenotypic variation bestows an advantage over specialization.

Phenotypic Variation and Fitness in a Metapopulation of Tubeworms (Ridgeia piscesae Jones) at Hydrothermal Vents

PubMed Central

Tunnicliffe, Verena; St. Germain, Candice; Hilário, Ana

2014-01-01

We examine the nature of variation in a hot vent tubeworm, Ridgeia piscesae, to determine how phenotypes are maintained and how reproductive potential is dictated by habitat. This foundation species at northeast Pacific hydrothermal sites occupies a wide habitat range in a highly heterogeneous environment. Where fluids supply high levels of dissolved sulphide for symbionts, the worm grows rapidly in a “short-fat” phenotype characterized by lush gill plumes; when plumes are healthy, sperm package capture is higher. This form can mature within months and has a high fecundity with continuous gamete output and a lifespan of about three years in unstable conditions. Other phenotypes occupy low fluid flux habitats that are more stable and individuals grow very slowly; however, they have low reproductive readiness that is hampered further by small, predator cropped branchiae, thus reducing fertilization and metabolite uptake. Although only the largest worms were measured, only 17% of low flux worms were reproductively competent compared to 91% of high flux worms. A model of reproductive readiness illustrates that tube diameter is a good predictor of reproductive output and that few low flux worms reached critical reproductive size. We postulate that most of the propagules for the vent fields originate from the larger tubeworms that live in small, unstable habitat patches. The large expanses of worms in more stable low flux habitat sustain a small, but long-term, reproductive output. Phenotypic variation is an adaptation that fosters both morphological and physiological responses to differences in chemical milieu and predator pressure. This foundation species forms a metapopulation with variable growth characteristics in a heterogeneous environment where a strategy of phenotypic variation bestows an advantage over specialization. PMID:25337895

Resistance to amoxicillin-clavulanate and its relation to virulence-related factors in Yersinia enterocolitica biovar 1A.

PubMed

Singhal, N; Kumar, M; Virdi, J S

2016-01-01

Recent studies have reported that the virulence factors (VFs) were detected more frequently in amoxicillin-clavulanate (AMC) susceptible clinical isolates of Escherichia coli. Here, we have evaluated the relationship between VFs and AMC-resistance phenotype in clinical isolates of Y. enterocolitica biovar 1A. The presence/absence of VFs was compared with their minimum inhibitory concentrations for AMC in strains of two serovars. We observed that the strains of the serovar O: 6, 30-6, 31 showed a similar relationship between the number of VFs and resistance to clavulanic acid as in E. coli but not of serovar O: 6, 30. Variations in the promoters/complete coding sequences (CCDSs) of β-lactamase gene (bla A) or the serological characteristics could not account for unusual susceptibility to AMC displayed by the strains of the serovar O: 6, 30. Therefore, we speculate that since the clinical strains of serovar O: 6, 30-6, 31 originated from the environment they were less exposed to antibiotics compared to clinical strains of serovar O: 6, 30. Thus, AMC susceptibility seems to be influenced by factors other than serotypes or promoters/CCDS of β-lactamase genes.

Protection, pathogenesis and phenotypic plasticity in Plasmodium falciparum malaria.

PubMed

Roberts, D J; Biggs, B A; Brown, G; Newbold, C I

1993-08-01

Why does Plasmodium falciparum cause severe illness in some but not all infections? How is clinical immunity acquired? These questions have intrigued investigators since the clinical epidemiology of malaria was first described. The search for answers to both questions has highlighted the changes that take place at the surface of infected red blood cells during the last half of the erythrocytic cycle. These changes specify the antigenic and adhesive or cytoadherence phenotypes for the infected cell. Now the antigenic and adhesive phenotypes appear to be linked and together undergo clonal variation. In this article David Roberts, Beverley-Ann Biggs, Graham Brown and Christopher Newbold explain how clonal phenotypic variation and the linkage between adhesive and antigenic types contribute to our understanding of naturally acquired immunity and of pathogenesis of severe malaria.

Selective Pressure along a Latitudinal Gradient Affects Subindividual Variation in Plants

PubMed Central

Sobral, Mar; Guitián, José; Guitián, Pablo; Larrinaga, Asier R.

2013-01-01

Individual plants produce repeated structures such as leaves, flowers or fruits, which, although belonging to the same genotype, are not phenotypically identical. Such subindividual variation reflects the potential of individual genotypes to vary with micro-environmental conditions. Furthermore, variation in organ traits imposes costs to foraging animals such as time, energy and increased predation risk. Therefore, animals that interact with plants may respond to this variation and affect plant fitness. Thus, phenotypic variation within an individual plant could be, in part, an adaptive trait. Here we investigated this idea and we found that subindividual variation of fruit size of Crataegus monogyna, in different populations throughout the latitudinal gradient in Europe, was explained at some extent by the selective pressures exerted by seed-dispersing birds. These findings support the hypothesis that within-individual variation in plants is an adaptive trait selected by interacting animals which may have important implications for plant evolution. PMID:24069297

Stressful environments induce novel phenotypic variation: hierarchical reaction norms for sperm performance of a pervasive invader

PubMed Central

Purchase, Craig F; Moreau, Darek T R

2012-01-01

Genetic variation for phenotypic plasticity is ubiquitous and important. However, the scale of such variation including the relative variability present in reaction norms among different hierarchies of biological organization (e.g., individuals, populations, and closely related species) is unknown. Complicating interpretation is a trade-off in environmental scale. As plasticity can only be inferred over the range of environments tested, experiments focusing on fine tuned responses to normal or benign conditions may miss cryptic phenotypic variation expressed under novel or stressful environments. Here, we sought to discern the presence and shape of plasticity in the performance of brown trout sperm as a function of optimal to extremely stressful river pH, and demarcate if the reaction norm varies among genotypes. Our overarching goal was to determine if deteriorating environmental quality increases expressed variation among individuals. A more applied aim was to ascertain whether maintaining sperm performance over a wide pH range could help explain how brown trout are able to invade diverse river systems when transplanted outside of their native range. Individuals differed in their reaction norms of phenotypic expression of an important trait in response to environmental change. Cryptic variation was revealed under stressful conditions, evidenced through increasing among-individual variability. Importantly, data on population averages masked this variability in plasticity. In addition, canalized reaction norms in sperm swimming velocities of many individuals over a very large range in water chemistry may help explain why brown trout are able to colonize a wide variety of habitats. PMID:23145341

Genome-Wide Association Studies of Quantitatively Measured Skin, Hair, and Eye Pigmentation in Four European Populations

PubMed Central

Candille, Sophie I.; Absher, Devin M.; Beleza, Sandra; Bauchet, Marc; McEvoy, Brian; Garrison, Nanibaa’ A.; Li, Jun Z.; Myers, Richard M.; Barsh, Gregory S.; Tang, Hua; Shriver, Mark D.

2012-01-01

Pigmentation of the skin, hair, and eyes varies both within and between human populations. Identifying the genes and alleles underlying this variation has been the goal of many candidate gene and several genome-wide association studies (GWAS). Most GWAS for pigmentary traits to date have been based on subjective phenotypes using categorical scales. But skin, hair, and eye pigmentation vary continuously. Here, we seek to characterize quantitative variation in these traits objectively and accurately and to determine their genetic basis. Objective and quantitative measures of skin, hair, and eye color were made using reflectance or digital spectroscopy in Europeans from Ireland, Poland, Italy, and Portugal. A GWAS was conducted for the three quantitative pigmentation phenotypes in 176 women across 313,763 SNP loci, and replication of the most significant associations was attempted in a sample of 294 European men and women from the same countries. We find that the pigmentation phenotypes are highly stratified along axes of European genetic differentiation. The country of sampling explains approximately 35% of the variation in skin pigmentation, 31% of the variation in hair pigmentation, and 40% of the variation in eye pigmentation. All three quantitative phenotypes are correlated with each other. In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the lack of major genes affecting skin and hair color variation within Europe and suggesting that not only careful phenotyping but also larger cohorts are required to understand the genetic architecture of these complex quantitative traits. Interestingly, we also see that in each of these four populations, men are more lightly pigmented in the unexposed skin of the inner arm than women, a fact that is underappreciated and may vary across the world. PMID:23118974

Endodontic management of an unusual maxillary first molar with a single buccal root.

PubMed

Nayak, Gurudutt; Dahiya, Surya; Singh, Inderpreet; Mohammad, Faiz Hasan

2014-05-01

The aim of this clinical article is to describe the unusual anatomy that was detected in a maxillary first molar during routine endodontic treatment. Variation in Root and Root canal morphology especially in multirooted teeth presents a constant challenge for a clinician in their detection and management. The literature is replete with cases that have extra canal or Root but cases with fused Root and fewer numbers of canals are sparse. This case report describes the endodontic management of one such unusual case of maxillary first molar presenting with a single fused buccal and a palatal Root. The confirmatory diagnosis of this morphologic aberration was done with the help of spiral computerized tomography, which revealed that the contralateral tooth also had a similar morphology. Dental practitioners should always be aware of the fact that abnormalities need not be in form of extra Roots or Root canals; anomalies can also be in form of fewer number of Roots or Root canals. A thorough knowledge of the complexities and variations of the Root canal system would help in avoiding some of the common iatrogenic access opening errors like perforations and excessive tooth removal caused during the search for the missing or extracanal.

Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans

PubMed Central

McDaniell, Ryan; Lee, Bum-Kyu; Song, Lingyun; Liu, Zheng; Boyle, Alan P.; Erdos, Michael R.; Scott, Laura J.; Morken, Mario A.; Kucera, Katerina S.; Battenhouse, Anna; Keefe, Damian; Collins, Francis S.; Willard, Huntington F.; Lieb, Jason D.; Furey, Terrence S.; Crawford, Gregory E.; Iyer, Vishwanath R.; Birney, Ewan

2010-01-01

The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. PMID:20299549

Diagnostic Value of Run Chart Analysis: Using Likelihood Ratios to Compare Run Chart Rules on Simulated Data Series

PubMed Central

Anhøj, Jacob

2015-01-01

Run charts are widely used in healthcare improvement, but there is little consensus on how to interpret them. The primary aim of this study was to evaluate and compare the diagnostic properties of different sets of run chart rules. A run chart is a line graph of a quality measure over time. The main purpose of the run chart is to detect process improvement or process degradation, which will turn up as non-random patterns in the distribution of data points around the median. Non-random variation may be identified by simple statistical tests including the presence of unusually long runs of data points on one side of the median or if the graph crosses the median unusually few times. However, there is no general agreement on what defines “unusually long” or “unusually few”. Other tests of questionable value are frequently used as well. Three sets of run chart rules (Anhoej, Perla, and Carey rules) have been published in peer reviewed healthcare journals, but these sets differ significantly in their sensitivity and specificity to non-random variation. In this study I investigate the diagnostic values expressed by likelihood ratios of three sets of run chart rules for detection of shifts in process performance using random data series. The study concludes that the Anhoej rules have good diagnostic properties and are superior to the Perla and the Carey rules. PMID:25799549

Vertically transmitted fecal IgA levels distinguish extra-chromosomal phenotypic variation

PubMed Central

Wallace, Meghan A.; D, Carey-Ann; Burnham; Virgin, Herbert W.; Stappenbeck, Thaddeus S.

2014-01-01

Summary The proliferation of genetically modified mouse models has exposed phenotypic variation between investigators and institutions that has been challenging to control1-5. In many cases, the microbiota is the presumed culprit of the variation. Current solutions to account for phenotypic variability include littermate and maternal controls or defined microbial consortia in gnotobiotic mice6,7. In conventionally raised mice, the microbiome is transmitted from the dam2,8,9. Here we show that microbially–driven dichotomous fecal IgA levels in WT mice within the same facility mimic the effects of chromosomal mutations. We observed in multiple facilities that vertically-transmissible bacteria in IgA-Low mice dominantly lowered fecal IgA levels in IgA-High mice after cohousing or fecal transplantation. In response to injury, IgA-Low mice showed increased damage that was transferable by fecal transplantation and driven by fecal IgA differences. We found that bacteria from IgA-Low mice degraded the secretory component (SC) of SIgA as well as IgA itself. These data indicate that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. We propose fecal IgA as one marker of microbial variability and conclude that cohousing and/or fecal transplantation enables analysis of progeny from different dams. PMID:25686606

Phenotypic plasticity in the scaling of avian basal metabolic rate

PubMed Central

McKechnie, Andrew E; Freckleton, Robert P; Jetz, Walter

2006-01-01

Many birds exhibit short-term, reversible adjustments in basal metabolic rate (BMR), but the overall contribution of phenotypic plasticity to avian metabolic diversity remains unclear. The available BMR data include estimates from birds living in natural environments and captive-raised birds in more homogenous, artificial environments. All previous analyses of interspecific variation in BMR have pooled these data. We hypothesized that phenotypic plasticity is an important contributor to interspecific variation in avian BMR, and that captive-raised populations exhibit general differences in BMR compared to wild-caught populations. We tested this hypothesis by fitting general linear models to BMR data for 231 bird species, using the generalized least-squares approach to correct for phylogenetic relatedness when necessary. The scaling exponent relating BMR to body mass in captive-raised birds (0.670) was significantly shallower than in wild-caught birds (0.744). The differences in metabolic scaling between captive-raised and wild-caught birds persisted when migratory tendency and habitat aridity were controlled for. Our results reveal that phenotypic plasticity is a major contributor to avian interspecific metabolic variation. The finding that metabolic scaling in birds is partly determined by environmental factors provides further support for models that predict variation in scaling exponents, such as the allometric cascade model. PMID:16627278

Developmental origins of novel gut morphology in frogs

PubMed Central

Bloom, Stephanie; Ledon-Rettig, Cris; Infante, Carlos; Everly, Anne; Hanken, James; Nascone-Yoder, Nanette

2013-01-01

SUMMARY Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation. PMID:23607305

Shell shape variation of queen conch Strombus gigas (Mesograstropoda: Strombidae) from Southwest Caribbean.

PubMed

Márquez, Edna Judith; Restrepo-Escobar, Natalia; Montoya-Herrera, Francisco Luis

2016-12-01

The endangered species Strombus gigas is a marine gastropod of significant economic importance through the Greater Caribbean region. In contrast to phenotypic plasticity, the role of genetics on shell variations in S. gigas has not been addressed so far, despite its importance in evolution, management and conservation of this species. This work used geometric morphometrics to investigate the phenotypic variation of 219 shells of S. gigas from eight sites of the Colombian Southwest Caribbean. Differences in mean size between sexes and among sites were contrasted by analysis of variance. Allometry was tested by multivariate regression and the hypothesis of common slope was contrasted by covariance multivariate analysis. Differences in the shell shape among sites were analyzed by principal component analysis. Sexual size dimorphism was not significant, whereas sexual shape dimorphism was significant and variable across sites. Differences in the shell shape among sites were concordant with genetic differences based on microsatellite data, supporting its genetic background. Besides, differences in the shell shape between populations genetically similar suggest a role of phenotypic plasticity in the morphometric variation of the shell shape. These outcomes evidence the role of genetic background and phenotypic plasticity in the shell shape of S. gigas. Thus, geometric morphometrics of shell shape may constitute a complementary tool to explore the genetic diversity of this species.

Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency.

PubMed

Davies, Jeffrey S; Gevers, Evelien F; Stevenson, Amy E; Coschigano, Karen T; El-Kasti, Muna M; Bull, Melanie J; Elford, Carole; Evans, Bronwen A J; Kopchick, John J; Wells, Timothy

2007-05-01

This study describes the previously uncharacterized ontogeny and regulation of truncal adipose reserves in the profoundly GH-deficient dwarf (dw/dw) rat. We show that, despite normal proportionate food intake, dw/dw rats develop abdominal leanness and hypoleptinemia (circulating leptin halved in dw/dw males, P < 0.05) during puberty. This contrasts with the hyperleptinemia seen in moderately GH-deficient Tgr rats (circulating leptin doubled at 6 wk of age, P < 0.05) and in GH receptor-binding protein (GHR/BP)-null mice (circulating leptin doubled; P < 0.05). This lean/hypoleptinemic phenotype was not completely normalized by GH treatment, but dw/dw rats developed abdominal obesity in response to neonatal MSG treatment or maintenance on a high-fat diet. Unlike Tgr rats, dw/dw rats did not become obese with age; plasma leptin levels and fat pad weights became similar to those in wild-type rats. In contrast with truncal leanness, tibial marrow adiposity was normal in male and doubled in female dwarves (P < 0.01), this increase being attributable to increased adipocyte number (P < 0.01). Neonatal MSG treatment and high-fat feeding elevated marrow adiposity in dw/dw rats by inducing adipocyte enlargement (P < 0.05). These results demonstrate that, despite lipolytic influence of GH, severe GH deficiency in dw/dw rats is accompanied by a paradoxical leanness. This lean/hypoleptinemic phenotype is not solely attributable to reduced GH signaling and does not appear to result from a reduction in nutrient intake or the ability of dw/dw adipocytes to accumulate lipid. Disruption of preadipocyte differentiation or adipocyte proliferation in the dw/dw rat may lead to the development of this unusually lean/hypoleptinemic phenotype.

Consistent sex ratio bias of individual female dragon lizards

PubMed Central

Uller, Tobias; Mott, Beth; Odierna, Gaetano; Olsson, Mats

2006-01-01

Sex ratio evolution relies on genetic variation in either the phenotypic traits that influence sex ratios or sex-determining mechanisms. However, consistent variation among females in offspring sex ratio is rarely investigated. Here, we show that female painted dragons (Ctenophorus pictus) have highly repeatable sex ratios among clutches within years. A consistent effect of female identity could represent stable phenotypic differences among females or genetic variation in sex-determining mechanisms. Sex ratios were not correlated with female size, body condition or coloration. Furthermore, sex ratios were not influenced by incubation temperature. However, the variation among females resulted in female-biased mean population sex ratios at hatching both within and among years. PMID:17148290

Post-transcriptional Mechanisms Contribute Little to Phenotypic Variation in Snake Venoms.

PubMed

Rokyta, Darin R; Margres, Mark J; Calvin, Kate

2015-09-09

Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes undergoing study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom gland transcriptomes and venom proteomes for 10 of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms. Copyright © 2015 Rokyta et al.

Analysis of copy number variations among cattle breeds

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in the modern domesticated cattle using array comparative genomic hybridization (array CGH) and quanti...

A RE-EXAMINATION OF VARIATION ASSOCIATED WITH ENVIRONMENTALLY STRESSED ORGANISMS

EPA Science Inventory

Variation is an essential feature of biological systems. Populations adapt to dynamic environments, in part, because of this variation. In this review, we re-examine phenotypic variation, especially in organisms living in polluted environments. A recent goal of ecotoxicology is t...

Evolution of plasticity and adaptive responses to climate change along climate gradients.

PubMed

Kingsolver, Joel G; Buckley, Lauren B

2017-08-16

The relative contributions of phenotypic plasticity and adaptive evolution to the responses of species to recent and future climate change are poorly understood. We combine recent (1960-2010) climate and phenotypic data with microclimate, heat balance, demographic and evolutionary models to address this issue for a montane butterfly, Colias eriphyle , along an elevational gradient. Our focal phenotype, wing solar absorptivity, responds plastically to developmental (pupal) temperatures and plays a central role in thermoregulatory adaptation in adults. Here, we show that both the phenotypic and adaptive consequences of plasticity vary with elevation. Seasonal changes in weather generate seasonal variation in phenotypic selection on mean and plasticity of absorptivity, especially at lower elevations. In response to climate change in the past 60 years, our models predict evolutionary declines in mean absorptivity (but little change in plasticity) at high elevations, and evolutionary increases in plasticity (but little change in mean) at low elevation. The importance of plasticity depends on the magnitude of seasonal variation in climate relative to interannual variation. Our results suggest that selection and evolution of both trait means and plasticity can contribute to adaptive response to climate change in this system. They also illustrate how plasticity can facilitate rather than retard adaptive evolutionary responses to directional climate change in seasonal environments. © 2017 The Author(s).

Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons.

PubMed

Specchia, Valeria; Piacentini, Lucia; Tritto, Patrizia; Fanti, Laura; D'Alessandro, Rosalba; Palumbo, Gioacchino; Pimpinelli, Sergio; Bozzetti, Maria P

2010-02-04

The canalization concept describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways, indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability. Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis.

Facilitation of environmental adaptation and evolution by epigenetic phenotype variation: insights from clonal, invasive, polyploid, and domesticated animals

PubMed Central

Vogt, Günter

2017-01-01

Abstract There is increasing evidence, particularly from plants, that epigenetic mechanisms can contribute to environmental adaptation and evolution. The present article provides an overview on this topic for animals and highlights the special suitability of clonal, invasive, hybrid, polyploid, and domesticated species for environmental and evolutionary epigenetics. Laboratory and field studies with asexually reproducing animals have shown that epigenetically diverse phenotypes can be produced from the same genome either by developmental stochasticity or environmental induction. The analysis of invasions revealed that epigenetic phenotype variation may help to overcome genetic barriers typically associated with invasions such as bottlenecks and inbreeding. Research with hybrids and polyploids established that epigenetic mechanisms are involved in consolidation of speciation by contributing to reproductive isolation and restructuring of the genome in the neo-species. Epigenetic mechanisms may even have the potential to trigger speciation but evidence is still meager. The comparison of domesticated animals and their wild ancestors demonstrated heritability and selectability of phenotype modulating DNA methylation patterns. Hypotheses, model predictions, and empirical results are presented to explain how epigenetic phenotype variation could facilitate adaptation and speciation. Clonal laboratory lineages, monoclonal invaders, and adaptive radiations of different evolutionary age seem particularly suitable to empirically test the proposed ideas. A respective research agenda is presented. PMID:29492304

Risk of herbivore attack and heritability of ontogenetic trajectories in plant defense.

PubMed

Ochoa-López, Sofía; Rebollo, Roberto; Barton, Kasey E; Fornoni, Juan; Boege, Karina

2018-06-01

Ontogeny has been identified as a main source of variation in the expression of plant phenotypes. However, there is limited information on the mechanisms behind the evolution of ontogenetic trajectories in plant defense. We explored if risk of attack, herbivore damage, heritability, and phenotypic plasticity can promote or constrain the evolutionary potential of ontogenetic trajectories in three defensive traits. We exposed 20 genotypes of Turnera velutina to contrasting environments (shadehouse and field plots), and measured the cyanogenic potential, trichome density, and sugar content in extrafloral nectar in seedlings, juveniles and reproductive plants. We also assessed risk of attack through oviposition preferences, and quantified herbivore damage in the field. We estimated genetic variance, broad sense heritability, and evolvability of the defensive traits at each ontogenetic stage, and of the ontogenetic trajectories themselves. For plants growing in the shadehouse, we found genetic variation and broad sense heritability for cyanogenic potential in seedlings, and for trichome density at all ontogenetic stages. Genetic variation and heritability of ontogenetic trajectories was detected for trichome density only. These genetic pre-requisites for evolution, however, were not detected in the field, suggesting that environmental variation and phenotypic plastic responses mask any heritable variation. Finally, ontogenetic trajectories were found to be plastic, differing between shadehouse and field conditions for the same genetic families. Overall, we provide support for the idea that changes in herbivore pressure can be a mechanism behind the evolution of ontogenetic trajectories. This evolutionary potential, however, can be constrained by phenotypic plasticity expressed in heterogeneous environments.

Genotype-by-environment interactions leads to variable selection on life-history strategy in Common Evening Primrose (Oenothera biennis).

PubMed

Johnson, M T J

2007-01-01

Monocarpic plant species, where reproduction is fatal, frequently exhibit variation in the length of their prereproductive period prior to flowering. If this life-history variation in flowering strategy has a genetic basis, genotype-by-environment interactions (G x E) may maintain phenotypic diversity in flowering strategy. The native monocarpic plant Common Evening Primrose (Oenothera biennis L., Onagraceae) exhibits phenotypic variation for annual vs. biennial flowering strategies. I tested whether there was a genetic basis to variation in flowering strategy in O. biennis, and whether environmental variation causes G x E that imposes variable selection on flowering strategy. In a field experiment, I randomized more than 900 plants from 14 clonal families (genotypes) into five distinct habitats that represented a natural productivity gradient. G x E strongly affected the lifetime fruit production of O. biennis, with the rank-order in relative fitness of genotypes changing substantially between habitats. I detected genetic variation in annual vs. biennial strategies in most habitats, as well as a G x E effect on flowering strategy. This variation in flowering strategy was correlated with genetic variation in relative fitness, and phenotypic and genotypic selection analyses revealed that environmental variation resulted in variable directional selection on annual vs. biennial strategies. Specifically, a biennial strategy was favoured in moderately productive environments, whereas an annual strategy was favoured in low-productivity environments. These results highlight the importance of variable selection for the maintenance of genetic variation in the life-history strategy of a monocarpic plant.

Hypervirulence and hypermucoviscosity: Two different but complementary Klebsiella spp. phenotypes?

PubMed Central

Catalán-Nájera, Juan Carlos; Garza-Ramos, Ulises; Barrios-Camacho, Humberto

2017-01-01

ABSTRACT Since the hypermucoviscous variants of Klebsiella pneumoniae were first reported, many cases of primary liver abscesses and other invasive infections caused by this pathogen have been described worldwide. Hypermucoviscosity is a phenotypic feature characterized by the formation of a viscous filament ≥5 mm when a bacterial colony is stretched by a bacteriological loop; this is the so-called positive string test. Hypermucoviscosity appears to be associated with this unusual and aggressive type of infection, and therefore, the causal strains are considered hypervirulent. Since these first reports, the terms hypermucoviscosity and hypervirulence have often been used synonymously. However, new evidence has suggested that hypermucoviscosity and hypervirulence are 2 different phenotypes that should not be used synonymously. Moreover, it is important to establish that a negative string test is insufficient in determining whether a strain is or is not hypervirulent. On the other hand, hypervirulence- and hypermucoviscosity-associated genes must be identified, considering that these phenotypes correspond to 2 different phenomena, regardless of whether they can act in synergy under certain circumstances. Therefore, it is essential to quickly identify the genetic determinants behind the hypervirulent phenotype to develop effective methodologies that can diagnose in a prompt and effective way these hypervirulent variants of K. pneumoniae. PMID:28402698

Comparative population genomics of latitudinal variation in Drosophila simulans and Drosophila melanogaster

PubMed Central

MACHADO, HEATHER E.; BERGLAND, ALAN O.; O’BRIEN, KATHERINE R.; BEHRMAN, EMILY L.; SCHMIDT, PAUL S.; PETROV, DMITRI A.

2016-01-01

Examples of clinal variation in phenotypes and genotypes across latitudinal transects have served as important models for understanding how spatially varying selection and demographic forces shape variation within species. Here, we examine the selective and demographic contributions to latitudinal variation through the largest comparative genomic study to date of Drosophila simulans and Drosophila melanogaster, with genomic sequence data from 382 individual fruit flies, collected across a spatial transect of 19 degrees latitude and at multiple time points over 2 years. Consistent with phenotypic studies, we find less clinal variation in D. simulans than D. melanogaster, particularly for the autosomes. Moreover, we find that clinally varying loci in D. simulans are less stable over multiple years than comparable clines in D. melanogaster. D. simulans shows a significantly weaker pattern of isolation by distance than D. melanogaster and we find evidence for a stronger contribution of migration to D. simulans population genetic structure. While population bottlenecks and migration can plausibly explain the differences in stability of clinal variation between the two species, we also observe a significant enrichment of shared clinal genes, suggesting that the selective forces associated with climate are acting on the same genes and phenotypes in D. simulans and D. melanogaster. PMID:26523848

Phenotypic diversity, population structure and stress protein-based capacitoring in populations of Xeropicta derbentina, a heat-tolerant land snail species.

PubMed

Di Lellis, Maddalena A; Sereda, Sergej; Geißler, Anna; Picot, Adrien; Arnold, Petra; Lang, Stefanie; Troschinski, Sandra; Dieterich, Andreas; Hauffe, Torsten; Capowiez, Yvan; Mazzia, Christophe; Knigge, Thomas; Monsinjon, Tiphaine; Krais, Stefanie; Wilke, Thomas; Triebskorn, Rita; Köhler, Heinz-R

2014-11-01

The shell colour of many pulmonate land snail species is highly diverse. Besides a genetic basis, environmentally triggered epigenetic mechanisms including stress proteins as evolutionary capacitors are thought to influence such phenotypic diversity. In this study, we investigated the relationship of stress protein (Hsp70) levels with temperature stress tolerance, population structure and phenotypic diversity within and among different populations of a xerophilic Mediterranean snail species (Xeropicta derbentina). Hsp70 levels varied considerably among populations, and were significantly associated with shell colour diversity: individuals in populations exhibiting low diversity expressed higher Hsp70 levels both constitutively and under heat stress than those of phenotypically diverse populations. In contrast, population structure (cytochrome c oxidase subunit I gene) did not correlate with phenotypic diversity. However, genetic parameters (both within and among population differences) were able to explain variation in Hsp70 induction at elevated but non-pathologic temperatures. Our observation that (1) population structure had a high explanatory potential for Hsp70 induction and that (2) Hsp70 levels, in turn, correlated with phenotypic diversity while (3) population structure and phenotypic diversity failed to correlate provides empirical evidence for Hsp70 to act as a mediator between genotypic variation and phenotype and thus for chaperone-driven evolutionary capacitance in natural populations.

Beyond Punnett Squares: Student Word Association and Explanations of Phenotypic Variation through an Integrative Quantitative Genetics Unit Investigating Anthocyanin Inheritance and Expression in Brassica rapa Fast Plants

PubMed Central

Smith, Amber R.; Williams, Paul H.; McGee, Seth A.; Dósa, Katalin; Pfammatter, Jesse

2014-01-01

Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question “What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev),” we developed a 4-wk unit for an inquiry-based laboratory course focused on the inheritance and expression of a quantitative trait in varying environments. We utilized Brassica rapa Fast Plants as a model organism to study variation in the phenotype anthocyanin pigment intensity. As an initial curriculum assessment, we used free word association to examine students’ cognitive structures before and after the unit and explanations in students’ final research posters with particular focus on variation (Pv = Gv + Ev). Comparison of pre- and postunit word frequency revealed a shift in words and a pattern of co-occurring concepts indicative of change in cognitive structure, with particular focus on “variation” as a proposed threshold concept and primary goal for students’ explanations. Given review of 53 posters, we found ∼50% of students capable of intermediate to high-level explanations combining both Gv and Ev influence on expression of anthocyanin intensity (Pv). While far from “plug and play,” this conceptually rich, inquiry-based unit holds promise for effective integration of quantitative and Mendelian genetics. PMID:25185225

The Face of Noonan Syndrome: Does Phenotype Predict Genotype

PubMed Central

Allanson, Judith E.; Bohring, Axel; Dorr, Helmuth-Guenther; Dufke, Andreas; Gillessen-Kaesbach, Gabrielle; Horn, Denise; König, Rainer; Kratz, Christian P.; Kutsche, Kerstin; Pauli, Silke; Raskin, Salmo; Rauch, Anita; Turner, Anne; Wieczorek, Dagmar; Zenker, Martin

2011-01-01

The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway. Thirty-two of this cohort have PTPN11 mutations, 21 SOS1 mutations, 11 RAF1 mutations, and 17 KRAS mutations. The facial appearance of each person was judged to be typical of Noonan syndrome or atypical. In each gene category both typical and unusual faces were found. We determined that some individuals with mutations in the most commonly affected gene, PTPN11, which is correlated with the cardinal physical features, may have a quite atypical face. Conversely, some individuals with KRAS mutations, which may be associated with a less characteristic intellectual phenotype and a resemblance to Costello and cardio-facio-cutaneous syndromes, can have a very typical face. Thus, the facial phenotype, alone, is insufficient to predict the genotype, but certain facial features may facilitate an educated guess in some cases. PMID:20602484

A novel large deletion in the RYR1 gene in a Belgian family with late-onset and recessive core myopathy.

PubMed

Remiche, Gauthier; Kadhim, Hazim; Abramowicz, Marc; Mavroudakis, Nicolas; Monnier, Nicole; Lunardi, Joël

2015-05-01

We report a novel and particularly unusual type of mutation, namely, large deletion in the RYR1 gene, in a Belgian family with myopathy: Patients were found to be compound heterozygous and presented a clinico-pathological phenotype characterized by late-onset and recessive myopathy with cores. We depict the clinical, electrophysiological, pathological and molecular genetic characteristics of family members. To date, large deletions in the RYR1 gene have been reported in only two cases. Both involved different mutations and, in sharp contrast to our cases, presented with a very early-onset, neonatal, and a very severe or lethal phenotype. Overview of reported clinico-pathologic phenotypes, also highlights the rarity of combined late-onset/recessive co-occurrence in this group of myopathies with cores. Finally, this report underlines the broadening spectrum in this group of myopathologic disorders and highlights the concept of 'RYR1-associated/related core myopathies'. Copyright © 2015 Elsevier B.V. All rights reserved.

Links between Natural Variation in the Microbiome and Host Fitness in Wild Mammals.

PubMed

Suzuki, Taichi A

2017-10-01

Recent studies in model organisms have shown that compositional variation in the microbiome can affect a variety of host phenotypes including those related to digestion, development, immunity, and behavior. Natural variation in the microbiome within and between natural populations and species may also affect host phenotypes and thus fitness in the wild. Here, I review recent evidence that compositional variation in the microbiome may affect host phenotypes and fitness in wild mammals. Studies over the last decade indicate that natural variation in the mammalian microbiome may be important in the assistance of energy uptake from different diet types, detoxification of plant secondary compounds, protection from pathogens, chemical communication, and behavior. I discuss the importance of combining both field observations and manipulative experiments in a single system to fully characterize the functions and fitness effects of the microbiome. Finally, I discuss the evolutionary consequences of mammal-microbiome associations by proposing a framework to test how natural selection on hosts is mediated by the microbiome. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Both natural selection and isolation by distance explain phenotypic divergence in bill size and body mass between South Australian little penguin colonies.

PubMed

Colombelli-Négrel, Diane

2016-11-01

Morphological variation between populations of the same species can arise as a response to genetic variation, local environmental conditions, or a combination of both. In this study, I examined small-scale geographic variation in bill size and body mass in little penguins ( Eudyptula minor ) across five breeding colonies in South Australia separated by <150 km. To help understand patterns driving the differences, I investigated these variations in relation to environmental parameters (air temperature, sea surface temperature, and water depth) and geographic distances between the colonies. I found substantial morphological variation among the colonies for body mass and bill measurements (except bill length). Colonies further located from each other showed greater morphological divergence overall than adjacent colonies. In addition, phenotypic traits were somewhat correlated to environmental parameters. Birds at colonies surrounded by hotter sea surface temperatures were heavier with longer and larger bills. Birds with larger and longer bills were also found at colonies surrounded by shallower waters. Overall, the results suggest that both environmental factors (natural selection) and interpopulation distances (isolation by distance) are causes of phenotypic differentiation between South Australian little penguin colonies.

Analysis of copy number variations reveals differences among cattle breeds

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in the modern domesticated cattle using array comparative genomic hybridization (array CGH) and quanti...

No Association between Variation in Longevity Candidate Genes and Aging-related Phenotypes in Oldest-old Danes.

PubMed

Soerensen, Mette; Nygaard, Marianne; Debrabant, Birgit; Mengel-From, Jonas; Dato, Serena; Thinggaard, Mikael; Christensen, Kaare; Christiansen, Lene

2016-06-01

In this study we explored the association between aging-related phenotypes previously reported to predict survival in old age and variation in 77 genes from the DNA repair pathway, 32 genes from the growth hormone 1/ insulin-like growth factor 1/insulin (GH/IGF-1/INS) signalling pathway and 16 additional genes repeatedly considered as candidates for human longevity: APOE, APOA4, APOC3, ACE, CETP, HFE, IL6, IL6R, MTHFR, TGFB1, SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. Altogether, 1,049 single nucleotide polymorphisms (SNPs) were genotyped in 1,088 oldest-old (age 92-93 years) Danes and analysed with phenotype data on physical functioning (hand grip strength), cognitive functioning (mini mental state examination and a cognitive composite score), activity of daily living and self-rated health. Five SNPs showed association to one of the phenotypes; however, none of these SNPs were associated with a change in the relevant phenotype over time (7 years of follow-up) and none of the SNPs could be confirmed in a replication sample of 1,281 oldest-old Danes (age 94-100). Hence, our study does not support association between common variation in the investigated longevity candidate genes and aging-related phenotypes consistently shown to predict survival. It is possible that larger sample sizes are needed to robustly reveal associations with small effect sizes. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes related to gender, geographic population and habitat in the antennal phenotype of Triatoma patagonica Del Ponte, 1929 (Hemiptera: Reduviidae).

