Amount Of Phenotypic Variation Research Articles

Erratum: High-Throughput Identification of Resistance to Pseudomonas syringae pv. Tomato in Tomato using Seedling Flood Assay.

Erratum: High-Throughput Identification of Resistance to Pseudomonas syringae pv. Tomato in Tomato using Seedling Flood Assay.

Univariate and multivariate plasticity in response to incubation temperature in an Australian lizard.

Environments, particularly developmental environments, can generate a considerable amount of phenotypic variation through phenotypic plasticity. Plasticity in response to incubation temperature is well characterised in egg-laying reptiles. However, traits do not always vary independently of one another, and studies encompassing a broad range of traits spanning multiple categories are relatively rare but crucial to better understand whole-organism responses to environmental change, particularly if covariation among traits may constrain plasticity. In this study, we investigated multivariate plasticity in response to incubation across three temperatures in the delicate skink, Lampropholis delicata, and whether this was affected by covariation among traits. At approximately 1month of age, a suite of growth, locomotor performance, thermal physiology and behavioural traits were measured. Plasticity in the multivariate phenotype of delicate skinks was distinct for different incubation temperatures. Cool temperatures drove shifts in growth, locomotor performance and thermal physiology, while hot temperatures primarily caused changes in locomotor performance and behaviour. These differences are likely due to variation in thermal reaction norms, as there was little evidence that covariation among traits or phenotypic integration influenced plasticity, and there was no effect of incubation temperature on the direction or strength of covariation. While there were broad themes in terms of which trait categories were affected by different incubation treatments, traits appeared to be affected independently by developmental temperature. Comparing reaction norms of a greater range of traits and temperatures will enable better insight into these patterns among trait categories, as well as the impacts of environmental change.

Multivariate analyses of Ethiopian durum wheat revealed stable and high yielding genotypes.

Improving crop adaptation and stability across diverse and changing environmental conditions is essential to increasing grain yield per unit area. In turn, this contributes to meeting the increasing global food demand. Nevertheless, a number of factors challenge the efficiency of crop improvement programs, of which genotype-by-environment interaction (GEI) is one of the major factors. This study aimed to evaluate the performance and phenotypic stability of 385 Ethiopian durum wheat landraces and 35 cultivars; assess the pattern of genotype by environment interaction (GEI) effect, and identify stable and high-yielding landraces or cultivars using the additive main effect and multiplicative interaction (AMMI) and genotype main effect plus genotype by environment interaction biplot (GGE-biplot). The experiment was laid out in an alpha lattice design with two replications at five test sites (Akaki, Chefe Donsa, Holeta, Kulumsa, and Sinana). The combined analysis of variance revealed highly significant effects (P ≤ 0.01) of environments (E), genotype (G), and GEI on a phenotypic variation of traits evaluated, including grain yield. For all traits, the amount of phenotypic variance and GEI explained by the GGE biplot was higher than in AMMI2, but both exhibited significant effects of E and GEI on the genotypes. The AMMI model identified G169, G420, G413, G139, G415, G416, G417, and G418 as stable genotypes across testing sites. Whereas, the GGE biplot identified G169, G420, G415, G139, G106, G412, G413, and G417 as both high-yielding and stable across test sites. Hence, genotypes identified as stable and high yielding in the present study could be used in a durum wheat breeding program aimed at identifying genes and molecular markers associated with the crop’s productivity traits as well as developing stable and high-yielding cultivars for use in East Africa and beyond.

46,XX/46,XY Chimerism & Human Sexual Development

The term chimera refers to an organism with cell lines from two or more distinct zygotes. Human chimerism may occur naturally or artificially. Although rare, advancements in genetics and genomics have resulted in the identification of additional natural human chimeras. Three forms of naturally occurring chimerism have been documented in humans: blood group chimerism, microchimerism, and fusion chimerism. Fusion chimerism may occur through several means. Sex-chromosome discordant chimerism refers to individuals with both XX and XY cell lines. There is a large amount of phenotypic variability among 46,XX/46,XY chimeric individuals. The care of people with intersex traits or DSD (Disorders of Sexual Development) is controversial due in part to a history of unnecessary surgical intervention and power-imbalances between the intersex and medical communities. As more 46,XX/46,XY chimeric individuals with intersex traits or DSD are identified, the implications for their care will need to be clarified.

