Sources of Fungal Genetic Variation and Associating It with Phenotypic Diversity

Abstract Background Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, economically important traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing.Results A total of 1,747,604 CNVs were detected in this study, and 7,228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4,307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1,855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection.Conclusions In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

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Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders

Blood ◽

10.1182/blood-2007-06-095703 ◽

2008 ◽

Vol 111 (5) ◽

pp. 2785-2789 ◽

Cited By ~ 106

Author(s):

Animesh Pardanani ◽

Brooke L. Fridley ◽

Terra L. Lasho ◽

D. Gary Gilliland ◽

Ayalew Tefferi

Keyword(s):

Genetic Variation ◽

Odds Ratio ◽

Phenotypic Diversity ◽

Primary Myelofibrosis ◽

Myeloproliferative Disorders ◽

Single Nucleotide ◽

Disease Allele ◽

Phenotype Analysis ◽

Host Genetic ◽

Stimulating Factor

JAK2V617F is an acquired mutation associated with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We tested the hypothesis that the paradox of a single disease allele associated with 3 distinctive clinical phenotypes could be explained in part by host-modifying influences. We screened for genetic variation within 4 candidate genes involved in JAK-STAT signaling, including receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony-stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 white patients: 84 had PV, 58 had PMF, and 37 had ET. Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF. Three additional JAK2 SNPs (rs10758669, rs3808850, and rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with ET or PMF. Finally, intragene haplotypes in JAK2 were significantly associated with PV only. Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele.

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MSH1-Induced Non-Genetic Variation Provides a Source of Phenotypic Diversity in Sorghum bicolor

PLoS ONE ◽

10.1371/journal.pone.0108407 ◽

2014 ◽

Vol 9 (10) ◽

pp. e108407 ◽

Cited By ~ 24

Author(s):

Roberto de la Rosa Santamaria ◽

Mon-Ray Shao ◽

Guomei Wang ◽

David O. Nino-Liu ◽

Hardik Kundariya ◽

...

Keyword(s):

Genetic Variation ◽

Sorghum Bicolor ◽

Phenotypic Diversity

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Human genetic variation within neural crest enhancers: molecular and phenotypic implications

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0360 ◽

2013 ◽

Vol 368 (1620) ◽

pp. 20120360 ◽

Cited By ~ 12

Author(s):

Alvaro Rada-Iglesias ◽

Sara L. Prescott ◽

Joanna Wysocka

Keyword(s):

Genetic Variation ◽

Neural Crest ◽

Phenotypic Diversity ◽

Regulatory Elements ◽

Embryonic Cell ◽

Human Genetic Variation ◽

Nucleotide Polymorphisms ◽

Cooperative Relationships ◽

Developmental Gene Expression ◽

Genome Wide

Developmental gene expression programmes are coordinated by the specialized distal cis -regulatory elements called enhancers, which integrate lineage- and signalling-dependent inputs to guide morphogenesis. In previous work, we characterized the genome-wide repertoire of active enhancers in human neural crest cells (hNCC), an embryonic cell population with critical roles in craniofacial development. We showed that in hNCC, co-occupancy of a master regulator TFAP2A with nuclear receptors NR2F1 and NR2F2 correlates with the presence of permissive enhancer chromatin states. Here, we take advantage of pre-existing human genetic variation to further explore potential cooperation between TFAP2A and NR2F1/F2. We demonstrate that isolated single nucleotide polymorphisms affecting NR2F1/F2-binding sites within hNCC enhancers can alter TFAP2A occupancy and overall chromatin features at the same enhancer allele. We propose that a similar strategy can be used to elucidate other cooperative relationships between transcription factors involved in developmental transitions. Using the neural crest and its major contribution to human craniofacial phenotypes as a paradigm, we discuss how genetic variation might modulate the molecular properties and activity of enhancers, and ultimately impact human phenotypic diversity.