PubMed

Rodríguez, Claudia S; Crocco, Liliana; Altamirano, Alejandra; Catalá, Silvia

2013-02-01

Triatomines undergo morphological changes as an adaptive response to different habitats (wild, peridomestic, domestic, laboratory). The characterization of the antennal phenotype provides information on intraspecific variation caused by geographical origin and/or habitat. Triatoma patagonica Del Ponte, 1929 is known to occur in peridomiciles of rural areas in Argentina, where it also invades non-colonized dwellings. Here we describe and compare the antennal phenotype of T. patagonica in populations of different geographic origin, and explore possible modifications induced by laboratory rearing with the aim of investigating the range of phenotypic variation of the species for the first time. Sixty antennas of adult males and females of T. patagonica belonging to two peridomiciliary populations of different geographical origin were analyzed. Four types of sensilla were observed in three antennal segments, showing sexual dimorphism in the species. The multivariate analysis separated the populations of similar habitat (peridomicile) but different geographical origin, without showing differences between the peridomiciliary and laboratory populations of the same geographical origin. These results suggest phenotypic plasticity in T. patagonica, which would allow the species to adapt to a wide range of habitats without having a close association with a given host and its environment. The range of antennal phenotypic variation of T. patagonica would also be an indicator of its current stage of adaptation to the human environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Phenotypic and Genetic Variations in Obligate Parthenogenetic Populations of Eriosoma lanigerum Hausmann (Hemiptera: Aphididae).

PubMed

Ruiz-Montoya, L; Zúñiga, G; Cisneros, R; Salinas-Moreno, Y; Peña-Martínez, R; Machkour-M'Rabet, S

2015-12-01

The study of phenotypic and genetic variation of obligate parthenogenetic organisms contributes to an understanding of evolution in the absence of genetic variation produced by sexual reproduction. Eriosoma lanigerum Hausmann undergoes obligate parthenogenesis in Mexico City, Mexico, due to the unavailability of the host plants required for sexual reproduction. We analysed the phenotypic and genetic variation of E. lanigerum in relation to the dry and wet season and plant phenology. Aphids were collected on two occasions per season on a secondary host plant, Pyracantha koidzumii, at five different sites in the southern area of Mexico City, Mexico. Thirteen morphological characteristics were measured from 147 to 276 individuals per site and per season. A multivariate analysis of variance was performed to test the effect of the season, site and their interaction on morphological traits. Morphological variation was summarised using a principal component analysis. Genetic variation was described using six enzymatic loci, four of which were polymorphic. Our study showed that the site and season has a significant effect on morphological trait variation. The largest aphids were recorded during cold temperatures with low relative humidity and when the plant was at the end of the fruiting period. The mean genetic diversity was low (mean H e =  .161), and populations were genetically structured by season and site. Morphological and genetic variations appear to be associated with environmental factors that directly affect aphid development and/or indirectly by host plant phenology.

Linking stream ecology with morphological variability in a native freshwater fish from semi-arid Australia

PubMed Central

Lostrom, Samantha; Evans, Jonathan P; Grierson, Pauline F; Collin, Shaun P; Davies, Peter M; Kelley, Jennifer L

2015-01-01

Environmental variation is a potent force affecting phenotypic expression. While freshwater fishes have provided a compelling example of the link between the environment and phenotypic diversity, few studies have been conducted with arid-zone fishes, particularly those that occur in geographically isolated regions where species typically inhabit intermittent and ephemeral creeks. We investigated morphological variation of a freshwater fish (the western rainbowfish, Melanotaenia australis) inhabiting creeks in the Pilbara region of northwest Australia to determine whether body shape variation correlated with local environmental characteristics, including water velocity, habitat complexity, predator presence, and food availability. We expected that the geographic isolation of creeks within this arid region would result in habitat-specific morphological specializations. We used landmark-based geometric morphometrics to quantify the level of morphological variability in fish captured from 14 locations within three distinct subcatchments of a major river system. Western rainbowfish exhibited a range of morphologies, with variation in body depth accounting for a significant proportion (>42%) of the total variance in shape. Sexual dimorphism was also apparent, with males displaying deeper bodies than females. While the measured local habitat characteristics explained little of the observed morphological variation, fish displayed significant morphological differentiation at the level of the subcatchment. Local adaptation may partly explain the geographic patterns of body shape variation, but fine-scale genetic studies are required to disentangle the effects of genetic differentiation from environmentally determined phenotypic plasticity in body shape. Developing a better understanding of environment–phenotype relationships in species from arid regions will provide important insights into ecological and evolutionary processes in these unique and understudied habitats. PMID:26380663

A test of phenotypic selection on petal form in the wild carnation, Dianthus inoxianus.

PubMed

Herrera, J; Balao, F

2015-11-01

Floral phenotypes are considered a product of pollinator-mediated selection, which also has the side effect of decreasing floral variation within species. Correlates of flower visibility and function were studied in a carnation species (Dianthus inoxianus), which has crepuscular anthesis and scent-based pollination by the hawkmoth Hyles livornica. We also assessed constancy of flower form in nature and in cultivation and, using fruit set as an estimate of plant relative fitness, tested whether the main pollinator exerted phenotypic selection on floral traits. Petal claw, which is roughly equivalent to the average depth at which an insect's proboscis must be inserted to reach nectar, was remarkably constant among wild plants (coefficient of variation 8%). In contrast, the area of the visible part of the petal, and the intensity of a coloured dot pattern on the petal was very variable (respectively CV = 34% and 102%). Cultivation in a common environment revealed significant variation among genotypes as regards petal area, degree of laciniation and extension of the dot pattern, but not petal claw length, which remained steady. Petal area, shape and colour did not affect relative fitness during the year of study, but plants with intermediate petal claws (i.e. floral tubes) set significantly more fruit. Results are compatible with low response of the main pollinator to variation in visual traits (petal area, laciniation, colour) and high responsiveness to variation in other aspects (tube length). Inconsistent phenotypic selection by pollinators may add to other causes of floral variation in the genus Dianthus, the causes of which are discussed. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

Genetic architecture of a feeding adaptation: garter snake (Thamnophis) resistance to tetrodotoxin bearing prey.

PubMed

Feldman, Chris R; Brodie, Edmund D; Brodie, Edmund D; Pfrender, Michael E

2010-11-07

Detailing the genetic basis of adaptive variation in natural populations is a first step towards understanding the process of adaptive evolution, yet few ecologically relevant traits have been characterized at the genetic level in wild populations. Traits that mediate coevolutionary interactions between species are ideal for studying adaptation because of the intensity of selection and the well-characterized ecological context. We have previously described the ecological context, evolutionary history and partial genetic basis of tetrodotoxin (TTX) resistance in garter snakes (Thamnophis). Derived mutations in a voltage-gated sodium channel gene (Na(v)1.4) in three garter snake species are associated with resistance to TTX, the lethal neurotoxin found in their newt prey (Taricha). Here we evaluate the contribution of Na(v)1.4 alleles to TTX resistance in two of those species from central coastal California. We measured the phenotypes (TTX resistance) and genotypes (Na(v)1.4 and microsatellites) in a local sample of Thamnophis atratus and Thamnophis sirtalis. Allelic variation in Na(v)1.4 explains 23 per cent of the variation in TTX resistance in T. atratus while variation in a haphazard sample of the genome (neutral microsatellite markers) shows no association with the phenotype. Similarly, allelic variation in Na(v)1.4 correlates almost perfectly with TTX resistance in T. sirtalis, but neutral variation does not. These strong correlations suggest that Na(v)1.4 is a major effect locus. The simple genetic architecture of TTX resistance in garter snakes may significantly impact the dynamics of phenotypic coevolution. Fixation of a few alleles of major effect in some garter snake populations may have led to the evolution of extreme phenotypes and an 'escape' from the arms race with newts.

Soil coring at multiple field environments can directly quantify variation in deep root traits to select wheat genotypes for breeding.

PubMed

Wasson, A P; Rebetzke, G J; Kirkegaard, J A; Christopher, J; Richards, R A; Watt, M

2014-11-01

We aim to incorporate deep root traits into future wheat varieties to increase access to stored soil water during grain development, which is twice as valuable for yield as water captured at younger stages. Most root phenotyping efforts have been indirect studies in the laboratory, at young plant stages, or using indirect shoot measures. Here, soil coring to 2 m depth was used across three field environments to directly phenotype deep root traits on grain development (depth, descent rate, density, length, and distribution). Shoot phenotypes at coring included canopy temperature depression, chlorophyll reflectance, and green leaf scoring, with developmental stage, biomass, and yield. Current varieties, and genotypes with breeding histories and plant architectures expected to promote deep roots, were used to maximize identification of variation due to genetics. Variation was observed for deep root traits (e.g. 111.4-178.5cm (60%) for depth; 0.09-0.22cm/°C day (144%) for descent rate) using soil coring in the field environments. There was significant variation for root traits between sites, and variation in the relative performance of genotypes between sites. However, genotypes were identified that performed consistently well or poorly at both sites. Furthermore, high-performing genotypes were statistically superior in root traits than low-performing genotypes or commercial varieties. There was a weak but significant negative correlation between green leaf score (-0.5), CTD (0.45), and rooting depth and a positive correlation for chlorophyll reflectance (0.32). Shoot phenotypes did not predict other root traits. This study suggests that field coring can directly identify variation in deep root traits to speed up selection of genotypes for breeding programmes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Genetics and variation

Treesearch

John R. Jones; Norbert V. DeByle

1985-01-01

The broad genotypic variability in quaking aspen (Populus tremuloides Michx.), that results in equally broad phenotypic variability among clones is important to the ecology and management of this species. This chapter considers principles of aspen genetics and variation, variation in aspen over its range, and local variation among clones. For a more...

Naturally occurring variation in tadpole morphology and performance linked to predator regime

PubMed Central

Johnson, James B; Saenz, Daniel; Adams, Cory K; Hibbitts, Toby J

2015-01-01

Divergent natural selection drives a considerable amount of the phenotypic and genetic variation observed in natural populations. For example, variation in the predator community can generate conflicting selection on behavioral, life-history, morphological, and performance traits. Differences in predator regime can subsequently increase phenotypic and genetic variations in the population and result in the evolution of reproductive barriers (ecological speciation) or phenotypic plasticity. We evaluated morphology and swimming performance in field collected Bronze Frog larvae (Lithobates clamitans) in ponds dominated by predatory fish and those dominated by invertebrate predators. Based on previous experimental findings, we hypothesized that tadpoles from fish-dominated ponds would have small bodies, long tails, and large tail muscles and that these features would facilitate fast-start speed. We also expected to see increased tail fin depth (i.e., the tail-lure morphology) in tadpoles from invertebrate-dominated ponds. Our results support our expectations with respect to morphology in affecting swimming performance of tadpoles in fish-dominated ponds. Furthermore, it is likely that divergent natural selection is playing a role in the diversification on morphology and locomotor performance in this system. PMID:26357533

Molar intercuspal dimensions: genetic input to phenotypic variation.

PubMed

Townsend, G; Richards, L; Hughes, T

2003-05-01

Molecular studies indicate that epigenetic events are important in determining how the internal enamel epithelium folds during odontogenesis. Since this process of folding leads to the subsequent arrangement of cusps on molar teeth, we hypothesized that intercuspal distances of human molar teeth would display greater phenotypic variation but lower heritabilities than overall crown diameters. Intercuspal distances and maximum crown diameters were recorded from digitized images of dental casts in 100 monozygotic and 74 dizygotic twin pairs. Intercuspal distances displayed less sexual dimorphism in mean values but greater relative variability and fluctuating asymmetry than overall crown measures. Correlations between intercuspal distances and overall crown measures were low. Models incorporating only environmental effects accounted for observed variation in several intercuspal measures. For those intercuspal variables displaying significant additive genetic variance, estimates of heritability ranged from 43 to 79%, whereas those for overall crown size were higher generally, ranging from 60 to 82%. Our finding of high phenotypic variation in intercuspal distances with only moderate genetic contribution is consistent with substantial epigenetic influence on the progressive folding of the internal enamel epithelium, following formation of the primary and secondary enamel knots.

Inheritance and world variation in thermal requirements for egg hatch in Lymantria dispar (Lepidoptera: Erebidae)

Treesearch

M.A. Keena

2016-01-01

Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no...

[Analysis of bacterial small-colony variants isolated from clinical specimens].

PubMed

Matsumoto, Takehisa

2014-07-01

There is a slow-growing subpopulation of bacteria with distinctive phenotypic and pathogenic traits called bacterial small-colony variants (SCVs). Phenotypically, SCVs show a slow growth rate, atypical colony morphology, and unusual biochemical characteristics. SCV strains often grow on blood agar or Drigalski agar as non-pigmented or pinpoint pigmented colonies, and key biochemical tests for them are often non-reactive. This review describes analyses of hemin-dependent Escherichia coli SCV and Staphylococcus aureus thymidine-dependent SCVs based on our case reports. Because SCVs exhibit fastidious growth characteristics, clinical microbiologists may easily miss or misidentify them in the clinical laboratory. Therefore, we must elucidate the cause of SCVs, and improve laboratory methods for the identification and assessment of the susceptibility of SCVs in the clinical laboratory.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability.

PubMed

Gamba, Bruno F; Zechi-Ceide, Roseli M; Kokitsu-Nakata, Nancy M; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C V; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-11-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A , DUF1220 , and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

Interstitial 1q21.1 Microdeletion Is Associated with Severe Skeletal Anomalies, Dysmorphic Face and Moderate Intellectual Disability

PubMed Central

Gamba, Bruno F.; Zechi-Ceide, Roseli M.; Kokitsu-Nakata, Nancy M.; Vendramini-Pittoli, Siulan; Rosenberg, Carla; Krepischi Santos, Ana C.V.; Ribeiro-Bicudo, Lucilene; Richieri-Costa, Antonio

2016-01-01

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date. PMID:27920638

The social phenotype of Williams syndrome.

PubMed

Järvinen, Anna; Korenberg, Julie R; Bellugi, Ursula

2013-06-01

Williams syndrome (WS) offers an exciting model for social neuroscience because its genetic basis is well-defined, and the unique phenotype reflects dimensions of prosocial behaviors. WS is associated with a strong drive to approach strangers, a gregarious personality, heightened social engagement yet difficult peer interactions, high nonsocial anxiety, unusual bias toward positive affect, and diminished sensitivity to fear. New neurobiological evidence points toward alterations in structure, function, and connectivity of the social brain (amygdala, fusiform face area, orbital-frontal regions). Recent genetic studies implicate gene networks in the WS region with the dysregulation of prosocial neuropeptides. The study of WS has implications for understanding human social development, and may provide insight for translating genetic and neuroendocrine evidence into treatments for disorders of social behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

Array-CGH in patients with Kabuki-like phenotype: Identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration

PubMed Central

Cuscó, Ivon; del Campo, Miguel; Vilardell, Mireia; González, Eva; Gener, Blanca; Galán, Enrique; Toledo, Laura; Pérez-Jurado, Luis A

2008-01-01

Background Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered. PMID:18405349

Array-CGH in patients with Kabuki-like phenotype: identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration.

PubMed

Cuscó, Ivon; del Campo, Miguel; Vilardell, Mireia; González, Eva; Gener, Blanca; Galán, Enrique; Toledo, Laura; Pérez-Jurado, Luis A

2008-04-11

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

UNUSUAL FLORAL ORGANS Controls Meristem Identity and Organ Primordia Fate in Arabidopsis.

PubMed

Wilkinson, M. D.; Haughn, G. W.

1995-09-01

A novel gene that is involved in regulating flower initiation and development has been identified in Arabidopsis. This gene has been designated UNUSUAL FLORAL ORGANS (UFO), with five corresponding nuclear recessive alleles designated ufo[middot]1 to ufo[middot]5. Under short day-length conditions, ufo homozygotes generate more coflorescences than do the wild type, and coflorescences often appear apical to the first floral shoot, resulting in a period of inflorescence development in which regions of floral and coflorescence shoots are produced alternately. ufo enhances the phenotype of weak leafy alleles, and the double mutant Ufo-1 Apetala1-1 produces only coflorescence-like shoots, suggesting that these two genes control different aspects of floral initiation. Floral development was also altered in Ufo plants. Ufo flowers have an altered organ number in all whorls, and organs in the first, second, and third whorls exhibit variable homeotic transformations. Ufo single and double mutant phenotypes suggest that the floral changes result from reduction in class B floral homeotic gene expression and fluctuations in the expression boundaries of class C function and FLO10. Surprisingly, in situ hybridization analysis revealed no obvious differences in expression pattern or level in developing Ufo flowers compared with that of the wild type for any class B or C gene studied. We propose that UFO acts in concert with known floral initiation genes and regulates the domains of floral homeotic gene function.

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.

PubMed

Cobb, Joshua N; Declerck, Genevieve; Greenberg, Anthony; Clark, Randy; McCouch, Susan

2013-04-01

More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties.

Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts.

PubMed

Matveeva, Natalia M; Fishman, Veniamin S; Zakharova, Irina S; Shevchenko, Alexander I; Pristyazhnyuk, Inna E; Menzorov, Aleksei G; Serov, Oleg L

2017-12-22

For the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34-43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25-29% of these genes display intermediate levels of expression, and 12-16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.

Report of a Rare Case: A Maxillary First Molar with Seven Canals Confirmed with Cone-Beam Computed Tomography

PubMed Central

Kumar, Rahul

2014-01-01

Introduction: Coronal anatomic variations in permanent maxillary molars are unusual; conversely variations involving the number of root canals or number of roots are more common. Methods and Materials: This case report presents a successful nonsurgical endodontic therapy of left maxillary first molar with three roots and seven root canals. This unusual morphology was diagnosed using a dental operating microscope (DOM) and confirmed with the help of cone-beam computed tomography (CBCT) images. Results: CBCT axial images showed that both of the palatal and distobuccal roots had Vertucci type II canal pattern, whereas the mesiobuccal root canal showed a Sert and Bayirli’s type XV configuration. Conclusion: The use of a DOM and CBCT imaging in endodontically challenging cases can facilitate a better understanding of the complex root canal anatomy, which ultimately enables the clinician to explore the root canal system, and therefore treat it far more efficiently. PMID:24688587

Morphometry, ultrastructure, myosin isoforms, and metabolic capacities of the "mini muscles" favoured by selection for high activity in house mice.

PubMed

Guderley, Helga; Houle-Leroy, Philippe; Diffee, Gary M; Camp, Dana M; Garland, Theodore

2006-07-01

Prolonged selective breeding of mice (Mus musculus) for high levels of voluntary wheel running has favoured an unusual phenotype ("mini muscles"), apparently caused by a single Mendelian recessive allele, in which most hind-limb muscles are markedly reduced in mass, but have increased mass-specific activities of mitochondrial enzymes. We examined whether these changes reflect changes in fibre size, number or ultrastructure in normal and "mini-muscle" mice within the two (of four) selectively bred lines (lab designations L3 and L6) that exhibit the phenotype at generations 26 and 27. In both lines, the gastrocnemius and plantaris muscles are smaller in mass (by >50% and 20%, respectively) in affected individuals. The mass-specific activities of mitochondrial enzymes in the gastrocnemius and plantaris muscles were increased in the mini phenotype in both lines, with stronger effects in the gastrocnemius muscle. In the gastrocnemius, the % myosin heavy chain (MHC) IIb was reduced by 50% in L3 and by 30% in L6, whereas the % MHC IIa and I were higher, particularly in L3. Fibre number in the plantaris muscle did not significantly differ between mini and normal muscles, although muscle mass was a significant positive correlate of fibre number. Small fibres were more abundant in mini than normal muscles in L3. Mitochondrial volume density was significantly higher in mini than normal muscle fibres in L3, but not in L6. Microscopy revealed a surprising attribute of the mini muscles: an abundance of small, minimally differentiated, myofibril-containing cells positioned in a disorderly fashion, particularly in the surface layer. We hypothesise that these unusual cells may be satellite cells or type IIb fibres that did not complete their differentiation. Together, these observations suggest that mice with the mini phenotype have reduced numbers of type IIb fibres in many of their hind-limb muscles, leading to a decrease in mass and an increase in mass-specific aerobic capacity in muscles that typically have a high proportion of type IIb fibres. Moreover, the several statistically significant interactions between muscle phenotype and line indicate that the effect of the underlying allele is altered by genetic background.

Genome-wide association implicates numerous genes and pleiotropy underlying ecological trait variation in natural populations of Populus trichocarpa

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKown, Athena; Klapste, Jaroslav; Guy, Robert

2014-01-01

To uncover the genetic basis of phenotypic trait variation, we used 448 unrelated wild accessions of black cottonwood (Populus trichocarpa Torr. & Gray) from natural populations throughout western North America. Extensive information from large-scale trait phenotyping (with spatial and temporal replications within a common garden) and genotyping (with a 34K Populus SNP array) of all accessions were used for gene discovery in a genome-wide association study (GWAS).

Sexual variation in assimilation efficiency: its link to phenotype and potential role in sexual dimorphism.

PubMed

Stahlschmidt, Zachary R; Davis, Jon R; Denardo, Dale F

2011-04-01

Sex-specific variation in morphology (sexual dimorphism) is a prevalent phenomenon among animals, and both dietary intake and resource allocation strategies influence sexually dimorphic traits (e.g., body size or composition). However, we investigated whether assimilation efficiency (AE), an intermediate step between dietary intake and allocation, can also vary between the sexes. Specifically, we tested whether sex-based differences in AE can explain variation in phenotypic traits. We measured morphometric characteristics (i.e., body length, mass, condition, and musculature) and AE of total energy, crude protein, and crude fat in post-reproductive adult Children's pythons (which exhibit a limited female-biased sexual size dimorphism) fed both low and high dietary intakes. Meal size was negatively related to AE of energy. Notably, male snakes absorbed crude protein more efficiently and increased epaxial (dorsal) musculature faster than females, which demonstrates a link between AE and phenotype. However, females grew in body length faster but did not absorb any nutrient more efficiently than males. Although our results do not provide a direct link between AE and sexual size dimorphism, they demonstrate that sexual variation in nutrient absorption exists and can contribute to other types of sex-based differences in phenotype (i.e., sexual dimorphism in growth of musculature). Hence, testing the broader applicability of AE's role in sexually dimorphic traits among other species is warranted.

Developmental origins of a novel gut morphology in frogs.

PubMed

Bloom, Stephanie; Ledon-Rettig, Cris; Infante, Carlos; Everly, Anne; Hanken, James; Nascone-Yoder, Nanette

2013-05-01

Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation. © 2013 Wiley Periodicals, Inc.

Genomic regions controlling shape variation in the first upper molar of the house mouse

PubMed Central

Pantalacci, Sophie; Turner, Leslie M; Steingrimsson, Eirikur; Renaud, Sabrina

2017-01-01

Numerous loci of large effect have been shown to underlie phenotypic variation between species. However, loci with subtle effects are presumably more frequently involved in microevolutionary processes but have rarely been discovered. We explore the genetic basis of shape variation in the first upper molar of hybrid mice between Mus musculus musculus and M. m. domesticus. We performed the first genome-wide association study for molar shape and used 3D surface morphometrics to quantify subtle variation between individuals. We show that many loci of small effect underlie phenotypic variation, and identify five genomic regions associated with tooth shape; one region contained the gene microphthalmia-associated transcription factor Mitf that has previously been associated with tooth malformations. Using a panel of five mutant laboratory strains, we show the effect of the Mitf gene on tooth shape. This is the first report of a gene causing subtle but consistent variation in tooth shape resembling variation in nature. PMID:29091026

Patterns of among- and within-species variation in heterospecific pollen receipt: The importance of ecological generalization.

PubMed

Arceo-Gómez, Gerardo; Abdala-Roberts, Luis; Jankowiak, Anneka; Kohler, Clare; Meindl, George A; Navarro-Fernández, Carmen M; Parra-Tabla, Víctor; Ashman, Tia-Lynn; Alonso, Conchita

2016-03-01

Coflowering plants are at risk for receiving pollen from heterospecifics as well as conspecifics, yet evidence shows wide variation in the degree that heterospecific pollen transfer occurs. Evaluation of patterns and correlates of among- and within-species variation in heterospecific pollen (HP) receipt is key to understanding its importance for floral evolution and species coexistence; however, the rarity of deeply sampled multispecies comparisons has precluded such an evaluation. We evaluated patterns of among- and within-species variation in HP load size and diversity in 19 species across three distinct plant communities. We assessed the importance of phenotypic specialization (floral phenotype), ecological specialization (contemporary visitor assemblage), and conspecific flower density as determinants of among-species variation. We present hypotheses for different accrual patterns of HP within species based on the evenness and quality of floral visitors and evaluated these by characterizing the relationship between conspecific pollen (CP) and HP receipt. We found that within-species variation in HP receipt was greater than among-species and among-communities variation. Among species, ecological generalization emerged as the strongest driver of variation in HP receipt irrespective of phenotypic specialization. Within-species variation in HP load size and diversity was predicted most often from two CP-HP relationships (linear or exponentially decreasing), suggesting that two distinct types of plant-pollinator interactions prevail. Our results give important insights into the potential drivers of among- and within-species variation in HP receipt. They also highlight the value of explorations of patterns at the intraspecific level, which can ultimately shed light on plant-pollinator-mediated selection in diverse plant communities. © 2016 Botanical Society of America.

[Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association. Clinical case].

PubMed

Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A

2017-06-01

Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.

Effects of assortative mate choice on the genomic and morphological structure of a hybrid zone between two bird subspecies.

PubMed

Semenov, Georgy A; Scordato, Elizabeth S C; Khaydarov, David R; Smith, Chris C R; Kane, Nolan C; Safran, Rebecca J

2017-11-01

Phenotypic differentiation plays an important role in the formation and maintenance of reproductive barriers. In some cases, variation in a few key aspects of phenotype can promote and maintain divergence; hence, the identification of these traits and their associations with patterns of genomic divergence is crucial for understanding the patterns and processes of population differentiation. We studied hybridization between the alba and personata subspecies of the white wagtail (Motacilla alba), and quantified divergence and introgression of multiple morphological traits and 19,437 SNP loci on a 3,000 km transect. Our goal was to identify traits that may contribute to reproductive barriers and to assess how variation in these traits corresponds to patterns of genome-wide divergence. Variation in only one trait-head plumage patterning-was consistent with reproductive isolation. Transitions in head plumage were steep and occurred over otherwise morphologically and genetically homogeneous populations, whereas cline centres for other traits and genomic ancestry were displaced over 100 km from the head cline. Field observational data show that social pairs mated assortatively by head plumage, suggesting that these phenotypes are maintained by divergent mating preferences. In contrast, variation in all other traits and genetic markers could be explained by neutral diffusion, although weak ecological selection cannot be ruled out. Our results emphasize that assortative mating may maintain phenotypic differences independent of other processes shaping genome-wide variation, consistent with other recent findings that raise questions about the relative importance of mate choice, ecological selection and selectively neutral processes for divergent evolution. © 2017 John Wiley & Sons Ltd.

Elevated temperature is more effective than elevated [CO2 ] in exposing genotypic variation in Telopea speciosissima growth plasticity: implications for woody plant populations under climate change.

PubMed

Huang, Guomin; Rymer, Paul D; Duan, Honglang; Smith, Renee A; Tissue, David T

2015-10-01

Intraspecific variation in phenotypic plasticity is a critical determinant of plant species capacity to cope with climate change. A long-standing hypothesis states that greater levels of environmental variability will select for genotypes with greater phenotypic plasticity. However, few studies have examined how genotypes of woody species originating from contrasting environments respond to multiple climate change factors. Here, we investigated the main and interactive effects of elevated [CO2 ] (CE ) and elevated temperature (TE ) on growth and physiology of Coastal (warmer, less variable temperature environment) and Upland (cooler, more variable temperature environment) genotypes of an Australian woody species Telopea speciosissima. Both genotypes were positively responsive to CE (35% and 29% increase in whole-plant dry mass and leaf area, respectively), but only the Coastal genotype exhibited positive growth responses to TE . We found that the Coastal genotype exhibited greater growth response to TE (47% and 85% increase in whole-plant dry mass and leaf area, respectively) when compared with the Upland genotype (no change in dry mass or leaf area). No intraspecific variation in physiological plasticity was detected under CE or TE , and the interactive effects of CE and TE on intraspecific variation in phenotypic plasticity were also largely absent. Overall, TE was a more effective climate factor than CE in exposing genotypic variation in our woody species. Our results contradict the paradigm that genotypes from more variable climates will exhibit greater phenotypic plasticity in future climate regimes. © 2015 John Wiley & Sons Ltd.

Genome-wide Association Study Identifies Loci for the Polled Phenotype in Yak

PubMed Central

Wu, Xiaoyun; Wang, Kun; Ding, Xuezhi; Wang, Mingcheng; Chu, Min; Xie, Xiuyue; Qiu, Qiang; Yan, Ping

2016-01-01

The absence of horns, known as the polled phenotype, is an economically important trait in modern yak husbandry, but the genomic structure and genetic basis of this phenotype have yet to be discovered. Here, we conducted a genome-wide association study with a panel of 10 horned and 10 polled yaks using whole genome sequencing. We mapped the POLLED locus to a 200-kb interval, which comprises three protein-coding genes. Further characterization of the candidate region showed recent artificial selection signals resulting from the breeding process. We suggest that expressional variations rather than structural variations in protein probably contribute to the polled phenotype. Our results not only represent the first and important step in establishing the genomic structure of the polled region in yak, but also add to our understanding of the polled trait in bovid species. PMID:27389700

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dighe, Kalpak Arvind

Several 40+ hour data records obtained in Oct 2010 from the Los Alamos Portable Pulser Facility (LAPP) Operational clocks show variations of {approx} 27 nsec. Several 16+ hour data records obtained in Aug 2010 from non-operational clocks like those used operationally from 2005 to the present show variations of {approx} 35 nsec. SLRE variability is xxx +/- yyy sec (std dev). SLRE occasionally show unusual events such as those discussed by Pongratz. We will continue to study and monitor.

Unusual Observations during the December 2006 Solar Energetic Particle Events within an Interplanetary Coronal Mass Ejection at 1 AU

NASA Astrophysics Data System (ADS)

Mulligan, T.; Blake, J. B.; Mewaldt, R. A.; Leske, R. A.

2008-08-01

In mid December 2006 several flares on the Sun occurred in rapid succession, spawning several CMEs and bathing the Earth in multiple solar energetic particle (SEP) events. One such SEP event occurring on December 14 was observed at the Earth just as an interplanetary CME (ICME) from a previous flare on December 13 was transiting the Earth. Although solar wind observations during this time show typical energetic proton fluxes from the prior SEP event and IP shock driven ahead of the ICME, as the ICME passes the Earth unusual energetic particle signatures are observed. Measurements from ACE, Wind, and STEREO show proton flux variations at energies ranging from ~3 MeV up to greater than 70 MeV. Energetic electron signatures from ACE show similar variations. Within the Earth's magnetosphere Polar HIST also sees these proton flux variations at energies greater than 10 MeV while crossing open field lines in the southern polar cap. Although no such variation in the energetic proton flux is observed at the GOES 11 spacecraft in geosynchronous orbit near the subsolar region, differential fluxes observed at GOES 11 and GOES 12 in the 15-40 MeV energy range do show some variability, indicating the signature is observable near dawn and dusk.

Transcriptome analysis of a wild bird reveals physiological responses to the urban environment

PubMed Central

Watson, Hannah; Videvall, Elin; Andersson, Martin N.; Isaksson, Caroline

2017-01-01

Identifying the molecular basis of environmentally induced phenotypic variation presents exciting opportunities for furthering our understanding of how ecological processes and the environment can shape the phenotype. Urban and rural environments present free-living organisms with different challenges and opportunities, which have marked consequences for the phenotype, yet little is known about responses at the molecular level. We characterised transcriptomes from an urban and a rural population of great tits Parus major, demonstrating striking differences in gene expression profiles in both blood and liver tissues. Differentially expressed genes had functions related to immune and inflammatory responses, detoxification, protection against oxidative stress, lipid metabolism, and regulation of gene expression. Many genes linked to stress responses were expressed at higher levels in the urban birds, in accordance with our prediction that urban animals are exposed to greater environmental stress. This is one of the first studies to reveal transcriptional differences between urban- and rural-dwelling animals and suggests an important role for epigenetics in mediating environmentally induced physiological variation. The study provides valuable resources for developing further in-depth studies of the mechanisms driving phenotypic variation in the urban context at larger spatial and temporal scales. PMID:28290496

Evolutionary genomics of animal personality.

PubMed

van Oers, Kees; Mueller, Jakob C

2010-12-27

Research on animal personality can be approached from both a phenotypic and a genetic perspective. While using a phenotypic approach one can measure present selection on personality traits and their combinations. However, this approach cannot reconstruct the historical trajectory that was taken by evolution. Therefore, it is essential for our understanding of the causes and consequences of personality diversity to link phenotypic variation in personality traits with polymorphisms in genomic regions that code for this trait variation. Identifying genes or genome regions that underlie personality traits will open exciting possibilities to study natural selection at the molecular level, gene-gene and gene-environment interactions, pleiotropic effects and how gene expression shapes personality phenotypes. In this paper, we will discuss how genome information revealed by already established approaches and some more recent techniques such as high-throughput sequencing of genomic regions in a large number of individuals can be used to infer micro-evolutionary processes, historical selection and finally the maintenance of personality trait variation. We will do this by reviewing recent advances in molecular genetics of animal personality, but will also use advanced human personality studies as case studies of how molecular information may be used in animal personality research in the near future.

Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

PubMed

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-03-09

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

Metabolomic phenotyping of a cloned pig model

PubMed Central

2011-01-01

Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5) was for the first time elucidated by nuclear magnetic resonance (NMR)-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6) by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals. PMID:21859467

Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments.

PubMed

Rubio de Casas, R; Vargas, P; Pérez-Corona, E; Cano, E; Manrique, E; García-Verdugo, C; Balaguer, L

2009-05-01

Evergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and beta-carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.

3D Laser Triangulation for Plant Phenotyping in Challenging Environments

PubMed Central

Kjaer, Katrine Heinsvig; Ottosen, Carl-Otto

2015-01-01

To increase the understanding of how the plant phenotype is formed by genotype and environmental interactions, simple and robust high-throughput plant phenotyping methods should be developed and considered. This would not only broaden the application range of phenotyping in the plant research community, but also increase the ability for researchers to study plants in their natural environments. By studying plants in their natural environment in high temporal resolution, more knowledge on how multiple stresses interact in defining the plant phenotype could lead to a better understanding of the interaction between plant responses and epigenetic regulation. In the present paper, we evaluate a commercial 3D NIR-laser scanner (PlantEye, Phenospex B.V., Herleen, The Netherlands) to track daily changes in plant growth with high precision in challenging environments. Firstly, we demonstrate that the NIR laser beam of the scanner does not affect plant photosynthetic performance. Secondly, we demonstrate that it is possible to estimate phenotypic variation amongst the growth pattern of ten genotypes of Brassica napus L. (rapeseed), using a simple linear correlation between scanned parameters and destructive growth measurements. Our results demonstrate the high potential of 3D laser triangulation for simple measurements of phenotypic variation in challenging environments and in a high temporal resolution. PMID:26066990

Natural variation in stomatal abundance of Arabidopsis thaliana includes cryptic diversity for different developmental processes

PubMed Central

Delgado, Dolores; Alonso-Blanco, Carlos; Fenoll, Carmen; Mena, Montaña

2011-01-01

Background and Aims Current understanding of stomatal development in Arabidopsis thaliana is based on mutations producing aberrant, often lethal phenotypes. The aim was to discover if naturally occurring viable phenotypes would be useful for studying stomatal development in a species that enables further molecular analysis. Methods Natural variation in stomatal abundance of A. thaliana was explored in two collections comprising 62 wild accessions by surveying adaxial epidermal cell-type proportion (stomatal index) and density (stomatal and pavement cell density) traits in cotyledons and first leaves. Organ size variation was studied in a subset of accessions. For all traits, maternal effects derived from different laboratory environments were evaluated. In four selected accessions, distinct stomatal initiation processes were quantitatively analysed. Key Results and Conclusions Substantial genetic variation was found for all six stomatal abundance-related traits, which were weakly or not affected by laboratory maternal environments. Correlation analyses revealed overall relationships among all traits. Within each organ, stomatal density highly correlated with the other traits, suggesting common genetic bases. Each trait correlated between organs, supporting supra-organ control of stomatal abundance. Clustering analyses identified accessions with uncommon phenotypic patterns, suggesting differences among genetic programmes controlling the various traits. Variation was also found in organ size, which negatively correlated with cell densities in both organs and with stomatal index in the cotyledon. Relative proportions of primary and satellite lineages varied among the accessions analysed, indicating that distinct developmental components contribute to natural diversity in stomatal abundance. Accessions with similar stomatal indices showed different lineage class ratios, revealing hidden developmental phenotypes and showing that genetic determinants of primary and satellite lineage initiation combine in several ways. This first systematic, comprehensive natural variation survey for stomatal abundance in A. thaliana reveals cryptic developmental genetic variation, and provides relevant relationships amongst stomatal traits and extreme or uncommon accessions as resources for the genetic dissection of stomatal development. PMID:21447490

Good neighbors make good defenses: associational refuges reduce defense investment in African savanna plants.

