Genetic Analysis of Mitochondrial Sorting from the MSC3 Mosaic Mutant of Cucumber

Cucumber (Cucumis sativus) plants regenerated from cell cultures occasionally possess mosaic (MSC) phenotypes on cotyledons and leaves. Lines MSC3 and MSC16 have distinct MSC phenotypes and originated from plants regenerated from different cell-culture experiments established using a highly inbred wild-type cucumber. Both the mitochondrial (mt) DNA and MSC phenotype of cucumber show paternal transmission, and MSC3 and MSC16 have different mt coding regions at significantly lower copy numbers relative to wild-type plants. A nuclear locus, Paternal sorting of mitochondria (Psm), conditions a high proportion of wild-type progenies, specifically when MSC16 is crossed as the male with wild-type female plants. During this research, we identified plants that produced a high proportion of wild-type progenies in crosses with MSC3 as the male parent. Plants from an F2 family were crossed with MSC3 as the male, progenies were scored for numbers of MSC vs. wild-type plants, and single-nucleotide polymorphisms (SNP) were identified for genetic mapping. A major quantitative trait locus on chromosome 3 was associated with a higher frequency of wild-type progenies from MSC3 as the male parent, and the 1.5-logarithm-of-odds interval for the most significant SNP was located 627 kb from Psm. These results reveal that separate genetic factors control sorting to the wild-type phenotype in progenies from crosses with different MSC parents. The identification of causal genes controlling mitochondrial sorting in cucumber should provide insight regarding nuclear-mitochondrial interactions affecting the prevalence of specific mitochondrial DNA in plants.

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Genetic Mapping of Mitochondrial Sorting of the MSC3 Mosaic Mutant of Cucumber

10.21203/rs.3.rs-256288/v1 ◽

2021 ◽

Author(s):

Lyle T. Wallace ◽

Michael J. Havey

Keyword(s):

Genetic Mapping ◽

Genomic Region ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Paternal Transmission ◽

Regenerated Plants ◽

Mitochondrial Dnas ◽

Trait Locus ◽

Nuclear Locus

Abstract Passage of the highly inbred line ‘B’ of cucumber through cell cultures has produced regenerated plants with a mosaic (MSC) phenotype on cotyledons and leaves, as well as rearrangements in the mitochondrial DNA. Both of these characteristics show paternal transmission. MSC3 and MSC16 were derived from independent cell-culture experiments and have distinct mosaic phenotypes and different under-represented regions in their mitochondrial DNAs. A nuclear locus, Psm for paternal transmission of mitochondria, conditions a high proportion of wild type progenies when MSC16 is crossed as the male with female plants carrying the Psm- allele. Plants with homozygous genotypes at Psm were crossed with both MSC3 and MSC16, and segregation of wild-type versus mosaic progenies in these families were not consistent suggesting that sorting of wild-type progenies from crosses with MSC3 and MSC16 have different genetic bases. We identified cucumber plants that produced a high proportion of wild-type progenies in crosses with MSC3 as the male parent. Plants from a segregating F2 family were crossed with MSC3 as the male and progenies scored for numbers of mosaic versus wild-type progenies. The same F2 plants were genotyped-by-sequencing and single nucleotide polymorphisms identified for genetic mapping. Quantitative analysis of the proportion of wild-type testcross progenies identified a major quantitative trait locus (QTL) in the same genomic region as the Psm locus; however the most significant SNP associated with this QTL was located approximately 856 kilobases from Psm. Eventual identification of a candidate gene controlling this unique mitochondrial sorting in cucumber should reveal important aspects of mitochondrial-nuclear interactions affecting the prevalence of specific mitochondrial DNAs.

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PSI-40 Two mitochondrial lineages revealed in North American yak

Journal of Animal Science ◽

10.1093/jas/skaa278.833 ◽

2020 ◽

Vol 98 (Supplement_4) ◽

pp. 477-477

Author(s):

Leah K Treffer ◽

Edward S Rice ◽

Anna M Fuller ◽

Samuel Cutler ◽

Jessica L Petersen

Keyword(s):