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Genetic diversity in Puccinia striiformis Westend. f.sp. tritici revealed by pathogen genome-specific repetitive sequence

Canadian Journal of Botany ◽

10.1139/b98-035 ◽

1998 ◽

Vol 76 (4) ◽

pp. 587-595 ◽

Cited By ~ 9

Author(s):

Wei-xing Shan ◽

Shou-yi Chen ◽

Zhen-sheng Kang ◽

Li-ren Wu ◽

Zhen-qi Li

Keyword(s):

Genetic Diversity ◽

Genetic Variation ◽

Dna Fingerprinting ◽

Puccinia Striiformis ◽

Phenotypic Diversity ◽

Molecular Evidence ◽

Polymorphism Analysis ◽

Dna Fingerprints ◽

High Level ◽

Virulence Variation

DNA fingerprinting was used to examine genetic variation in populations of Puccinia striiformis Westend. f.sp. tritici, an obligate fungus that causes wheat stripe rust, using as a probe a moderately repetitive DNA sequence PSR331 that shows species specificity in the genome of this pathogen. One hundred and sixty isolates sampled from six provinces throughout China were examined for genetic variation over 26 putative genetic loci defined by PSR331 and the restriction enzyme BglII. Because of the dikaryotic nature of this fungus, DNA fingerprints can not differentiate heterozygotes from homozygotes. We refer to the PSR DNA fingerprints as phenotypes rather than genotypes. Phenotypic diversity analysis revealed a high level of genetic variation. A total of 97 phenotypes was detected among 160 isolates. Phenotypic diversity varied among regions, ranging from 0.3742 in Shaanxi to 0.9380 in Gansu, as calculated with the normalized Shannon's index. Genetic subdivision analysis revealed a low level of genetic differentiation (GST = 0.0084) among regions (Gansu, Henan, Shaanxi, Sichuan, and Yunnan provinces) as well as within regions (Gansu and Sichuan provinces). This, together with the detection of the same phenotypes among regions, provided the molecular evidence for gene flow in P. striiformis f.sp. tritici. The results support conclusions from virulence surveys that Tianshui of southern Gansu is probably the most important "hotspot" area with respect to the potential to generate and maintain virulence variation. DNA polymorphism analysis also detected potential hotspot areas in addition to southern Gansu. This may result in more difficulties in management of genetic variation and thus the potential virulence variation in P. striiformis f.sp. tritici as well as providing opportunities for searching disease resistance factors.Key words: genetic diversity, Puccinia striiformis, DNA fingerprinting, virulence variation.

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Slc1a3-2A-CreERT2 mice reveal unique features of Bergmann glia and augment a growing collection of Cre drivers and effectors in the 129S4 genetic background

Scientific Reports ◽

10.1038/s41598-021-84887-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lech Kaczmarczyk ◽

Nicole Reichenbach ◽

Nelli Blank ◽

Maria Jonson ◽

Lars Dittrich ◽

...

Keyword(s):

Genetic Variation ◽

Phenotypic Diversity ◽

Expression Patterns ◽

Cell Types ◽

Inbred Strains ◽

Brain Regions ◽

Genetically Engineered ◽

Disease Models ◽

Calcium Indicator ◽

High Consistency

AbstractGenetic variation is a primary determinant of phenotypic diversity. In laboratory mice, genetic variation can be a serious experimental confounder, and thus minimized through inbreeding. However, generalizations of results obtained with inbred strains must be made with caution, especially when working with complex phenotypes and disease models. Here we compared behavioral characteristics of C57Bl/6—the strain most widely used in biomedical research—with those of 129S4. In contrast to 129S4, C57Bl/6 demonstrated high within-strain and intra-litter behavioral hyperactivity. Although high consistency would be advantageous, the majority of disease models and transgenic tools are in C57Bl/6. We recently established six Cre driver lines and two Cre effector lines in 129S4. To augment this collection, we genetically engineered a Cre line to study astrocytes in 129S4. It was validated with two Cre effector lines: calcium indicator gCaMP5g-tdTomato and RiboTag—a tool widely used to study cell type-specific translatomes. These reporters are in different genomic loci, and in both the Cre was functional and astrocyte-specific. We found that calcium signals lasted longer and had a higher amplitude in cortical compared to hippocampal astrocytes, genes linked to a single neurodegenerative disease have highly divergent expression patterns, and that ribosome proteins are non-uniformly expressed across brain regions and cell types.

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A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing

10.21203/rs.2.16764/v2 ◽

2020 ◽

Author(s):

Chao Yuan ◽

Zengkui Lu ◽

Tingting Guo ◽

Yaojing Yue ◽

Xijun Wang ◽

...