PubMed

Coverdale, Tyler C; Goheen, Jacob R; Palmer, Todd M; Pringle, Robert M

2018-06-25

Intraspecific variation in plant defense phenotype is common and has wide-ranging ecological consequences. Yet prevailing theories of plant defense allocation, which primarily account for interspecific differences in defense phenotype, often fail to predict intraspecific patterns. Furthermore, although individual variation in defense phenotype is often attributed to ecological interactions, few general mechanisms have been proposed to explain the ubiquity of variable defense phenotype within species. Here, we show experimentally that associational refuges and induced resistance interact to create predictable intraspecific variation in defense phenotype in African savanna plants. Physically defended species from four families (Acanthaceae, Asparagaceae, Cactaceae, and Solanaceae) growing in close association with spinescent Acacia trees had 39-78% fewer spines and thorns than did isolated conspecifics. For a subset of these species, we used a series of manipulative experiments to show that this variability is maintained primarily by a reduction in induced responses among individuals that seldom experience mammalian herbivory, whether due to association with Acacia trees or to experimental herbivore exclusion. Unassociated plants incurred 4- to 16-fold more browsing damage than did associated individuals and increased spine density by 16-38% within one month following simulated browsing. In contrast, experimental clipping induced no net change in spine density among plants growing beneath Acacia canopies or inside long-term herbivore exclosures. Associated and unassociated individuals produced similar numbers of flowers and seeds, but seedling recruitment and survival were vastly greater in refuge habitats, suggesting a net fitness benefit of association. We conclude that plant-plant associations consistently decrease defense investment in this system by reducing both the frequency of herbivory and the intensity of induced responses, and that inducible responses enable plants to capitalize on such associations in heterogeneous environments. Given the prevalence of associational and induced defenses in plant communities worldwide, our results suggest a potentially general mechanism by which biotic interactions might predictably shape intraspecific variation in plant defense phenotype. © 2018 by the Ecological Society of America.

Asynchrony of senescence among phenotypic traits in a wild mammal population

PubMed Central

Hayward, Adam D.; Moorad, Jacob; Regan, Charlotte E.; Berenos, Camillo; Pilkington, Jill G.; Pemberton, Josephine M.; Nussey, Daniel H.

2015-01-01

The degree to which changes in lifespan are coupled to changes in senescence in different physiological systems and phenotypic traits is a central question in biogerontology. It is underpinned by deeper biological questions about whether or not senescence is a synchronised process, or whether levels of synchrony depend on species or environmental context. Understanding how natural selection shapes patterns of synchrony in senescence across physiological systems and phenotypic traits demands the longitudinal study of many phenotypes under natural conditions. Here, we examine the patterns of age-related variation in late adulthood in a wild population of Soay sheep (Ovis aries) that have been the subject of individual-based monitoring for thirty years. We examined twenty different phenotypic traits in both males and females, encompassing vital rates (survival and fecundity), maternal reproductive performance (offspring birth weight, birth date and survival), male rutting behaviour, home range measures, parasite burdens, and body mass. We initially quantified age-related variation in each trait having controlled for annual variation in the environment, among-individual variation and selective disappearance effects. We then standardised our age-specific trait means and tested whether age trajectories could be meaningfully grouped according to sex or the type of trait. Whilst most traits showed age-related declines in later life, we found striking levels of asynchrony both within and between the sexes. Of particular note, female fecundity and reproductive performance declined with age, but male annual reproductive success did not. We also discovered that whilst home range size and quality decline with age in females, home range size increases with age in males. Our findings highlight the complexity of phenotypic ageing under natural conditions and, along with emerging data from other wild populations and laboratory models, suggest that the long-standing hypothesis within evolutionary biology that fitness-related traits should senesce in a synchronous manner is seriously flawed. PMID:26277618

Revisiting Darwin's hypothesis: Does greater intraspecific variability increase species' ecological breadth?

PubMed

Sides, Colby B; Enquist, Brian J; Ebersole, James J; Smith, Marielle N; Henderson, Amanda N; Sloat, Lindsey L

2014-01-01

Darwin first proposed that species with larger ecological breadth have greater phenotypic variation. We tested this hypothesis by comparing intraspecific variation in specific leaf area (SLA) to species' local elevational range and by assessing how external (abiotic) filters may influence observed differences in ecological breadth among species. Understanding the patterns of individual variation within and between populations will help evaluate differing hypotheses for structuring of communities and distribution of species. We selected 21 species with varying elevational ranges and compared the coefficient of variation of SLA for each species against its local elevational range. We examined the influence of external filters on local trait composition by determining if intraspecific changes in SLA with elevation have the same direction and similar rates of change as the change in community mean SLA value. In support of Darwin's hypothesis, we found a positive relationship between species' coefficient of variation for SLA with species' local elevational range. Intraspecific changes in SLA had the same sign, but generally lower magnitude than the community mean SLA. The results indicate that wide-ranging species are indeed characterized by greater intraspecific variation and that species' phenotypes shift along environmental gradients in the same direction as the community phenotypes. However, across species, the rate of intraspecific trait change, reflecting plastic and/or adaptive changes across populations, is limited and prevents species from adjusting to environmental gradients as quickly as interspecific changes resulting from community assembly.

Genome-Wide Association Mapping and Genomic Prediction Elucidate the Genetic Architecture of Morphological Traits in Arabidopsis.

PubMed

Kooke, Rik; Kruijer, Willem; Bours, Ralph; Becker, Frank; Kuhn, André; van de Geest, Henri; Buntjer, Jaap; Doeswijk, Timo; Guerra, José; Bouwmeester, Harro; Vreugdenhil, Dick; Keurentjes, Joost J B

2016-04-01

Quantitative traits in plants are controlled by a large number of genes and their interaction with the environment. To disentangle the genetic architecture of such traits, natural variation within species can be explored by studying genotype-phenotype relationships. Genome-wide association studies that link phenotypes to thousands of single nucleotide polymorphism markers are nowadays common practice for such analyses. In many cases, however, the identified individual loci cannot fully explain the heritability estimates, suggesting missing heritability. We analyzed 349 Arabidopsis accessions and found extensive variation and high heritabilities for different morphological traits. The number of significant genome-wide associations was, however, very low. The application of genomic prediction models that take into account the effects of all individual loci may greatly enhance the elucidation of the genetic architecture of quantitative traits in plants. Here, genomic prediction models revealed different genetic architectures for the morphological traits. Integrating genomic prediction and association mapping enabled the assignment of many plausible candidate genes explaining the observed variation. These genes were analyzed for functional and sequence diversity, and good indications that natural allelic variation in many of these genes contributes to phenotypic variation were obtained. For ACS11, an ethylene biosynthesis gene, haplotype differences explaining variation in the ratio of petiole and leaf length could be identified. © 2016 American Society of Plant Biologists. All Rights Reserved.

Evolutionary constraints or opportunities?

PubMed

Sharov, Alexei A

2014-09-01

Natural selection is traditionally viewed as a leading factor of evolution, whereas variation is assumed to be random and non-directional. Any order in variation is attributed to epigenetic or developmental constraints that can hinder the action of natural selection. In contrast I consider the positive role of epigenetic mechanisms in evolution because they provide organisms with opportunities for rapid adaptive change. Because the term "constraint" has negative connotations, I use the term "regulated variation" to emphasize the adaptive nature of phenotypic variation, which helps populations and species to survive and evolve in changing environments. The capacity to produce regulated variation is a phenotypic property, which is not described in the genome. Instead, the genome acts as a switchboard, where mostly random mutations switch "on" or "off" preexisting functional capacities of organism components. Thus, there are two channels of heredity: informational (genomic) and structure-functional (phenotypic). Functional capacities of organisms most likely emerged in a chain of modifications and combinations of more simple ancestral functions. The role of DNA has been to keep records of these changes (without describing the result) so that they can be reproduced in the following generations. Evolutionary opportunities include adjustments of individual functions, multitasking, connection between various components of an organism, and interaction between organisms. The adaptive nature of regulated variation can be explained by the differential success of lineages in macro-evolution. Lineages with more advantageous patterns of regulated variation are likely to produce more species and secure more resources (i.e., long-term lineage selection). Published by Elsevier Ireland Ltd.

THE EVOLUTION OF CANALIZATION AND THE BREAKING OF VON BAER'S LAWS: MODELING THE EVOLUTION OF DEVELOPMENT WITH EPISTASIS.

PubMed

Rice, Sean H

1998-06-01

Evolution can change the developmental processes underlying a character without changing the average expression of the character itself. This sort of change must occur in both the evolution of canalization, in which a character becomes increasingly buffered against genetic or developmental variation, and in the phenomenon of closely related species that show similar adult phenotypes but different underlying developmental patterns. To study such phenomena, I develop a model that follows evolution on a surface representing adult phenotype as a function of underlying developmental characters. A contour on such a "phenotype landscape" is a set of states of developmental characters that produce the same adult phenotype. Epistasis induces curvature of this surface, and degree of canalization is represented by the slope along a contour. I first discuss the geometric properties of phenotype landscapes, relating epistasis to canalization. I then impose a fitness function on the phenotype and model evolution of developmental characters as a function of the fitness function and the local geometry of the surface. This model shows how canalization evolves as a population approaches an optimum phenotype. It further shows that under some circumstances, "decanalization" can occur, in which the expression of adult phenotype becomes increasingly sensitive to developmental variation. This process can cause very similar populations to diverge from one another developmentally even when their adult phenotypes experience identical selection regimes. © 1998 The Society for the Study of Evolution.

Discordant introgression in a rapidly expanding hybrid swarm

USGS Publications Warehouse

Ward, Jessica L.; Blum, Mike J.; Walters, David M.; Porter, Brady A.; Burkhead, Noel; Freeman, Byron

2012-01-01

The erosion of species boundaries can involve rapid evolutionary change. Consequently, many aspects of the process remain poorly understood, including the formation, expansion, and evolution of hybrid swarms. Biological invasions involving hybridization present exceptional opportunities to study the erosion of species boundaries because timelines of interactions and outcomes are frequently well known. Here, we examined clinal variation across codominant and maternally inherited genetic markers as well as phenotypic traits to characterize the expansion and evolution of a hybrid swarm between native Cyprinella venusta and invasive Cyprinella lutrensis minnows. Discordant introgression of phenotype, microsatellite multilocus genotype, and mtDNA haplotype indicates that the observable expansion of the C. venusta x C. lutrensis hybrid swarm is a false invasion front. Both parental and hybrid individuals closely resembling C. lutrensis are numerically dominant in the expansion wake, indicating that the non-native parental phenotype may be selectively favored. These findings show that cryptic introgression can extend beyond the phenotypic boundaries of hybrid swarms and that hybrid swarms likely expand more rapidly than can be documented from phenotypic variation alone. Similarly, dominance of a single parental phenotype following an introduction event may lead to instances of species erosion being mistaken for species displacement without hybridization.

Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across two abiotic environmental gradients in Poecilia mexicana.

PubMed

Tobler, Michael; Dewitt, Thomas J; Schlupp, Ingo; García de León, Francisco J; Herrmann, Roger; Feulner, Philine G D; Tiedemann, Ralph; Plath, Martin

2008-10-01

Divergent natural selection drives evolutionary diversification. It creates phenotypic diversity by favoring developmental plasticity within populations or genetic differentiation and local adaptation among populations. We investigated phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along two abiotic environmental gradients. These fish typically inhabit nonsulfidic surface rivers, but also colonized sulfidic and cave habitats. We assessed phenotypic variation among a factorial combination of habitat types using geometric and traditional morphometrics, and genetic divergence using quantitative and molecular genetic analyses. Fish in caves (sulfidic or not) exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface or cave) exhibited larger heads and longer gill filaments. Common-garden rearing suggested that these morphological differences are partly heritable. Population genetic analyses using microsatellites as well as cytochrome b gene sequences indicate high population differentiation over small spatial scale and very low rates of gene flow, especially among different habitat types. This suggests that divergent environmental conditions constitute barriers to gene flow. Strong molecular divergence over short distances as well as phenotypic and quantitative genetic divergence across habitats in directions classic to fish ecomorphology suggest that divergent selection is structuring phenotypic variation in this system.

Genomic imprinting as a probable explanation for variable intrafamilial phenotypic expression of an unusual chromosome 3 abnormality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fryburg, J.S.; Shashi, V.; Kelly, T.E.

1994-09-01

We present a 4 generation family in which an abnormal chromosome 3 with dup(3)(q25) segregated from great-grandmother to grandmother to son without phenotypic effect. The son`s 2 daughters have dysmorphic features, mild developmental delays and congenital heart disease. Both girls have the abnormal chr. 3 but are the only family members with the abnormality to have phenotypic effects. An unaffected son of the father has normal chromosomes. FISH with whole chromosome paints for chromosomes 1, 2, 6, 7, 8, 14, 18, and 22 excluded these as the origin of the extra material. Chromosome 3-specific paint revealed a uniform pattern, suggestingmore » that the extra material is from chromosome 3. Comparative genomic hybridization and DNA studies are pending. Possible explanations for the discordance in phenotypes between the 4th generation offspring and the first 3 generations include: an undetected rearrangement in the previous generations that is unbalanced in the two affected individuals; the chromosome abnormality may be a benign variant and unrelated to the phenotype; or, most likely, genomic imprinting. Genomic imprinting is suggested by the observation that a phenotypic effect was only seen after the chromosome was inherited from the father. The mothers in the first two generations appear to have passed the abnormal chr. 3 on without effect. This is an opportunity to delineate a region of the human genome affected by paternal imprinting.« less

The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics.

PubMed

Goswami, Anjali; Binder, Wendy J; Meachen, Julie; O'Keefe, F Robin

2015-04-21

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change.

The covariance between genetic and environmental influences across ecological gradients: reassessing the evolutionary significance of countergradient and cogradient variation.

PubMed

Conover, David O; Duffy, Tara A; Hice, Lyndie A

2009-06-01

Patterns of phenotypic change across environmental gradients (e.g., latitude, altitude) have long captivated the interest of evolutionary ecologists. The pattern and magnitude of phenotypic change is determined by the covariance between genetic and environmental influences across a gradient. Cogradient variation (CoGV) occurs when covariance is positive: that is, genetic and environmental influences on phenotypic expression are aligned and their joint influence accentuates the change in mean trait value across the gradient. Conversely, countergradient variation (CnGV) occurs when covariance is negative: that is, genetic and environmental influences on phenotypes oppose one another, thereby diminishing the change in mean trait expression across the gradient. CnGV has so far been found in at least 60 species, with most examples coming from fishes, amphibians, and insects across latitudinal or altitudinal gradients. Traits that display CnGV most often involve metabolic compensation, that is, the elevation of various physiological rates processes (development, growth, feeding, metabolism, activity) to counteract the dampening effect of reduced temperature, growing season length, or food supply. Far fewer examples of CoGV have been identified (11 species), and these most often involve morphological characters. Increased knowledge of spatial covariance patterns has furthered our understanding of Bergmann size clines, phenotypic plasticity, species range limits, tradeoffs in juvenile growth rate, and the design of conservation strategies for wild species. Moreover, temporal CnGV explains some cases of an apparent lack of phenotypic response to directional selection and provides a framework for predicting evolutionary responses to climate change.

The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics

PubMed Central

Goswami, Anjali; Binder, Wendy J.; Meachen, Julie; O’Keefe, F. Robin

2015-01-01

Variation is the raw material for natural selection, but the factors shaping variation are still poorly understood. Genetic and developmental interactions can direct variation, but there has been little synthesis of these effects with the extrinsic factors that can shape biodiversity over large scales. The study of phenotypic integration and modularity has the capacity to unify these aspects of evolutionary study by estimating genetic and developmental interactions through the quantitative analysis of morphology, allowing for combined assessment of intrinsic and extrinsic effects. Data from the fossil record in particular are central to our understanding of phenotypic integration and modularity because they provide the only information on deep-time developmental and evolutionary dynamics, including trends in trait relationships and their role in shaping organismal diversity. Here, we demonstrate the important perspective on phenotypic integration provided by the fossil record with a study of Smilodon fatalis (saber-toothed cats) and Canis dirus (dire wolves). We quantified temporal trends in size, variance, phenotypic integration, and direct developmental integration (fluctuating asymmetry) through 27,000 y of Late Pleistocene climate change. Both S. fatalis and C. dirus showed a gradual decrease in magnitude of phenotypic integration and an increase in variance and the correlation between fluctuating asymmetry and overall integration through time, suggesting that developmental integration mediated morphological response to environmental change in the later populations of these species. These results are consistent with experimental studies and represent, to our knowledge, the first deep-time validation of the importance of developmental integration in stabilizing morphological evolution through periods of environmental change. PMID:25901310

Anatomic variation of the abducens nerve in a single cadaver dissection: the "petrobasilar canal".

PubMed

Pizzolorusso, Felice; Cirotti, Andrea; Pizzolorusso, Gianfranco

2017-04-01

Anatomic variations of the petrosphenoid ligament, Dorello's canal and the course of the abducens nerve have been extensively described over the past years. In the present report of a single cadaver dissection, we describe an unusual course of the abducens nerve at the level of the petrous bone. The right abducens nerve did not enter Dorello's canal, but ran below the petrous bone through a narrow canal in the petrobasilar suture, which we called the "petrobasilar canal". No anatomic variations of the left abducens nerve were noted.

Localized sudden changes in the geomagnetic secular variation.

USGS Publications Warehouse

Alldredge, L.R.

1987-01-01

There is much debate as to whether there was a worldwide geomagnetic jerk in 1969 or 1970. It is agreed that there was an unusual sharp change in the secular variation in the east component, Y, in Europe at that time. This note points out how a localized sudden change in the secular variation pattern of one component in Europe can occur without having any large worldwide effects in any of the components. The accompanying changes in the spherical harmonic coefficients for such a localized change are also discussed. -after Author

Inheritance and World Variation in Thermal Requirements for Egg Hatch in Lymantria dispar (Lepidoptera: Erebidae).

PubMed

Keena, M A

2016-02-01

Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no evidence for sex-linkage or cytoplasmic effects with either gene. Eggs from 43 geographic populations were evaluated for hatch characteristics after being held for 60 d at 5°C followed by incubation at 25°C. There was considerable variation both within and among the populations in the proportion able to hatch, time to first hatch, and average time to hatch. Egg masses with reduced requirement for low temperatures before the eggs were ready to hatch were present in all subspecies of L. dispar and the phenotype was not fixed in most populations. The populations clustered into three distinct groups, and climatic variables were found to be rough predictors of those groups. Variation in hatch phenotypes between populations is likely an adaptation to local climate and within a population provides a bet-hedging strategy to ensure that at least some hatch synchronizes with host leaf-out. Continued vigilance to prevent movement of populations both within and between countries is warranted, because some of the alleles that confer nondiapause or reduced low temperature requirements before egg hatch are not present in all populations and their introduction would increase variation in egg hatch within a population. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by a US Government employee and is in the public domain in the US.

Differential Expression of Ecdysone Receptor Leads to Variation in Phenotypic Plasticity across Serial Homologs

PubMed Central

Tong, Xiaoling; Bear, Ashley; Liew, Seng Fatt; Bhardwaj, Shivam; Wasik, Bethany R.; Dinwiddie, April; Bastianelli, Carole; Cheong, Wei Fun; Wenk, Markus R.; Cao, Hui

2015-01-01

Bodies are often made of repeated units, or serial homologs, that develop using the same core gene regulatory network. Local inputs and modifications to this network allow serial homologs to evolve different morphologies, but currently we do not understand which modifications allow these repeated traits to evolve different levels of phenotypic plasticity. Here we describe variation in phenotypic plasticity across serial homologous eyespots of the butterfly Bicyclus anynana, hypothesized to be under selection for similar or different functions in the wet and dry seasonal forms. Specifically, we document the presence of eyespot size and scale brightness plasticity in hindwing eyespots hypothesized to vary in function across seasons, and reduced size plasticity and absence of brightness plasticity in forewing eyespots hypothesized to have the same function across seasons. By exploring the molecular and physiological causes of this variation in plasticity across fore and hindwing serial homologs we discover that: 1) temperature experienced during the wandering stages of larval development alters titers of an ecdysteroid hormone, 20-hydroxyecdysone (20E), in the hemolymph of wet and dry seasonal forms at that stage; 2) the 20E receptor (EcR) is differentially expressed in the forewing and hindwing eyespot centers of both seasonal forms during this critical developmental stage; and 3) manipulations of EcR signaling disproportionately affected hindwing eyespots relative to forewing eyespots. We propose that differential EcR expression across forewing and hindwing eyespots at a critical stage of development explains the variation in levels of phenotypic plasticity across these serial homologues. This finding provides a novel signaling pathway, 20E, and a novel molecular candidate, EcR, for the regulation of levels of phenotypic plasticity across body parts or serial homologs. PMID:26405828

Limited Phylogeographic Signal in Sex-Linked and Autosomal Loci Despite Geographically, Ecologically, and Phenotypically Concordant Structure of mtDNA Variation in the Holarctic Avian Genus Eremophila

PubMed Central

Drovetski, Sergei V.; Raković, Marko; Semenov, Georgy; Fadeev, Igor V.; Red’kin, Yaroslav A.

2014-01-01

Phylogeographic studies of Holarctic birds are challenging because they involve vast geographic scale, complex glacial history, extensive phenotypic variation, and heterogeneous taxonomic treatment across countries, all of which require large sample sizes. Knowledge about the quality of phylogeographic information provided by different loci is crucial for study design. We use sequences of one mtDNA gene, one sex-linked intron, and one autosomal intron to elucidate large scale phylogeographic patterns in the Holarctic lark genus Eremophila. The mtDNA ND2 gene identified six geographically, ecologically, and phenotypically concordant clades in the Palearctic that diverged in the Early - Middle Pleistocene and suggested paraphyly of the horned lark (E. alpestris) with respect to the Temminck's lark (E. bilopha). In the Nearctic, ND2 identified five subclades which diverged in the Late Pleistocene. They overlapped geographically and were not concordant phenotypically or ecologically. Nuclear alleles provided little information on geographic structuring of genetic variation in horned larks beyond supporting the monophyly of Eremophila and paraphyly of the horned lark. Multilocus species trees based on two nuclear or all three loci provided poor support for haplogroups identified by mtDNA. The node ages calculated using mtDNA were consistent with the available paleontological data, whereas individual nuclear loci and multilocus species trees appeared to underestimate node ages. We argue that mtDNA is capable of discovering independent evolutionary units within avian taxa and can provide a reasonable phylogeographic hypothesis when geographic scale, geologic history, and phenotypic variation in the study system are too complex for proposing reasonable a priori hypotheses required for multilocus methods. Finally, we suggest splitting the currently recognized horned lark into five Palearctic and one Nearctic species. PMID:24498139

Quantitative assessment of skin, hair, and iris variation in a diverse sample of individuals and associated genetic variation.

PubMed

Norton, Heather L; Edwards, Melissa; Krithika, S; Johnson, Monique; Werren, Elizabeth A; Parra, Esteban J

2016-08-01

The main goals of this study are to 1) quantitatively measure skin, hair, and iris pigmentation in a diverse sample of individuals, 2) describe variation within and between these samples, and 3) demonstrate how quantitative measures can facilitate genotype-phenotype association tests. We quantitatively characterize skin, hair, and iris pigmentation using the Melanin (M) Index (skin) and CIELab values (hair) in 1,450 individuals who self-identify as African American, East Asian, European, Hispanic, or South Asian. We also quantify iris pigmentation in a subset of these individuals using CIELab values from high-resolution iris photographs. We compare mean skin M index and hair and iris CIELab values among populations using ANOVA and MANOVA respectively and test for genotype-phenotype associations in the European sample. All five populations are significantly different for skin (P <2 × 10(-16) ) and hair color (P <2 × 10(-16) ). Our quantitative analysis of iris and hair pigmentation reinforces the continuous, rather than discrete, nature of these traits. We confirm the association of three loci (rs16891982, rs12203592, and rs12913832) with skin pigmentation and four loci (rs12913832, rs12203592, rs12896399, and rs16891982) with hair pigmentation. Interestingly, the derived rs12203592 T allele located within the IRF4 gene is associated with lighter skin but darker hair color. The quantitative methods used here provide a fine-scale assessment of pigmentation phenotype and facilitate genotype-phenotype associations, even with relatively small sample sizes. This represents an important expansion of current investigations into pigmentation phenotype and associated genetic variation by including non-European and admixed populations. Am J Phys Anthropol 160:570-581, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Genome-wide epigenetic perturbation jump-starts patterns of heritable variation found in nature.

PubMed

Roux, Fabrice; Colomé-Tatché, Maria; Edelist, Cécile; Wardenaar, René; Guerche, Philippe; Hospital, Frédéric; Colot, Vincent; Jansen, Ritsert C; Johannes, Frank

2011-08-01

We extensively phenotyped 6000 Arabidopsis plants with experimentally perturbed DNA methylomes as well as a diverse panel of natural accessions in a common garden. We found that alterations in DNA methylation not only caused heritable phenotypic diversity but also produced heritability patterns closely resembling those of the natural accessions. Our findings indicate that epigenetically induced and naturally occurring variation in complex traits share part of their polygenic architecture and may offer complementary adaptation routes in ecological settings.

Age Dependent Variability in Gene Expression in Fischer 344 ...

EPA Pesticide Factsheets

Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response does increase with age. However, few reports address the question of variation in gene expression as an underlying cause for increased variability of phenotypic response in the aged. In this study, we utilized global analysis to compare variation in constitutive gene expression in the retinae of young (4 mos), middle-aged (11 mos) and aged (23 mos) Fischer 344 rats. Three hundred and forty transcripts were identified in which variance in expression increased from 4 to 23 mos of age, while only twelve transcripts were found for which it decreased. Functional roles for identified genes were clustered in basic biological categories including cell communication, function, metabolism and response to stimuli. Our data suggest that population stochastically-induced variability should be considered in assessing sensitivity due to old age. Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response does increase with age. However, few reports address the question of variation in

Genome-wide recombination dynamics are associated with phenotypic variation in maize.

PubMed

Pan, Qingchun; Li, Lin; Yang, Xiaohong; Tong, Hao; Xu, Shutu; Li, Zhigang; Li, Weiya; Muehlbauer, Gary J; Li, Jiansheng; Yan, Jianbing

2016-05-01

Meiotic recombination is a major driver of genetic diversity, species evolution, and agricultural improvement. Thus, an understanding of the genetic recombination landscape across the maize (Zea mays) genome will provide insight and tools for further study of maize evolution and improvement. Here, we used c. 50 000 single nucleotide polymorphisms to precisely map recombination events in 12 artificial maize segregating populations. We observed substantial variation in the recombination frequency and distribution along the ten maize chromosomes among the 12 populations and identified 143 recombination hot regions. Recombination breakpoints were partitioned into intragenic and intergenic events. Interestingly, an increase in the number of genes containing recombination events was accompanied by a decrease in the number of recombination events per gene. This kept the overall number of intragenic recombination events nearly invariable in a given population, suggesting that the recombination variation observed among populations was largely attributed to intergenic recombination. However, significant associations between intragenic recombination events and variation in gene expression and agronomic traits were observed, suggesting potential roles for intragenic recombination in plant phenotypic diversity. Our results provide a comprehensive view of the maize recombination landscape, and show an association between recombination, gene expression and phenotypic variation, which may enhance crop genetic improvement. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Two unusual anatomic variations create a diagnostic dilemma in distal ulnar nerve compression.

PubMed

Kiehn, Mark W; Derrick, Allison J; Iskandar, Bermans J

2008-09-01

Diagnosis of peripheral neuropathies is based upon patterns of functional deficits and electrodiagnostic testing. However, anatomic variations can lead to confounding patterns of physical and electrodiagnostic findings. Authors present a case of ulnar nerve compression due to a rare combination of anatomic variations, aberrant branching pattern, and FCU insertion at the wrist, which posed a diagnostic and therapeutic dilemma. The literature related to isolated distal ulnar motor neuropathy and anatomic variations of the ulnar nerve and adjacent structures is also reviewed. This case demonstrates how anatomic variations can complicate the interpretation of clinical and electrodiagnostic findings and underscores the importance of thorough exploration of the nerve in consideration for possible variations. (c) 2008 Wiley-Liss, Inc.

Collective Functionality through Bacterial Individuality

NASA Astrophysics Data System (ADS)

Ackermann, Martin

According to the conventional view, the properties of an organism are a product of nature and nurture - of its genes and the environment it lives in. Recent experiments with unicellular organisms have challenged this view: several molecular mechanisms generate phenotypic variation independently of environmental signals, leading to variation in clonal groups. My presentation will focus on the causes and consequences of this microbial individuality. Using examples from bacterial genetic model systems, I will first discuss different molecular and cellular mechanisms that give rise to bacterial individuality. Then, I will discuss the consequences of individuality, and focus on how phenotypic variation in clonal populations of bacteria can promote interactions between individuals, lead to the division of labor, and allow clonal groups of bacteria to cope with environmental uncertainty. Variation between individuals thus provides clonal groups with collective functionality.

Comparative biology of the crab Goniopsis cruentata: geographic variation of body size, sexual maturity, and allometric growth

NASA Astrophysics Data System (ADS)

de Lira, José Jonathas Pereira Rodrigues; Calado, Tereza Cristina dos Santos; Rezende, Carla Ferreira; Silva, José Roberto Feitosa

2015-12-01

Geographic variation of phenotypic traits is common across species and is often associated with variation in environmental conditions. Here, we found larger bodies and larger size at maturity in a northward, lower latitude population of the crab Goniopsis cruentata, which inhabits a hotter, drier environment in comparison with a southward, higher latitude population. Furthermore, the juvenile male gonopods grow more relative to body size in the population characterized by maturation at a smaller size. In contrast, the female abdomen widens at a higher rate among the late maturing population. These results provide further evidence that local environmental conditions play a role in phenotypic variation between populations inhabiting different latitudes. Moreover, they also show that variation in size at maturity and body size can lead to divergent allometric patterns of sexual characteristics that can have a sex-specific response.

Architecture and functional ecology of the human gastrocnemius muscle-tendon unit.

PubMed

Butler, Erin E; Dominy, Nathaniel J

2016-04-01

The gastrocnemius muscle-tendon unit (MTU) is central to human locomotion. Structural variation in the human gastrocnemius MTU is predicted to affect the efficiency of locomotion, a concept most often explored in the context of performance activities. For example, stiffness of the Achilles tendon varies among individuals with different histories of competitive running. Such a finding highlights the functional variation of individuals and raises the possibility of similar variation between populations, perhaps in response to specific ecological or environmental demands. Researchers often assume minimal variation in human populations, or that industrialized populations represent the human species as well as any other. Yet rainforest hunter-gatherers, which often express the human pygmy phenotype, contradict such assumptions. Indeed, the human pygmy phenotype is a potential model system for exploring the range of ecomorphological variation in the architecture of human hindlimb muscles, a concept we review here. © 2015 Anatomical Society.

Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus cattle

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We previously reported an initial analysis of copy number variations (CNVs) in Angus cattle selected for resistance or susceptibility to gastrointestinal nematodes. In this study, we performed a lar...

Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus Cattle

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. We previously reported an initial analysis of copy number variations (CNVs) in Angus cattle selected for resistance or susceptibility to intestinal nematodes. In this study, we performed a large sca...

Mutation in Torenia fournieri Lind. UFO homolog confers loss of TfLFY interaction and results in a petal to sepal transformation.

PubMed

Sasaki, Katsutomo; Yamaguchi, Hiroyasu; Aida, Ryutaro; Shikata, Masahito; Abe, Tomoko; Ohtsubo, Norihiro

2012-09-01

We identified a Torenia fournieri Lind. mutant (no. 252) that exhibited a sepaloid phenotype in which the second whorls were changed to sepal-like organs. This mutant had no stamens, and the floral organs consisted of sepals and carpels. Although the expression of a torenia class B MADS-box gene, GLOBOSA (TfGLO), was abolished in the 252 mutant, no mutation of TfGLO was found. Among torenia homologs such as APETALA1 (AP1), LEAFY (LFY), and UNUSUAL FLORAL ORGANS (UFO), which regulate expression of class B genes in Arabidopsis, only accumulation of the TfUFO transcript was diminished in the 252 mutant. Furthermore, a missense mutation was found in the coding region of the mutant TfUFO. Intact TfUFO complemented the mutant phenotype whereas mutated TfUFO did not; in addition, the transgenic phenotype of TfUFO-knockdown torenias coincided with the mutant phenotype. Yeast two-hybrid analysis revealed that the mutated TfUFO lost its ability to interact with TfLFY protein. In situ hybridization analysis indicated that the transcripts of TfUFO and TfLFY were partially accumulated in the same region. These results clearly demonstrate that the defect in TfUFO caused the sepaloid phenotype in the 252 mutant due to the loss of interaction with TfLFY. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Fertilization Is Not a New Beginning: The Relationship between Sperm Longevity and Offspring Performance

PubMed Central

Crean, Angela J.; Dwyer, John M.; Marshall, Dustin J.

2012-01-01

Sperm are the most diverse cell type known: varying not only among- and within- species, but also among- and within-ejaculates of a single male. Recently, the causes and consequences of variability in sperm phenotypes have received much attention, but the importance of within-ejaculate variability remains largely unknown. Correlative evidence suggests that reduced within-ejaculate variation in sperm phenotype increases a male’s fertilization success in competitive conditions; but the transgenerational consequences of within-ejaculate variation in sperm phenotype remain relatively unexplored. Here we examine the relationship between sperm longevity and offspring performance in a marine invertebrate with external fertilization, Styela plicata. Offspring sired by longer-lived sperm had higher performance compared to offspring sired by freshly-extracted sperm of the same ejaculate, both in the laboratory and the field. This indicates that within-ejaculate differences in sperm longevity can influence offspring fitness – a source of variability in offspring phenotypes that has not previously been considered. Links between sperm phenotype and offspring performance may constrain responses to selection on either sperm or offspring traits, with broad ecological and evolutionary implications. PMID:23155458

Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.

PubMed

Kreznar, Julia H; Keller, Mark P; Traeger, Lindsay L; Rabaglia, Mary E; Schueler, Kathryn L; Stapleton, Donald S; Zhao, Wen; Vivas, Eugenio I; Yandell, Brian S; Broman, Aimee Teo; Hagenbuch, Bruno; Attie, Alan D; Rey, Federico E

2017-02-14

Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses.

PubMed

Hummel, Barbara; Hansen, Erik C; Yoveva, Aneliya; Aprile-Garcia, Fernando; Hussong, Rebecca; Sawarkar, Ritwick

2017-03-01

Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development. Our data based on natural variations in the mouse genome show that genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific ERV-insertion sites. The evolutionary-capacitor function of HSP90 may thus have facilitated the exaptation of ERVs as key modifiers of gene expression and morphological diversification. Our findings add a new regulatory layer through which HSP90 uncouples phenotypic outcomes from individual genotypes.

Landscape genomic prediction for restoration of a Eucalyptus foundation species under climate change.

PubMed

Supple, Megan Ann; Bragg, Jason G; Broadhurst, Linda M; Nicotra, Adrienne B; Byrne, Margaret; Andrew, Rose L; Widdup, Abigail; Aitken, Nicola C; Borevitz, Justin O

2018-04-24

As species face rapid environmental change, we can build resilient populations through restoration projects that incorporate predicted future climates into seed sourcing decisions. Eucalyptus melliodora is a foundation species of a critically endangered community in Australia that is a target for restoration. We examined genomic and phenotypic variation to make empirical based recommendations for seed sourcing. We examined isolation by distance and isolation by environment, determining high levels of gene flow extending for 500 km and correlations with climate and soil variables. Growth experiments revealed extensive phenotypic variation both within and among sampling sites, but no site-specific differentiation in phenotypic plasticity. Model predictions suggest that seed can be sourced broadly across the landscape, providing ample diversity for adaptation to environmental change. Application of our landscape genomic model to E. melliodora restoration projects can identify genomic variation suitable for predicted future climates, thereby increasing the long term probability of successful restoration. © 2018, Supple et al.