Sequence Data ◽

Haplotype Network ◽

Ovis Aries ◽

Similar Species ◽

Nucleotide Polymorphisms ◽

Mt Dna ◽

Protein Coding ◽

Sister Clade ◽

Mtdna Sequence ◽

The Impact

Abstract Domestic yak (Bos grunniens) are bovids native to the Asian Qinghai-Tibetan Plateau. Studies of Asian yak have revealed that introgression with domestic cattle has contributed to the evolution of the species. When imported to North America (NA), some hybridization with B. taurus did occur. The objective of this study was to use mitochondrial (mt) DNA sequence data to better understand the mtDNA origin of NA yak and their relationship to Asian yak and related species. The complete mtDNA sequence of 14 individuals (12 NA yak, 1 Tibetan yak, 1 Tibetan B. indicus) was generated and compared with sequences of similar species from GeneBank (B. indicus, B. grunniens (Chinese), B. taurus, B. gaurus, B. primigenius, B. frontalis, Bison bison, and Ovis aries). Individuals were aligned to the B. grunniens reference genome (ARS_UNL_BGru_maternal_1.0), which was also included in the analyses. The mtDNA genes were annotated using the ARS-UCD1.2 cattle sequence as a reference. Ten unique NA yak haplotypes were identified, which a haplotype network separated into two clusters. Variation among the NA haplotypes included 93 nonsynonymous single nucleotide polymorphisms. A maximum likelihood tree including all taxa was made using IQtree after the data were partitioned into twenty-two subgroups using PartitionFinder2. Notably, six NA yak haplotypes formed a clade with B. indicus; the other four haplotypes grouped with B. grunniens and fell as a sister clade to bison, gaur and gayal. These data demonstrate two mitochondrial origins of NA yak with genetic variation in protein coding genes. Although these data suggest yak introgression with B. indicus, it appears to date prior to importation into NA. In addition to contributing to our understanding of the species history, these results suggest the two major mtDNA haplotypes in NA yak may functionally differ. Characterization of the impact of these differences on cellular function is currently underway.

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Common genetic variants with fetal effects on birth weight are enriched for proximity to genes implicated in rare developmental disorders

Human Molecular Genetics ◽

10.1093/hmg/ddab060 ◽

2021 ◽

Author(s):

Robin N Beaumont ◽

Isabelle K Mayne ◽

Rachel M Freathy ◽

Caroline F Wright

Keyword(s):

Birth Weight ◽

Statistical Power ◽

Developmental Disorders ◽

Association Studies ◽

Later Life ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genome Wide ◽

Common Genetic Variants ◽

Causal Genes

Abstract Birth weight is an important factor in newborn survival; both low and high birth weights are associated with adverse later-life health outcomes. Genome-wide association studies (GWAS) have identified 190 loci associated with maternal or fetal effects on birth weight. Knowledge of the underlying causal genes is crucial to understand how these loci influence birth weight and the links between infant and adult morbidity. Numerous monogenic developmental syndromes are associated with birth weights at the extreme ends of the distribution. Genes implicated in those syndromes may provide valuable information to prioritize candidate genes at the GWAS loci. We examined the proximity of genes implicated in developmental disorders (DDs) to birth weight GWAS loci using simulations to test whether they fall disproportionately close to the GWAS loci. We found birth weight GWAS single nucleotide polymorphisms (SNPs) fall closer to such genes than expected both when the DD gene is the nearest gene to the birth weight SNP and also when examining all genes within 258 kb of the SNP. This enrichment was driven by genes causing monogenic DDs with dominant modes of inheritance. We found examples of SNPs in the intron of one gene marking plausible effects via different nearby genes, highlighting the closest gene to the SNP not necessarily being the functionally relevant gene. This is the first application of this approach to birth weight, which has helped identify GWAS loci likely to have direct fetal effects on birth weight, which could not previously be classified as fetal or maternal owing to insufficient statistical power.

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Transcriptomic profiling of wheat near-isogenic lines reveals candidate genes on chromosome 3A for pre-harvest sprouting resistance

BMC Plant Biology ◽

10.1186/s12870-021-02824-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xingyi Wang ◽

Hui Liu ◽

Kadambot H. M. Siddique ◽

Guijun Yan

Keyword(s):