Genome-wide association studies dissect the genetic architecture of seed shape and size in common bean.

Seed weight and size are important yield components. Thus, selecting for large seeds has been a key objective in crop domestication and breeding. In common bean, seed shape is also important since it influences industrial processing and plays a vital role in determining the choices of consumers and farmers. In this study, we performed genome-wide association studies on a core collection of common bean accessions to dissect the genetic architecture and identify genomic regions associated with seed morphological traits related to weight, size, and shape. Phenotypic data were collected by high-throughput image-based approaches, and utilized to test associations with 10,362 single-nucleotide polymorphism markers using multilocus mixed models. We searched within genome-associated regions for candidate genes putatively involved in seed phenotypic variation. The collection exhibited high variability for the entire set of seed traits, and the Andean gene pool was found to produce larger, heavier seeds than the Mesoamerican gene pool. Strong pairwise correlations were verified for most seed traits. Genome-wide association studies identified marker–trait associations accounting for a considerable amount of phenotypic variation in length, width, projected area, perimeter, and circularity in 4 distinct genomic regions. Promising candidate genes were identified, e.g. those encoding an AT-hook motif nuclear-localized protein 8, type 2C protein phosphatases, and a protein Mei2-like 4 isoform, known to be associated with seed size and weight regulation. Moreover, the genes that were pinpointed are also good candidates for functional analysis to validate their influence on seed shape and size in common bean and other related crops.

P–374 Investigating causality of risk factors for miscarriage – a Mendelian randomization analysis

Abstract Study question Do modifiable risk factors such as smoking, alcohol or coffee consumption, and adiposity causally increase the risk of sporadic or recurrent miscarriage? Summary answer We found evidence for a causal relationship between smoking initiation and sporadic miscarriage, but not for any other risk factor tested. What is known already Miscarriage is estimated to end between 10–25% of clinically confirmed pregnancies, and many observational studies have suggested numerous lifestyle factors, such as coffee and alcohol consumption, smoking and increased adiposity, may increase miscarriage risk. However, results are not always consistent across studies, and definitive causal relationships between various risk factors and miscarriage have not yet been demonstrated. Mendelian randomization utilizes genetic variants significantly associated with heritable risk factors (i.e. at P-values <5x10–8 in large genome-wide association studies) as instrumental variables to investigate causality of risk factors in population health outcomes. Study design, size, duration We conducted two-sample Mendelian randomization analyses to investigate causality of smoking (initiation and quantity), alcohol and coffee consumption (quantity), and adiposity (body mass index and waist-hip ratio) in sporadic and recurrent miscarriage. Data included in this study were taken from previously published summary genetic association statistics (betas, standard errors and P-values) from large-scale genome-wide association studies (GWAS) for each risk factor, and from our recently published GWAS of sporadic and recurrent miscarriage. Participants/materials, setting, methods Instrumental variables were constructed using 5–306 genetic variants significantly associated with the listed risk factors in published GWAS (minimum N = 178,000 individuals). Two instrumental variables were constructed per risk factor using data from different GWAS. Associations of the instrumental variables with miscarriage were investigated using summary association data from women of European ancestry included in our miscarriage GWAS, including 49,996 sporadic miscarriage cases and 174,109 female controls, and 750 recurrent miscarriage cases and 150,215 female controls. Main results and the role of chance We found a significant association between sporadic miscarriage and the instrumental variables for two smoking measures: smoking initiation (inverse variance weighted Odds Ratio = 1.17, 95% confidence intervals = 1.10–1.24, P = 2.7 x 10–07) and lifetime smoking (inverse variance weighted Odds Ratio = 1.22, 95% confidence intervals 1.11–1.35, P = 4.2x10–5). No other risk factors (smoking quantity, coffee or alcohol consumption, or BMI or waist-hip ratio) were associated with either sporadic or recurrent miscarriage. A priori power calculations considering the amount of phenotypic variance in each risk factor explained by the associated SNPs suggested our analysis to have at least 75% power to detect an association with Odds Ratio of 1.2 with sporadic miscarriage for analyses of body mass index, waist hip ratio and smoking initiation, quantity and the lifetime smoking measure, but that the alcohol and coffee consumption analyses were underpowered (4.9% and 48%, respectively). All analyses were underpowered for recurrent miscarriage given the small case sample size (N = 750). Limitations, reasons for caution While data utilised here come from large-scale GWAS including 1000s of individuals, genetic variants significantly associated with each risk factor currently explain small percentages (0.02–6%) of the variance in each trait. Larger GWAS for specific risk factors, and for sporadic and recurrent miscarriage, are required to clarify some published associations. Wider implications of the findings: We find no evidence of a causal link between adiposity and miscarriage, indicating that observational findings of increased miscarriage risk with increasing body mass index require further explanation. Significant associations between measures of ever-smoking and sporadic miscarriage highlights that no amount of smoking is safe in regards to miscarriage risk. Trial registration number Not applicable