Time Periods of Unusual Density Behavior Observed by GRACE and CHAMP

NASA Astrophysics Data System (ADS)

McLaughlin, C. A.; Fattig, E.; Mysore Krishna, D.; Locke, T.; Mehta, P. M.

2011-12-01

Time periods of low cross correlation between precision orbit ephemeris (POE) derived density and accelerometer density for CHAMP and GRACE are examined. In particular, the cross correlation for GRACE dropped from typical values near 0.9 to much lower values and then returned to typical over the time period of late October to late December of 2005. This time period includes a maneuver where GRACE-A and GRACE-B swapped positions. However, the drop in cross correlation begins and reaches its low point before the maneuvers begin. In addition, the densities were found using GRACE-A, but GRACE-B did most of the maneuvering. The time period is characterized by high frequency variations in accelerometer density of the same magnitude as the daylight to eclipse variations over the course of an orbit. However, the daylight to eclipse variations are particularly small during this time period because the orbit plane is near the terminator. Additionally, the difference between the accelerometer and POE derived densities are not unusually large during this time period. This implies the variations are not unusual, just more significant when the orbit plane is near terminator. Cyclical variations in correlation of the POE derived densities with accelerometer derived densities are seen for both GRACE and CHAMP, but the magnitude of the variations are much larger for GRACE, possibly because of the higher altitude of GRACE. The cycles seem to be phased so that low correlations occur with low beta angle when the orbit plane is near the terminator. The low correlation is possibly caused by the lower amplitude of the daylight to eclipse signal making higher frequency variations relatively more important. However, another possible explanation is terminator waves in density that propagate to the thermosphere from lower in the atmosphere. These waves have been observed in CHAMP accelerometer data and global circulation model simulations. Further investigation is needed to see if the variations correspond to terminator waves or if they represent typical high frequency signal from another source that is more apparent when the orbit plane is near the terminator. 1. C. A. McLaughlin, E. Fattig, D. Mysore Krishna, and P. M. Mehta, "Time Periods of Anomalous Density for GRACE and CHAMP," AAS/AIAA Astrodynamics Specialists Conference, AAS 11-613, Girdwood, AK, August 2011. 2. C. A. McLaughlin, A. Hiatt, and T. Lechtenberg, "Calibrating Precision Orbit Derived Total Density," Journal of Spacecraft and Rockets, Vol. 48, No. 1, January-February 2011, pp. 166-174.

Environment-dependent variation in selection on life history across small spatial scales.

PubMed

Lange, Rolanda; Monro, Keyne; J Marshall, Dustin

2016-10-01

Variation in life-history traits is ubiquitous, even though genetic variation is thought to be depleted by selection. One potential mechanism for the maintenance of trait variation is spatially variable selection. We explored spatial variation in selection in the field for a colonial marine invertebrate that shows phenotypic differences across a depth gradient of only 3 m. Our analysis included life-history traits relating to module size, colony growth, and phenology. Directional selection on colony growth varied in strength across depths, while module size was under directional selection at one depth but not the other. Differences in selection may explain some of the observed phenotypic differentiation among depths for one trait but not another: instead, selection should actually erode the differences observed for this trait. Our results suggest selection is not acting alone to maintain trait variation within and across environments in this system. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Rice epigenomics and epigenetics: challenges and opportunities.

PubMed

Chen, Xiangsong; Zhou, Dao-Xiu

2013-05-01

During recent years rice genome-wide epigenomic information such as DNA methylation and histone modifications, which are important for genome activity has been accumulated. The function of a number of rice epigenetic regulators has been studied, many of which are found to be involved in a diverse range of developmental and stress-responsive pathways. Analysis of epigenetic variations among different rice varieties indicates that epigenetic modification may lead to inheritable phenotypic variation. Characterizing phenotypic consequences of rice epigenomic variations and the underlining chromatin mechanism and identifying epialleles related to important agronomic traits may provide novel strategies to enhance agronomically favorable traits and grain productivity in rice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Efficient modification of floral traits by heavy-ion beam irradiation on transgenic Torenia.

PubMed

Ohtsubo, Norihiro; Sasaki, Katsutomo; Aida, Ryutaro; Ryuto, Hiromichi; Ichida, Hiroyuki; Hayashi, Yoriko; Abe, Tomoko

2012-01-01

While heavy-ion beam irradiation is becoming popular technology for mutation breeding in Japan, the combination with genetic manipulation makes it more convenient to create greater variation in plant phenotypes. We have succeeded in producing over 200 varieties of transgenic torenia (Torenia fournieri Lind.) from over 2,400 regenerated plants by this procedure in only 2 years. Mutant phenotypes were observed mainly in flowers and showed wide variation in colour and shape. Higher mutation rates in the transgenics compared to those in wild type indicate the synergistic effect of genetic manipulation and heavy-ion beam irradiation, which might be advantageous to create greater variation in floral traits.

The Evolution of Human Genetic and Phenotypic Variation in Africa

PubMed Central

Campbell, Michael C.

2010-01-01

Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations. PMID:20178763

Most Colorful Example of Genetic Assimilation? Exploring the Evolutionary Destiny of Recurrent Phenotypic Accommodation.

PubMed

Badyaev, Alexander V; Potticary, Ahva L; Morrison, Erin S

2017-08-01

Evolution of adaptation requires both generation of novel phenotypic variation and retention of a locally beneficial subset of this variation. Such retention can be facilitated by genetic assimilation, the accumulation of genetic and molecular mechanisms that stabilize induced phenotypes and assume progressively greater control over their reliable production. A particularly strong inference into genetic assimilation as an evolutionary process requires a system where it is possible to directly evaluate the extent to which an induced phenotype is progressively incorporated into preexisting developmental pathways. Evolution of diet-dependent pigmentation in birds-where external carotenoids are coopted into internal metabolism to a variable degree before being integrated with a feather's developmental processes-provides such an opportunity. Here we combine a metabolic network view of carotenoid evolution with detailed empirical study of feather modifications to show that the effect of physical properties of carotenoids on feather structure depends on their metabolic modification, their environmental recurrence, and biochemical redundancy, as predicted by the genetic assimilation hypothesis. Metabolized carotenoids caused less stochastic variation in feather structure and were more closely integrated with feather growth than were dietary carotenoids of the same molecular weight. These patterns were driven by the recurrence of organism-carotenoid associations: commonly used dietary carotenoids and biochemically redundant derived carotenoids caused less stochastic variation in feather structure than did rarely used or biochemically unique compounds. We discuss implications of genetic assimilation processes for the evolutionary diversification of diet-dependent animal coloration.

A novel dominant GJB2 (DFNA3) mutation in a Chinese family

NASA Astrophysics Data System (ADS)

Wang, Hongyang; Wu, Kaiwen; Yu, Lan; Xie, Linyi; Xiong, Wenping; Wang, Dayong; Guan, Jing; Wang, Qiuju

2017-01-01

To decipher the phenotype and genotype of a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) and a novel dominant missense mutation in the GJB2 gene (DFNA3), mutation screening of GJB2 was performed on the propositus from a five-generation ADNSHL family through polymerase chain reaction amplification and Sanger sequencing. The candidate variation and the co-segregation of the phenotype were verified in all ascertained family members. Targeted genes capture and next-generation sequencing (NGS) were performed to explore additional genetic variations. We identified the novel GJB2 mutation c.524C > A (p.P175H), which segregated with high frequency and was involved in progressive sensorineural hearing loss. One subject with an additional c.235delC mutation showed a more severe phenotype than did the other members with single GJB2 dominant variations. Four patients diagnosed with noise-induced hearing loss did not carry this mutation. No other pathogenic variations or modifier genes were identified by NGS. In conclusion, a novel missense mutation in GJB2 (DFNA3), affecting the second extracellular domain of the protein, was identified in a family with ADNSHL.

Variation in reaction norms: Statistical considerations and biological interpretation.

PubMed

Morrissey, Michael B; Liefting, Maartje

2016-09-01

Analysis of reaction norms, the functions by which the phenotype produced by a given genotype depends on the environment, is critical to studying many aspects of phenotypic evolution. Different techniques are available for quantifying different aspects of reaction norm variation. We examine what biological inferences can be drawn from some of the more readily applicable analyses for studying reaction norms. We adopt a strongly biologically motivated view, but draw on statistical theory to highlight strengths and drawbacks of different techniques. In particular, consideration of some formal statistical theory leads to revision of some recently, and forcefully, advocated opinions on reaction norm analysis. We clarify what simple analysis of the slope between mean phenotype in two environments can tell us about reaction norms, explore the conditions under which polynomial regression can provide robust inferences about reaction norm shape, and explore how different existing approaches may be used to draw inferences about variation in reaction norm shape. We show how mixed model-based approaches can provide more robust inferences than more commonly used multistep statistical approaches, and derive new metrics of the relative importance of variation in reaction norm intercepts, slopes, and curvatures. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Identification of Genomic Regions Associated with Phenotypic Variation between Dog Breeds using Selection Mapping

PubMed Central

Derrien, Thomas; Axelsson, Erik; Rosengren Pielberg, Gerli; Sigurdsson, Snaevar; Fall, Tove; Seppälä, Eija H.; Hansen, Mark S. T.; Lawley, Cindy T.; Karlsson, Elinor K.; Bannasch, Danika; Vilà, Carles; Lohi, Hannes; Galibert, Francis; Fredholm, Merete; Häggström, Jens; Hedhammar, Åke; André, Catherine; Lindblad-Toh, Kerstin; Hitte, Christophe; Webster, Matthew T.

2011-01-01

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease. PMID:22022279

Identification of genomic regions associated with phenotypic variation between dog breeds using selection mapping.

PubMed

Vaysse, Amaury; Ratnakumar, Abhirami; Derrien, Thomas; Axelsson, Erik; Rosengren Pielberg, Gerli; Sigurdsson, Snaevar; Fall, Tove; Seppälä, Eija H; Hansen, Mark S T; Lawley, Cindy T; Karlsson, Elinor K; Bannasch, Danika; Vilà, Carles; Lohi, Hannes; Galibert, Francis; Fredholm, Merete; Häggström, Jens; Hedhammar, Ake; André, Catherine; Lindblad-Toh, Kerstin; Hitte, Christophe; Webster, Matthew T

2011-10-01

The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.

Unification of multi-species vertebrate anatomy ontologies for comparative biology in Uberon

PubMed Central

2014-01-01

Background Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent ‘natural’ phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes. Results Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued. Conclusions The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. The ontology release files associated with the ontology merge described in this manuscript are available at: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ Current ontology release files are available always available at: http://purl.obolibrary.org/obo/uberon/releases/ PMID:25009735

A high-resolution cattle CNV map by population-scale genome sequencing

USDA-ARS?s Scientific Manuscript database

Copy Number Variations (CNVs) are common genomic structural variations that have been linked to human diseases and phenotypic traits. CNVs represent an important type of genetic variation among cattle breeds and even individual animals; however, only low-resolution maps of cattle CNVs currently exis...

Genetic and epigenetic changes in somatic hybrid introgression lines between wheat and tall wheatgrass

USDA-ARS?s Scientific Manuscript database

Broad phenotypic variations were induced in derivatives of an asymmetric somatic hybridization of bread wheat (Triticum aestivum) and tall wheatgrass (Thinopyrum ponticum Podp); however, how did these variations happened was unknown. We explored the nature of these variations by cytogenetic assays ...

Phylogeny of Fomitopsis pinicola: A species complex

Treesearch

John Haight; Gary A. Laursen; Jessie A. Glaeser; D. Lee Taylor

2016-01-01

Fungal species with a broad distribution may exhibit considerable genetic variation over their geographic ranges. Variation may develop among populations based on geographic isolation, lack of migration, and genetic drift, though this genetic variation may not always be evident when examining phenotypic characters. Fomitopsis pinicola is an...

Geographical Variation in Egg Mass and Egg Content in a Passerine Bird

PubMed Central

Ruuskanen, Suvi; Siitari, Heli; Eeva, Tapio; Belskii, Eugen; Järvinen, Antero; Kerimov, Anvar; Krams, Indrikis; Moreno, Juan; Morosinotto, Chiara; Mänd, Raivo; Möstl, Erich; Orell, Markku; Qvarnström, Anna; Salminen, Juha-Pekka; Slater, Fred; Tilgar, Vallo; Visser, Marcel E.; Winkel, Wolfgang; Zang, Herwig; Laaksonen, Toni

2011-01-01

Reproductive, phenotypic and life-history traits in many animal and plant taxa show geographic variation, indicating spatial variation in selection regimes. Maternal deposition to avian eggs, such as hormones, antibodies and antioxidants, critically affect development of the offspring, with long-lasting effects on the phenotype and fitness. Little is however known about large-scale geographical patterns of variation in maternal deposition to eggs. We studied geographical variation in egg components of a passerine bird, the pied flycatcher (Ficedula hypoleuca), by collecting samples from 16 populations and measuring egg and yolk mass, albumen lysozyme activity, yolk immunoglobulins, yolk androgens and yolk total carotenoids. We found significant variation among populations in most egg components, but ca. 90% of the variation was among individuals within populations. Population however explained 40% of the variation in carotenoid levels. In contrast to our hypothesis, we found geographical trends only in carotenoids, but not in any of the other egg components. Our results thus suggest high within-population variation and leave little scope for local adaptation and genetic differentiation in deposition of different egg components. The role of these maternally-derived resources in evolutionary change should be further investigated. PMID:22110579

Epigenetic supersimilarity of monozygotic twin pairs

USDA-ARS?s Scientific Manuscript database

Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. Here, by analyzing data from a genome-scale stud...

Genetic variability of environmental sensitivity revealed by phenotypic variation in body weight and (its) correlations to physiological and behavioral traits

PubMed Central

Quillet, Edwige; Bégout, Marie-Laure; Aupérin, Benoit; Khaw, Hooi Ling; Millot, Sandie; Valotaire, Claudiane; Kernéis, Thierry; Labbé, Laurent; Prunet, Patrick; Dupont-Nivet, Mathilde

2017-01-01

Adaptive phenotypic plasticity is a key component of the ability of organisms to cope with changing environmental conditions. Fish have been shown to exhibit a substantial level of phenotypic plasticity in response to abiotic and biotic factors. In the present study, we investigate the link between environmental sensitivity assessed globally (revealed by phenotypic variation in body weight) and more targeted physiological and behavioral indicators that are generally used to assess the sensitivity of a fish to environmental stressors. We took advantage of original biological material, the rainbow trout isogenic lines, which allowed the disentangling of the genetic and environmental parts of the phenotypic variance. Ten lines were characterized for the changes of body weight variability (weight measurements taken every month during 18 months), the plasma cortisol response to confinement stress (3 challenges) and a set of selected behavioral indicators. This study unambiguously demonstrated the existence of genetic determinism of environmental sensitivity, with some lines being particularly sensitive to environmental fluctuations and others rather insensitive. Correlations between coefficient of variation (CV) for body weight and behavioral and physiological traits were observed. This confirmed that CV for body weight could be used as an indicator of environmental sensitivity. As the relationship between indicators (CV weight, risk-taking, exploration and cortisol) was shown to be likely depending on the nature and intensity of the stressor, the joint use of several indicators should help to investigate the biological complexity of environmental sensitivity. PMID:29253015

Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

PubMed Central

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-01-01

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phenotypes” that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. PMID:25758824

Environmental Heat and Salt Stress Induce Transgenerational Phenotypic Changes in Arabidopsis thaliana

PubMed Central

Suter, Léonie; Widmer, Alex

2013-01-01

Plants that can adapt their phenotype may be more likely to survive changing environmental conditions. Heritable epigenetic variation could provide a way to rapidly adapt to such changes. Here we tested whether environmental stress induces heritable, potentially adaptive phenotypic changes independent of genetic variation over few generations in Arabidopsis thaliana. We grew two accessions (Col-0, Sha-0) of A. thaliana for three generations under salt, heat and control conditions and tested for induced heritable phenotypic changes in the fourth generation (G4) and in reciprocal F1 hybrids generated in generation three. Using these crosses we further tested whether phenotypic changes were maternally or paternally transmitted. In generation five (G5), we assessed whether phenotypic effects persisted over two generations in the absence of stress. We found that exposure to heat stress in previous generations accelerated flowering under G4 control conditions in Sha-0, but heritable effects disappeared in G5 after two generations without stress exposure. Previous exposure to salt stress increased salt tolerance in one of two reciprocal F1 hybrids. Transgenerational effects were maternally and paternally inherited. Lacking genetic variability, maternal and paternal inheritance and reversibility of transgenerational effects together indicate that stress can induce heritable, potentially adaptive phenotypic changes, probably through epigenetic mechanisms. These effects were strongly dependent on plant genotype and may not be a general response to stress in A. thaliana. PMID:23585834

Evolutionary constraints or opportunities?

PubMed

Sharov, Alexei A

2014-04-22

Natural selection is traditionally viewed as a leading factor of evolution, whereas variation is assumed to be random and non-directional. Any order in variation is attributed to epigenetic or developmental constraints that can hinder the action of natural selection. In contrast I consider the positive role of epigenetic mechanisms in evolution because they provide organisms with opportunities for rapid adaptive change. Because the term "constraint" has negative connotations, I use the term "regulated variation" to emphasize the adaptive nature of phenotypic variation, which helps populations and species to survive and evolve in changing environments. The capacity to produce regulated variation is a phenotypic property, which is not described in the genome. Instead, the genome acts as a switchboard, where mostly random mutations switch "on" or "off" preexisting functional capacities of organism components. Thus, there are two channels of heredity: informational (genomic) and structure-functional (phenotypic). Functional capacities of organisms most likely emerged in a chain of modifications and combinations of more simple ancestral functions. The role of DNA has been to keep records of these changes (without describing the result) so that they can be reproduced in the following generations. Evolutionary opportunities include adjustments of individual functions, multitasking, connection between various components of an organism, and interaction between organisms. The adaptive nature of regulated variation can be explained by the differential success of lineages in macro-evolution. Lineages with more advantageous patterns of regulated variation are likely to produce more species and secure more resources (i.e., long-term lineage selection). Copyright © 2014. Published by Elsevier Ireland Ltd.

Siblings with opposite chromosome constitutions, dup(2q)/del(7q) and del(2q)/dup(7q).

PubMed

Shim, Sung Han; Shim, Jae Sun; Min, Kyunghoon; Lee, Hee Song; Park, Ji Eun; Park, Sang Hee; Hwang, Euna; Kim, Minyoung

2014-01-15

Chromosome 7q36 microdeletion syndrome is a rare genomic disorder characterized by underdevelopment of the brain, microcephaly, anomalies of the sex organs, and language problems. Developmental delay, intellectual disability, autistic spectrum disorders, BDMR syndrome, and unusual facial morphology are the key features of the chromosome 2q37 microdeletion syndrome. A genetic screening for two brothers with global developmental delay using high-resolution chromosomal analysis and subtelomeric multiplex ligation-dependent probe amplification revealed subtelomeric rearrangements on the same sites of 2q37.2 and 7q35, with reversed deletion and duplication. Both of them showed dysmorphic facial features, severe disability of physical and intellectual development, and abnormal genitalia with differential abnormalities in their phenotypes. The family did not have abnormal genetic phenotypes. According to the genetic analysis of their parents, adjacent-1 segregation from their mother's was suggested as a mechanism of their gene mutation. By comparing the phenotypes of our patients with previous reports on similar patients, we tried to obtain the information of related genes and their chromosomal locations. © 2013.

B-cell acute lymphoblastic leukemia with mature phenotype and MLL rearrangement: report of five new cases and review of the literature.

PubMed

Sajaroff, Elisa Olga; Mansini, Adrian; Rubio, Patricia; Alonso, Cristina Noemí; Gallego, Marta S; Coccé, Mariela C; Eandi-Eberle, Silvia; Bernasconi, Andrea Raquel; Ampatzidou, Maria; Paterakis, George; Papadhimitriou, Stefanos I; Petrikkos, Loizos; Papadakis, Vassilios; Polychronopoulou, Sophia; Rossi, Jorge G; Felice, Maria Sara

2016-10-01

The association between mature-B phenotype and MLL abnormalities in acute lymphoblastic leukemia (ALL) is a very unusual finding; only 14 pediatric cases have been reported so far. We describe the clinical and biological characteristics and outcome of five pediatric cases of newly diagnosed B lineage ALL with MLL abnormalities and mature immunophenotype based on light chain restriction and surface Ig expression. Blasts showed variable expression of CD10/CD34/TdT. MLL abnormalities with no MYC involvement were detected in all patients by G-banding, FISH, and/or RT-PCR. Three patients were treated according to Interfant protocol, one to ALLIC-09, and one received B-NHL-BFM-2004. All patients achieved complete remission and three of them relapsed. Despite the small cohort size, it could be postulated that B lineage ALL with MLL abnormalities and mature phenotype is a distinct entity that differs both from the typical Pro B ALL observed in infants and mature B-ALL with high MYC expression.

Estimating variation in stomatal frequency at intra-individual, intra-site, and inter-taxonomic levels in populations of the Leonardoxa africana (Fabaceae) complex over environmental gradients in Cameroon

NASA Astrophysics Data System (ADS)

Finsinger, Walter; Dos Santos, Thibaut; McKey, Doyle

2013-07-01

Variation of stomatal frequency (stomatal density and stomatal index) includes genetically-based, potentially-adaptive variation, and variation due to phenotypic plasticity, the degree of which may be fundamental to the ability to maintain high water-use efficiency and thus to deal with environmental change. We analysed stomatal frequency and morphology (pore length, pore width) in leaves from several individuals from nine populations of four sub-species of the Leonardoxa africana complex. The dataset represents a hierarchical sampling wherein factors are nested within each level (leaves in individuals, individuals in sites, etc.), allowing estimation of the contribution of different levels to overall variation, using variance-component analysis. SI showed significant variation among sites ("site" is largely confounded with "sub-species"), being highest in the sub-species localized in the highest-elevation site. However, most of the observed variance was accounted for at intra-site and intra-individual levels. This variance could reflect great phenotypic plasticity, presumably in response to highly local variation in micro-environmental conditions.

Endodontic management of middle mesial canal of the mandibular molar

PubMed Central

Sundaresh, K J; Srinivasan, Raghu; Mallikarjuna, Rachappa; Rajalbandi, Sandeep

2013-01-01

Thorough knowledge of root canal morphology and unusual anatomy of the tooth is critical for successful endodontic treatment. Although the most common configuration is two roots and three root canals, mandibular molars might have many different combinations. In the literature, it is less described about three mesial canals and two distal canals in mandibular second molars, indicating a rare anatomical configuration. A case of unusual root canal morphology is presented to demonstrate anatomical variations in mandibular molars. Endodontic therapy was performed in a mandibular second molar with five separate canals, three mesial and two distal. This report points out the importance of looking for additional canals and unusual canal morphology, because knowledge of their existence might occasionally enable clinicians to treat a case successfully that otherwise might have ended in failure. In conclusion, every attempt should be made to find and treat all root canals of a tooth. PMID:23349182

Copy Number Variation in Fungi and Its Implications for Wine Yeast Genetic Diversity and Adaptation

PubMed Central

Steenwyk, Jacob L.; Rokas, Antonis

2018-01-01

In recent years, copy number (CN) variation has emerged as a new and significant source of genetic polymorphisms contributing to the phenotypic diversity of populations. CN variants are defined as genetic loci that, due to duplication and deletion, vary in their number of copies across individuals in a population. CN variants range in size from 50 base pairs to whole chromosomes, can influence gene activity, and are associated with a wide range of phenotypes in diverse organisms, including the budding yeast Saccharomyces cerevisiae. In this review, we introduce CN variation, discuss the genetic and molecular mechanisms implicated in its generation, how they can contribute to genetic and phenotypic diversity in fungal populations, and consider how CN variants may influence wine yeast adaptation in fermentation-related processes. In particular, we focus on reviewing recent work investigating the contribution of changes in CN of fermentation-related genes in yeast wine strains and offer notable illustrations of such changes, including the high levels of CN variation among the CUP genes, which confer resistance to copper, a metal with fungicidal properties, and the preferential deletion and duplication of the MAL1 and MAL3 loci, respectively, which are responsible for metabolizing maltose and sucrose. Based on the available data, we propose that CN variation is a substantial dimension of yeast genetic diversity that occurs largely independent of single nucleotide polymorphisms. As such, CN variation harbors considerable potential for understanding and manipulating yeast strains in the wine fermentation environment and beyond. PMID:29520259

Co-Gradient Variation in Growth Rate and Development Time of a Broadly Distributed Butterfly

PubMed Central

Barton, Madeleine; Sunnucks, Paul; Norgate, Melanie; Murray, Neil; Kearney, Michael

2014-01-01

Widespread species often show geographic variation in thermally-sensitive traits, providing insight into how species respond to shifts in temperature through time. Such patterns may arise from phenotypic plasticity, genetic adaptation, or their interaction. In some cases, the effects of genotype and temperature may act together to reduce, or to exacerbate, phenotypic variation in fitness-related traits across varying thermal environments. We find evidence for such interactions in life-history traits of Heteronympha merope, a butterfly distributed across a broad latitudinal gradient in south-eastern Australia. We show that body size in this butterfly is negatively related to developmental temperature in the laboratory, in accordance with the temperature-size rule, but not in the field, despite very strong temperature gradients. A common garden experiment on larval thermal responses, spanning the environmental extremes of H. merope's distribution, revealed that butterflies from low latitude (warmer climate) populations have relatively fast intrinsic growth and development rates compared to those from cooler climates. These synergistic effects of genotype and temperature across the landscape (co-gradient variation) are likely to accentuate phenotypic variation in these traits, and this interaction must be accounted for when predicting how H. merope will respond to temperature change through time. These results highlight the importance of understanding how variation in life-history traits may arise in response to environmental change. Without this knowledge, we may fail to detect whether organisms are tracking environmental change, and if they are, whether it is by plasticity, adaptation or both. PMID:24743771

Genetic associations with viral respiratory illnesses and asthma control in children

PubMed Central

Loisel, Dagan A; Du, Gaixin; Ahluwalia, Tarunveer Singh; Tisler, Christopher J.; Evans, Michael D.; Myers, Rachel A.; Gangnon, Ronald E.; Kreiner-Møller, Eskil; Bønnelykke, Klaus; Bisgaard, Hans; Jackson, Daniel J.; Lemanske, Robert F.; Nicolae, Dan L.; Gern, James E.; Ober, Carole

2015-01-01

Background Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. Objective We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. Methods The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2,128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma birth cohort study (COAST). Results A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. Conclusions We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma. PMID:26399222

Variation in Adult Plant Phenotypes and Partitioning among Seed and Stem-Borne Roots across Brachypodium distachyon Accessions to Exploit in Breeding Cereals for Well-Watered and Drought Environments.

PubMed

Chochois, Vincent; Vogel, John P; Rebetzke, Gregory J; Watt, Michelle

2015-07-01

Seedling roots enable plant establishment. Their small phenotypes are measured routinely. Adult root systems are relevant to yield and efficiency, but phenotyping is challenging. Root length exceeds the volume of most pots. Field studies measure partial adult root systems through coring or use seedling roots as adult surrogates. Here, we phenotyped 79 diverse lines of the small grass model Brachypodium distachyon to adults in 50-cm-long tubes of soil with irrigation; a subset of 16 lines was droughted. Variation was large (total biomass, ×8; total root length [TRL], ×10; and root mass ratio, ×6), repeatable, and attributable to genetic factors (heritabilities ranged from approximately 50% for root growth to 82% for partitioning phenotypes). Lines were dissected into seed-borne tissues (stem and primary seminal axile roots) and stem-borne tissues (tillers and coleoptile and leaf node axile roots) plus branch roots. All lines developed one seminal root that varied, with branch roots, from 31% to 90% of TRL in the well-watered condition. With drought, 100% of TRL was seminal, regardless of line because nodal roots were almost always inhibited in drying topsoil. Irrigation stimulated nodal roots depending on genotype. Shoot size and tillers correlated positively with roots with irrigation, but partitioning depended on genotype and was plastic with drought. Adult root systems of B. distachyon have genetic variation to exploit to increase cereal yields through genes associated with partitioning among roots and their responsiveness to irrigation. Whole-plant phenotypes could enhance gain for droughted environments because root and shoot traits are coselected. © 2015 American Society of Plant Biologists. All Rights Reserved.

High prevalence of low HDL-c in the Philippines compared to the U.S.: population differences in associations with diet and BMI

PubMed Central

Rutherford, Julienne N.; McDade, Thom W.; Feranil, Alan; Adair, Linda; Kuzawa, Christopher

2011-01-01

Cardiovascular disease (CVD) is a leading cause of death in the Philippines, although few studies here have examined the lipid profiles underlying disease risk. The isolated low high density lipoprotein cholesterol (HDL-c) phenotype has been implicated as a CVD risk factor, the prevalence of which exhibits significant variation across populations. To assess population variation in individual lipid components and their associations with diet and anthropometric characteristics, we compare lipid profiles in a population of adult Filipino women (n=1877) to U.S. women participating in the National Health and Nutrition Examination Survey (n=477). We conducted multilinear regression models to assess the relationship between lipid components and BMI and dietary variables in the two populations. We measured the prevalence of lipid phenotypes, and logistic regression models determined the predictors of the isolated low HDL-c phenotype. HDL-c was lower in the Philippines (40.8±0.2 mg/dL) than in NHANES (60.7±0.7 mg/dL). The prevalence of the isolated low HDL-c phenotype was 28.8%, compared to 2.10% in NHANES. High prevalence among Filipinos was relatively invariant across all levels of BMI, but was strongly inversely related to BMI in NHANES and exhibited only at the BMI>25 kg/m2 threshold. Diet did not predict the low-HDL phenotype in Filipinos. Filipino women exhibit a high prevalence of the isolated low HDL-c phenotype, which is largely decoupled from anthropometric factors. The relationship of CVD to population variation in dyslipidemia and body composition needs further study, particularly in populations where the burden of cardiovascular and metabolic disease is rapidly increasing. PMID:20199988

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example. PMID:23515190

Geographical variation in relationships between parental body size and offspring phenotype at birth

PubMed Central

Leary, Sam; Fall, Caroline; Osmond, Clive; Lovel, Hermione; Campbell, Doris; Eriksson, Johan; Forrester, Terrence; Godfrey, Keith; Hill, Jacqui; Jie, Mi; Law, Catherine; Newby, Rachel; Robinson, Sian; Yajnik, Chittaranjan

2009-01-01

Background Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birthweight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype. Methods Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures including estimates of muscle and fat (derived at 30-weeks gestation, N=16 418), and also paternal size (N=3 733) on neonatal phenotype, for singleton, liveborn, term births. Results After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head circumference, and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Data from fathers were limited to height and body mass index, but when compared with maternal height and body mass index, paternal effects were weaker in most studies. Conclusions Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms which influence fetal growth. PMID:16929411

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-offs on Phenotype Robustness in Biological Networks. Part III: Synthetic Gene Networks in Synthetic Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties that are observed in biological systems at many different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be large enough to confer: intrinsic robustness for tolerating intrinsic parameter fluctuations; genetic robustness for buffering genetic variations; and environmental robustness for resisting environmental disturbances. Network robustness is needed so phenotype stability of biological network can be maintained, guaranteeing phenotype robustness. Synthetic biology is foreseen to have important applications in biotechnology and medicine; it is expected to contribute significantly to a better understanding of functioning of complex biological systems. This paper presents a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation for synthetic gene networks in synthetic biology. Further, from the unifying mathematical framework, we found that the phenotype robustness criterion for synthetic gene networks is the following: if intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness, then the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in synthetic biology can also be investigated through corresponding phenotype robustness criteria from the systematic point of view. Finally, a robust synthetic design that involves network evolution algorithms with desired behavior under intrinsic parameter fluctuations, genetic variations, and environmental disturbances, is also proposed, together with a simulation example.

Vegetable Intake in College-Aged Adults Is Explained by Oral Sensory Phenotypes and TAS2R38 Genotype

PubMed Central

Hayes, John E.; Davidson, Andrew C.; Kidd, Judith R.; Kidd, Kenneth K.; Bartoshuk, Linda M.

2010-01-01

Taste and oral sensations vary in humans. Some of this variation has a genetic basis, and two commonly measured phenotypes are the bitterness of propylthiouracil (PROP) and the number of fungiform papillae on the anterior tongue. While the genetic control of fungiform papilla is unclear, PROP bitterness associates with allelic variation in the taste receptor gene, TAS2R38. The two common alleles are AVI and PAV (proline, alanine, valine, and isoleucine); AVI/AVI homozygotes taste PROP as less bitter than heterozygous or homozygous PAV carriers. In this laboratory-based study, we determined whether taste of a bitter probe (quinine) and vegetable intake varied by taste phenotypes and TAS2R38 genotype in healthy adults (mean age=26 years). Vegetable intake was assessed via two validated, complementary methods: food records (Food Pyramid servings standardized to energy intake) and food frequency questionnaire (general intake question and composite vegetable groups). Quinine bitterness varied with phenotypes but not TAS2R38; quinine was more bitter to those who tasted PROP as more bitter or had more papillae. Nontasters by phenotype or genotype reported greater consumption of vegetables, regardless of type (i.e., the effect generalized to all vegetables and was not restricted to those typically thought of as being bitter). Furthermore, nontasters with more papillae reported greater vegetable consumption than nontasters with fewer papillae, suggesting that when bitterness does not predominate, more papillae enhance vegetable liking. These findings suggest that genetic variation in taste, measured by multiple phenotypes or TAS2R38 genotype, can explain differences in overall consumption of vegetables, and this was not restricted to vegetables that are predominantly bitter. PMID:21157576

An end to endless forms: epistasis, phenotype distribution bias, and nonuniform evolution.

PubMed

Borenstein, Elhanan; Krakauer, David C

2008-10-01

Studies of the evolution of development characterize the way in which gene regulatory dynamics during ontogeny constructs and channels phenotypic variation. These studies have identified a number of evolutionary regularities: (1) phenotypes occupy only a small subspace of possible phenotypes, (2) the influence of mutation is not uniform and is often canalized, and (3) a great deal of morphological variation evolved early in the history of multicellular life. An important implication of these studies is that diversity is largely the outcome of the evolution of gene regulation rather than the emergence of new, structural genes. Using a simple model that considers a generic property of developmental maps-the interaction between multiple genetic elements and the nonlinearity of gene interaction in shaping phenotypic traits-we are able to recover many of these empirical regularities. We show that visible phenotypes represent only a small fraction of possibilities. Epistasis ensures that phenotypes are highly clustered in morphospace and that the most frequent phenotypes are the most similar. We perform phylogenetic analyses on an evolving, developmental model and find that species become more alike through time, whereas higher-level grades have a tendency to diverge. Ancestral phenotypes, produced by early developmental programs with a low level of gene interaction, are found to span a significantly greater volume of the total phenotypic space than derived taxa. We suggest that early and late evolution have a different character that we classify into micro- and macroevolutionary configurations. These findings complement the view of development as a key component in the production of endless forms and highlight the crucial role of development in constraining biotic diversity and evolutionary trajectories.

Beyond Punnett squares: Student word association and explanations of phenotypic variation through an integrative quantitative genetics unit investigating anthocyanin inheritance and expression in Brassica rapa Fast plants.

PubMed

Batzli, Janet M; Smith, Amber R; Williams, Paul H; McGee, Seth A; Dósa, Katalin; Pfammatter, Jesse

2014-01-01

Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question "What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev)," we developed a 4-wk unit for an inquiry-based laboratory course focused on the inheritance and expression of a quantitative trait in varying environments. We utilized Brassica rapa Fast Plants as a model organism to study variation in the phenotype anthocyanin pigment intensity. As an initial curriculum assessment, we used free word association to examine students' cognitive structures before and after the unit and explanations in students' final research posters with particular focus on variation (Pv = Gv + Ev). Comparison of pre- and postunit word frequency revealed a shift in words and a pattern of co-occurring concepts indicative of change in cognitive structure, with particular focus on "variation" as a proposed threshold concept and primary goal for students' explanations. Given review of 53 posters, we found ∼50% of students capable of intermediate to high-level explanations combining both Gv and Ev influence on expression of anthocyanin intensity (Pv). While far from "plug and play," this conceptually rich, inquiry-based unit holds promise for effective integration of quantitative and Mendelian genetics. © 2014 J. M. Batzli et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The alignment between phenotypic plasticity, the major axis of genetic variation and the response to selection.