Keyword(s):

Genetic Variation ◽

Complex Traits ◽

Phenotypic Diversity ◽

Average Length ◽

Global Analysis ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Economic Traits ◽

Nutrient Metabolism ◽

Relaxin Family

Abstract Background: Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, important economic traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing. Results: A total of 1747604 CNVs were detected in this study, and 7228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4307.17 bp. “Deletion” events took place more frequently than “duplication” or “both” events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39%–55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective elimination of CNVRs, and it was found that the relaxin family peptide receptor 2 ( RXFP2 ) gene was strongly influenced by selection. Conclusions: In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.

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Insights into calcium signaling and gene expression in astrocytes uncovered with 129S4 Slc1a3-2A-CreERT2 knock-in mice

10.1101/2020.04.06.027714 ◽

2020 ◽

Author(s):

Lech Kaczmarczyk ◽

Nicole Reichenbach ◽

Nelli Blank ◽

Maria Jonson ◽

Lars Dittrich ◽

...

Keyword(s):

Genetic Variation ◽

Phenotypic Diversity ◽

Expression Patterns ◽

Cell Types ◽

Inbred Strains ◽

Brain Regions ◽

Genetically Engineered ◽

Calcium Currents ◽

Activity Levels ◽

Genomic Locus

AbstractGenetic variation is a primary determinant of phenotypic diversity within populations. In laboratory mice, genetic variation has often been regarded as a serious experimental confounder, and thus minimized through inbreeding. However, generalizations of results obtained with inbred strains need to be made with caution. Effects of genetic background on traits need to be controlled, especially when working with complex phenotypes and disease models. Here we compared behavioral parameters of C57Bl/6 – the mouse strain most widely used for biomedical research - with those of 129S4. Our data demonstrate high within-strain and intra-litter behavioral hyperactivity in C57Bl/6. In contrast, 129S4 had relatively consistent activity levels throughout life. This consistency would be advantageous for studying neurodegeneration and aging, when mice need to be analyzed for long periods. However, the majority of mouse models and transgenic tools are on a C57Bl/6 background. We recently established six popular Cre driver lines and two Cre effector lines in 129S4. To augment this collection, we genetically engineered a Cre mouse line to study astrocytes directly in 129S4, which we describe here. For functional validation, it was crossed with two Cre effector lines, each in a different genomic locus, and showed in both cases that it was functional and astrocyte-specific. Calcium currents studied with gCaMP5g-tdTomato were more heterogenous, lasted longer and had a higher amplitude in cortical compared to hippocampal astrocytes. Translatomes studied with RiboTag revealed that some genes thought to mark neurons are also expressed in astrocytes, that genes linked to a single neurodegenerative disease have highly divergent expression patterns, and that ribosome proteins are non-uniformly expressed across brain regions and cell types.

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Mechanisms underlying divergent responses of genetically distinct macrophages to IL-4

10.1101/2020.11.02.365742 ◽

2020 ◽

Author(s):

Marten A. Hoeksema ◽

Zeyang Shen ◽

Inge R. Holtman ◽

An Zheng ◽

Nathan Spann ◽

...

Keyword(s):

Gene Expression ◽

Genetic Variation ◽

Disease Risk ◽

Phenotypic Diversity ◽

Inbred Strains ◽

Dynamic Responses ◽

Interleukin 4 ◽

Enhancer Activity ◽

Inbred Strains Of Mice ◽

Mutation Analyses

AbstractMechanisms by which non-coding genetic variation influences gene expression remain only partially understood but are considered to be major determinants of phenotypic diversity and disease risk. Here, we evaluated effects of >50 million SNPs and InDels provided by five inbred strains of mice on the responses of macrophages to interleukin 4 (IL-4), a cytokine that plays pleiotropic roles in immunity and tissue homeostasis. Remarkably, of >600 genes induced >2-fold by IL-4 across the five strains, only 26 genes reached this threshold in all strains. By applying deep learning and motif mutation analyses to epigenetic data for macrophages from each strain, we identified the dominant combinations of lineage determining and signal-dependent transcription factors driving late enhancer activation. These studies further revealed mechanisms by which non-coding genetic variation influences absolute levels of enhancer activity and their dynamic responses to IL-4, thereby contributing to strain-differential patterns of gene expression and phenotypic diversity.

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