The relationships among sire’s predicted transmitting ability for daughter pregnancy rate and cow conception rate and daughter’s reproductive performance in Canadian Holstein cows

The objectives of this study were to (1) characterize the variability for sire’s predicted transmitting ability (PTA) for daughter’s pregnancy rate (DPR) and cow conception rate (CCR), (2) determine the relationships among sire’s PTA for DPR, sire’s PTA for CCR, daughter’s parity, and daughter’s 305-d mature-equivalent (ME) milk production, and (3) evaluate the associations among sire’s PTA for DPR and CCR and daughter’s reproductive performance [pregnancy to first artificial insemination (P/AI), pregnancy by 150 d in milk (PR150) and pregnancy loss (PL) after first AI] in Canadian Holstein cows. The data were obtained from 822 lactating Holstein cows from 10 commercial dairy herds located in Alberta. Overall mean (range) for sire’s PTA for DPR and CCR was −0.09 (−9.6 to 8.2) and −0.05 (−9.9 to 7.4), respectively. Sire’s PTA for DPR was strongly and positively associated with sire’s PTA for CCR (r = 0.89; P < 0.01). Sire’s PTA for DPR and CCR were weakly and negatively associated with parity (r = −0.15 and −0.17, respectively; P < 0.01); however, the amount of phenotypic variation in sire’s PTA for DPR and CCR explainable by parity was small (coefficient of determination; R2 = 0.02). The daughter’s 305-d ME milk production tended to be weakly but positively associated with sire’s PTA for DPR (r = 0.06; P = 0.07) and CCR (r = 0.06; P = 0.10); however, the amount of phenotypic variation in daughter’s 305-d ME milk production explainable by changes in sire’s PTA for DPR or CCR was small (R2 = 0.004 and 0.003, respectively). Overall P/AI, PR150 and PL were 38, 65 and 12%, respectively. Sire’s PTA for DPR tended to be associated with P/AI (P = 0.08) but was significantly associated with PR150 (P = 0.03). For every unit increase in sire’s PTA for DPR, the estimated probabilities for P/AI and PR150 increased by 6.2 and 7.5%, respectively. Sire’s PTA for CCR was not associated with P/AI or PR150. Neither sire’s PTA for DPR nor CCR were associated with PL. In summary, sire’s PTA for DPR and CCR were highly variable and positively correlated. Sire’s PTA for DPR was associated with daughter’s P/AI and PR150, but sire’s PTA for CCR was not associated with any of the measured reproductive outcomes. Therefore, selecting sires with high PTA for DPR has the potential to improve the reproductive efficiency of Canadian dairy herds.