PubMed

Lind, Martin I; Yarlett, Kylie; Reger, Julia; Carter, Mauricio J; Beckerman, Andrew P

2015-10-07

Phenotypic plasticity is the ability of a genotype to produce more than one phenotype in order to match the environment. Recent theory proposes that the major axis of genetic variation in a phenotypically plastic population can align with the direction of selection. Therefore, theory predicts that plasticity directly aids adaptation by increasing genetic variation in the direction favoured by selection and reflected in plasticity. We evaluated this theory in the freshwater crustacean Daphnia pulex, facing predation risk from two contrasting size-selective predators. We estimated plasticity in several life-history traits, the G matrix of these traits, the selection gradients on reproduction and survival, and the predicted responses to selection. Using these data, we tested whether the genetic lines of least resistance and the predicted response to selection aligned with plasticity. We found predator environment-specific G matrices, but shared genetic architecture across environments resulted in more constraint in the G matrix than in the plasticity of the traits, sometimes preventing alignment of the two. However, as the importance of survival selection increased, the difference between environments in their predicted response to selection increased and resulted in closer alignment between the plasticity and the predicted selection response. Therefore, plasticity may indeed aid adaptation to new environments. © 2015 The Authors.

Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus.

PubMed

Self, James E; Shawkat, Fatima; Malpas, Crispin T; Thomas, N Simon; Harris, Christopher M; Hodgkins, Peter R; Chen, Xiaoli; Trump, Dorothy; Lotery, Andrew J

2007-09-01

To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.

Variations in endothelin receptor B subtype 2 (EDNRB2) coding sequences and mRNA expression levels in 4 Muscovy duck plumage colour phenotypes.

PubMed

Wu, N; Qin, H; Wang, M; Bian, Y; Dong, B; Sun, G; Zhao, W; Chang, G; Xu, Q; Chen, G

2017-04-01

1. Endothelin receptor B subtype 2 (EDNRB2) is a paralog of EDNRB, which encodes a 7-transmembrane G-protein coupled receptor. Previous studies reported that EDNRB was essential for melanoblast migration in mammals and ducks. 2. Muscovy ducks have different plumage colour phenotypes. Variations in EDNRB2 coding sequences (CDSs) and mRNA expression levels were investigated in 4 different Muscovy duck plumage colour phenotypes, including black, black mutant, silver and white head. 3. The EDNRB2 gene from Muscovy duck was cloned; it had a length of 6435 bp and encoded 437 amino acids. The coding region was screened and potential single nucleotide polymorphisms were identified. Eight mutations were obtained, including one missense variant (c.64C > T) and 7 synonymous substitutions. The substitutions were associated with plumage colour phenotypes. 4. The EDNRB2 mRNA expression levels were compared between feather pulp from black birds and black mutant birds. The results indicated that EDNRB2 transcripts in feather pulp were significantly higher in black feathers than in white feathers. 5. The results determined the variation of EDNRB2 CDS and mRNA expression in Muscovy ducks of various plumage colours.

Convergent evolution and divergent selection: lizards at the White Sands ecotone.

PubMed

Rosenblum, Erica Bree

2006-01-01

Ecological transition zones, where organismal phenotypes result from a delicate balance between selection and migration, highlight the interplay of local adaptation and gene flow. Here, I study the response of an entire species assemblage to natural selection across a common ecotone. Three lizard species, distributed along a dramatic environmental gradient in substrate color, display convergent adaptation of blanched coloration on the gypsum dunes of White Sands National Monument. I investigate the role of gene flow in modulating phenotypic response to selection by quantifying color variation and genetic variation across the ecotone. I find species differences in degree of background matching and in genetic connectivity of populations across the ecotone. Differences among species in phenotypic response to selection scale precisely to levels of genetic isolation. Species with higher levels of gene flow across the ecotone exhibit less dramatic responses to selection. Results also reveal a strong signal of ecologically mediated divergence for White Sands lizards. For all species, phenotypic variation is better explained by habitat similarity than genetic similarity. Convergent evolution of blanched coloration at White Sands clearly reflects the action of strong divergent selection; however, adaptive response appears to be modulated by gene flow and demographic history and can be predicted by divergence-with-gene-flow models.

Propagule Limitation, Disparate Habitat Quality, and Variation in Phenotypic Selection at a Local Species Range Boundary

PubMed Central

Moore, Kara A.; Stanton, Maureen L.

2014-01-01

Adaptation to novel conditions beyond current range boundaries requires the presence of suitable sites within dispersal range, but may be impeded when emigrants encounter poor habitat and sharply different selection pressures. We investigated fine-scale spatial heterogeneity in ecological dynamics and selection at a local population boundary of the annual plant Gilia tricolor. In two years, we planted G. tricolor seeds in core habitat, margin habitat at the edge of the local range, and exterior habitat in order to measure spatial and temporal variation in habitat quality, opportunity for selection, and selection on phenotypic traits. We found a striking decline in average habitat quality with distance from the population core, yet some migrant seeds were successful in suitable, unoccupied microsites at and beyond the range boundary. Total and direct selection on four out of five measured phenotypic traits varied across habitat zones, as well as between years. Moreover, the margin habitat often exerted unique selection pressures that were not intermediate between core and exterior habitats. This study reveals that a combination of ecological and evolutionary forces, including propagule limitation, variation in habitat quality and spatial heterogeneity in phenotypic selection may reduce opportunities for adaptive range expansion, even across a very local population boundary. PMID:24717472

Two Species with an Unusual Combination of Traits Dominate Responses of British Grasshoppers and Crickets to Environmental Change.

PubMed

Beckmann, Björn C; Purse, Bethan V; Roy, David B; Roy, Helen E; Sutton, Peter G; Thomas, Chris D

2015-01-01

There are large variations in the responses of species to the environmental changes of recent decades, heightening interest in whether their traits may explain inter-specific differences in range expansions and contractions. Using a long-term distributional dataset, we calculated range changes of grasshoppers and crickets in Britain between the 1980s and the 2000s and assessed whether their traits (resource use, life history, dispersal ability, geographic location) explain relative performance of different species. Our analysis showed large changes in the distributions of some species, and we found a positive relationship between three traits and range change: ranges tended to increase for habitat generalists, species that oviposit in the vegetation above ground, and for those with a southerly distribution. These findings accord well with the nature of environmental changes over this period (climatic warming; reductions in the diversity and increases in the height of vegetation). However, the trait effects applied mainly to just two species, Conocephalus discolor and Metrioptera roeselii, which had shown the greatest range increases. Once they were omitted from the analysis, trait effects were no longer statistically significant. Previous studies on these two species emphasised wing-length dimorphism as the key to their success, resulting in a high phenotypic plasticity of dispersal and evolutionary-ecological feedback at their expanding range margins. This, combined with our results, suggests that an unusual combination of traits have enabled these two species to undertake extremely rapid responses to recent environmental changes. The fact that our results are dominated by two species only became apparent through cautious testing of the results' robustness, not through standard statistical checks. We conclude that trait-based analyses may contribute to the assessment of species responses to environmental change and provide insights into underlying mechanisms, but results need to be interpreted with caution and may have limited predictive power.

Temporal variation in phenotypic gender and expected functional gender within and among individuals in an annual plant.

PubMed

Austen, Emily J; Weis, Arthur E

2014-07-01

Adaptive explanations for variation in sex allocation centre on variation in resource status and variation in the mating environment. The latter can occur when dichogamy causes siring opportunity to vary across the flowering season. In this study, it is hypothesized that the widespread tendency towards declining fruit-set from first to last flowers on plants can similarly lead to a varying mating environment by causing a temporal shift in the quality (not quantity) of siring opportunities. A numerical model was developed to examine the effects of declining fruit-set on the expected male versus female reproductive success (functional gender) of first and last flowers on plants, and of early- and late-flowering plants. Within- and among-plant temporal variation in pollen production, ovule production and fruit-set in 70 Brassica rapa plants was then characterized to determine if trends in male and female investment mirror expected trends in functional gender. Under a wide range of model conditions, functional femaleness decreased sharply in the last flowers on plants, and increased from early- to late-flowering plants in the population. In B. rapa, pollen production decreased more rapidly than ovule production from first to last flowers, leading to a within-plant increase in phenotypic femaleness. Among plants, ovule production decreased from early- to late-flowering plants, causing a temporal decrease in phenotypic femaleness. The numerical model confirmed that declining fruit-set can drive temporal variation in functional gender, especially among plants. The discrepancy between observed trends in phenotypic gender in B. rapa and expected functional gender predicted by the numerical model does not rule out the possibility that male reproductive success decreases with later flowering onset. If so, plants may experience selection for early flowering through male fitness. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

RNA sequencing to study gene expression and single nucleotide polymorphism variation associated with citrate content in cow milk.

PubMed

Cánovas, A; Rincón, G; Islas-Trejo, A; Jimenez-Flores, R; Laubscher, A; Medrano, J F

2013-04-01

The technological properties of milk have significant importance for the dairy industry. Citrate, a normal constituent of milk, forms one of the main buffer systems that regulate the equilibrium between Ca(2+) and H(+) ions. Higher-than-normal citrate content is associated with poor coagulation properties of milk. To identify the genes responsible for the variation of citrate content in milk in dairy cattle, the metabolic steps involved in citrate and fatty acid synthesis pathways in ruminant mammary tissue using RNA sequencing were studied. Genetic markers that could influence milk citrate content in Holstein cows were used in a marker-trait association study to establish the relationship between 74 single nucleotide polymorphisms (SNP) in 20 candidate genes and citrate content in 250 Holstein cows. This analysis revealed 6 SNP in key metabolic pathway genes [isocitrate dehydrogenase 1 (NADP+), soluble (IDH1); pyruvate dehydrogenase (lipoamide) β (PDHB); pyruvate kinase (PKM2); and solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1 (SLC25A1)] significantly associated with increased milk citrate content. The amount of the phenotypic variation explained by the 6 SNP ranged from 10.1 to 13.7%. Also, genotype-combination analysis revealed the highest phenotypic variation was explained combining IDH1_23211, PDHB_5562, and SLC25A1_4446 genotypes. This specific genotype combination explained 21.3% of the phenotypic variation. The largest citrate associated effect was in the 3' untranslated region of the SLC25A1 gene, which is responsible for the transport of citrate across the mitochondrial inner membrane. This study provides an approach using RNA sequencing, metabolic pathway analysis, and association studies to identify genetic variation in functional target genes determining complex trait phenotypes. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Inter- and Intraspecific Variation in the Germination Response to Light Quality and Scarification in Grasses Growing in Two-phase Mosaics of the Chihuahuan Desert

PubMed Central

PEZZANI, FABIANA; MONTAÑA, CARLOS

2006-01-01

• Background and Aims In many locations, plants are faced with adjacent, contrasting environments, and the between-species differential evolution of life history traits can be interpreted as an evolutionary response to this environmental heterogeneity. However, there has been little research on the intraspecific variability in these attributes as a possible evolutionary response of plants. • Methods In the two-phase mosaic of the Chihuahuan Desert (adjacent patches with contrasting resource availability), analyses were carried out of the germination response to the scarification and light quality to which grass seeds growing on these patches are exposed (open and closed habitats). • Key Results Species that grow in open habitats exhibited a higher germination success than those from closed habitats after scarification. At both the inter- and intraspecific level, there were differences in the germination percentage and in the germination speed in response to light quality. Intraspecific variation in the species from the closed habitat (Pleuraphis mutica and Trichloris crinita) and in Chloris virgata (which grows in both habitats) was due to genetic variation (the family factor was significant), but there was no genetic variation in phenotypic plasticity (non-significant interaction between family and light quality). In contrast, for the species that grows only in the open habitat (Dasyochloa pulchella), the family did not have a significant effect, but there was genetic variation in the phenotypic plasticity (significant interaction between family and light quality). • Conclusions In C. virgata, P. mutica and T. crinita, natural selection could be favouring those genotypes that responded better in each light environment, but it is not possible that the natural selection resulted in different optimal phenotypes in each habitat. On the contrary, in D. pulchella, selection could have reduced the genetic variation, but there is the possibility of the evolution of reaction norms, resulting in the selection of alternative phenotypes for each habitat. PMID:16621861

Inter- and intraspecific variation in the germination response to light quality and scarification in grasses growing in two-phase mosaics of the Chihuahuan Desert.

PubMed

Pezzani, Fabiana; Montaña, Carlos

2006-06-01

In many locations, plants are faced with adjacent, contrasting environments, and the between-species differential evolution of life history traits can be interpreted as an evolutionary response to this environmental heterogeneity. However, there has been little research on the intraspecific variability in these attributes as a possible evolutionary response of plants. In the two-phase mosaic of the Chihuahuan Desert (adjacent patches with contrasting resource availability), analyses were carried out of the germination response to the scarification and light quality to which grass seeds growing on these patches are exposed (open and closed habitats). Species that grow in open habitats exhibited a higher germination success than those from closed habitats after scarification. At both the inter- and intraspecific level, there were differences in the germination percentage and in the germination speed in response to light quality. Intraspecific variation in the species from the closed habitat (Pleuraphis mutica and Trichloris crinita) and in Chloris virgata (which grows in both habitats) was due to genetic variation (the family factor was significant), but there was no genetic variation in phenotypic plasticity (non-significant interaction between family and light quality). In contrast, for the species that grows only in the open habitat (Dasyochloa pulchella), the family did not have a significant effect, but there was genetic variation in the phenotypic plasticity (significant interaction between family and light quality). In C. virgata, P. mutica and T. crinita, natural selection could be favouring those genotypes that responded better in each light environment, but it is not possible that the natural selection resulted in different optimal phenotypes in each habitat. On the contrary, in D. pulchella, selection could have reduced the genetic variation, but there is the possibility of the evolution of reaction norms, resulting in the selection of alternative phenotypes for each habitat.

PhenStat | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

PhenStat is a freely available R package that provides a variety of statistical methods for the identification of phenotypic associations from model organisms developed for the International Mouse Phenotyping Consortium (IMPC at www.mousephenotype.org ). The methods have been developed for high throughput phenotyping pipelines implemented across various experimental designs with an emphasis on managing temporal variation and is being adapted for analysis with PDX mouse strains.

The Second Report on the State of the World's Animal Genetic Resources for Food and Agriculture, Part 4, The State of the Art: Box 4A4: A digital enumeration method for collecting phenotypic data for genome association

USDA-ARS?s Scientific Manuscript database

Consistent data across animal populations are required to inform genomic science aimed at finding important adaptive genetic variations. The ADAPTMap Digital Phenotype Collection- Prototype Method will yield a new procedure to provide consistent phenotypic data by digital enumeration of categorical ...

Contingency, convergence and hyper-astronomical numbers in biological evolution.

PubMed

Louis, Ard A

2016-08-01

Counterfactual questions such as "what would happen if you re-run the tape of life?" turn on the nature of the landscape of biological possibilities. Since the number of potential sequences that store genetic information grows exponentially with length, genetic possibility spaces can be so unimaginably vast that commentators frequently reach of hyper-astronomical metaphors that compare their size to that of the universe. Re-run the tape of life and the likelihood of encountering the same sequences in such hyper-astronomically large spaces is infinitesimally small, suggesting that evolutionary outcomes are highly contingent. On the other hand, the wide-spread occurrence of evolutionary convergence implies that similar phenotypes can be found again with relative ease. How can this be? Part of the solution to this conundrum must lie in the manner that genotypes map to phenotypes. By studying simple genotype-phenotype maps, where the counterfactual space of all possible phenotypes can be enumerated, it is shown that strong bias in the arrival of variation may explain why certain phenotypes are (repeatedly) observed in nature, while others never appear. This biased variation provides a non-selective cause for certain types of convergence. It illustrates how the role of randomness and contingency may differ significantly between genetic and phenotype spaces. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunohistochemical null-phenotype for mismatch repair proteins in colonic carcinoma associated with concurrent MLH1 hypermethylation and MSH2 somatic mutations.

PubMed

Wang, Tao; Stadler, Zsofia K; Zhang, Liying; Weiser, Martin R; Basturk, Olca; Hechtman, Jaclyn F; Vakiani, Efsevia; Saltz, Lenard B; Klimstra, David S; Shia, Jinru

2018-04-01

Microsatellite instability, a well-established driver pathway in colorectal carcinogenesis, can develop in both sporadic and hereditary conditions via different molecular alterations in the DNA mismatch repair (MMR) genes. MMR protein immunohistochemistry (IHC) is currently widely used for the detection of MMR deficiency in solid tumors. The IHC test, however, can show varied staining patterns, posing challenges in the interpretation of the staining results in some cases. Here we report a case of an 80-year-old female with a colonic adenocarcinoma that exhibited an unusual "null" IHC staining pattern with complete loss of all four MMR proteins (MLH1, MSH2, MSH6, and PMS2). This led to subsequent MLH1 methylation testing and next generation sequencing which demonstrated that the loss of all MMR proteins was associated with concurrent promoter hypermethylation of MLH1 and double somatic truncating mutations in MSH2. These molecular findings, in conjunction with the patient's age being 80 years and the fact that the patient had no personal or family cancer history, indicated that the MMR deficiency was highly likely sporadic in nature. Thus, the stringent Lynch syndrome type surveillance programs were not recommended to the patient and her family members. This case illustrates a rare but important scenario where a null IHC phenotype signifies complex underlying molecular alternations that bear clinical management implications, highlighting the need for recognition and awareness of such unusual IHC staining patterns.

UNUSUAL FLORAL ORGANS Controls Meristem Identity and Organ Primordia Fate in Arabidopsis.

PubMed Central

Wilkinson, M. D.; Haughn, G. W.

1995-01-01

A novel gene that is involved in regulating flower initiation and development has been identified in Arabidopsis. This gene has been designated UNUSUAL FLORAL ORGANS (UFO), with five corresponding nuclear recessive alleles designated ufo[middot]1 to ufo[middot]5. Under short day-length conditions, ufo homozygotes generate more coflorescences than do the wild type, and coflorescences often appear apical to the first floral shoot, resulting in a period of inflorescence development in which regions of floral and coflorescence shoots are produced alternately. ufo enhances the phenotype of weak leafy alleles, and the double mutant Ufo-1 Apetala1-1 produces only coflorescence-like shoots, suggesting that these two genes control different aspects of floral initiation. Floral development was also altered in Ufo plants. Ufo flowers have an altered organ number in all whorls, and organs in the first, second, and third whorls exhibit variable homeotic transformations. Ufo single and double mutant phenotypes suggest that the floral changes result from reduction in class B floral homeotic gene expression and fluctuations in the expression boundaries of class C function and FLO10. Surprisingly, in situ hybridization analysis revealed no obvious differences in expression pattern or level in developing Ufo flowers compared with that of the wild type for any class B or C gene studied. We propose that UFO acts in concert with known floral initiation genes and regulates the domains of floral homeotic gene function. PMID:12242408

Fanconi-Bickel syndrome: GLUT2 mutations associated with a mild phenotype.

PubMed

Grünert, Sarah Catharina; Schwab, Karl Otfried; Pohl, Martin; Sass, Jörn Oliver; Santer, René

2012-03-01

Fanconi-Bickel syndrome (FBS, OMIM #227810), a congenital disorder of carbohydrate metabolism, is caused by mutations in GLUT2 (SLC2A2), the gene encoding the glucose transporter protein-2. The typical clinical picture is characterized by hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired utilization of glucose and galactose, proximal tubular nephropathy, rickets, and severe short stature. We report on two siblings with FBS and an unusually mild clinical course. A 9.5-year-old boy with failure to thrive was diagnosed at the age of 9 months, his younger sister (4.5 years) was investigated in the first months of life and also diagnosed with FBS. Both patients were found to be compound heterozygous for the novel GLUT2 (SLC2A2) mutations c.457_462delCTTATA (p.153_4delLI) and c.1250C>G (p.P417R). On a diet restricted in free glucose and galactose, both children showed normal growth. Hepatomegaly, nephromegaly and hypophosphatemic rickets have never been observed. Glucosuria and tubular proteinuria were only mild compared to previously reported patients with FBS. This report describes an unusually mild phenotype of FBS expanding the spectrum of this disease. Some clinical signs that have been considered hallmarks of FBS like hepatomegaly and short stature may be absent in this condition. As a consequence, clinicians will have to look for GLUT2 mutations even in patients with isolated glucosuria. Copyright © 2011 Elsevier Inc. All rights reserved.

The effects of stabilizing and directional selection on phenotypic and genotypic variation in a population of RNA enzymes.

PubMed

Hayden, Eric J; Bratulic, Sinisa; Koenig, Iwo; Ferrada, Evandro; Wagner, Andreas

2014-02-01

The distribution of variation in a quantitative trait and its underlying distribution of genotypic diversity can both be shaped by stabilizing and directional selection. Understanding either distribution is important, because it determines a population's response to natural selection. Unfortunately, existing theory makes conflicting predictions about how selection shapes these distributions, and very little pertinent experimental evidence exists. Here we study a simple genetic system, an evolving RNA enzyme (ribozyme) in which a combination of high throughput genotyping and measurement of a biochemical phenotype allow us to address this question. We show that directional selection, compared to stabilizing selection, increases the genotypic diversity of an evolving ribozyme population. In contrast, it leaves the variance in the phenotypic trait unchanged.

Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders.

PubMed

Cross, E M; Hare, D J

2013-03-01

The mucopolysaccharide disorders (MPS) are a group of recessively inherited metabolic disorders resulting in progressive physical and cognitive decline. MEDLINE, PsycINFO and Embase databases were searched, alongside manual screening, to identify relevant literature. Papers were included in the review if they were published in a peer reviewed journal and conducted empirical research into cognitive, motor, social or linguistic development or behaviour in one or more MPS disorders. Twenty-five papers were reviewed. Two papers used methodology of a sufficiently high standard to demonstrate a behavioural phenotype; both found sleep disturbance to be part of the phenotype of MPS III. Fearfulness and sleep disturbance were frequently observed in people with MPS I and II. Cognitive and motor impairment and decline, and challenging behaviour were highly prevalent in the severe form of MPS II. Cognitive decline and severe behavioural problems relating to aggression, hyperactivity, orality, unusual affect and temper tantrums were seen in MPS III. Sleep disturbance is part of the behavioural phenotype of MPS III, and challenging behaviour is highly prevalent in MPS II and MPS III, therefore the efficacy of behavioural interventions for these populations should be investigated. Further research into the behaviour and adaptive skills of children with MPS III and MPS IV is required.

Aluminum tolerance is associated with higher MATE1 gene copy-number in maize

USDA-ARS?s Scientific Manuscript database

Genome structure variation, including copy-number (CNV) and presence/absence variation (PAV), comprise a large extent of maize genetic diversity but their effect on phenotypes remains largely unexplored. Here we describe how copy-number variation in a major aluminum (Al) tolerance locus contributes ...

A European multi-centre External Quality Assessment (EQA) study on phenotypic and genotypic methods used for Herpes Simplex Virus (HSV) drug resistance testing.

PubMed

Afshar, Baharak; Bibby, David F; Piorkowska, Renata; Ohemeng-Kumi, Natasha; Snoeck, Robert; Andrei, Graciela; Gillemot, Sarah; Morfin, Florence; Frobert, Emilie; Burrel, Sonia; Boutolleau, David; Crowley, Brendan; Mbisa, Jean L

2017-11-01

Herpes Simplex Virus (HSV) drug resistance is a significant public health concern among immunocompromised individuals. Phenotypic assays are considered the gold standard method for detecting HSV drug resistance. However, plaque reduction assays (PRAs) are technically demanding, often with long turnaround times of up to four weeks. In contrast, genotypic tests can be performed within a few days. The development and coordination of the first European External Quality Assessment (EQA) study to evaluate phenotypic and genotypic methods used for HSV drug resistance testing in specialised reference laboratories. Four HSV-1 or HSV-2 strains with different antiviral susceptibility profiles were isolated from clinical samples. Isolates were quantified by qPCR, and aliquoted in culture medium. One isolate was distributed at two dilutions to help assess assay sensitivity. The panel was distributed to five European centres with a six-week deadline for the return of phenotypic and genotypic results, together with clinical reports. Four out of five participating labs returned results by the deadline. Limited results were later available from the fifth lab. Phenotypic and genotypic data were largely, but not completely, concordant. An unusual resistance profile shown by one of the samples was explained by the detection of a mixed virus population after extensive further investigation by one of the centres. Discordant clinical outputs reflecting the diversity of phenotypic methodologies demonstrated the utility of this exercise. With emerging genotypic technologies looking to supplant phenotyping, there is a need for curated public databases, accessible interpretation tools and standardised control materials for quality management. By establishing a network of testing laboratories, we hope that this EQA scheme will facilitate ongoing progress in this area. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Phenotypic and genomic analysis of a fast neutron mutant population resource in soybean

USDA-ARS?s Scientific Manuscript database

Mutagenized populations have become indispensable resources for introducing variation and studying gene function in plant genomics research. We utilized fast neutron radiation to induce deletion mutations in the soybean genome and phenotypically screened the resulting population. We exposed approxim...

An experimental phylogeny to benchmark ancestral sequence reconstruction

PubMed Central

Randall, Ryan N.; Radford, Caelan E.; Roof, Kelsey A.; Natarajan, Divya K.; Gaucher, Eric A.

2016-01-01

Ancestral sequence reconstruction (ASR) is a still-burgeoning method that has revealed many key mechanisms of molecular evolution. One criticism of the approach is an inability to validate its algorithms within a biological context as opposed to a computer simulation. Here we build an experimental phylogeny using the gene of a single red fluorescent protein to address this criticism. The evolved phylogeny consists of 19 operational taxonomic units (leaves) and 17 ancestral bifurcations (nodes) that display a wide variety of fluorescent phenotypes. The 19 leaves then serve as ‘modern' sequences that we subject to ASR analyses using various algorithms and to benchmark against the known ancestral genotypes and ancestral phenotypes. We confirm computer simulations that show all algorithms infer ancient sequences with high accuracy, yet we also reveal wide variation in the phenotypes encoded by incorrectly inferred sequences. Specifically, Bayesian methods incorporating rate variation significantly outperform the maximum parsimony criterion in phenotypic accuracy. Subsampling of extant sequences had minor effect on the inference of ancestral sequences. PMID:27628687

Carotenoid production and phenotypic variation in Azospirillum brasilense.

PubMed

Brenholtz, Gal Reem; Tamir-Ariel, Dafna; Okon, Yaacov; Burdman, Saul

2017-06-01

We assessed the occurrence of phenotypic variation in Azospirillum brasilense strains Sp7, Cd, Sp245, Az39 and phv2 during growth in rich media, screening for variants altered in colony pigmentation or extracellular polysaccharide (EPS) production. Previous studies showed that EPS-overproducing variants of Sp7 appear frequently following starvation or growth in minimal medium. In contrast, no such variants were detected during growth in rich media in the tested strains except for few variants of phv2. Regarding alteration in colony pigmentation (from pink to white in strain Cd and from white to pink in the others), strain Sp7 showed a relatively high frequency of variation (0.009-0.026%). Strain Cd showed a lower frequency of alteration in pigmentation (0-0.008%), and this type of variation was not detected in the other strains. In A. brasilense, carotenoid synthesis is controlled by two RpoE sigma factors and their cognate ChrR anti-sigma factors, the latter acting as negative regulators of carotenoid synthesis. Here, all tested (n = 28) pink variants of Sp7 carried mutations in one of the anti-sigma factor genes, chrR1. Our findings indicate that, in A. brasilense, phenotypic variation is strain- and environment-dependent and support the central role of ChrR1 in regulation of carotenoid production. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

A simple genetic architecture underlies morphological variation in dogs.

PubMed

Boyko, Adam R; Quignon, Pascale; Li, Lin; Schoenebeck, Jeffrey J; Degenhardt, Jeremiah D; Lohmueller, Kirk E; Zhao, Keyan; Brisbin, Abra; Parker, Heidi G; vonHoldt, Bridgett M; Cargill, Michele; Auton, Adam; Reynolds, Andy; Elkahloun, Abdel G; Castelhano, Marta; Mosher, Dana S; Sutter, Nathan B; Johnson, Gary S; Novembre, John; Hubisz, Melissa J; Siepel, Adam; Wayne, Robert K; Bustamante, Carlos D; Ostrander, Elaine A

2010-08-10

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (< or = 3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

Genetic and environmental factors affecting cryptic variations in gene regulatory networks

PubMed Central

2013-01-01

Background Cryptic genetic variation (CGV) is considered to facilitate phenotypic evolution by producing visible variations in response to changes in the internal and/or external environment. Several mechanisms enabling the accumulation and release of CGVs have been proposed. In this study, we focused on gene regulatory networks (GRNs) as an important mechanism for producing CGVs, and examined how interactions between GRNs and the environment influence the number of CGVs by using individual-based simulations. Results Populations of GRNs were allowed to evolve under various stabilizing selections, and we then measured the number of genetic and phenotypic variations that had arisen. Our results showed that CGVs were not depleted irrespective of the strength of the stabilizing selection for each phenotype, whereas the visible fraction of genetic variation in a population decreased with increasing strength of selection. On the other hand, increasing the number of different environments that individuals encountered within their lifetime (i.e., entailing plastic responses to multiple environments) suppressed the accumulation of CGVs, whereas the GRNs with more genes and interactions were favored in such heterogeneous environments. Conclusions Given the findings that the number of CGVs in a population was largely determined by the size (order) of GRNs, we propose that expansion of GRNs and adaptation to novel environments are mutually facilitating and sustainable sources of evolvability and hence the origins of biological diversity and complexity. PMID:23622056

Genetic and environmental factors affecting cryptic variations in gene regulatory networks.

PubMed

Iwasaki, Watal M; Tsuda, Masaki E; Kawata, Masakado

2013-04-26

Cryptic genetic variation (CGV) is considered to facilitate phenotypic evolution by producing visible variations in response to changes in the internal and/or external environment. Several mechanisms enabling the accumulation and release of CGVs have been proposed. In this study, we focused on gene regulatory networks (GRNs) as an important mechanism for producing CGVs, and examined how interactions between GRNs and the environment influence the number of CGVs by using individual-based simulations. Populations of GRNs were allowed to evolve under various stabilizing selections, and we then measured the number of genetic and phenotypic variations that had arisen. Our results showed that CGVs were not depleted irrespective of the strength of the stabilizing selection for each phenotype, whereas the visible fraction of genetic variation in a population decreased with increasing strength of selection. On the other hand, increasing the number of different environments that individuals encountered within their lifetime (i.e., entailing plastic responses to multiple environments) suppressed the accumulation of CGVs, whereas the GRNs with more genes and interactions were favored in such heterogeneous environments. Given the findings that the number of CGVs in a population was largely determined by the size (order) of GRNs, we propose that expansion of GRNs and adaptation to novel environments are mutually facilitating and sustainable sources of evolvability and hence the origins of biological diversity and complexity.

Genome-Wide Survey on Genomic Variation, Expression Divergence, and Evolution in Two Contrasting Rice Genotypes under High Salinity Stress

PubMed Central

Jiang, Shu-Ye; Ma, Ali; Ramamoorthy, Rengasamy; Ramachandran, Srinivasan

2013-01-01

Expression profiling is one of the most important tools for dissecting biological functions of genes and the upregulation or downregulation of gene expression is sufficient for recreating phenotypic differences. Expression divergence of genes significantly contributes to phenotypic variations. However, little is known on the molecular basis of expression divergence and evolution among rice genotypes with contrasting phenotypes. In this study, we have implemented an integrative approach using bioinformatics and experimental analyses to provide insights into genomic variation, expression divergence, and evolution between salinity-sensitive rice variety Nipponbare and tolerant rice line Pokkali under normal and high salinity stress conditions. We have detected thousands of differentially expressed genes between these two genotypes and thousands of up- or downregulated genes under high salinity stress. Many genes were first detected with expression evidence using custom microarray analysis. Some gene families were preferentially regulated by high salinity stress and might play key roles in stress-responsive biological processes. Genomic variations in promoter regions resulted from single nucleotide polymorphisms, indels (1–10 bp of insertion/deletion), and structural variations significantly contributed to the expression divergence and regulation. Our data also showed that tandem and segmental duplication, CACTA and hAT elements played roles in the evolution of gene expression divergence and regulation between these two contrasting genotypes under normal or high salinity stress conditions. PMID:24121498

A Simple Genetic Architecture Underlies Morphological Variation in Dogs

PubMed Central

Schoenebeck, Jeffrey J.; Degenhardt, Jeremiah D.; Lohmueller, Kirk E.; Zhao, Keyan; Brisbin, Abra; Parker, Heidi G.; vonHoldt, Bridgett M.; Cargill, Michele; Auton, Adam; Reynolds, Andy; Elkahloun, Abdel G.; Castelhano, Marta; Mosher, Dana S.; Sutter, Nathan B.; Johnson, Gary S.; Novembre, John; Hubisz, Melissa J.; Siepel, Adam; Wayne, Robert K.; Bustamante, Carlos D.; Ostrander, Elaine A.

2010-01-01

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness. Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species. PMID:20711490

Unusual Congenital Aortic Anomaly with Rare Common Celiamesenteric Trunk Variation: MR Angiography and Digital Substraction Angiography Findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tosun, Ozgur; Sanlidilek, Umman; Cetin, Huseyin

2007-09-15

Magnetic resonance angiography and digital substraction angiography (DSA) findings in a case with a rare congenital thoracoabdominal aortic hypoplasia and common celiamesenteric trunk variation with occlusion of infrarenal abdominal aorta are described here. To our knowledge, this aortic anomaly has not been previously described in the English literature. DSA is the optimum imaging modality for determination of aortic hypoplasia, associated vascular malformations, collateral vessels, and direction of flow within vessels.

Discordance between genomic divergence and phenotypic variation in a rapidly evolving avian genus (Motacilla).

PubMed

Harris, Rebecca B; Alström, Per; Ödeen, Anders; Leaché, Adam D

2018-03-01

Generally, genotypes and phenotypes are expected to be spatially congruent; however, in widespread species complexes with few barriers to dispersal, multiple contact zones, and limited reproductive isolation, discordance between phenotypes and phylogeographic groups is more probable. Wagtails (Motacilla) are a genus of birds with striking plumage pattern variation across the Old World. Up to 13 subspecies are recognized within a single species, yet previous studies using mitochondrial DNA have supported polyphyletic phylogeographic groups that are inconsistent with subspecies plumage characteristics. In this study, we investigate the link between phenotypes and genotype by taking a phylogenetic approach. We use genome-wide SNPs, nuclear introns, and mitochondrial DNA to estimate population structure, isolation by distance, and species relationships. Together, our genetic sampling includes complete species-level sampling and comprehensive coverage of the three most phenotypically diverse Palearctic species. Our study provides strong evidence for species-level patterns of differentiation, however population-level differentiation is less pronounced. SNPs provide a robust estimate of species-level relationships, which are mostly corroborated by a combined analysis of mtDNA and nuclear introns (the first time-calibrated species tree for the genus). However, the mtDNA tree is strongly incongruent and is considered to misrepresent the species phylogeny. The extant wagtail lineages originated during the Pliocene and the Eurasian lineage underwent rapid diversification during the Pleistocene. Three of four widespread Eurasian species exhibit an east-west divide that contradicts both subspecies taxonomy and phenotypic variation. Indeed, SNPs fail to distinguish between phenotypically distinct subspecies within the M. alba and M. flava complexes, and instead support geographical regions, each of which is home to two or more different looking subspecies. This is a major step towards our understanding of wagtail phylogeny compared to previous analyses of fewer species and considerably less sequence data. Copyright © 2017 Elsevier Inc. All rights reserved.

Unusual X-chromosome inactivation pattern in patients with Xp11.23-p11.22 duplication: Report and review.