Candidate Genes ◽

Quantitative Trait ◽

Genomic Region ◽

Nucleotide Polymorphisms ◽

Near Isogenic Lines ◽

Gene Effects ◽

Isogenic Lines ◽

Trait Locus ◽

Grain Yield And Quality ◽

Sprouting Resistance

Abstract Background Pre-harvest sprouting (PHS) in wheat can cause severe damage to both grain yield and quality. Resistance to PHS is a quantitative trait controlled by many genes located across all 21 wheat chromosomes. The study targeted a large-effect quantitative trait locus (QTL) QPhs.ccsu-3A.1 for PHS resistance using several sets previously developed near-isogenic lines (NILs). Two pairs of NILs with highly significant phenotypic differences between the isolines were examined by RNA sequencing for their transcriptomic profiles on developing seeds at 15, 25 and 35 days after pollination (DAP) to identify candidate genes underlying the QTL and elucidate gene effects on PHS resistance. At each DAP, differentially expressed genes (DEGs) between the isolines were investigated. Results Gene ontology and KEGG pathway enrichment analyses of key DEGs suggested that six candidate genes underlie QPhs.ccsu-3A.1 responsible for PHS resistance in wheat. Candidate gene expression was further validated by quantitative RT-PCR. Within the targeted QTL interval, 16 genetic variants including five single nucleotide polymorphisms (SNPs) and 11 indels showed consistent polymorphism between resistant and susceptible isolines. Conclusions The targeted QTL is confirmed to harbor core genes related to hormone signaling pathways that can be exploited as a key genomic region for marker-assisted selection. The candidate genes and SNP/indel markers detected in this study are valuable resources for understanding the mechanism of PHS resistance and for marker-assisted breeding of the trait in wheat.

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Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan

Pharmaceuticals ◽

10.3390/ph14030235 ◽

2021 ◽

Vol 14 (3) ◽

pp. 235

Author(s):

Jen-Sheng Pei ◽

Chao-Chun Chen ◽

Wen-Shin Chang ◽

Yun-Chi Wang ◽

Jaw-Chyun Chen ◽

...

Keyword(s):

Confidence Interval ◽

Childhood Leukemia ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Genotypic Distribution ◽

Heterozygous Variant ◽

Significant Difference ◽

The Difference

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08–2.14, p = 0.0429) and 1.94 (95%CI, 1.15–3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13–1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

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Identification of a Cis-Acting Regulatory Polymorphism in a Eucalypt COBRA-Like Gene Affecting Cellulose Content

Genetics ◽

10.1534/genetics.109.106591 ◽

2009 ◽

Vol 183 (3) ◽

pp. 1153-1164 ◽

Cited By ~ 68

Author(s):

Bala R. Thumma ◽

Bronwyn A. Matheson ◽

Deqiang Zhang ◽

Christian Meeske ◽

Roger Meder ◽

...

Keyword(s):

Quantitative Traits ◽

Association Studies ◽

Allelic Expression ◽

Cellulose Content ◽

Nucleotide Polymorphisms ◽

Cis Acting ◽

Functional Polymorphisms ◽

Functional Variants ◽

Regulatory Polymorphism ◽

Trait Locus

Populations with low linkage disequilibrium (LD) offer unique opportunities to study functional variants influencing quantitative traits. We exploited the low LD in forest trees to identify functional polymorphisms in a Eucalyptus nitens COBRA-like gene (EniCOBL4A), whose Arabidopsis homolog has been implicated in cellulose deposition. Linkage analysis in a full-sib family revealed that EniCOBL4A is the most strongly associated marker in a quantitative trait locus (QTL) region for cellulose content. Analysis of LD by genotyping 11 common single-nucleotide polymorphisms (SNPs) and a simple sequence repeat (SSR) in an association population revealed that LD declines within the length of the gene. Using association studies we fine mapped the effect of the gene to SNP7, a synonymous SNP in exon 5, which occurs between two small haplotype blocks. We observed patterns of allelic expression imbalance (AEI) and differential binding of nuclear proteins to the SNP7 region that indicate that SNP7 is a cis-acting regulatory polymorphism affecting allelic expression. We also observed AEI in SNP7 heterozygotes in a full-sib family that is linked to heritable allele-specific methylation near SNP7. This study demonstrates the potential to reveal functional polymorphisms underlying quantitative traits in low LD populations.

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Tumor formation in p53 mutant ovaries transplanted into wild-type female hosts

Oncogene ◽

10.1038/sj.onc.1208037 ◽

2004 ◽

Vol 23 (46) ◽

pp. 7722-7725 ◽

Cited By ~ 13

Author(s):

Chun-Ming Chen ◽

Junn-Liang Chang ◽

Richard R Behringer

Keyword(s):

Tumor Formation ◽

Wild Type ◽

Wild Type Female

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The UDP N-Acetylgalactosamine 4-Epimerase Gene Is Essential for Mesophilic Aeromonas hydrophila Serotype O34 Virulence

Infection and Immunity ◽

10.1128/iai.74.1.537-548.2006 ◽

2006 ◽

Vol 74 (1) ◽

pp. 537-548 ◽

Cited By ~ 23

Author(s):

Rocío Canals ◽

Natalia Jiménez ◽

Silvia Vilches ◽

Miguel Regué ◽

Susana Merino ◽

...