Unraveling the genetic architecture for carbon and nitrogen related traits and leaf hydraulic conductance in soybean using genome-wide association analyses

BackgroundDrought stress is a major limiting factor of soybean [Glycine max (L.) Merr.] production around the world. Soybean plants can ameliorate this stress with improved water-saving, sustained N2 fixation during water deficits, and/or limited leaf hydraulic conductance. In this study, carbon isotope composition (δ13C), which can relate to variation in water-saving capability, was measured. Additionally, nitrogen isotope composition (δ15N) and nitrogen concentration that relate to nitrogen fixation were evaluated. Decrease in transpiration rate (DTR) of de-rooted soybean shoots in a silver nitrate (AgNO3) solution compared to deionized water under high vapor pressure deficit (VPD) conditions was used as a surrogate measurement for limited leaf hydraulic conductance. A panel of over 200 genetically diverse soybean accessions genotyped with the SoySNP50K iSelect BeadChips was evaluated for the carbon and nitrogen related traits in two field environments (Athens, GA in 2015 and 2016) and for transpiration response to AgNO3 in a growth chamber. A multiple loci linear mixed model was implemented in FarmCPU to perform genome-wide association analyses for these traits.ResultsThirty two, 23, 26, and nine loci for δ13C, δ15N, nitrogen concentration, and transpiration response to AgNO3, respectively, were significantly associated with these traits. Candidate genes that relate to drought stress tolerance enhancement or response were identified near certain loci that could be targets for improving and understanding these traits. Soybean accessions with favorable breeding values were also identified. Low correlations were observed between many of the traits and the genetic loci associated with each trait were largely unique, indicating that these drought tolerance related traits are governed by different genetic loci.ConclusionsThe genomic regions and germplasm identified in this study can be used by breeders to understand the genetic architecture for these traits and to improve soybean drought tolerance. Phenotyping resources needed, trait heritability, and relationship to the target environment should be considered before deciding which of these traits to ultimately employ in a specific breeding program. Potential marker-assisted selection efforts could focus on loci which explain the greatest amount of phenotypic variation for each trait, but may be challenging due to the quantitative nature of these traits.

Genetic variation of HvXYN1 associated with endoxylanase activity and TAX content in barley (Hordeum vulgare L.)

BackgroundEndo-β-1,4-xylanase1 (EA), the key endoxylanase in plants, is involved in the degradation of arabinoxylan during grain germination. In barley (Hordeum vulgare L.), one gene (HvXYN-1) that encode a endo-beta-1,4-xylanase, has been cloned. However, the single nucleotide polymorphisms (SNPs) that affect the endoxylanase activity and total arabinoxylan (TAX) content have yet to be characterized. The investigation of genetic variation in HvXYN1 may facilitate a better understanding of the relationship between TAX content and EA activity in barley.ResultsIn the current study, 56 polymorphisms were detected in HvXYN1 among 210 barley accessions collected from 34 countries, with 10 distinct haplotypes identified. The SNPs at positions 110, 305, 1045, 1417, 1504, 1597, 1880 bp in the genomic region of HvXYN1 were significantly associated with EA activity (P < 0.0001), and the sites 110, 305, and 1045 were highly significantly associated with TAX content. The amount of phenotypic variation in a given trait explained by each associated polymorphism ranged from 6.96 to 9.85%. Most notably, we found two variants at positions 1504 bp and 1880 bp in the second exon that significantly (P < 0.0001) affected EA activity; this result could be used in breeding programs to improve beer quality. In addition, African accessions had the highest EA activity and TAX content, and the richest germplasm resources were from Asia, indicating the high potential value of Asian barley.ConclusionThis study provided insight into understanding the relationship, EA activity, TAX content with the SNPs of HvXYN1 in barley. These SNPs can be applied as DNA markers in breeding programs to improve the quality of barley for beer brewing after further validation.

English

The objectives of this study were to assess phenotypic diversity of Bambara groundnut germplasm from C&ocirc;te d&rsquo;Ivoire using qualitative traits and to understand the genetic diversity at different levels. Hundred and one accessions collected from four agro-ecological zones (central, eastern, northern, western) were characterized in a randomised complete block design with three replications. Thirteen qualitative traits were recorded from seedling emergence to physiological maturity of the crop species. All recorded traits were found to be polymorphic with three or four phenotypic classes. The results revealed a considerable amount of phenotypic variation in the germplasm studied. The phenotypic variation was expressed in color, shape, texture, flexibility, growth habit, pilosity and hardness in both the aerial organs and the underground pods. Cluster analysis grouped together accessions into six genetically distinct groups independently to their geographical origin, suggesting seeds exchanges between growing-zones. The chi-square analysis highlighted the presence of phenotypic variability within and between accessions from each agro-climatic zone for most of the traits evaluated indicating some adaptive forms related to the four zones. Estimates of Shanon-Weaver diversity index (H&rsquo;) for all agro-climatic zones ranged from 0.32 to 0.66 with a mean of 0.46. The northern zone appeared phenotypically more diversified (H&#39; = 0.66) than the others. These results are useful to ensure efficient germplasm collection, conservation and management strategies. &nbsp; Key words: Bambara groundnut, accession, agroclimatic zones, phenotypic diversity, qualitative traits.