PubMed

Di-Battista, Adriana; Meloni, Vera Ayres; da Silva, Magnus Dias; Moysés-Oliveira, Mariana; Melaragno, Maria Isabel

2016-12-01

In females carrying structural rearrangements of an X-chromosome, cells with the best dosage balance are preferentially selected, frequently resulting in a skewed inactivation pattern and amelioration of the phenotype. The Xp11.23-p11.22 region is involved in a recently described microduplication syndrome associated with severe clinical consequences in males and females, causing intellectual disability, behavior problems, epilepsy with electroencephalogram anomalies, minor facial anomalies, and early onset of puberty. Female carriers usually present an unusual X-chromosome inactivation pattern in favor of the aberrant chromosome, resulting in functional disomy of the duplicated segment. Here, we describe a girl carrying a de novo ∼9.7 Mb Xp11.3-p11.22 duplication of paternal origin and skewed X-chromosome inactivation pattern of the normal X-chromosome. We reviewed other cases previously reported and determined the minimal critical region possibly responsible for this unusual inactivation pattern. The critical region encompasses 36 RefSeq genes, including at least 10 oncogenes and/or genes related to the cell cycle control. We discuss the molecular mechanisms that underlie the positive selection of the cells with the active duplicated chromosome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Regulation of ciaXRH Operon Expression and Identification of the CiaR Regulon in Streptococcus mutans▿

PubMed Central

Wu, Chenggang; Ayala, Eduardo A.; Downey, Jennifer S.; Merritt, Justin; Goodman, Steven D.; Qi, Fengxia

2010-01-01

The ciaRH operon in Streptococcus mutans contains 3 contiguous genes, ciaXRH. Unlike the CiaRH system in other streptococci, only the ciaH-null mutant displays defective phenotypes, while the ciaR-null mutant behaves like the wild type. The objective of this study was to determine the mechanism of this unusual property. We demonstrate that the ciaH mutation caused a >20-fold increase in ciaR transcript synthesis. A ciaRH double deletion reversed the ciaH phenotype, suggesting that overexpressed ciaR might be responsible for the observed ciaH phenotypes. When ciaR was forced to be overexpressed by a transcriptional fusion to the ldh promoter in the wild-type background, the same ciaH phenotypes were restored, confirming the involvement of overexpressed ciaR in the ciaH phenotypes. The ciaH mutation and ciaR overexpression also caused transcriptional alterations in 100 genes, with 15 genes upregulated >5-fold. Bioinformatics analysis identified a putative CiaR regulon consisting of 8 genes/operons, including the ciaXRH operon itself, all of which were upregulated. In vitro footprinting on 4 of the 8 promoters revealed a protected region of 26 to 28 bp encompassing two direct repeats, NTTAAG-n5-WTTAAG, 10 bp upstream of the −10 region, indicating direct binding of the CiaR protein to these promoters. Taken together, we conclude that overexpressed CiaR, as a result of either ciaH deletion or forced expression from a constitutive promoter, is a mediator in the CiaH-regulated phenotypes. PMID:20639331

Fossilized venom: the unusually conserved venom profiles of Heloderma species (beaded lizards and gila monsters).

PubMed

Koludarov, Ivan; Jackson, Timothy N W; Sunagar, Kartik; Nouwens, Amanda; Hendrikx, Iwan; Fry, Bryan G

2014-12-22

Research into snake venoms has revealed extensive variation at all taxonomic levels. Lizard venoms, however, have received scant research attention in general, and no studies of intraclade variation in lizard venom composition have been attempted to date. Despite their iconic status and proven usefulness in drug design and discovery, highly venomous helodermatid lizards (gila monsters and beaded lizards) have remained neglected by toxinological research. Proteomic comparisons of venoms of three helodermatid lizards in this study has unravelled an unusual similarity in venom-composition, despite the long evolutionary time (~30 million years) separating H. suspectum from the other two species included in this study (H. exasperatum and H. horridum). Moreover, several genes encoding the major helodermatid toxins appeared to be extremely well-conserved under the influence of negative selection (but with these results regarded as preliminary due to the scarcity of available sequences). While the feeding ecologies of all species of helodermatid lizard are broadly similar, there are significant morphological differences between species, which impact upon relative niche occupation.

Radiation sensitivities of 31 human oesophageal squamous cell carcinoma cell lines

PubMed Central

Ban, Sadayuki; Michikawa, Yuichi; Ishikawa, Ken-ichi; Sagara, Masashi; Watanabe, Koji; Shimada, Yutaka; Inazawa, Johji; Imai, Takashi

2005-01-01

The purpose of this study was to determine the radiosensitivities of 31 human oesophageal squamous cell carcinoma cell lines with a colony-formation assay. A large variation in radiosensitivity existed among 31 cell lines. Such a large variation may partly explain the poor result of radiotherapy for this cancer. One cell line (KYSE190) demonstrated an unusual radiosensitivity. Ataxia-telangiectasia-mutated (ATM) gene in these cells had five missense mutations, and ATM protein was truncated or degraded. Inability to phosphorylate Chk2 in the irradiated KYSE190 cells suggests that the ATM protein in these cells had lost its function. The dysfunctional ATM protein may be a main cause of unusual radiosensitivity of KYSE190 cells. Because the donor of these cells was not diagnosed with ataxia telangiectasia, mutations in ATM gene might have occurred during the initiation and progression of cancer. Radiosensitive cancer developed in non-hereditary diseased patients must be a good target for radiotherapy. PMID:16045545

Unusual sex differences in tuberculosis notifications across Pakistan and the role of environmental factors.

PubMed

Khan, M S; Khan, M S; Hasan, R; Godfrey-Faussett, P

2013-09-01

In developing countries, only one-third of new tuberculosis cases notified are from women. It is not clear whether tuberculosis incidence is lower in women than men, or whether notification figures reflect under-detection of tuberculosis in women. Pakistan, however, presents an unusual pattern of sex differences in tuberculosis notifications. While 2 of the 4 provinces (Sindh and Punjab) report more notifications from men (female to male ratios 0.81 and 0.89 respectively in 2009), the other 2 provinces (Khyber-Pakhtunkhwa and Balochistan) consistently report higher numbers of smear-positive tuberculosis notifications from women than men (1.37 and 1.40). No other country is known to have such a large variation in the sex ratios of notifications across regions. Large variations in female to male smear-positive notification ratios in different settings across a single country may indicate that environmental factors, rather than endogenous biological factors, are important in influencing the observed sex differences in tuberculosis notifications.

Genome Variation Map: a data repository of genome variations in BIG Data Center

PubMed Central

Tian, Dongmei; Li, Cuiping; Tang, Bixia; Dong, Lili; Xiao, Jingfa; Bao, Yiming; Zhao, Wenming; He, Hang

2018-01-01

Abstract The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. As a core resource in the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to collect, integrate and visualize genome variations for a wide range of species, accepts submissions of different types of genome variations from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Unlike existing related databases, GVM features integration of a large number of genome variations for a broad diversity of species including human, cultivated plants and domesticated animals. Specifically, the current implementation of GVM not only houses a total of ∼4.9 billion variants for 19 species including chicken, dog, goat, human, poplar, rice and tomato, but also incorporates 8669 individual genotypes and 13 262 manually curated high-quality genotype-to-phenotype associations for non-human species. In addition, GVM provides friendly intuitive web interfaces for data submission, browse, search and visualization. Collectively, GVM serves as an important resource for archiving genomic variation data, helpful for better understanding population genetic diversity and deciphering complex mechanisms associated with different phenotypes. PMID:29069473

Variations in the rotation of the earth

NASA Astrophysics Data System (ADS)

Carter, W. E.; Robertson, D. S.; Pettey, J. E.; Tapley, B. D.; Schutz, B. E.; Eanes, R. J.; Miao, L.

Variations in the earth's rotation (UTI) and length of day have been tracked at the submillisecond level by astronomical radio interferometry and laser ranging to the LAGEOS satellite. Three years of regular measurements reveal complex patterns of variations including UTI fluctuations as large as 5 milliseconds in a few weeks. Comparison of the observed changes in length of day with variations in the global atmospheric angular momentum indicates that the dominant cause of changes in the earth's spin rate, on time scales from a week to several years, is the exchange of angular momentum between the atmosphere and the mantle. The unusually intense El Nino of 1982-1983 was marked by a strong peak in the length of day.

Unusual anatomy of a maxillary first molar with two palatal roots: a case report.

PubMed

Tomazinho, Flávia S F; Baratto-Filho, Flares; Zaitter, Suellen; Leonardi, Denise P; Gonzaga, Carla C

2010-03-01

The success of endodontic therapy is based on good endodontic access, correct cleaning and shaping, and adequate root canal obturation. However, endodontic treatment is also dependent on a sound knowledge of the internal anatomy of human teeth, especially when anatomical variations are present. Certain anatomical changes may be present to varying degrees, and it is important to report these to improve the understanding and expertise of endodontic specialists. With this aim in mind, this study reports an example of a maxillary first molar showing unusual anatomy (four roots and six root canals) and describes the endodontic treatment that was employed.

Population genomics of divergence among extreme and intermediate color forms in a polymorphic insect

USDA-ARS?s Scientific Manuscript database

Geographic variation in insect coloration is among the most intriguing examples of rapid phenotypic evolution and provides ideal opportunities to study the mechanisms of phenotypic change and diversification in closely related lineages. The bumble bee Bombus bifarius comprises two geographically dis...

Mining natural variation for maize improvement: Selection on phenotypes and genes

USDA-ARS?s Scientific Manuscript database

Maize is highly genetically and phenotypically diverse. Tropical maize and teosinte are important genetic resources that harbor unique alleles not found in temperate maize hybrids. To access these resources, breeders must be able to extract favorable unique alleles from tropical maize and teosinte f...

More than two decades of Apc modeling in rodents

PubMed Central

Zeineldin, Maged; Neufeld, Kristi L.

2013-01-01

Mutation of tumor suppressor gene Adenomatous polyposis coli (APC) is an initiating step in most colon cancers. This review summarizes Apc models in mice and rats, with particular concentration on those most recently developed, phenotypic variation among different models, and genotype/ phenotype correlations. PMID:23333833

Molecular diagnosis of cystic fibrosis.

PubMed

Shrimpton, Antony E

2002-05-01

A review of the current molecular diagnosis of cystic fibrosis including an introduction to cystic fibrosis, the gene function, the phenotypic variation, who should be screened for which mutation, newborn and couple screening, quality assurance, phenotype-genotype correlation, methods and method limitations, options, statements, recommendations, useful Websites and treatments.

High Genetic and Epigenetic Stability in Coffea arabica Plants Derived from Embryogenic Suspensions and Secondary Embryogenesis as Revealed by AFLP, MSAP and the Phenotypic Variation Rate

PubMed Central

Bobadilla Landey, Roberto; Cenci, Alberto; Georget, Frédéric; Bertrand, Benoît; Camayo, Gloria; Dechamp, Eveline; Herrera, Juan Carlos; Santoni, Sylvain; Lashermes, Philippe; Simpson, June; Etienne, Hervé

2013-01-01

Embryogenic suspensions that involve extensive cell division are risky in respect to genome and epigenome instability. Elevated frequencies of somaclonal variation in embryogenic suspension-derived plants were reported in many species, including coffee. This problem could be overcome by using culture conditions that allow moderate cell proliferation. In view of true-to-type large-scale propagation of C. arabica hybrids, suspension protocols based on low 2,4-D concentrations and short proliferation periods were developed. As mechanisms leading to somaclonal variation are often complex, the phenotypic, genetic and epigenetic changes were jointly assessed so as to accurately evaluate the conformity of suspension-derived plants. The effects of embryogenic suspensions and secondary embryogenesis, used as proliferation systems, on the genetic conformity of somatic embryogenesis-derived plants (emblings) were assessed in two hybrids. When applied over a 6 month period, both systems ensured very low somaclonal variation rates, as observed through massive phenotypic observations in field plots (0.74% from 200 000 plant). Molecular AFLP and MSAP analyses performed on 145 three year-old emblings showed that polymorphism between mother plants and emblings was extremely low, i.e. ranges of 0–0.003% and 0.07–0.18% respectively, with no significant difference between the proliferation systems for the two hybrids. No embling was found to cumulate more than three methylation polymorphisms. No relation was established between the variant phenotype (27 variants studied) and a particular MSAP pattern. Chromosome counting showed that 7 of the 11 variant emblings analyzed were characterized by the loss of 1–3 chromosomes. This work showed that both embryogenic suspensions and secondary embryogenesis are reliable for true-to-type propagation of elite material. Molecular analyses revealed that genetic and epigenetic alterations are particularly limited during coffee somatic embryogenesis. The main change in most of the rare phenotypic variants was aneuploidy, indicating that mitotic aberrations play a major role in somaclonal variation in coffee. PMID:23418563

Environmental effects on molecular and phenotypic variation in populations of Eruca sativa across a steep climatic gradient

PubMed Central

Westberg, Erik; Ohali, Shachar; Shevelevich, Anatoly; Fine, Pinchas; Barazani, Oz

2013-01-01

Abstract In Israel Eruca sativa has a geographically narrow distribution across a steep climatic gradient that ranges from mesic Mediterranean to hot desert environments. These conditions offer an opportunity to study the influence of the environment on intraspecific genetic variation. For this, we combined an analysis of neutral genetic markers with a phenotypic evaluation in common-garden experiments, and environmental characterization of populations that included climatic and edaphic parameters, as well as geographic distribution. A Bayesian clustering of individuals from nine representative populations based on amplified fragment length polymorphism (AFLP) divided the populations into a southern and a northern geographic cluster, with one admixed population at the geographic border between them. Linear mixed models, with cluster added as a grouping factor, revealed no clear effects of environment or geography on genetic distances, but this may be due to a strong association of geography and environment with genetic clusters. However, environmental factors accounted for part of the phenotypic variation observed in the common-garden experiments. In addition, candidate loci for selection were identified by association with environmental parameters and by two outlier methods. One locus, identified by all three methods, also showed an association with trichome density and herbivore damage, in net-house and field experiments, respectively. Accordingly, we propose that because trichomes are directly linked to defense against both herbivores and excess radiation, they could potentially be related to adaptive variation in these populations. These results demonstrate the value of combining environmental and phenotypic data with a detailed genetic survey when studying adaptation in plant populations. This article describes the use of several types of data to estimate the influence of the environment on intraspecific genetic variation in populations originating from a steep climatic gradient. In addition to molecular marker data, we made use of phenotypic evaluation from common garden experiments, and a broad GIS based environmental data with edaphic information gathered in the field. This study, among others, lead to the identification of an outlier locus with an association to trichome formation and herbivore defense, and its ecological adaptive value is discussed. PMID:24567822

Using Machine Learning to Discover Latent Social Phenotypes in Free-Ranging Macaques

PubMed Central

Madlon-Kay, Seth; Brent, Lauren J. N.; Heller, Katherine A.; Platt, Michael L.

2017-01-01

Investigating the biological bases of social phenotypes is challenging because social behavior is both high-dimensional and richly structured, and biological factors are more likely to influence complex patterns of behavior rather than any single behavior in isolation. The space of all possible patterns of interactions among behaviors is too large to investigate using conventional statistical methods. In order to quantitatively define social phenotypes from natural behavior, we developed a machine learning model to identify and measure patterns of behavior in naturalistic observational data, as well as their relationships to biological, environmental, and demographic sources of variation. We applied this model to extensive observations of natural behavior in free-ranging rhesus macaques, and identified behavioral states that appeared to capture periods of social isolation, competition over food, conflicts among groups, and affiliative coexistence. Phenotypes, represented as the rate of being in each state for a particular animal, were strongly and broadly influenced by dominance rank, sex, and social group membership. We also identified two states for which variation in rates had a substantial genetic component. We discuss how this model can be extended to identify the contributions to social phenotypes of particular genetic pathways. PMID:28754001

Phenotypic variations in osmotic lysis of Sahel goat erythrocytes in non-ionic glucose media.

PubMed

Igbokwe, Nanacha Afifi; Igbokwe, Ikechukwu Onyebuchi

2016-03-01

Erythrocyte osmotic lysis in deionised glucose media is regulated by glucose influx, cation efflux, and changes in cell volume after water diffusion. Transmembrane fluxes may be affected by varied expression of glucose transporter protein and susceptibility of membrane proteins to glucose-induced glycosylation and oxidation in various physiologic states. Variations in haemolysis of Sahel goat erythrocytes after incubation in hyposmotic non-ionic glucose media, associated with sex, age, late pregnancy, and lactation, were investigated. The osmotic fragility curve in glucose media was sigmoidal with erythrocytes from goats in late pregnancy (PRE) or lactation (LAC) or from kid (KGT) or middle-aged (MGT) goats. Non-sigmoidal phenotype occurred in yearlings (YGT) and old (OGT) goats. The composite fragility phenotype for males and non-pregnant dry (NPD) females was non-sigmoidal. Erythrocytes with non-sigmoidal curves were more stable than those with sigmoidal curves because of inflectional shift of the curve to the left. Erythrocytes tended to be more fragile with male than female sex, KGT and MGT than YGT and OGT, and LAC and PRE than NPD. Thus, sex, age, pregnancy, and lactation affected the haemolytic pattern of goat erythrocytes in glucose media. The physiologic state of the goat affected the in vitro interaction of glucose with erythrocytes, causing variations in osmotic stability with variants of fragility phenotype. Variations in the effect of high extracellular glucose concentrations on the functions of membrane-associated glucose transporter, aquaporins, and the cation cotransporter were presumed to be relevant in regulating the physical properties of goat erythrocytes under osmotic stress.

Genetic Dissection of Leaf Development in Brassica rapa Using a Genetical Genomics Approach1[W

PubMed Central

Xiao, Dong; Wang, Huange; Basnet, Ram Kumar; Zhao, Jianjun; Lin, Ke; Hou, Xilin; Bonnema, Guusje

2014-01-01

The paleohexaploid crop Brassica rapa harbors an enormous reservoir of morphological variation, encompassing leafy vegetables, vegetable and fodder turnips (Brassica rapa, ssp. campestris), and oil crops, with different crops having very different leaf morphologies. In the triplicated B. rapa genome, many genes have multiple paralogs that may be regulated differentially and contribute to phenotypic variation. Using a genetical genomics approach, phenotypic data from a segregating doubled haploid population derived from a cross between cultivar Yellow sarson (oil type) and cultivar Pak choi (vegetable type) were used to identify loci controlling leaf development. Twenty-five colocalized phenotypic quantitative trait loci (QTLs) contributing to natural variation for leaf morphological traits, leaf number, plant architecture, and flowering time were identified. Genetic analysis showed that four colocalized phenotypic QTLs colocalized with flowering time and leaf trait candidate genes, with their cis-expression QTLs and cis- or trans-expression QTLs for homologs of genes playing a role in leaf development in Arabidopsis (Arabidopsis thaliana). The leaf gene BRASSICA RAPA KIP-RELATED PROTEIN2_A03 colocalized with QTLs for leaf shape and plant height; BRASSICA RAPA ERECTA_A09 colocalized with QTLs for leaf color and leaf shape; BRASSICA RAPA LONGIFOLIA1_A10 colocalized with QTLs for leaf size, leaf color, plant branching, and flowering time; while the major flowering time gene, BRASSICA RAPA FLOWERING LOCUS C_A02, colocalized with QTLs explaining variation in flowering time, plant architectural traits, and leaf size. Colocalization of these QTLs points to pleiotropic regulation of leaf development and plant architectural traits in B. rapa. PMID:24394778

Diagnostic Challenges in Retinitis Pigmentosa: Genotypic Multiplicity and Phenotypic Variability

PubMed Central

Chang, Susie; Vaccarella, Leah; Olatunji, Sunday; Cebulla, Colleen; Christoforidis, John

2011-01-01

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders. Diagnosis can be challenging as more than 40 genes are known to cause non-syndromic RP and phenotypic expression can differ significantly resulting in variations in disease severity, age of onset, rate of progression, and clinical findings. We describe the clinical manifestations of RP, the more commonly known causative gene mutations, and the genotypic-phenotypic correlation of RP. PMID:22131872

Genetic Architecture of Micro-Environmental Plasticity in Drosophila melanogaster.

PubMed

Morgante, Fabio; Sørensen, Peter; Sorensen, Daniel A; Maltecca, Christian; Mackay, Trudy F C

2015-05-06

Individuals of the same genotype do not have the same phenotype for quantitative traits when reared under common macro-environmental conditions, a phenomenon called micro-environmental plasticity. Genetic variation in micro-environmental plasticity is assumed in models of the evolution of phenotypic variance, and is important in applied breeding and personalized medicine. Here, we quantified genetic variation for micro-environmental plasticity for three quantitative traits in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel. We found substantial genetic variation for micro-environmental plasticity for all traits, with broad sense heritabilities of the same magnitude or greater than those of trait means. Micro-environmental plasticity is not correlated with residual segregating variation, is trait-specific, and has genetic correlations with trait means ranging from zero to near unity. We identified several candidate genes associated with micro-environmental plasticity of startle response, including Drosophila Hsp90, setting the stage for future genetic dissection of this phenomenon.

Does the central dogma still stand?

PubMed

Koonin, Eugene V

2012-08-23

Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

Ploidy-Regulated Variation in Biofilm-Related Phenotypes in Natural Isolates of Saccharomyces cerevisiae

PubMed Central

Hope, Elyse A.; Dunham, Maitreya J.

2014-01-01

The ability of yeast to form biofilms contributes to better survival under stressful conditions. We see the impact of yeast biofilms and “flocs” (clumps) in human health and industry, where forming clumps enables yeast to act as a natural filter in brewing and forming biofilms enables yeast to remain virulent in cases of fungal infection. Despite the importance of biofilms in yeast natural isolates, the majority of our knowledge about yeast biofilm genetics comes from work with a few tractable laboratory strains. A new collection of sequenced natural isolates from the Saccharomyces Genome Resequencing Project enabled us to examine the breadth of biofilm-related phenotypes in geographically, ecologically, and genetically diverse strains of Saccharomyces cerevisiae. We present a panel of 31 haploid and 24 diploid strains for which we have characterized six biofilm-related phenotypes: complex colony morphology, complex mat formation, flocculation, agar invasion, polystyrene adhesion, and psuedohyphal growth. Our results show that there is extensive phenotypic variation between and within strains, and that these six phenotypes are primarily uncorrelated or weakly correlated, with the notable exception of complex colony and complex mat formation. We also show that the phenotypic strength of these strains varies significantly depending on ploidy, and the diploid strains demonstrate both decreased and increased phenotypic strength with respect to their haploid counterparts. This is a more complex view of the impact of ploidy on biofilm-related phenotypes than previous work with laboratory strains has suggested, demonstrating the importance and enormous potential of working with natural isolates of yeast. PMID:25060625

Ploidy-regulated variation in biofilm-related phenotypes in natural isolates of Saccharomyces cerevisiae.

PubMed

Hope, Elyse A; Dunham, Maitreya J

2014-07-24

The ability of yeast to form biofilms contributes to better survival under stressful conditions. We see the impact of yeast biofilms and "flocs" (clumps) in human health and industry, where forming clumps enables yeast to act as a natural filter in brewing and forming biofilms enables yeast to remain virulent in cases of fungal infection. Despite the importance of biofilms in yeast natural isolates, the majority of our knowledge about yeast biofilm genetics comes from work with a few tractable laboratory strains. A new collection of sequenced natural isolates from the Saccharomyces Genome Resequencing Project enabled us to examine the breadth of biofilm-related phenotypes in geographically, ecologically, and genetically diverse strains of Saccharomyces cerevisiae. We present a panel of 31 haploid and 24 diploid strains for which we have characterized six biofilm-related phenotypes: complex colony morphology, complex mat formation, flocculation, agar invasion, polystyrene adhesion, and psuedohyphal growth. Our results show that there is extensive phenotypic variation between and within strains, and that these six phenotypes are primarily uncorrelated or weakly correlated, with the notable exception of complex colony and complex mat formation. We also show that the phenotypic strength of these strains varies significantly depending on ploidy, and the diploid strains demonstrate both decreased and increased phenotypic strength with respect to their haploid counterparts. This is a more complex view of the impact of ploidy on biofilm-related phenotypes than previous work with laboratory strains has suggested, demonstrating the importance and enormous potential of working with natural isolates of yeast. Copyright © 2014 Hope and Dunham.

Genome-wide copy number variation in the bovine genome detected using low coverage sequence of popular beef breeds

USDA-ARS?s Scientific Manuscript database

Genomic structural variations are an important source of genetic diversity. Copy number variations (CNVs), gains and losses of large regions of genomic sequence between individuals of a species, are known to be associated with both diseases and phenotypic traits. Deeply sequenced genomes are often u...

Characteristics of Rare or Recently Described Corynebacterium Species Recovered from Human Clinical Material in Canada

PubMed Central

Bernard, K. A.; Munro, C.; Wiebe, D.; Ongsansoy, E.

2002-01-01

Nineteen new Corynebacterium species or taxa described since 1995 have been associated with human disease. We report the characteristics of 72 strains identified as or most closely resembling 14 of these newer, medically relevant Corynebacterium species or taxa, as well as describe in brief an isolate of Corynebacterium bovis, a rare pathogen for humans. The bacteria studied in this report were nearly all derived from human clinical specimens and were identified by a polyphasic approach. Most were characterized by nearly full 16S rRNA gene sequence analysis. Some isolates were recovered from previously unreported sources and exhibited unusual phenotypes or represented the first isolates found outside Europe. Products of fermentation, with emphasis on the presence or absence of propionic acid, were also studied in order to provide an additional characteristic with which to differentiate among phenotypically similar species. PMID:12409436

T-cell/histiocyte-rich large B-cell lymphoma of stomach.

PubMed

Barut, Figen; Kandemir, Nilufer Onak; Gun, Banu Dogan; Ozdamar, Sukru Oguz

2016-07-01

T-cell/histiocyte-rich large B-cell lymphoma is an unusually encountered lymphoid neoplasm of stomach with aggressive course, and is an uncommon morphologic variant of diffuse large B-cell lymphoma. An ulcerated mass, 7x5x1 cm in size was observed within the gastrectomy specimen of a 76-year-old female patient. In cross sections, besides mature lymphoid cells displaying T-cell phenotype, a neoplastic formation composed of large, pleomorphic atypical lymphoid cells with, prominent nucleoli, vesicular nuclei and abundant eosinophilic cytoplasm displaying B-cell phenotype were observed. Meanwhile, histiocyte-like mononuclear cells and Reed-Sternberg-like multinuclear cells expressing CD68 and Mac387 were also observed. The diagnosis of the case was T cell/histiocyte-rich large B-cell lymphoma. This rarely encountered neoplasm should be kept in mind in the differential diagnosis of primary gastric lymphomas.

Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii

PubMed Central

Sakaguchi, Kouhei; Ohno, Ryoko; Yoshida, Kentaro

2017-01-01

Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids. PMID:28463975

Evaluation of Lactococcus lactis Isolates from Nondairy Sources with Potential Dairy Applications Reveals Extensive Phenotype-Genotype Disparity and Implications for a Revised Species

PubMed Central

Cavanagh, Daniel; Casey, Aidan; Altermann, Eric; Cotter, Paul D.; Fitzgerald, Gerald F.

2015-01-01

Lactococcus lactis is predominantly associated with dairy fermentations, but evidence suggests that the domesticated organism originated from a plant niche. L. lactis possesses an unusual taxonomic structure whereby strain phenotypes and genotypes often do not correlate, which in turn has led to confusion in L. lactis classification. A bank of L. lactis strains was isolated from various nondairy niches (grass, vegetables, and bovine rumen) and was further characterized on the basis of key technological traits, including growth in milk and key enzyme activities. Phenotypic analysis revealed all strains from nondairy sources to possess an L. lactis subsp. lactis phenotype (lactis phenotype); however, seven of these strains possessed an L. lactis subsp. cremoris genotype (cremoris genotype), determined by two separate PCR assays. Multilocus sequence typing (MLST) showed that strains with lactis and cremoris genotypes clustered together regardless of habitat, but it highlighted the increased diversity that exists among “wild” strains. Calculation of average nucleotide identity (ANI) and tetranucleotide frequency correlation coefficients (TETRA), using the JSpecies software tool, revealed that L. lactis subsp. cremoris and L. lactis subsp. lactis differ in ANI values by ∼14%, below the threshold set for species circumscription. Further analysis of strain TIFN3 and strains from nonindustrial backgrounds revealed TETRA values of <0.99 in addition to ANI values of <95%, implicating that these two groups are separate species. These findings suggest the requirement for a revision of L. lactis taxonomy. PMID:25841018

Variation in seed lipids in Calendula germplasm

USDA-ARS?s Scientific Manuscript database

Calendula officinalis (pot marigold) has considerable promise as an industrial crop, with a long history as an ornamental and medicinal plant. It is also marketed as an ingredient in cosmetics and a colorant. It produces unusual seed lipids, which can provide an additional market for commercial Ca...

Understanding Williams Syndrome: Behavioral Patterns and Interventions.

ERIC Educational Resources Information Center

Semel, Eleanor; Rosner, Sue R.

This guide to Williams syndrome (WS), a congenital disorder characterized by developmental/cognitive limitations but relatively high verbal and social skills, explains the strengths, difficulties and variations found among individuals with the condition and offers guidelines for intervention in the unusual properties of the WS behavioral profile.…

Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change.

PubMed

Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

2014-01-01

Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data.

A molecular signaling approach to linking intraspecific variation and macro-evolutionary patterns.

PubMed

Swanson, Eli M; Snell-Rood, Emilie C

2014-11-01

Macro-evolutionary comparisons are a valued tool in evolutionary biology. Nevertheless, our understanding of how systems involved in molecular signaling change in concert with phenotypic diversification has lagged. We argue that integrating our understanding of the evolution of molecular signaling systems with phylogenetic comparative methods is an important step toward understanding the processes linking variation among individuals with variation among species. Focusing mostly on the endocrine system, we discuss how the complexity and mechanistic nature of molecular signaling systems may influence the application and interpretation of macro-evolutionary comparisons. We also detail five hypotheses concerning the role that physiological mechanisms can play in shaping macro-evolutionary patterns, and discuss ways in which these hypotheses could influence phenotypic diversification. Finally, we review a series of tools able to analyze the complexity of physiological systems and the way they change in concert with the phenotypes for which they coordinate development. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Insights into mammalian biology from the wild house mouse Mus musculus

PubMed Central

Phifer-Rixey, Megan; Nachman, Michael W

2015-01-01

The house mouse, Mus musculus, was established in the early 1900s as one of the first genetic model organisms owing to its short generation time, comparatively large litters, ease of husbandry, and visible phenotypic variants. For these reasons and because they are mammals, house mice are well suited to serve as models for human phenotypes and disease. House mice in the wild consist of at least three distinct subspecies and harbor extensive genetic and phenotypic variation both within and between these subspecies. Wild mice have been used to study a wide range of biological processes, including immunity, cancer, male sterility, adaptive evolution, and non-Mendelian inheritance. Despite the extensive variation that exists among wild mice, classical laboratory strains are derived from a limited set of founders and thus contain only a small subset of this variation. Continued efforts to study wild house mice and to create new inbred strains from wild populations have the potential to strengthen house mice as a model system. DOI: http://dx.doi.org/10.7554/eLife.05959.001 PMID:25875302

Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change

PubMed Central

Urban, Mark C; Richardson, Jonathan L; Freidenfelds, Nicole A

2014-01-01

Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta-analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data. PMID:24454550

Assessing hidden species diversity in the coral Pocillopora damicornis from Eastern Australia

NASA Astrophysics Data System (ADS)

Schmidt-Roach, S.; Lundgren, P.; Miller, K. J.; Gerlach, G.; Noreen, A. M. E.; Andreakis, N.

2013-03-01

The incredible range of morphological plasticity present in scleractinian corals has confused the taxonomy of the group, prompting the introduction of "ecomorphs" to explain the observed correlation between local environmental conditions and phenotypic variation. Pocillopora damicornis (Linnaeus, 1758) represents one of the best known examples of eco-phenotypic variation in scleractinian corals with a variety of forms and reproductive strategies reported across its global distribution range. Here, we reconstruct genealogical relationships of P. damicornis colonies collected from thirteen locations along the East Australian coast to examine the relationship between genetic and phenotypic diversity in this species. Haplotype networks computed from two mitochondrial DNA regions (CR, ORF) indicate that the range of morphotypes observed within this taxon fall into at least five genetically distinct mitochondrial lineages. Nuclear (HSP70, ITS2) haplowebs on the other hand recover sharp genetic discontinuities among three of the morphological groups. We conclude that P. damicornis from Eastern Australia constitutes a cryptic species complex. The misinterpretation of taxonomical units within P. damicornis may well explain its perceived variation in the ecology, biology and life history across its range.

Association of GSK-3β genetic variation with GSK-3β expression, prefrontal cortical thickness, prefrontal physiology, and schizophrenia.

PubMed

Blasi, Giuseppe; Napolitano, Francesco; Ursini, Gianluca; Di Giorgio, Annabella; Caforio, Grazia; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Attrotto, Maria Teresa; Colagiorgio, Lucia; Todarello, Giovanna; Piva, Francesco; Papazacharias, Apostolos; Masellis, Rita; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Rampino, Antonio; Quarto, Tiziana; Giulietti, Matteo; Lipska, Barbara K; Kleinman, Joel E; Popolizio, Teresa; Weinberger, Daniel R; Usiello, Alessandro; Bertolino, Alessandro

2013-08-01

OBJECTIVE Glycogen synthase kinase 3β (GSK-3β) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3β gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk. METHOD Based on computer predictions, the authors investigated in humans the association of GSK-3β functional variation with 1) GSK-3β mRNA expression from postmortem prefrontal cortex, 2) GSK-3β and β-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia. RESULTS Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3β (rs12630592) was associated with reduced GSK-3β mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3β protein expression and kinase activity, as well as with downstream effects on β-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia. CONCLUSIONS These results suggest that GSK-3β variation is implicated in multiple phenotypes relevant to schizophrenia.

Clonal Expansion of the Pseudogymnoascus destructans Genotype in North America Is Accompanied by Significant Variation in Phenotypic Expression

PubMed Central

Khankhet, Jordan; Vanderwolf, Karen J.; McAlpine, Donald F.; McBurney, Scott; Overy, David P.; Slavic, Durda; Xu, Jianping

2014-01-01

Pseudogymnoascus destructans is the causative agent of an emerging infectious disease that threatens populations of several North American bat species. The fungal disease was first observed in 2006 and has since caused the death of nearly six million bats. The disease, commonly known as white-nose syndrome, is characterized by a cutaneous infection with P. destructans causing erosions and ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on sequences from eight loci have found that isolates of P. destructans from bats in the US all belong to one multilocus genotype. Using the same multilocus sequence typing method, we found that isolates from eastern and central Canada also had the same genotype as those from the US, consistent with the clonal expansion of P. destructans into Canada. However, our PCR fingerprinting revealed that among the 112 North American isolates we analyzed, three, all from Canada, showed minor genetic variation. Furthermore, we found significant variations among isolates in mycelial growth rate; the production of mycelial exudates; and pigment production and diffusion into agar media. These phenotypic differences were influenced by culture medium and incubation temperature, indicating significant variation in environmental condition - dependent phenotypic expression among isolates of the clonal P. destructans genotype in North America. PMID:25122221

Clonal expansion of the Pseudogymnoascus destructans genotype in North America is accompanied by significant variation in phenotypic expression.

PubMed

Khankhet, Jordan; Vanderwolf, Karen J; McAlpine, Donald F; McBurney, Scott; Overy, David P; Slavic, Durda; Xu, Jianping

2014-01-01

Pseudogymnoascus destructans is the causative agent of an emerging infectious disease that threatens populations of several North American bat species. The fungal disease was first observed in 2006 and has since caused the death of nearly six million bats. The disease, commonly known as white-nose syndrome, is characterized by a cutaneous infection with P. destructans causing erosions and ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on sequences from eight loci have found that isolates of P. destructans from bats in the US all belong to one multilocus genotype. Using the same multilocus sequence typing method, we found that isolates from eastern and central Canada also had the same genotype as those from the US, consistent with the clonal expansion of P. destructans into Canada. However, our PCR fingerprinting revealed that among the 112 North American isolates we analyzed, three, all from Canada, showed minor genetic variation. Furthermore, we found significant variations among isolates in mycelial growth rate; the production of mycelial exudates; and pigment production and diffusion into agar media. These phenotypic differences were influenced by culture medium and incubation temperature, indicating significant variation in environmental condition--dependent phenotypic expression among isolates of the clonal P. destructans genotype in North America.

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress

PubMed Central

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association (r2 = 0.3–0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association (P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H9 will help us to identify significant loci and alleles that made H9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions. PMID:28878785

Phenotypic Stability of Zea mays Grain Yield and Its Attributing Traits under Drought Stress.

PubMed

Ali, Fawad; Ahsan, Muhammad; Ali, Qurban; Kanwal, Naila

2017-01-01

Phenotypic stability under stress environment facilitate the fitness of genotype and opens new horizons to explore the cryptic genetic variation. Variation in tolerance to drought stress, a major grain yield constraint to global maize production, was identified, at the phenotypic and genotypic level. Here we found a prominent hybrid H 9 that showed fitness over four growing seasons for grain yield under water stress conditions. Genotypic and phenotypic correlation of yield attributing traits over four seasons demonstrated that cobs per plant, 100 seed weight, number of grains rows per cob, total dry matter, cob diameter had positive association ( r 2 = 0.3-0.9) to grain yield. The perturbation was found for chlorophyll content as it showed moderate to strong association ( P < 0.01) over four seasons, might be due to environment or genotype dependent. Highest heritability (95%) and genetic advance (79%) for grain yield was found in H 9 over four consecutive crop growing seasons. Combined analysis over four seasons showed that studied variables together explained 85% of total variation in dependent structure (grain yield) obtained by Principal component analysis. This significant finding is the best example of phenotypic stability of grain yield in H 9 and made it best fitted for grain yield under drought stress scenario. Detailed genetic analysis of H 9 will help us to identify significant loci and alleles that made H 9 the best fitted and it could serve as a potential source to generate novel transgressive levels of tolerance for drought stress in arid/semiarid regions.