Keyword(s):

Aeromonas Hydrophila ◽

Type Strain ◽

Wild Type Strain ◽

Sugar Residue ◽

Serum Resistance ◽

Single Mutation ◽

Wild Type ◽

O Antigen ◽

Wild Type Phenotype

ABSTRACT Mesophilic Aeromonas hydrophila strains of serotype O34 typically express smooth lipopolysaccharide (LPS) on their surface. A single mutation in the gene that codes for UDP N-acetylgalactosamine 4-epimerase (gne) confers the O− phenotype (LPS without O-antigen molecules) on a strain in serotypes O18 and O34, but not in serotypes O1 and O2. The gne gene is present in all the mesophilic Aeromonas strains tested. No changes were observed for the LPS core in a gne mutant from A. hydrophila strain AH-3 (serotype O34). O34 antigen LPS contains N-acetylgalactosamine, while no such sugar residue forms part of the LPS core from A. hydrophila AH-3. Some of the pathogenic features of A. hydrophila AH-3 gne mutants are drastically reduced (serum resistance or adhesion to Hep-2 cells), and the gne mutants are less virulent for fish and mice compared to the wild-type strain. Strain AH-3, like other mesophilic Aeromonas strains, possess two kinds of flagella, and the absence of O34 antigen molecules by gne mutation in this strain reduced motility without any effect on the biogenesis of both polar and lateral flagella. The reintroduction of the single wild-type gne gene in the corresponding mutants completely restored the wild-type phenotype (presence of smooth LPS) independently of the O wild-type serotype, restored the virulence of the wild-type strain, and restored motility (either swimming or swarming).

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Associations between varied susceptibilities of PfATP4 inhibitors and genotypes in Ugandan Plasmodium falciparum isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00771-21 ◽

2021 ◽

Author(s):

Oriana Kreutzfeld ◽

Stephanie A. Rasmussen ◽

Aarti A. Ramanathan ◽

Patrick K. Tumwebaze ◽

Oswald Byaruhanga ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Single Nucleotide Polymorphisms ◽

Ex Vivo ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Field Isolates ◽

Frequent Mutations ◽

Mixed Field ◽

P Type

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda from 2016-2019. Median IC 50 s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many non-synonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%) and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92 and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites.

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Rescue of the mutant phenotype by reexpression of full-length vinculin in null F9 cells; effects on cell locomotion by domain deleted vinculin

Journal of Cell Science ◽

10.1242/jcs.111.11.1535 ◽

1998 ◽

Vol 111 (11) ◽

pp. 1535-1544 ◽

Cited By ~ 7

Author(s):

W. Xu ◽

J.L. Coll ◽

E.D. Adamson

Keyword(s):

Marked Effect ◽

Control Cell ◽

Covalent Attachment ◽

Tail Domain ◽

Wild Type ◽

F9 Cells ◽

Wild Type Phenotype ◽

Correct Location ◽

Low Levels ◽

Lamellipodia Formation

Vinculin plays a role in signaling between integrins and the actin cytoskeleton. We reported earlier that F9-derived cells lacking vinculin are less spread, less adhesive, and move two times faster than wild-type F9 cells. Expression of intact vinculin in null cells restored all wild-type characteristics. In contrast, expression of the head (90 kDa) fragment exaggerated mutant characteristics, especially locomotion, which was double that of vinculin null cells. Expression of the tail domain also had a marked effect on locomotion in the opposite direction, reducing it to very low levels. The expression of the head plus tail domains together (no covalent attachment) effected a partial rescue towards wild-type phenotype, thus indicating that reexpressed polypeptides may be in their correct location and are interacting normally. Therefore, we conclude that: (1) the head domain is part of the locomotory force of the cell, modulated by the tail, and driven by the integrin/matrix connection; (2) intact vinculin is required for normal regulation of cell behavior, suggesting that vinculin head-tail interactions control cell adhesion, spreading, lamellipodia formation and locomotion.

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