Neutral Genetic and Phenotypic Variation within and among Isolated Headwater Populations of Brook Trout

AbstractIsolated populations are challenging to manage and conserve, as they are particularly vulnerable to genetic drift, allelic fixation, and inbreeding and may express markedly reduced phenotypic variability. We sought to improve our understanding of how spatial isolation, occupancy range, and restricted gene flow influence contemporary phenotypic variation within and among native populations of Brook Trout Salvelinus fontinalis by examining the neutral genetic and phenotypic characteristics of 35 isolated headwater populations from Great Smoky Mountains National Park. Across a suite of 13 neutral microsatellite loci, we observed high levels of allelic fixation and considerable genetic differentiation among populations, subwatersheds, and watersheds that were consistent with patterns of isolation. We found significant positive correlations between allelic diversity and estimates of effective population size. In contrast, we observed considerably less phenotypic structure among streams, subwatersheds, and watersheds. Much of the observed phenotypic variation occurred among individuals within populations. Pairwise Mann–Whitney tests revealed no significant phenotypic differences among the populations of Brook Trout we examined. Similarly, there was no significant relationship between the amount of phenotypic variation within populations and any of the examined measures of genetic diversity or the amount of occupied habitat sampled, which suggests that unmeasured variables may be influencing morphometric and meristic variation within isolated populations. The observed patterns of isolation, genetic drift, and allelic fixation highlight the importance of enhancing population connectivity but also suggest that considerable phenotypic variability may persist within small, fragmented populations. Our results elucidate some challenges associated with managing and conserving isolated populations of Brook Trout and reinforce the importance of conducting genetic studies on fragmented populations to inform management decisions.

Abstract 2778: Shared genetics of breast cancer risk factors across life stages

Abstract Breast cancer clusters in families and many of its established risk factors are under strong genetic control. Understanding the genetic architecture shared by breast cancer risk factors highlight the causal pathways through which these risk factors affect breast cancer risk. Traditionally, pedigree studies are used to estimate genetic correlations between complex traits but such estimates can be confounded by shared environmental factors. Recent methodological developments make it possible to estimate disease heritability and genetic correlations using data from genome-wide association studies (GWAS). We used GWAS of unrelated individuals to estimate the proportion of variance in breast cancer risk factors that can be explained by GWAS SNPs. We also quantified the shared genetic contribution to all pairs of the following traits: body mass index (BMI), gender-specific BMI, height, age at menarche, age at natural menopause, and childhood body fatness. We obtained GWAS and phenotypic information from a total of 20,769 subjects from the Nurses’ Health Study I &amp; II, Health Professional Follow-up Study, and Physician Health study. Using linear mixed models, we estimated single trait heritability and genetic correlation between two traits. We observed a significant amount of phenotypic variation explained by genotyped SNPs for all traits except age at natural menopause (hg2 = 0.15, se = 0.09). Heritability ranged from 0.18 (se = 0.004) for childhood body fatness to 0.35 (se = 0.05) for age at menarche. We found significant negative genetic correlation between adult BMI and height (corr = -0.20; se = 0.07, pvalue = 0.005), BMI and age at menarche (corr = -0.50; se = 0.07, pvalue = 8.8×10e-8), and age at menarche and childhood body fatness (corr = -0.57, se = 0.12, pvalue = 2.8×10e-6). We observed a positive genetic correlation between adult BMI and childhood body fatness (corr = 0.59, se = 0.12, pvalue = 8.0×10e-8) and such correlation is statistically different from 0 and 1, implying only a partially shared genetic signature between these two traits. The genetics underlying BMI in men and women were highly correlated (corr = 0.84, se = 0.26, pvalue = 9.7×10e-4). In addition, we found no significant shared genetic components between age at natural menopause and any of the traits, suggesting a different genetic architecture underlying the mechanism of menopause in comparison with other breast cancer risk factors. Using genome-wide SNP data in unrelated individuals to estimate heritability helps eliminate possible influence from unmeasured shared environmental factors that is commonly seen in family studies. Our findings improve the understanding of shared genetic architecture of breast cancer risk factors and provide important insights in breast cancer etiology. Citation Format: Chi Gao, Rulla M. Tamimi, Peter Kraft, Sara Lindstrom. Shared genetics of breast cancer risk factors across life stages. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2778. doi:10.1158/1538-7445.AM2015-2778