Functional Coding Variation in Recombinant Inbred Mouse Lines Reveals Novel Serotonin Transporter-Associated Phenotypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carneiro, Ana; Airey, David; Thompson, Brent

The human serotonin (5-hydroxytryptamine, 5-HT) transporter (hSERT, SLC6A4) figures prominently in the etiology or treatment of many prevalent neurobehavioral disorders including anxiety, alcoholism, depression, autism and obsessive-compulsive disorder (OCD). Here we utilize naturally occurring polymorphisms in recombinant inbred (RI) lines to identify novel phenotypes associated with altered SERT function. The widely used mouse strain C57BL/6J, harbors a SERT haplotype defined by two nonsynonymous coding variants (Gly39 and Lys152 (GK)). At these positions, many other mouse lines, including DBA/2J, encode Glu39 and Arg152 (ER haplotype), assignments found also in hSERT. Synaptosomal 5-HT transport studies revealed reduced uptake associated with the GKmore » variant. Heterologous expression studies confirmed a reduced SERT turnover rate for the GK variant. Experimental and in silico approaches using RI lines (C57Bl/6J X DBA/2J=BXD) identifies multiple anatomical, biochemical and behavioral phenotypes specifically impacted by GK/ER variation. Among our findings are multiple traits associated with anxiety and alcohol consumption, as well as of the control of dopamine (DA) signaling. Further bioinformatic analysis of BXD phenotypes, combined with biochemical evaluation of SERT knockout mice, nominates SERT-dependent 5-HT signaling as a major determinant of midbrain iron homeostasis that, in turn, dictates ironregulated DA phenotypes. Our studies provide a novel example of the power of coordinated in vitro, in vivo and in silico approaches using murine RI lines to elucidate and quantify the system-level impact of gene variation.« less

Similar bleeding phenotype in young children with haemophilia A or B: a cohort study.

PubMed

Clausen, N; Petrini, P; Claeyssens-Donadel, S; Gouw, S C; Liesner, R

2014-11-01

The bleeding phenotype has been suggested to differ between haemophilia A and B. More knowledge on the bleeding phenotype at initiation of treatment is important to optimize patient care. The aim of this study was to investigate the severity of the bleeding phenotype and the variation in bleeding in children with severe or moderate haemophilia A and B. Consecutive, previously untreated patients with severe or moderate haemophilia A and B (factor VIII or IX activity <0.01 or 0.01-0.05 IU mL(-1) respectively) born between January 1st 2000 and January 1st 2010 were included. Primary outcome was severity of bleeding tendency. Secondary outcome was variation in bleeding pattern. A total of 582 patients with severe haemophilia A and 76 with severe haemophilia B did not differ in age at first exposure to clotting factor (0.81 vs. 0.88 years, P = 0.20), age at first bleed (0.82 vs. 0.88 years, P = 0.36), and age at first joint bleed (1.18 vs. 1.20 years, P = 0.59). Patients with moderate haemophilia were older compared to patients with severe haemophilia. In patients with moderate haemophilia there were no clear differences between haemophilia A and B. Severity and variation in bleeding phenotype are similar during the early stage of treatment in patients with severe and moderate haemophilia A and B respectively. The findings imply that children with haemophilia B should be observed and treated as vigilantly as those with haemophilia A. © 2014 John Wiley & Sons Ltd.

Inappropriate analysis does not reveal the ecological causes of evolution of stickleback armour: a critique of Spence et al. 2013.

PubMed

MacColl, Andrew D C; Aucott, Beth

2014-09-01

In a recent paper in this journal, Spence et al. (2013) sought to identify the ecological causes of morphological evolution in three-spined sticklebacks Gasterosteus aculeatus, by examining phenotypic and environmental variation between populations on the island of North Uist, Scotland. However, by using simple qualitative assessments of phenotype and inappropriate measures of environmental variation, Spence et al. have come to a conclusion that is diametrically opposite to that which we have arrived at in studying the same populations. Our criticisms of their paper are threefold: (1) using a binomial qualitative measure of the variation in stickleback armour ("low" versus "minimal" (i.e., "normal" low-plated freshwater sticklebacks versus spineless and/or plateless fish)) does not represent the full range of phenotypes that can be described by quantitative measures of the individual elements of armour. (2) Their use of unspecified test kits, with a probable accuracy of 4 ppm, may not be accurate in the range of water chemistry on North Uist (1 to 30 ppm calcium). (3) Their qualitative assessment of the abundance of brown trout Salmo trutta as the major predator of sticklebacks does not accurately describe the variation in brown trout abundance that is revealed by catch-per-unit-effort statistics. Repeating Spence et al.'s analysis using our own measurements, we find, in direct contradiction to them, that variation in stickleback bony armour is strongly correlated with variation in trout abundance, and unrelated to variation in the concentration of calcium in the lochs in which they live. Field studies in ecology and evolution seldom address the same question in the same system at the same time, and it is salutary that in this rare instance two such studies arrived at diametrically opposite answers.

Relaxed selection on the CBF/DREB1 regulatory genes and reduced freezing tolerance in the southern range of Arabidopsis thaliana.

PubMed

Zhen, Ying; Ungerer, Mark C

2008-12-01

Elucidating the molecular basis of adaptive phenotypic variation represents a central aim in evolutionary biology. Traits exhibiting patterns of clinal variation represent excellent models for studies of molecular adaptation, especially when variation in phenotype can be linked to organismal fitness in different environments. Natural accessions of the model plant species Arabidopsis thaliana exhibit clinal variation in freezing tolerance that follows a gradient of temperature variability across the species' native range (Zhen Y, Ungerer MC. 2008. Clinal variation in freezing tolerance among natural accessions of A. thaliana. New Phytol. 177:419-427). Here, we report that this pattern of variation is attributable, at least in part, to relaxed purifying selection on members of a small family of transcriptional activators (the CBF/DREB1s) in the species' southern range. These regulatory genes play a critical role in the ability of A. thaliana plants to undergo cold acclimation and thereby achieve maximum freezing tolerance. Relative to accessions from northern regions, accessions of A. thaliana from the southern part of their geographic range exhibit levels of nonsynonymous nucleotide polymorphism that are approximately 2.8-fold higher across this small gene subfamily. Relaxed selection on the CBF/DREB1s in southern accessions also has resulted in multiple mutations in regulatory regions resulting in abrogated expression of particular subfamily members in particular accessions. These coding-region and regulatory mutations compromise the ability of these genes to act as efficient transcriptional activators during the cold acclimation process, as determined by reductions in rates of induction and maximum levels of expression in the downstream genes they regulate. This study highlights the potential role of regulatory genes in underlying adaptive phenotypic variation in nature.

Intra-specific variation in genome size in maize: cytological and phenotypic correlates

PubMed Central

Realini, María Florencia; Poggio, Lidia; Cámara-Hernández, Julián; González, Graciela Esther

2016-01-01

Genome size variation accompanies the diversification and evolution of many plant species. Relationships between DNA amount and phenotypic and cytological characteristics form the basis of most hypotheses that ascribe a biological role to genome size. The goal of the present research was to investigate the intra-specific variation in the DNA content in maize populations from Northeastern Argentina and further explore the relationship between genome size and the phenotypic traits seed weight and length of the vegetative cycle. Moreover, cytological parameters such as the percentage of heterochromatin as well as the number, position and sequence composition of knobs were analysed and their relationships with 2C DNA values were explored. The populations analysed presented significant differences in 2C DNA amount, from 4.62 to 6.29 pg, representing 36.15 % of the inter-populational variation. Moreover, intra-populational genome size variation was found, varying from 1.08 to 1.63-fold. The variation in the percentage of knob heterochromatin as well as in the number, chromosome position and sequence composition of the knobs was detected among and within the populations. Although a positive relationship between genome size and the percentage of heterochromatin was observed, a significant correlation was not found. This confirms that other non-coding repetitive DNA sequences are contributing to the genome size variation. A positive relationship between DNA amount and the seed weight has been reported in a large number of species, this relationship was not found in the populations studied here. The length of the vegetative cycle showed a positive correlation with the percentage of heterochromatin. This result allowed attributing an adaptive effect to heterochromatin since the length of this cycle would be optimized via selection for an appropriate percentage of heterochromatin. PMID:26644343

Phenotypic Variation and FMRP Levels in Fragile X

ERIC Educational Resources Information Center

Loesch, Danuta Z.; Huggins, Richard M.; Hagerman, Randi J.

2004-01-01

Data on the relationships between cognitive and physical phenotypes, and a deficit of fragile X mental retardation 1 (FMR1) gene-specific protein product, FMRP, are presented and discussed in context with earlier findings. The previously unpublished results obtained, using standard procedures of regression and correlations, showed highly…

Demographic and phenotypic responses of juvenile steelhead trout to spatial predictability of food resources

Treesearch

Matthew R. Sloat; Gordon H. Reeves

2014-01-01

We manipulated food inputs among patches within experimental streams to determine how variation in foraging behavior influenced demographic and phenotypic responses of juvenile steelhead trout (Oncorhynchus mykiss) to the spatial predictability of food resources. Demographic responses included compensatory adjustments in fish abundance, mean fish...

Enzyme polymorphism in forest trees

Treesearch

M. T. Conkle

1974-01-01

In studies of genetic differences among trees, forest biologists have found that variations fall into two categories. In the first, characterized by metric traits, the phenotypic response results from the combined activity of many genes having minor effects. In the other, characterized by mutants and some resin and disease resistance factors, the phenotypic response...

The first step toward genetic selection for host tolerance to infectious pathogens: obtaining the tolerance phenotype through group estimates

PubMed Central

Doeschl-Wilson, Andrea B.; Villanueva, Beatriz; Kyriazakis, Ilias

2012-01-01

Reliable phenotypes are paramount for meaningful quantification of genetic variation and for estimating individual breeding values on which genetic selection is based. In this paper, we assert that genetic improvement of host tolerance to disease, although desirable, may be first of all handicapped by the ability to obtain unbiased tolerance estimates at a phenotypic level. In contrast to resistance, which can be inferred by appropriate measures of within host pathogen burden, tolerance is more difficult to quantify as it refers to change in performance with respect to changes in pathogen burden. For this reason, tolerance phenotypes have only been specified at the level of a group of individuals, where such phenotypes can be estimated using regression analysis. However, few stsudies have raised the potential bias in these estimates resulting from confounding effects between resistance and tolerance. Using a simulation approach, we demonstrate (i) how these group tolerance estimates depend on within group variation and co-variation in resistance, tolerance, and vigor (performance in a pathogen free environment); and (ii) how tolerance estimates are affected by changes in pathogen virulence over the time course of infection and by the timing of measurements. We found that in order to obtain reliable group tolerance estimates, it is important to account for individual variation in vigor, if present, and that all individuals are at the same stage of infection when measurements are taken. The latter requirement makes estimation of tolerance based on cross-sectional field data challenging, as individuals become infected at different time points and the individual onset of infection is unknown. Repeated individual measurements of within host pathogen burden and performance would not only be valuable for inferring the infection status of individuals in field conditions, but would also provide tolerance estimates that capture the entire time course of infection. PMID:23412990

Linked genetic variants on chromosome 10 control ear morphology and body mass among dog breeds.

PubMed

Webster, Matthew T; Kamgari, Nona; Perloski, Michele; Hoeppner, Marc P; Axelsson, Erik; Hedhammar, Åke; Pielberg, Gerli; Lindblad-Toh, Kerstin

2015-06-23

The domestic dog is a rich resource for mapping the genetic components of phenotypic variation due to its unique population history involving strong artificial selection. Genome-wide association studies have revealed a number of chromosomal regions where genetic variation associates with morphological characters that typify dog breeds. A region on chromosome 10 is among those with the highest levels of genetic differentiation between dog breeds and is associated with body mass and ear morphology, a common motif of animal domestication. We characterised variation in this region to uncover haplotype structure and identify candidate functional variants. We first identified SNPs that strongly associate with body mass and ear type by comparing sequence variation in a 3 Mb region between 19 breeds with a variety of phenotypes. We next genotyped a subset of 123 candidate SNPs in 288 samples from 46 breeds to identify the variants most highly associated with phenotype and infer haplotype structure. A cluster of SNPs that associate strongly with the drop ear phenotype is located within a narrow interval downstream of the gene MSRB3, which is involved in human hearing. These SNPs are in strong genetic linkage with another set of variants that correlate with body mass within the gene HMGA2, which affects human height. In addition we find evidence that this region has been under selection during dog domestication, and identify a cluster of SNPs within MSRB3 that are highly differentiated between dogs and wolves. We characterise genetically linked variants that potentially influence ear type and body mass in dog breeds, both key traits that have been modified by selective breeding that may also be important for domestication. The finding that variants on long haplotypes have effects on more than one trait suggests that genetic linkage can be an important determinant of the phenotypic response to selection in domestic animals.

Phenotypic Variation in the Plant Pathogenic Bacterium Acidovorax citrulli

PubMed Central

Shrestha, Ram Kumar; Rosenberg, Tally; Makarovsky, Daria; Eckshtain-Levi, Noam; Zelinger, Einat; Kopelowitz, June; Sikorski, Johannes; Burdman, Saul

2013-01-01

Acidovorax citrulli causes bacterial fruit blotch (BFB) of cucurbits, a disease that threatens the cucurbit industry worldwide. Despite the economic importance of BFB, little is known about pathogenicity and fitness strategies of the bacterium. We have observed the phenomenon of phenotypic variation in A. citrulli. Here we report the characterization of phenotypic variants (PVs) of two strains, M6 and 7a1, isolated from melon and watermelon, respectively. Phenotypic variation was observed following growth in rich medium, as well as upon isolation of bacteria from inoculated plants or exposure to several stresses, including heat, salt and acidic conditions. When grown on nutrient agar, all PV colonies possessed a translucent appearance, in contrast to parental strain colonies that were opaque. After 72 h, PV colonies were bigger than parental colonies, and had a fuzzy appearance relative to parental strain colonies that are relatively smooth. A. citrulli colonies are generally surrounded by haloes detectable by the naked eye. These haloes are formed by type IV pilus (T4P)-mediated twitching motility that occurs at the edge of the colony. No twitching haloes could be detected around colonies of both M6 and 7a1 PVs, and microscopy observations confirmed that indeed the PVs did not perform twitching motility. In agreement with these results, transmission electron microscopy revealed that M6 and 7a1 PVs do not produce T4P under tested conditions. PVs also differed from their parental strain in swimming motility and biofilm formation, and interestingly, all assessed variants were less virulent than their corresponding parental strains in seed transmission assays. Slight alterations could be detected in some DNA fingerprinting profiles of 7a1 variants relative to the parental strain, while no differences at all could be seen among M6 variants and parental strain, suggesting that, at least in the latter, phenotypic variation is mediated by slight genetic and/or epigenetic alterations. PMID:24023830

Clinical and demographic factors and outcome of amyotrophic lateral sclerosis in relation to population ancestral origin.

PubMed

Marin, Benoît; Logroscino, Giancarlo; Boumédiene, Farid; Labrunie, Anaïs; Couratier, Philippe; Babron, Marie-Claude; Leutenegger, Anne Louise; Preux, Pierre Marie; Beghi, Ettore

2016-03-01

To review how the phenotype and outcome of amyotrophic lateral sclerosis (ALS) change with variations in population ancestral origin (PAO). Knowledge of how PAO modifies ALS phenotype may provide important insight into the risk factors and pathogenic mechanisms of the disease. We performed a systematic review and meta-analysis of the literature concerning differences in phenotype and outcome of ALS that relate to PAO. A review of 3111 records identified 78 population-based studies. The 40 that were included covered 40 geographical areas in 10 subcontinents. Around 12,700 ALS cases were considered. The results highlight the phenotypic heterogeneity of ALS at time of onset [age, sex ratio (SR), bulbar onset], age at diagnosis, occurrence of comorbidities in the first year after diagnosis, and outcome (survival). Subcontinent is a major explanatory factor for the variability of the ALS phenotype in population-based studies. Some markers of ALS phenotype were homogeneously distributed in western countries (SR, mean age at onset/diagnosis) but their distributions in other subcontinents were remarkably different. Other markers presented variations in European subcontinents (familial ALS, bulbar onset) and in other continents. As a consequence, ALS outcome strongly varied, with a median survival time from onset ranging from 24 months (Northern Europe) to 48 months (Central Asia). This review sets the scene for a collaborative study involving a wide international consortium to investigate, using a standard methodology, the link between ancestry, environment, and ALS phenotype.

CYP3A variation and the evolution of salt-sensitivity variants.

PubMed

Thompson, E E; Kuttab-Boulos, H; Witonsky, D; Yang, L; Roe, B A; Di Rienzo, A

2004-12-01

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude.

CYP3A Variation and the Evolution of Salt-Sensitivity Variants

PubMed Central

Thompson, E. E.; Kuttab-Boulos, H.; Witonsky, D.; Yang, L.; Roe, B. A.; Di Rienzo, A.

2004-01-01

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude. PMID:15492926

Parallels between UNUSUAL FLORAL ORGANS and FIMBRIATA, genes controlling flower development in Arabidopsis and Antirrhinum.

PubMed

Ingram, G C; Goodrich, J; Wilkinson, M D; Simon, R; Haughn, G W; Coen, E S

1995-09-01

The unusual floral organs (ufo) mutant of Arabidopsis has flowers with variable homeotic organ transformations and inflorescence-like characteristics. To determine the relationship between UFO and previously characterized meristem and organ identity genes, we cloned UFO and determined its expression pattern. The UFO gene shows extensive homology with FIMBRIATA (FIM), a gene mediating between meristem and organ identity genes in Antirrhinum. All three UFO mutant alleles that we sequenced are predicted to produce truncated proteins. UFO transcripts were first detected in early floral meristems, before organ identity genes had been activated. At later developmental stages, UFO expression is restricted to the junction between sepal and petal primordia. Phenotypic, genetic, and expression pattern comparisons between UFO and FIM suggest that they are cognate homologs and play a similar role in mediating between meristem and organ identity genes. However, some differences in the functions and genetic interactions of UFO and FIM were apparent, indicating that changes in partially redundant pathways have occurred during the evolutionary divergence of Arabidopsis and Antirrhinum.

Enduring Mental Health: Prevalence and Prediction

PubMed Central

2016-01-01

We review epidemiological evidence indicating that most people will develop a diagnosable mental disorder, suggesting that only a minority experience enduring mental health. This minority has received little empirical study, leaving the prevalence and predictors of enduring mental health unknown. We turn to the population-representative Dunedin cohort, followed from birth to midlife, to compare people never-diagnosed with mental disorder (N = 171; 17% prevalence) to those diagnosed at 1–2 study waves, the cohort mode (N = 409). Surprisingly, compared to this modal group, never-diagnosed Study members were not born into unusually well-to-do families, nor did their enduring mental health follow markedly sound physical health, or unusually high intelligence. Instead, they tended to have an advantageous temperament/personality style, and negligible family history of mental disorder. As adults, they report superior educational and occupational attainment, greater life satisfaction, and higher-quality relationships. Our findings draw attention to “enduring mental health” as a revealing psychological phenotype and suggest it deserves further study. PMID:27929304

To what extent is altitudinal variation of functional traits driven by genetic adaptation in European oak and beech?

PubMed

Bresson, Caroline C; Vitasse, Yann; Kremer, Antoine; Delzon, Sylvain

2011-11-01

The phenotypic responses of functional traits in natural populations are driven by genetic diversity and phenotypic plasticity. These two mechanisms enable trees to cope with rapid climate change. We studied two European temperate tree species (sessile oak and European beech), focusing on (i) in situ variations of leaf functional traits (morphological and physiological) along two altitudinal gradients and (ii) the extent to which these variations were under environmental and/or genetic control using a common garden experiment. For all traits, altitudinal trends tended to be highly consistent between species and transects. For both species, leaf mass per area displayed a positive linear correlation with altitude, whereas leaf size was negatively correlated with altitude. We also observed a significant increase in leaf physiological performance with increasing altitude: populations at high altitudes had higher maximum rates of assimilation, stomatal conductance and leaf nitrogen content than those at low altitudes. In the common garden experiment, genetic differentiation between populations accounted for 0-28% of total phenotypic variation. However, only two traits (leaf mass per area and nitrogen content) exhibited a significant cline. The combination of in situ and common garden experiments used here made it possible to demonstrate, for both species, a weaker effect of genetic variation than of variations in natural conditions, suggesting a strong effect of the environment on leaf functional traits. Finally, we demonstrated that intrapopulation variability was systematically higher than interpopulation variability, whatever the functional trait considered, indicating a high potential capacity to adapt to climate change.

Estimating the actual subject-specific genetic correlations in behavior genetics.

PubMed

Molenaar, Peter C M

2012-10-01

Generalization of the standard behavior longitudinal genetic factor model for the analysis of interindividual phenotypic variation to a genetic state space model for the analysis of intraindividual variation enables the possibility to estimate subject-specific heritabilities.

CONAN: copy number variation analysis software for genome-wide association studies

PubMed Central

2010-01-01

Background Genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs) promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs. Results CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data. Conclusions CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at http://genepi-conan.i-med.ac.at. PMID:20546565

Colony social structure in native and invasive populations of the social wasp Vespula pensylvanica

USGS Publications Warehouse

Hanna, Cause; Cook, Erin D.; Thompson, Ariel R.; Dare, Lyndzey E.; Palaski, Amanda L.; Foote, David; Goodisman, Michael A. D.

2014-01-01

Social insects rank among the most invasive of terrestrial species. The success of invasive social insects stems, in part, from the flexibility derived from their social behaviors. We used genetic markers to investigate if the social system of the invasive wasp, Vespula pensylvanica, differed in its introduced and native habitats in order to better understand variation in social phenotype in invasive social species. We found that (1) nestmate workers showed lower levels of relatedness in introduced populations than native populations, (2) introduced colonies contained workers produced by multiple queens whereas native colonies contained workers produced by only a single queen, (3) queen mate number did not differ significantly between introduced and native colonies, and (4) workers from introduced colonies were frequently produced by queens that originated from foreign nests. Thus, overall, native and introduced colonies differed substantially in social phenotype because introduced colonies more frequently contained workers produced by multiple, foreign queens. In addition, the similarity in levels of genetic variation in introduced and native habitats, as well as observed variation in colony social phenotype in native populations, suggest that colony structure in invasive populations may be partially associated with social plasticity. Overall, the differences in social structure observed in invasive V. pensylvanica parallel those in other, distantly related invasive social insects, suggesting that insect societies often develop similar social phenotypes upon introduction into new habitats.

Bacterial genospecies that are not ecologically coherent: population genomics of Rhizobium leguminosarum

PubMed Central

Kumar, Nitin; Lad, Ganesh; Giuntini, Elisa; Kaye, Maria E.; Udomwong, Piyachat; Shamsani, N. Jannah; Young, J. Peter W.; Bailly, Xavier

2015-01-01

Biological species may remain distinct because of genetic isolation or ecological adaptation, but these two aspects do not always coincide. To establish the nature of the species boundary within a local bacterial population, we characterized a sympatric population of the bacterium Rhizobium leguminosarum by genomic sequencing of 72 isolates. Although all strains have 16S rRNA typical of R. leguminosarum, they fall into five genospecies by the criterion of average nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome, support this division: recombination of core genes has been largely within genospecies. Nevertheless, variation in ecological properties, including symbiotic host range and carbon-source utilization, cuts across these genospecies, so that none of these phenotypes is diagnostic of genospecies. This phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr criteria for biological species in respect of their core genes, but do not correspond to coherent ecological groups, so periodic selection may not be effective in purging variation within them. The population structure is incompatible with traditional ‘polyphasic taxonomy′ that requires bacterial species to have both phylogenetic coherence and distinctive phenotypes. More generally, genomics has revealed that many bacterial species share adaptive modules by horizontal gene transfer, and we envisage a more consistent taxonomic framework that explicitly recognizes this. Significant phenotypes should be recognized as ‘biovars' within species that are defined by core gene phylogeny. PMID:25589577

Predicting adaptive phenotypes from multilocus genotypes in Sitka spruce (Picea sitchensis) using random forest.

PubMed

Holliday, Jason A; Wang, Tongli; Aitken, Sally

2012-09-01

Climate is the primary driver of the distribution of tree species worldwide, and the potential for adaptive evolution will be an important factor determining the response of forests to anthropogenic climate change. Although association mapping has the potential to improve our understanding of the genomic underpinnings of climatically relevant traits, the utility of adaptive polymorphisms uncovered by such studies would be greatly enhanced by the development of integrated models that account for the phenotypic effects of multiple single-nucleotide polymorphisms (SNPs) and their interactions simultaneously. We previously reported the results of association mapping in the widespread conifer Sitka spruce (Picea sitchensis). In the current study we used the recursive partitioning algorithm 'Random Forest' to identify optimized combinations of SNPs to predict adaptive phenotypes. After adjusting for population structure, we were able to explain 37% and 30% of the phenotypic variation, respectively, in two locally adaptive traits--autumn budset timing and cold hardiness. For each trait, the leading five SNPs captured much of the phenotypic variation. To determine the role of epistasis in shaping these phenotypes, we also used a novel approach to quantify the strength and direction of pairwise interactions between SNPs and found such interactions to be common. Our results demonstrate the power of Random Forest to identify subsets of markers that are most important to climatic adaptation, and suggest that interactions among these loci may be widespread.

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology

PubMed Central

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view. PMID:23515240

Data Sources for Trait Databases: Comparing the Phenomic Content of Monographs and Evolutionary Matrices.

PubMed

Dececchi, T Alex; Mabee, Paula M; Blackburn, David C

2016-01-01

Databases of organismal traits that aggregate information from one or multiple sources can be leveraged for large-scale analyses in biology. Yet the differences among these data streams and how well they capture trait diversity have never been explored. We present the first analysis of the differences between phenotypes captured in free text of descriptive publications ('monographs') and those used in phylogenetic analyses ('matrices'). We focus our analysis on osteological phenotypes of the limbs of four extinct vertebrate taxa critical to our understanding of the fin-to-limb transition. We find that there is low overlap between the anatomical entities used in these two sources of phenotype data, indicating that phenotypes represented in matrices are not simply a subset of those found in monographic descriptions. Perhaps as expected, compared to characters found in matrices, phenotypes in monographs tend to emphasize descriptive and positional morphology, be somewhat more complex, and relate to fewer additional taxa. While based on a small set of focal taxa, these qualitative and quantitative data suggest that either source of phenotypes alone will result in incomplete knowledge of variation for a given taxon. As a broader community develops to use and expand databases characterizing organismal trait diversity, it is important to recognize the limitations of the data sources and develop strategies to more fully characterize variation both within species and across the tree of life.

Data Sources for Trait Databases: Comparing the Phenomic Content of Monographs and Evolutionary Matrices

PubMed Central

Dececchi, T. Alex; Mabee, Paula M.; Blackburn, David C.

2016-01-01

Databases of organismal traits that aggregate information from one or multiple sources can be leveraged for large-scale analyses in biology. Yet the differences among these data streams and how well they capture trait diversity have never been explored. We present the first analysis of the differences between phenotypes captured in free text of descriptive publications (‘monographs’) and those used in phylogenetic analyses (‘matrices’). We focus our analysis on osteological phenotypes of the limbs of four extinct vertebrate taxa critical to our understanding of the fin-to-limb transition. We find that there is low overlap between the anatomical entities used in these two sources of phenotype data, indicating that phenotypes represented in matrices are not simply a subset of those found in monographic descriptions. Perhaps as expected, compared to characters found in matrices, phenotypes in monographs tend to emphasize descriptive and positional morphology, be somewhat more complex, and relate to fewer additional taxa. While based on a small set of focal taxa, these qualitative and quantitative data suggest that either source of phenotypes alone will result in incomplete knowledge of variation for a given taxon. As a broader community develops to use and expand databases characterizing organismal trait diversity, it is important to recognize the limitations of the data sources and develop strategies to more fully characterize variation both within species and across the tree of life. PMID:27191170

Polymorphisms of the tumor necrosis factor-alpha receptor 2 gene are associated with obesity phenotypes among 405 Caucasian nuclear families.

PubMed

Zhao, Lan-Juan; Xiong, Dong-Hai; Pan, Feng; Liu, Xiao-Gang; Recker, Robert R; Deng, Hong-Wen

2008-09-01

The plasma level of the tumor necrosis factor-alpha receptor 2 (TNFR2) is associated with obesity phenotypes. However, the genetic polymorphisms for such an association have rarely been explored and are generally unknown. In this study, by employing a large sample of 1,873 subjects from 405 Caucasian nuclear families, we explored the association of 12 SNPs of the TNFR2 gene and obesity-related phenotypes, including body mass index (BMI), fat mass, and percentage fat mass (PFM). The within-family quantitative transmission disequilibrium test, which is robust to sample stratification, was implemented to evaluate the association of TNFR2 gene with obesity phenotypes. Evidence of association was obtained at SNP9 (rs5746059) with fat mass (P = 0.0002), BMI (P = 0.002), and PFM (P = 0.0006). The contribution of this polymorphism to the variation of fat mass and PFM was 6.24 and 7.82%, respectively. Individuals carrying allele A at the SNP9 site had a 4.6% higher fat mass and a 2.5% increased PFM compared to noncarriers. The results remained significant even after correction for multiple testing. Evidence of association between the TNFR2 gene and obesity phenotypes are also found in 700 independent Chinese Han and 1,000 random Caucasians samples. The results suggest that the TNFR2 gene polymorphisms contribute to the variation of obesity phenotypes.

Genetic and Phenotypic Characterization of a Salmonella enterica serovar Enteritidis Emerging Strain with Superior Intra-macrophage Replication Phenotype

PubMed Central

Shomer, Inna; Avisar, Alon; Desai, Prerak; Azriel, Shalhevet; Smollan, Gill; Belausov, Natasha; Keller, Nathan; Glikman, Daniel; Maor, Yasmin; Peretz, Avi; McClelland, Michael; Rahav, Galia; Gal-Mor, Ohad

2016-01-01

Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the ubiquitous Salmonella serovars worldwide and a major cause of food-born outbreaks, which are often associated with poultry and poultry derivatives. Here we report a nation-wide S. Enteritidis clonal outbreak that occurred in Israel during the last third of 2015. Pulsed field gel electrophoresis and whole genome sequencing identified genetically related strains that were circulating in Israel as early as 2008. Global comparison linked this outbreak strain to several clinical and marine environmental isolates that were previously isolated in California and Canada, indicating that similar strains are prevalent outside of Israel. Phenotypic comparison between the 2015 outbreak strain and other clinical and reference S. Enteritidis strains showed only limited intra-serovar phenotypic variation in growth in rich medium, invasion into Caco-2 cells, uptake by J774.1A macrophages, and host cell cytotoxicity. In contrast, significant phenotypic variation was shown among different S. Enteritidis isolates when biofilm-formation, motility, invasion into HeLa cells and uptake by THP-1 human macrophages were studied. Interestingly, the 2015 outbreak clone was found to possess superior intra-macrophage replication ability within both murine and human macrophages in comparison to the other S. Enteritidis strains studied. This phenotype is likely to play a role in the virulence and host-pathogen interactions of this emerging clone. PMID:27695450

A Unifying Mathematical Framework for Genetic Robustness, Environmental Robustness, Network Robustness and their Trade-off on Phenotype Robustness in Biological Networks Part I: Gene Regulatory Networks in Systems and Evolutionary Biology.

PubMed

Chen, Bor-Sen; Lin, Ying-Po

2013-01-01

Robust stabilization and environmental disturbance attenuation are ubiquitous systematic properties observed in biological systems at different levels. The underlying principles for robust stabilization and environmental disturbance attenuation are universal to both complex biological systems and sophisticated engineering systems. In many biological networks, network robustness should be enough to confer intrinsic robustness in order to tolerate intrinsic parameter fluctuations, genetic robustness for buffering genetic variations, and environmental robustness for resisting environmental disturbances. With this, the phenotypic stability of biological network can be maintained, thus guaranteeing phenotype robustness. This paper presents a survey on biological systems and then develops a unifying mathematical framework for investigating the principles of both robust stabilization and environmental disturbance attenuation in systems and evolutionary biology. Further, from the unifying mathematical framework, it was discovered that the phenotype robustness criterion for biological networks at different levels relies upon intrinsic robustness + genetic robustness + environmental robustness ≦ network robustness. When this is true, the phenotype robustness can be maintained in spite of intrinsic parameter fluctuations, genetic variations, and environmental disturbances. Therefore, the trade-offs between intrinsic robustness, genetic robustness, environmental robustness, and network robustness in systems and evolutionary biology can also be investigated through their corresponding phenotype robustness criterion from the systematic point of view.

Genetic diversity affects colony survivorship in commercial honey bee colonies

USDA-ARS?s Scientific Manuscript database

Honey bee (Apis mellifera) queens mate with unusually high numbers of males (average of approximately 12 drones), although there is much variation among queens. One main consequence of such extreme polyandry is an increased diversity of worker genotypes within a colony, which has been shown empirica...

Is NF-1 gene deletion the molecular mechanism of neurofibromatosis type 1 with destinctive facies?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leppig, K.A.; Stephens, K.G.; Viskochill, D.

We have studied a patient with neurofibromatosis type 1 and unusual facial features using fluorescence in situ hybridization (FISH) and found that the patient had a deletion that minimially encompasses exon 2-11 of the NF-1 gene. The patient was one of two individuals initially described by Kaplan and Rosenblatt who suggested that another condition aside from neurofibromatosis type 1 may account for the unusual facial features observed in these patients with neurofibromatosis type 1. FISH studies were performed using a P1 clone probe, P1-9, which contains exons 2-11 of the NF-1 gene on chromosomes prepared from the patients. In allmore » 20 metaphase cells analyzed, one of the chromosome 17 homologues was deleted for the P1-9 probe. Therefore, this patient had neurofibromatosis type 1 and unusual facial features as the result of a deletion which minimally includes exons 2-11 of the NF-1 gene. The extent of the deletion is being mapped by FISH and somatic cell hybrid analysis. The patient studied was a 7-year-old male with mild developmental delays, normal growth parameters, and physical findings consistent with neurofibromatosis type 1, including multiple cafe au lait spots, several curaneous neurofibroma, and speckling of the irises. In addition, his unusual facial features consisted of telecanthus, antimongoloid slant of the palpebral fissures, a broad base of the nose, low set and mildly posteriorly rotated ears, thick helices, high arched palate, short and pointed chin, and low posterior hairline. We propose that deletions of the NF-1 gene and/or contiguous genes are the etiology of neurofibromatosis type 1 and unusual facial features. This particular facial appearance was inherited from the patient`s mother and has been described in other individuals with neurofibromatosis type 1. We are using FISH to rapidly screen patients with this phenotype for large deletions involving the NF-1 gene and flanking DNA sequences.« less

EvolQG - An R package for evolutionary quantitative genetics

PubMed Central

Melo, Diogo; Garcia, Guilherme; Hubbe, Alex; Assis, Ana Paula; Marroig, Gabriel

2016-01-01

We present an open source package for performing evolutionary quantitative genetics analyses in the R environment for statistical computing. Evolutionary theory shows that evolution depends critically on the available variation in a given population. When dealing with many quantitative traits this variation is expressed in the form of a covariance matrix, particularly the additive genetic covariance matrix or sometimes the phenotypic matrix, when the genetic matrix is unavailable and there is evidence the phenotypic matrix is sufficiently similar to the genetic matrix. Given this mathematical representation of available variation, the \\textbf{EvolQG} package provides functions for calculation of relevant evolutionary statistics; estimation of sampling error; corrections for this error; matrix comparison via correlations, distances and matrix decomposition; analysis of modularity patterns; and functions for testing evolutionary hypotheses on taxa diversification. PMID:27785352

Racial stereotypes and interracial attraction: phenotypic prototypicality and perceived attractiveness of Asians.

PubMed

Wilkins, Clara L; Chan, Joy F; Kaiser, Cheryl R

2011-10-01

What does it take to find a member of a different race attractive? In this research, we suggest that for Whites, attraction to Asians may be based, in part, on stereotypes and variations in Asians' racial appearance. Study 1 reveals that Asians are stereotyped as being more feminine and less masculine than other racial groups-characteristics considered appealing for women but not for men to possess. Study 2 examines how variation in racial appearance, phenotypic prototypicality (PP), shapes the degree to which Asians are gender stereotyped and how PP relates to perceptions of attractiveness. Higher PP Asian men are perceived as being less masculine and less physically attractive than lower PP Asian men. These findings inform theory on how within-group variation in racial appearance affects stereotyping and other social outcomes.