Impact of domestication on the phenotypic architecture of durum wheat under contrasting nitrogen fertilization.

The process of domestication has led to dramatic morphological and physiological changes in crop species due to adaptation to cultivation and to the needs of farmers. To investigate the phenotypic architecture of shoot- and root-related traits and quantify the impact of primary and secondary domestication, we examined a collection of 36 wheat genotypes under optimal and nitrogen-starvation conditions. These represented three taxa that correspond to key steps in the recent evolution of tetraploid wheat (i.e. wild emmer, emmer, and durum wheat). Overall, nitrogen starvation reduced the shoot growth of all genotypes, while it induced the opposite effect on root traits, quantified using the automated phenotyping platform GROWSCREEN-Rhizo. We observed an overall increase in all of the shoot and root growth traits from wild emmer to durum wheat, while emmer was generally very similar to wild emmer but intermediate between these two subspecies. While the differences in phenotypic diversity due to the effects of primary domestication were not significant, the secondary domestication transition from emmer to durum wheat was marked by a large and significant decrease in the coefficient of additive genetic variation. In particular, this reduction was very strong under the optimal condition and less intense under nitrogen starvation. Moreover, although under the optimal condition both root and shoot traits showed significantly reduced diversity due to secondary domestication, under nitrogen starvation the reduced diversity was significant only for shoot traits. Overall, a considerable amount of phenotypic variation was observed in wild emmer and emmer, which could be exploited for the development of pre-breeding strategies.

A genome-wide association analysis for porcine serum lipid traits reveals the existence of age-specific genetic determinants.

BackgroundThe genetic determinism of blood lipid concentrations, the main risk factor for atherosclerosis, is practically unknown in species other than human and mouse. Even in model organisms, little is known about how the genetic determinants of lipid traits are modulated by age-specific factors. To gain new insights into this issue, we have carried out a genome-wide association study (GWAS) for cholesterol (CHOL), triglyceride (TRIG) and low (LDL) and high (HDL) density lipoprotein concentrations measured in Duroc pigs at two time points (45 and 190 days).ResultsAnalysis of data with mixed-model methods (EMMAX, GEMMA, GenABEL) and PLINK showed a low positional concordance between trait-associated regions (TARs) for serum lipids at 45 and 190 days. Besides, the proportion of phenotypic variance explained by SNPs at these two time points was also substantially different. The four analyses consistently detected two regions on SSC3 (124 Mb, CHOL and LDL at 190 days) and SSC6 (135 Mb, CHOL and TRIG at 190 days) with highly significant effects on the porcine blood lipid profile. Moreover, we have found that SNP variation within SSC3, SSC6, SSC10, SSC13 and SSC16 TARs is associated with the expression of several genes mapping to other chromosomes and related to lipid metabolism.ConclusionsOur data demonstrate that the effects of genomic determinants influencing lipid concentrations in pigs, as well as the amount of phenotypic variance they explain, are influenced by age-related factors.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-758) contains supplementary material, which is available to authorized users.

OP017 Cross-disease study determines extent of sharing of associated loci between five seronegative auto-inflammatory diseases

of genetic risk factors, including these 14 novel loci, were common to both European and non-European IBD. However, the amount of phenotypic variance explained by these loci between populations was clearly heterogeneous, driven by a combination of differences in effect size and allele frequency. Phenotype data was available for 3,986 non-European and 47,799 European patients. There was a male predominance for Crohn’s disease (69% vs 45%), more ileocolonic disease (54% vs. 39%) and lower colectomy rates in UC (4% vs 18%) in nonEuropean than European populations. Conclusions: In this largest study to date of genetic risk factors underlying non-European IBD, we identified 14 novel IBD loci increasing the total number of IBD loci to 177. There is pervasive sharing of genetic risk factors between different ethnicities; Despite shared genetics, the relative contributions for individual genes to the variance explained differ between ethnicities. Overall the clinical characteristics are remarkably similar between different ethnicities. The presented similarities and dissimilarities between populations add to the heterogeneity of IBD.

Body composition and gene expression QTL mapping in mice reveals imprinting and interaction effects

BackgroundShifts in body composition, such as accumulation of body fat, can be a symptom of many chronic human diseases; hence, efforts have been made to investigate the genetic mechanisms that underlie body composition. For example, a few quantitative trait loci (QTL) have been discovered using genome-wide association studies, which will eventually lead to the discovery of causal mutations that are associated with tissue traits. Although some body composition QTL have been identified in mice, limited research has been focused on the imprinting and interaction effects that are involved in these traits. Previously, we found that Myostatin genotype, reciprocal cross, and sex interacted with numerous chromosomal regions to affect growth traits.ResultsHere, we report on the identification of muscle, adipose, and morphometric phenotypic QTL (pQTL), translation and transcription QTL (tQTL) and expression QTL (eQTL) by applying a QTL model with additive, dominance, imprinting, and interaction effects. Using an F2 population of 1000 mice derived from the Myostatin-null C57BL/6 and M16i mouse lines, six imprinted pQTL were discovered on chromosomes 6, 9, 10, 11, and 18. We also identified two IGF1 and two Atp2a2 eQTL, which could be important trans-regulatory elements. pQTL, tQTL and eQTL that interacted with Myostatin, reciprocal cross, and sex were detected as well. Combining with the additive and dominance effect, these variants accounted for a large amount of phenotypic variation in this study.ConclusionsOur study indicates that both imprinting and interaction effects are important components of the genetic model of body composition traits. Furthermore, the integration of eQTL and traditional QTL mapping may help to explain more phenotypic variation than either alone, thereby uncovering more molecular details of how tissue traits are regulated.

Don'T fall off the adaptation cliff: when asymmetrical fitness selects for suboptimal traits.

The cliff-edge hypothesis introduces the counterintuitive idea that the trait value associated with the maximum of an asymmetrical fitness function is not necessarily the value that is selected for if the trait shows variability in its phenotypic expression. We develop a model of population dynamics to show that, in such a system, the evolutionary stable strategy depends on both the shape of the fitness function around its maximum and the amount of phenotypic variance. The model provides quantitative predictions of the expected trait value distribution and provides an alternative quantity that should be maximized (“genotype fitness”) instead of the classical fitness function (“phenotype fitness”). We test the model's predictions on three examples: (1) litter size in guinea pigs, (2) sexual selection in damselflies, and (3) the geometry of the human lung. In all three cases, the model's predictions give a closer match to empirical data than traditional optimization theory models. Our model can be extended to most ecological situations, and the evolutionary conditions for its application are expected to be common in nature.