Liver segment IV hypoplasia as a risk factor for bile duct injury.

PubMed

Mercado, Miguel Angel; Franssen, Bernardo; Arriola, Juan Carlos; Garcia-Badiola, Artemio; Arámburo, Rigoberto; Elnecavé, Alejandro; Cortés-González, Rubén

2011-09-01

Bile duct injury remains constant in the era of laparoscopic cholecystectomy and misidentification of structures remains one of the most common causes of such injuries. Abnormalities in liver segment IV, which is fully visible during laparoscopic cholecystectomy, may contribute to misidentification as proposed herein. We describe the case of a 36-year-old female who had a bile duct injury during a laparoscopic cholecystectomy where the surgeon noticed an unusually small distance between the gallbladder and the round ligament. We define hypoplasia of liver segment IV as well as describe the variation of the biliary anatomy in the case. We also intend to fit it in a broader spectrum of developmental anomalies that have both hyopoplasia of some portion of the liver and variations in gallbladder and bile duct anatomy that may contribute to bile duct injury. To our knowledge, hypoplasia of liver segment IV has not been suggested in the literature as a risk factor for bile duct injury except in the extreme case of a left-sided gallbladder. Surgeons should be vigilant during laparoscopic cholecystectomy when they become aware of an unusually small distance between the gallbladder bed and the round ligament prior to beginning their dissection, variations in the common bile duct and cystic duct should be expected.

Focusing homologous recombination: pilin antigenic variation in the pathogenic Neisseria

PubMed Central

Cahoon, Laty A.; Seifert, H. Steven

2011-01-01

Summary Some pathogenic microbes utilize homologous recombination to generate antigenic variability in targets of immune surveillance. These specialized systems rely on the cellular recombination machinery to catalyze dedicated, high-frequency reactions that provide extensive diversity in the genes encoding surface antigens. A description of the specific mechanisms that allow unusually high rates of recombination without deleterious effects on the genome in the well characterized pilin antigenic variation systems of Neisseria gonorrhoeae and Neisseria meningitidis is presented. We will also draw parallels to selected bacterial and eukaryotic antigenic variation systems, and suggest the most pressing unanswered questions related to understanding these important processes. PMID:21812841

Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake

USDA-ARS?s Scientific Manuscript database

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. In this study, we performed an initial analysis of CNVs using BovineHD SNP genotyping data from 147 Holstein cows identified as having high or low feed efficiency as estimated by residual feed intak...

Genome-wide identification of copy number variations between two chicken lines that differ in genetic resistance to Marek’s disease

USDA-ARS?s Scientific Manuscript database

Background: Copy number variation (CNV) is a major source of genome polymorphism that directly contributes to phenotypic variation such as resistance to infectious diseases. Lines 63 and 72 are two highly inbred experimental chicken lines that differ greatly in susceptibility to Marek’s disease (MD)...

Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution

PubMed Central

Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D.; Rainey, Paul B.; de Visser, J. Arjan G. M.; Baudry, Jean; Bibette, Jérôme

2016-01-01

Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes–via growth–over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology. PMID:27077662

Lineage Tracking for Probing Heritable Phenotypes at Single-Cell Resolution.

PubMed

Cottinet, Denis; Condamine, Florence; Bremond, Nicolas; Griffiths, Andrew D; Rainey, Paul B; de Visser, J Arjan G M; Baudry, Jean; Bibette, Jérôme

2016-01-01

Determining the phenotype and genotype of single cells is central to understand microbial evolution. DNA sequencing technologies allow the detection of mutants at high resolution, but similar approaches for phenotypic analyses are still lacking. We show that a drop-based millifluidic system enables the detection of heritable phenotypic changes in evolving bacterial populations. At time intervals, cells were sampled and individually compartmentalized in 100 nL drops. Growth through 15 generations was monitored using a fluorescent protein reporter. Amplification of heritable changes-via growth-over multiple generations yields phenotypically distinct clusters reflecting variation relevant for evolution. To demonstrate the utility of this approach, we follow the evolution of Escherichia coli populations during 30 days of starvation. Phenotypic diversity was observed to rapidly increase upon starvation with the emergence of heritable phenotypes. Mutations corresponding to each phenotypic class were identified by DNA sequencing. This scalable lineage-tracking technology opens the door to large-scale phenotyping methods with special utility for microbiology and microbial population biology.

Will phenotypic plasticity affecting flowering phenology keep pace with climate change?

Treesearch

Bryce A. Richardson; Linsay Chaney; Nancy L. Shaw; Shannon M. Still

2016-01-01

Rising temperatures have begun to shift flowering time, but it is unclear whether phenotypic plasticity can accommodate projected temperature change for this century. Evaluating clines in phenological traits and the extent and variation in plasticity can provide key information on assessing risk of maladaptation and developing strategies to mitigate climate change. In...

Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes

ERIC Educational Resources Information Center

Reinagel, Adam; Speth, Elena Bray

2016-01-01

In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students' understanding of 1) the origin of variation in a population…

Brief Report: No Association between Premorbid Adjustment in Adult-Onset Schizophrenia and Genetic Variation in Dysbindin

ERIC Educational Resources Information Center

Schirmbeck, Frederike; Georgi, Alexander; Strohmaier, Jana; Schmael, Christine; Boesshenz, Katja V.; Muhleisen, Thomas W.; Herms, Stefan; Hoffmann, Per; Jamra, Rami Abou; Schumacher, Johannes; Maier, Wolfgang; Propping, Peter; Nothen, Markus M.; Cichon, Sven; Rietschel, Marcella; Schulze, Thomas G.

2008-01-01

Whereas "Dysbindin" is considered a schizophrenia vulnerability gene, there is no consistency of findings. Phenotype refinement approaches may help to increase the genetic homogeneity and thus reconcile conflicting results. Premorbid adjustment (PMA) has been suggested to aid the phenotypic dissection. Gornick et al. ("J Autism Dev…

Natural and Unanticipated Modifiers of RNAi Activity in Caenorhabditis elegans

PubMed Central

Asad, Nadeem; Aw, Wen Yih; Timmons, Lisa

2012-01-01

Organisms used as model genomics systems are maintained as isogenic strains, yet evidence of sequence differences between independently maintained wild-type stocks has been substantiated by whole-genome resequencing data and strain-specific phenotypes. Sequence differences may arise from replication errors, transposon mobilization, meiotic gene conversion, or environmental or chemical assault on the genome. Low frequency alleles or mutations with modest effects on phenotypes can contribute to natural variation, and it has proven possible for such sequences to become fixed by adapted evolutionary enrichment and identified by resequencing. Our objective was to identify and analyze single locus genetic defects leading to RNAi resistance in isogenic strains of Caenorhabditis elegans. In so doing, we uncovered a mutation that arose de novo in an existing strain, which initially frustrated our phenotypic analysis. We also report experimental, environmental, and genetic conditions that can complicate phenotypic analysis of RNAi pathway defects. These observations highlight the potential for unanticipated mutations, coupled with genetic and environmental phenomena, to enhance or suppress the effects of known mutations and cause variation between wild-type strains. PMID:23209671

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

PubMed

Chande, Aroon T; Wang, Lu; Rishishwar, Lavanya; Conley, Andrew B; Norris, Emily T; Valderrama-Aguirre, Augusto; Jordan, I King

2018-05-18

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.

The locus of sexual selection: moving sexual selection studies into the post-genomics era.

PubMed

Wilkinson, G S; Breden, F; Mank, J E; Ritchie, M G; Higginson, A D; Radwan, J; Jaquiery, J; Salzburger, W; Arriero, E; Barribeau, S M; Phillips, P C; Renn, S C P; Rowe, L

2015-04-01

Sexual selection drives fundamental evolutionary processes such as trait elaboration and speciation. Despite this importance, there are surprisingly few examples of genes unequivocally responsible for variation in sexually selected phenotypes. This lack of information inhibits our ability to predict phenotypic change due to universal behaviours, such as fighting over mates and mate choice. Here, we discuss reasons for this apparent gap and provide recommendations for how it can be overcome by adopting contemporary genomic methods, exploiting underutilized taxa that may be ideal for detecting the effects of sexual selection and adopting appropriate experimental paradigms. Identifying genes that determine variation in sexually selected traits has the potential to improve theoretical models and reveal whether the genetic changes underlying phenotypic novelty utilize common or unique molecular mechanisms. Such a genomic approach to sexual selection will help answer questions in the evolution of sexually selected phenotypes that were first asked by Darwin and can furthermore serve as a model for the application of genomics in all areas of evolutionary biology. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Genome Variation Map: a data repository of genome variations in BIG Data Center.

PubMed

Song, Shuhui; Tian, Dongmei; Li, Cuiping; Tang, Bixia; Dong, Lili; Xiao, Jingfa; Bao, Yiming; Zhao, Wenming; He, Hang; Zhang, Zhang

2018-01-04

The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. As a core resource in the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to collect, integrate and visualize genome variations for a wide range of species, accepts submissions of different types of genome variations from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Unlike existing related databases, GVM features integration of a large number of genome variations for a broad diversity of species including human, cultivated plants and domesticated animals. Specifically, the current implementation of GVM not only houses a total of ∼4.9 billion variants for 19 species including chicken, dog, goat, human, poplar, rice and tomato, but also incorporates 8669 individual genotypes and 13 262 manually curated high-quality genotype-to-phenotype associations for non-human species. In addition, GVM provides friendly intuitive web interfaces for data submission, browse, search and visualization. Collectively, GVM serves as an important resource for archiving genomic variation data, helpful for better understanding population genetic diversity and deciphering complex mechanisms associated with different phenotypes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effects of intraspecific phenotypic variation on species coexistence.

PubMed

Hausch, Stephen; Vamosi, Steven M; Fox, Jeremy W

2018-06-01

Intraspecific variation can promote or inhibit species coexistence, both by increasing species' competitive abilities, and by altering the relative strengths of intraspecific and interspecific competition. Effects of intraspecific variation on coexistence can occur via complementarity of different variants, and via a selection effect: initially-variable populations are more likely to contain highly competitive variants that might determine the ability of the population as a whole to both invade and resist invasion. We tested the effects of intraspecific variation and composition on coexistence by assaying the mutual invasibility of populations of two competing bean weevil species (Callosobruchus maculatus and C. chinensis) when each was initiated with one, three, or five genetically- and phenotypically-distinct lineages. Our results reveal that intraspecific variation is a double-edged sword for species coexistence. Increasing intraspecific variation increased species' abilities to invade, and to resist invasion, via selection effects and intraspecific niche complementarity among conspecific lineages, thereby creating the potential for exclusion among mismatched competitors. But intraspecific variation also increased the scope for resource partitioning, creating the potential for stable coexistence. Stable coexistence occurred only when intraspecific variation caused species to exhibit both relatively evenly-matched competitive abilities and sufficiently-strong resource partitioning. Our work explains the conflicting results of previous studies. © 2018 by the Ecological Society of America.

Genetic variation in bacterial kidney disease (BKD) susceptibility in Lake Michigan Chinook Salmon and its progenitor population from the Puget Sound.

PubMed

Purcell, Maureen K; Hard, Jeffrey J; Neely, Kathleen G; Park, Linda K; Winton, James R; Elliott, Diane G

2014-03-01

Mass mortality events in wild fish due to infectious diseases are troubling, especially given the potential for long-term, population-level consequences. Evolutionary theory predicts that populations with sufficient genetic variation will adapt in response to pathogen pressure. Chinook Salmon Oncorhynchus tshawytscha were introduced into Lake Michigan in the late 1960s from a Washington State hatchery population. In the late 1980s, collapse of the forage base and nutritional stress in Lake Michigan were thought to contribute to die-offs of Chinook Salmon due to bacterial kidney disease (BKD). Previously, we demonstrated that Lake Michigan Chinook Salmon from a Wisconsin hatchery have greater survival following BKD challenge relative to their progenitor population. Here, we evaluated whether the phenotypic divergence of these populations in BKD susceptibility was due to selection rather than genetic drift. Comparison of the overall magnitude of quantitative trait to neutral marker divergence between the populations suggested selection had occurred but a direct test of quantitative trait divergence was not significant, preventing the rejection of the null hypothesis of differentiation through genetic drift. Estimates of phenotypic variation (VP ), additive genetic variation (VA ) and narrow-sense heritability (h (2)) were consistently higher in the Wisconsin relative to the Washington population. If selection had acted on the Wisconsin population there was no evidence of a concomitant loss of genetic variation in BKD susceptibility. The Renibacterium salmoninarum exposures were conducted at both 14°C and 9°C; the warmer temperature accelerated time to death in both populations and there was no evidence of phenotypic plasticity or a genotype-by-environment (G × E) interaction. High h (2) estimates for BKD susceptibility in the Wisconsin population, combined with a lack of phenotypic plasticity, predicts that future adaptive gains in BKD resistance are still possible and that these adaptive gains would be stable under the temperature range evaluated here.

Genetic variation in bacterial kidney disease (BKD) susceptibility in Lake Michigan Chinook Salmon and its progenitor population from the Puget Sound

USGS Publications Warehouse

Purcell, Maureen K.; Hard, Jeffrey J.; Neely, Kathleen G.; Park, Linda K.; Winton, James R.; Elliott, Diane G.

2014-01-01

Mass mortality events in wild fish due to infectious diseases are troubling, especially given the potential for long-term, population-level consequences. Evolutionary theory predicts that populations with sufficient genetic variation will adapt in response to pathogen pressure. Chinook Salmon Oncorhynchus tshawytscha were introduced into Lake Michigan in the late 1960s from a Washington State hatchery population. In the late 1980s, collapse of the forage base and nutritional stress in Lake Michigan were thought to contribute to die-offs of Chinook Salmon due to bacterial kidney disease (BKD). Previously, we demonstrated that Lake Michigan Chinook Salmon from a Wisconsin hatchery have greater survival following BKD challenge relative to their progenitor population. Here, we evaluated whether the phenotypic divergence of these populations in BKD susceptibility was due to selection rather than genetic drift. Comparison of the overall magnitude of quantitative trait to neutral marker divergence between the populations suggested selection had occurred but a direct test of quantitative trait divergence was not significant, preventing the rejection of the null hypothesis of differentiation through genetic drift. Estimates of phenotypic variation (VP), additive genetic variation (VA) and narrow-sense heritability (h2) were consistently higher in the Wisconsin relative to the Washington population. If selection had acted on the Wisconsin population there was no evidence of a concomitant loss of genetic variation in BKD susceptibility. The Renibacterium salmoninarum exposures were conducted at both 14°C and 9°C; the warmer temperature accelerated time to death in both populations and there was no evidence of phenotypic plasticity or a genotype-by-environment (G × E) interaction. High h2 estimates for BKD susceptibility in the Wisconsin population, combined with a lack of phenotypic plasticity, predicts that future adaptive gains in BKD resistance are still possible and that these adaptive gains would be stable under the temperature range evaluated here.

Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins

PubMed Central

Li, Shuxia; Kyvik, Kirsten Ohm; Pang, Zengchang; Zhang, Dongfeng; Duan, Haiping; Tan, Qihua; Hjelmborg, Jacob; Kruse, Torben; Dalgård, Christine

2016-01-01

Objective The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments. Materials and Methods The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18–65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23–64). The classical twin models were fitted to the longitudinal change in each phenotype (Δphenotype) to estimate the genetic and environmental contributions to the variation in Δphenotype. Results Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits. Conclusion Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples. PMID:26862898

Light and Nutrient Dependent Responses in Secondary Metabolites of Plantago lanceolata Offspring Are Due to Phenotypic Plasticity in Experimental Grasslands

PubMed Central

Miehe-Steier, Annegret; Roscher, Christiane; Reichelt, Michael; Gershenzon, Jonathan; Unsicker, Sybille B.

2015-01-01

A few studies in the past have shown that plant diversity in terms of species richness and functional composition can modify plant defense chemistry. However, it is not yet clear to what extent genetic differentiation of plant chemotypes or phenotypic plasticity in response to diversity-induced variation in growth conditions or a combination of both is responsible for this pattern. We collected seed families of ribwort plantain (Plantago lanceolata) from six-year old experimental grasslands of varying plant diversity (Jena Experiment). The offspring of these seed families was grown under standardized conditions with two levels of light and nutrients. The iridoid glycosides, catalpol and aucubin, and verbascoside, a caffeoyl phenylethanoid glycoside, were measured in roots and shoots. Although offspring of different seed families differed in the tissue concentrations of defensive metabolites, plant diversity in the mothers' environment did not explain the variation in the measured defensive metabolites of P. lanceolata offspring. However secondary metabolite levels in roots and shoots were strongly affected by light and nutrient availability. Highest concentrations of iridoid glycosides and verbascoside were found under high light conditions, and nutrient availability had positive effects on iridoid glycoside concentrations in plants grown under high light conditions. However, verbascoside concentrations decreased under high levels of nutrients irrespective of light. The data from our greenhouse study show that phenotypic plasticity in response to environmental variation rather than genetic differentiation in response to plant community diversity is responsible for variation in secondary metabolite concentrations of P. lanceolata in the six-year old communities of the grassland biodiversity experiment. Due to its large phenotypic plasticity P. lanceolata has the potential for a fast and efficient adjustment to varying environmental conditions in plant communities of different species richness and functional composition. PMID:26336100

Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies.

PubMed

Huber, B; Whibley, A; Poul, Y L; Navarro, N; Martin, A; Baxter, S; Shah, A; Gilles, B; Wirth, T; McMillan, W O; Joron, M

2015-05-01

Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima.

AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

PubMed Central

Song, Giltae; Dickins, Benjamin J. A.; Demeter, Janos; Engel, Stacia; Dunn, Barbara; Cherry, J. Michael

2015-01-01

The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community. PMID:25781462

Dysmorphometrics: the modelling of morphological abnormalities.

PubMed

Claes, Peter; Daniels, Katleen; Walters, Mark; Clement, John; Vandermeulen, Dirk; Suetens, Paul

2012-02-06

The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited. A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram. We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities. The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.

Cultural diversification promotes rapid phenotypic evolution in Xavánte Indians

PubMed Central

Hünemeier, Tábita; Gómez-Valdés, Jorge; Ballesteros-Romero, Mónica; de Azevedo, Soledad; Martínez-Abadías, Neus; Esparza, Mireia; Sjøvold, Torstein; Bonatto, Sandro L.; Salzano, Francisco Mauro; Bortolini, Maria Cátira; González-José, Rolando

2012-01-01

Shifts in social structure and cultural practices can potentially promote unusual combinations of allele frequencies that drive the evolution of genetic and phenotypic novelties during human evolution. These cultural practices act in combination with geographical and linguistic barriers and can promote faster evolutionary changes shaped by gene–culture interactions. However, specific cases indicative of this interaction are scarce. Here we show that quantitative genetic parameters obtained from cephalometric data taken on 1,203 individuals analyzed in combination with genetic, climatic, social, and life-history data belonging to six South Amerindian populations are compatible with a scenario of rapid genetic and phenotypic evolution, probably mediated by cultural shifts. We found that the Xavánte experienced a remarkable pace of evolution: the rate of morphological change is far greater than expected for its time of split from their sister group, the Kayapó, which occurred around 1,500 y ago. We also suggest that this rapid differentiation was possible because of strong social-organization differences. Our results demonstrate how human groups deriving from a recent common ancestor can experience variable paces of phenotypic divergence, probably as a response to different cultural or social determinants. We suggest that assembling composite databases involving cultural and biological data will be of key importance to unravel cases of evolution modulated by the cultural environment. PMID:22184238

Behavioral phenotypes of genetic mouse models of autism

PubMed Central

Kazdoba, T. M.; Leach, P. T.; Crawley, J. N.

2016-01-01

More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism. PMID:26403076

An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.

PubMed

Daou, Badih; Zanello, Marc; Varlet, Pascale; Brugieres, Laurence; Jabbour, Pascal; Caron, Olivier; Lavoine, Noémie; Dhermain, Frederic; Willekens, Christophe; Beuvon, Frederic; Malka, David; Lechapt-Zalcmann, Emmanuèle; Abi Lahoud, Georges

2015-07-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed. We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors. Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.

Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene.

PubMed

Raisingani, Manish; Contreras, Maria F; Prasad, Kris; Pappas, John G; Kluge, Michelle L; Shah, Bina; David, Raphael

2016-07-01

Gonadotropin independent sexual precocity (SP) may be due to congenital adrenal hyperplasia (CAH), and its timing usually depends on the type of mutation in the CYP21A2 gene. Compound heterozygotes are common and express phenotypes of varying severity. The objective of this case report was to investigate the hormonal pattern and unusual genetic profile in a 7-year-old boy who presented with pubic hair, acne, an enlarged phallus, slightly increased testicular volume and advanced bone age. Clinical, hormonal and genetic studies were undertaken in the patient as well as his parents. We found elevated serum 17-hydroxyprogesterone (17-OHP) and androstenedione that were suppressed with dexamethasone, and elevated testosterone that actually rose after giving dexamethasone, indicating activity of the hypothalamic-pituitary-gonadal (HPG) axis. An initial search for common mutations was negative, but a more detailed genetic analysis of the CYP21A2 gene revealed two mutations including R341W, a non-classical mutation inherited from his mother, and g.823G>A, a novel not previously reported consensus donor splice site mutation inherited from his father, which is predicted to be salt wasting. However, the child had a normal plasma renin activity. He was effectively treated with low-dose dexamethasone and a GnRH agonist. His father was an unaffected carrier, but his mother had evidence of mild non-classical CAH. In a male child presenting with gonadotropin independent SP it is important to investigate adrenal function with respect to the androgen profile, and to carry out appropriate genetic studies.

Genome-environment associations in sorghum landraces predict adaptive traits

PubMed Central

Lasky, Jesse R.; Upadhyaya, Hari D.; Ramu, Punna; Deshpande, Santosh; Hash, C. Tom; Bonnette, Jason; Juenger, Thomas E.; Hyma, Katie; Acharya, Charlotte; Mitchell, Sharon E.; Buckler, Edward S.; Brenton, Zachary; Kresovich, Stephen; Morris, Geoffrey P.

2015-01-01

Improving environmental adaptation in crops is essential for food security under global change, but phenotyping adaptive traits remains a major bottleneck. If associations between single-nucleotide polymorphism (SNP) alleles and environment of origin in crop landraces reflect adaptation, then these could be used to predict phenotypic variation for adaptive traits. We tested this proposition in the global food crop Sorghum bicolor, characterizing 1943 georeferenced landraces at 404,627 SNPs and quantifying allelic associations with bioclimatic and soil gradients. Environment explained a substantial portion of SNP variation, independent of geographical distance, and genic SNPs were enriched for environmental associations. Further, environment-associated SNPs predicted genotype-by-environment interactions under experimental drought stress and aluminum toxicity. Our results suggest that genomic signatures of environmental adaptation may be useful for crop improvement, enhancing germplasm identification and marker-assisted selection. Together, genome-environment associations and phenotypic analyses may reveal the basis of environmental adaptation. PMID:26601206

Comparative evaluation of matrix-assisted laser desorption ionisation-time of flight mass spectrometry and conventional phenotypic-based methods for identification of clinically important yeasts in a UK-based medical microbiology laboratory.

PubMed

Fatania, Nita; Fraser, Mark; Savage, Mike; Hart, Jason; Abdolrasouli, Alireza

2015-12-01

Performance of matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS) was compared in a side-by side-analysis with conventional phenotypic methods currently in use in our laboratory for identification of yeasts in a routine diagnostic setting. A diverse collection of 200 clinically important yeasts (19 species, five genera) were identified by both methods using standard protocols. Discordant or unreliable identifications were resolved by sequencing of the internal transcribed spacer region of the rRNA gene. MALDI-TOF and conventional methods were in agreement for 182 isolates (91%) with correct identification to species level. Eighteen discordant results (9%) were due to rarely encountered species, hence the difficulty in their identification using traditional phenotypic methods. MALDI-TOF MS enabled rapid, reliable and accurate identification of clinically important yeasts in a routine diagnostic microbiology laboratory. Isolates with rare, unusual or low probability identifications should be confirmed using robust molecular methods. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Short stature, unusual face, delta phalanx, and abnormal vertebrae and ribs in a girl born to half-siblings.

PubMed

Pogue, Robert; Marques, Felipe A; Kopacek, Cristiane; Rosa, Rosana C M; Dorfman, Luiza E; Mazzeu, Juliana F; Flores, José A M; Zen, Paulo R G; Rosa, Rafael F M

2017-05-01

Delta phalanx is a rare abnormality typically associated with additional features. We describe a patient with a phenotype resembling Catel-Manzke syndrome, but with delta phalanx and abnormal vertebrae and ribs. The patient was the only child of half siblings born with a marked prenatal growth deficiency. At 10 years of age, she had a short stature, long face, long and tubular nose with small alae nasi, high palate, short and broad thorax, and short index fingers with radial deviation. There were hyperpigmentations following Blaschko's lines. Radiology showed a proximal delta phalanx in the index finger of hands, abnormal vertebrae, and fused and small ribs. GTG-Banding karyotype and microarray analysis yielded normal results. Exome sequencing identified 25 genes that harbored homozygous variants, but none of these is assumed to be a good candidate to explain (part of) the phenotype. The here described patient may have a new condition, possibly following an autosomal recessive pattern of inheritance, although due to the high degree of consanguinity a compound etiology of the phenotype by variants in various genes may be present as well. © 2017 Wiley Periodicals, Inc.

Unravelling a biogeographical knot: origin of the 'leapfrog' distribution pattern of Australo-Papuan sooty owls (Strigiformes) and logrunners (Passeriformes).

PubMed

Norman, J A; Christidis, L; Joseph, L; Slikas, B; Alpers, D

2002-10-22

Molecular analysis of two Australo-Papuan rainforest birds exhibiting correlated 'leapfrog' patterns were used to elucidate the evolutionary origin of this unusual pattern of geographical differentiation. In both sooty owls (Tyto) and logrunners (Orthonyx), phenotypically similar populations occupy widely disjunct areas (central-eastern Australia and upland New Guinea) with a third, highly distinctive population, occurring between them in northeastern Queensland. Two mechanisms have been proposed to explain the origin of leapfrog patterns in avian distributions: recent shared ancestry of terminal populations and unequal rates or phenotypic change among populations. As the former should generate correlated patterns of phenotypic and genetic differentiation, we tested for a sister relationship between populations from New Guinea and central-eastern Australia using nuclear and mitochondrial DNA sequences. The resulting phylogenies not only refute recent ancestry as an explanation for the leapfrog pattern, but provide evidence of vastly different spatio-temporal histories for sooty owls and logrunners within the Australo-Papuan rainforests. This incongruence indicates that the evolutionary processes responsible for generating leapfrog patterns in these co-distributed taxa are complex, possibly involving a combination of selection and drift in sooty owls and convergence or retention of ancestral characteristics in logrunners.

Will phenotypic plasticity affecting flowering phenology keep pace with climate change?

PubMed

Richardson, Bryce A; Chaney, Lindsay; Shaw, Nancy L; Still, Shannon M

2017-06-01

Rising temperatures have begun to shift flowering time, but it is unclear whether phenotypic plasticity can accommodate projected temperature change for this century. Evaluating clines in phenological traits and the extent and variation in plasticity can provide key information on assessing risk of maladaptation and developing strategies to mitigate climate change. In this study, flower phenology was examined in 52 populations of big sagebrush (Artemisia tridentata) growing in three common gardens. Flowering date (anthesis) varied 91 days from late July to late November among gardens. Mixed-effects modeling explained 79% of variation in flowering date, of which 46% could be assigned to plasticity and genetic variation in plasticity and 33% to genetics (conditional R 2  = 0.79, marginal R 2  = 0.33). Two environmental variables that explained the genetic variation were photoperiod and the onset of spring, the Julian date of accumulating degree-days >5 °C reaching 100. The genetic variation was mapped for contemporary and future climates (decades 2060 and 2090), showing flower date change varies considerably across the landscape. Plasticity was estimated to accommodate, on average, a ±13-day change in flowering date. However, the examination of genetic variation in plasticity suggests that the magnitude of plasticity could be affected by variation in the sensitivity to photoperiod and temperature. In a warmer common garden, lower-latitude populations have greater plasticity (+16 days) compared to higher-latitude populations (+10 days). Mapped climatypes of flowering date for contemporary and future climates illustrate the wide breadth of plasticity and large geographic overlap. Our research highlights the importance of integrating information on genetic variation, phenotypic plasticity and climatic niche modeling to evaluate plant responses and elucidate vulnerabilities to climate change. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

How Reliable Are the Reported Genetic Associations in Disc Degeneration?: The Influence of Phenotypes, Age, Population Size, and Inclusion Sequence in 809 Patients.

PubMed

Rajasekaran, S; Kanna, Rishi Mugesh; Reddy, Ranjani Raja; Natesan, Senthil; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Kao, Patrick Y P; Yee, Anita; Shetty, Ajoy Prasad

2016-11-01

Prospective genetic association study. The aim of this study was to document the variations in the genetic associations, when different magnetic resonance imaging (MRI) phenotypes, age stratification, cohort size, and sequence of cohort inclusion are varied in the same study population. Genetic associations with disc degeneration have shown high inconsistency, generally attributed to hereditary factors and ethnic variations. However, the effect of different phenotypes, size of the study population, age of the cohort, etc have not been documented clearly. Seventy-one single-nucleotide polymorphisms (SNPs) of 41 candidate genes were correlated to six MRI markers of disc degeneration (annular tears, Pfirmann grading, Schmorl nodes, Modic changes, Total Endplate Damage score, and disc bulge) in 809 patients with back pain and/or sciatica. In the same study group, the correlations were then retested for different age groups, different sample, size and sequence of subject inclusion (first 404 and the second 405) and the differences documented. The mean age of population (M: 455, F: 354) was 36.7 ± 10.8 years. Different genetic associations were found with different phenotypes: disc bulge with three SNPs of CILP; annular tears with rs2249350 of ADAMTS5 and rs11247361 IGF1R; modic changes with VDR and MMP20; Pfirmann grading with three SNPs of MMP20 and Schmorl node with SNPs of CALM1 and FN1 and none with Total End Plate Score.Subgroup analysis based on three age groups and dividing the total population into two groups also completely changed the associations for all the six radiographic parameters. In the same study population, SNP associations completely change with different phenotypes. Variations in age, inclusion sequence, and sample size resulted in change of genetic associations. Our study questions the validity of previous studies and necessitates the need for standardizing the description of disc degeneration, phenotype selection, study sample size, age, and other variables in future studies. 4.

Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families.

PubMed

Liu, Yong-Jun; Rocha-Sanchez, Sonia M S; Liu, Peng-Yuan; Long, Ji-Rong; Lu, Yan; Elze, Leo; Recker, Robert R; Deng, Hong-Wen

2004-04-13

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (A/G), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.

Genetic and phenotypic variation along an ecological gradient in lake trout Salvelinus namaycush

USGS Publications Warehouse

Baillie, Shauna M.; Muir, Andrew M.; Hansen, Michael J.; Krueger, Charles C.; Bentzen, Paul

2016-01-01

BackgroundAdaptive radiation involving a colonizing phenotype that rapidly evolves into at least one other ecological variant, or ecotype, has been observed in a variety of freshwater fishes in post-glacial environments. However, few studies consider how phenotypic traits vary with regard to neutral genetic partitioning along ecological gradients. Here, we present the first detailed investigation of lake trout Salvelinus namaycushthat considers variation as a cline rather than discriminatory among ecotypes. Genetic and phenotypic traits organized along common ecological gradients of water depth and geographic distance provide important insights into diversification processes in a lake with high levels of human disturbance from over-fishing.ResultsFour putative lake trout ecotypes could not be distinguished using population genetic methods, despite morphological differences. Neutral genetic partitioning in lake trout was stronger along a gradient of water depth, than by locality or ecotype. Contemporary genetic migration patterns were consistent with isolation-by-depth. Historical gene flow patterns indicated colonization from shallow to deep water. Comparison of phenotypic (Pst) and neutral genetic variation (Fst) revealed that morphological traits related to swimming performance (e.g., buoyancy, pelvic fin length) departed more strongly from neutral expectations along a depth gradient than craniofacial feeding traits. Elevated phenotypic variance with increasing water depth in pelvic fin length indicated possible ongoing character release and diversification. Finally, differences in early growth rate and asymptotic fish length across depth strata may be associated with limiting factors attributable to cold deep-water environments.ConclusionWe provide evidence of reductions in gene flow and divergent natural selection associated with water depth in Lake Superior. Such information is relevant for documenting intraspecific biodiversity in the largest freshwater lake in the world for a species that recently lost considerable genetic diversity and is now in recovery. Unknown is whether observed patterns are a result of an early stage of incipient speciation, gene flow-selection equilibrium, or reverse speciation causing formerly divergent ecotypes to collapse into a single gene pool.

Genotyping in 46 patients with tentative diagnosis of Treacher Collins syndrome revealed unexpected phenotypic variation.

PubMed

Teber, Ozge Altug; Gillessen-Kaesbach, Gabriele; Fischer, Sven; Böhringer, Stefan; Albrecht, Beate; Albert, Angelika; Arslan-Kirchner, Mine; Haan, Eric; Hagedorn-Greiwe, Monika; Hammans, Christof; Henn, Wolfram; Hinkel, Georg Klaus; König, Rainer; Kunstmann, Erdmute; Kunze, Jürgen; Neumann, Luitgard M; Prott, Eva-Christina; Rauch, Anita; Rott, Hans-Dieter; Seidel, Heide; Spranger, Stephanie; Sprengel, Martin; Zoll, Barbara; Lohmann, Dietmar R; Wieczorek, Dagmar

2004-11-01

To define the range of phenotypic expression in Treacher Collins syndrome (TCS; Franceschetti-Klein syndrome), we performed mutation analysis in the TCOF1 gene in 46 patients with tentative diagnosis of TCS and evaluated the clinical data, including a scoring system. A total of 27 coding exons of TCOF1 and adjacent splice junctions were analysed by direct sequencing. In 36 patients with a clinically unequivocal diagnosis of TCS, we detected 28 pathogenic mutations, including 25 novel alterations. No mutation was identified in the remaining eight patients with unequivocal diagnosis of TCS and 10 further patients, in whom the referring diagnosis of TCS was clinically doubtful. There is no overt genotype-phenotype correlation except that conductive deafness is significantly less frequent in patients with mutations in the 3' part of the open reading frame. Inter- and intrafamilial variation is wide. Some mutation carriers, parents of typically affected patients, are so mildly affected that the diagnosis might be overlooked clinically. This suggests that modifying factors are important for phenotypic expression. Based on these findings, minimal diagnostic criteria were defined: downward slanting palpebral fissures and hypoplasia of the zygomatic arch. The difficulties in genetic counselling, especially diagnosis of family members with a mild phenotype, are described.

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

PubMed Central

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons. PMID:27698666

The influence of gene flow and drift on genetic and phenotypic divergence in two species of Zosterops in Vanuatu

PubMed Central

Clegg, Sonya M.; Phillimore, Albert B.

2010-01-01

Colonization of an archipelago sets the stage for adaptive radiation. However, some archipelagos are home to spectacular radiations, while others have much lower levels of diversification. The amount of gene flow among allopatric populations is one factor proposed to contribute to this variation. In island colonizing birds, selection for reduced dispersal ability is predicted to produce changing patterns of regional population genetic structure as gene flow-dominated systems give way to drift-mediated divergence. If this transition is important in facilitating phenotypic divergence, levels of genetic and phenotypic divergence should be associated. We consider population genetic structure and phenotypic divergence among two co-distributed, congeneric (Genus: Zosterops) bird species inhabiting the Vanuatu archipelago. The more recent colonist, Z. lateralis, exhibits genetic patterns consistent with a strong influence of distance-mediated gene flow. However, complex patterns of asymmetrical gene flow indicate variation in dispersal ability or inclination among populations. The endemic species, Z. flavifrons, shows only a partial transition towards a drift-mediated system, despite a long evolutionary history on the archipelago. We find no strong evidence that gene flow constrains phenotypic divergence in either species, suggesting that levels of inter-island gene flow do not explain the absence of a radiation across this archipelago. PMID:20194170

In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites.

PubMed

Irizarry, Kristopher J L; Bryden, Randall L

2016-01-01

Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1) that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus . Our results provide insight into pigment phenotypes in pythons.