Familial Nonsyndromic Patent Ductus Arteriosus Caused by Mutations in TFAP2B

Patent ductus arteriosus (PDA) is a common congenital heart disease that develops soon after birth when the arterial duct does not remodel. Mutations in TFAP2B, which encodes a neural crest-derived transcription factor, can cause Char syndrome, characterized by PDA, facial dysmorphism, and skeletal abnormalities of the hand. The TFAP2B mutations result in a great amount of phenotypic variability, and a novel TFAP2B mutation has been found in patients with nonsyndromic PDA. Therefore, this study investigated whether TFAP2B mutations can cause familial nonsyndromic PDA. Clinical data and peripheral blood specimens were collected from two kindreds (A and B) and from a cohort of 100 unrelated subjects with PDA. Kindred A spanned three generations, in which 5 of the 16 individuals had PDA, and kindred B spanned three generations, in which 2 of the 13 individuals had PDA. The study enrolled 100 unrelated healthy individuals as control subjects. Polymerase chain reaction (PCR) was used to amplify seven exons and flanking introns of the TFAP2B gene. A few exons of the TFAP2B gene were amplified using reverse transcription polymerase chain reaction (RT-PCR), and direct forward and reverse sequencing of the PCR products was performed. The acquired sequences were aligned with those in GenBank by using a basic local alignment search tool (BLAST). The following two types of mutations were identified in TFAP2B: c.601+5G>A and c.435_438delCCGG. The mutation c.601+5G>A was detected in the affected members of kindred A. Nested PCR showed a splice junction in intron 3 and a 61-bp deletion in exon 3. The mutation c.435_438delCCGG, found in the affected members of kindred B, was caused by a four-base deletion in exon 2, which in turn caused a frame shift that resulted in the formation of a premature stop codon, p.Arg145Argfsx45. None of these mutations was detected in the unaffected members of the kindred or in the control group. Furthermore, two novel single-nucleotide polymorphisms (SNPs), c.1-34G>A and c.539+62G>C, were detected in the introns. The variant c.1-34G>A was identified 34bp upstream of the transcription initiation site in the TFAP2B gene. Significant differences in the prevalence of the alleles G and A were observed in the control subjects and PDA patients (Z=-2.513, P=0.012). The study identified that another variant was c.539+62G>C but that the frequency of this variant was similar between the control subjects and the PDA patients (Z=-0.332, P=0.74). The TFAP2B mutations may be associated with isolated nonsyndromic, hereditary PDA in Chinese families. The authors propose that a TFAP2B mutation should be considered a risk factor for isolated PDA. However, the detailed genetic mechanism underlying nonsyndromic the PDA-causing TFAP2B mutation is yet to be elucidated.

Consequences of intraspecific niche variation: phenotypic similarity increases competition among recently metamorphosed frogs

Phenotype is often correlated with resource use, which suggests that as phenotypic variation in a population increases, intraspecific competition will decrease. However, few studies have experimentally tested the prediction that increased intraspecific phenotypic variation leads to reduced competitive effects (e.g., on growth rate, survival or reproductive rate). We investigated this prediction with two experiments on wood frogs (Rana sylvatica). In the first experiment, we found that a frog's size was positively correlated with the size of its preferred prey, indicating that the feeding niche of the frogs changed with size. In the second experiment, we used an experimental design in which we held the initial mass of "focal" frogs constant, but varied the initial mass of their competitors. We found a significant quadratic effect of the average mass of competitors: focal frog growth was lowest when raised with similar-sized competitors, and highest when raised with competitors that were larger or smaller. Our results demonstrate that growth rates increase (i.e., competitive intensity decreases) when individuals are less similar to other members of the population and exhibit less overlap in resource use. Thus, changes in the amount of phenotypic variation in a population may ultimately affect population-level processes, such as population growth rate and extinction risk.

GWAPower: a statistical power calculation software for genome-wide association studies with quantitative traits

BackgroundIn designing genome-wide association (GWA) studies it is important to calculate statistical power. General statistical power calculation procedures for quantitative measures often require information concerning summary statistics of distributions such as mean and variance. However, with genetic studies, the effect size of quantitative traits is traditionally expressed as heritability, a quantity defined as the amount of phenotypic variation in the population that can be ascribed to the genetic variants among individuals. Heritability is hard to transform into summary statistics. Therefore, general power calculation procedures cannot be used directly in GWA studies. The development of appropriate statistical methods and a user-friendly software package to address this problem would be welcomed.ResultsThis paper presents GWAPower, a statistical software package of power calculation designed for GWA studies with quantitative traits, where genetic effect is defined as heritability. Based on several popular one-degree-of-freedom genetic models, this method avoids the need to specify the non-centrality parameter of the F-distribution under the alternative hypothesis. Therefore, it can use heritability information directly without approximation. In GWAPower, the power calculation can be easily adjusted for adding covariates and linkage disequilibrium information. An example is provided to illustrate GWAPower, followed by discussions.ConclusionsGWAPower is a user-friendly free software package for calculating statistical power based on heritability in GWA studies with quantitative traits. The software is freely available at: http://dl.dropbox.com/u/10502931/GWAPower.zip