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PubMed2026

The curious case of sporadic nematode susceptibility in "Tifguard" peanut (Arachis hypogaea): seed mixture or genetic instability?

The Runner-type peanut (Arachis hypogaea L.) cultivar "Tifguard" carries an introgressed chromosomal segment on chromosome A09 from A. cardenasii that confers resistance to root-knot nematode (RKN). Despite this, a proportion of "Tifguard" plants show RKN symptoms, which could plausibly be attributed to seed mixture or outcrossing. However, recent work has shown that cultivated peanut exhibits surprisingly frequent large-scale chromosomal instability (1% to 5%); suggesting that resistance loss could arise from spontaneous structural genomic change. To test these possibilities, we grew foundation seed in an RKN-infested field and collected symptomatic and asymptomatic plants. Lineages derived by single-seed descent were genotyped using the Axiom Arachis 48K SNP array v2 and whole-genome sequencing. Symptomatic lineages lacked the A. cardenasii introgression on chromosome A09 and instead carried the complete endogenous A. hypogaea A09 region at the expected dosage. There was no evidence of large-scale homoeologous exchange, deletion, or other genomic instability affecting this chromosome. Most susceptible plants were closely related to resistant "Tifguard" but lacked the A09 introgression, with a smaller proportion assignable to known nematode-susceptible cultivars, implicating seed mixture with a possible contribution from cross-pollination rather than genomic instability. Because resistance depends on a single major-effect segment, rare events have disproportionate phenotypic impact, placing high demands on genetic purity. For important traits conferred by major loci, marker-based testing across seed-increase stages could verify trait retention directly, and is increasingly practical as marker costs decline.

Arachis↗

PubMed2003

Novel multilocus measure of linkage disequilibrium to estimate past effective population size.

Linkage disequilibrium (LD) between densely spaced, polymorphic genetic markers in humans and other species contains information about historical population size. Inferring past population size is of interest both from an evolutionary perspective (e.g., testing the "out of Africa" hypothesis of human evolution) and to improve models for mapping of disease and quantitative trait genes. We propose a novel multilocus measure of LD, the chromosome segment homozygosity (CSH). CSH is defined for a specific chromosome segment, up to the full length of the chromosome. In computer simulations CSH was generally less variable than the r(2) measure of LD, and variability of CSH decreased as the number of markers in the chromosome segment was increased. The essence and utility of our novel measure is that CSH over long distances reflects recent effective population size (N), whereas CSH over small distances reflects the effective size in the more distant past. We illustrate the utility of CSH by calculating CSH from human and dairy cattle SNP and microsatellite marker data, and predicting N at various times in the past for each species. Results indicated an exponentially increasing N in humans and a declining N in dairy cattle. CSH is a valuable statistic for inferring population histories from haplotype data, and has implications for mapping of disease loci.

Animals↗

PubMed1998

Effect of renin gene transfer on blood pressure in the spontaneously hypertensive rat.

To investigate whether molecular variation in the renin gene contributes to the greater blood pressure of spontaneously hypertensive rats (SHR) versus normotensive Brown Norway (BN) rats, we measured blood pressure in an SHR progenitor strain and an SHR congenic strain that are genetically identical except at the renin gene and an associated segment of chromosome 13 transferred from the BN strain. Backcross breeding and molecular selection at the renin locus were used to create the SHR congenic strain (designated SHR.BN-Ren) that carries the renin gene transferred from the normotensive BN strain. We found that transfer of the renin gene from the BN strain onto the genetic background of the SHR did not decrease blood pressure in rats fed either a normal or high-salt diet. In fact, the systolic blood pressures of the SHR congenic rats tended to be slightly greater than the systolic blood pressures of the SHR progenitor rats. However, the congenic strain exhibited lower serum high-density lipoprotein cholesterol, and greater levels of total cholesterol, very-low-density lipoprotein, and intermediate-density lipoprotein cholesterol during administration of a high-fat, high-cholesterol diet. These findings demonstrate that (1) under the environmental circumstances of the current study, the greater blood pressure of SHR versus BN rats cannot be explained by strain differences in the renin gene and (2) a quantitative trait locus affecting lipid metabolism exists on chromosome 13 within the transferred chromosome segment. The SHR.BN-Ren congenic strain may provide a useful new animal model for studying the interaction between high blood pressure and dyslipidemia in cardiovascular disease.

Animals↗

PubMed2004

Haplotype parsing: methods for extracting information from human genetic variations.

While the shared consensus genetic sequence of our species contains a great deal of information about our common biology, there is also much to be learned from the subtle genetic variations across our species. These variations are believed to be generally of little or no direct functional significance and predominantly reflect the chance accumulation of small genetic changes since our emergence as a species. Therefore, they carry little useful information when observed in a single individual. When tallied across a whole population though, these chance mutations can teach us a great deal about our evolutionary history and the patterns of inheritance in particular individuals. In particular, frequently observed patterns of single nucleotide polymorphisms (SNPs) in a population can identify segments of chromosome that have been passed down largely intact through long stretches of our evolution. Finding these frequently conserved chromosomal segments, or haplotypes, and developing methods to identify haplotype patterns in particular individuals, will in turn help us to identify those particular segments that carry genetic factors influencing risk for many common human diseases. To make the best use of this data, we will need to develop new models for the encoding of information in genome variations--the "language of genetic variation"--and new algorithms for fitting datasets to those models. This article surveys past work by the author and colleagues on this problem, utilising computational methods for locating frequent patterns in haploid sequence data, and "parsing" sequences so as to optimally explain them given the knowledge of the general population structure. The author's recent work in this area has been compiled into a set of computational tools available at http://www-2.cs.cmu.edu/~russells/software/hapmotif.html.

Algorithms↗

PubMed2004

Interstitial deletions including chromosome 3 common eliminated region 1 (C3CER1) prevail in human solid tumors from 10 different tissues.

A human chromosomal segment regularly lost during tumor formation of microcell hybrids in SCID mice has been mapped to 3p21.3. This segment, called chromosome 3 common eliminated region 1 (C3CER1, also referred to as CER1), may harbor multiple tumor-suppressor genes. Because it was found that similar regions were eliminated in an inter- and intraspecies system and in two tumor types (mouse fibrosarcoma and human renal cell carcinoma), we hypothesized that the importance of C3CER1 would transgress tissue specificity, that is, it could occur in tumors derived from multiple tissues. To evaluate the loss of C3CER1 in various human tumor types, we conducted loss of heterozygosity (LOH) analysis of 576 human solid tumors from 10 different tissues and compared the frequency of deletion in the C3CER1 area to that in two other regions on 3p: the FHIT/FRA3B region, at 3p14.2, and the VHL region, at 3p25.3. Deletions were detected in the C3CER1 region in 83% of informative tumors. Half (47%) the LOH-positive tumors showed LOH at all informative markers, indicating a large deletion. The other half (53%) had a discontinuous LOH pattern, suggesting interstitial deletions or breakpoints. The proportion of tumors with C3CER1 deletions was high in all tumor types investigated, ranging from 70% to 94%, except for the soft-tissue sarcomas (40%). In the VHL and FHIT regions, deletions were observed in 73% and 43%, respectively, of the tumors. Of the three 3p regions analyzed, the highest deletion frequency was observed in the C3CER1 region. Furthermore, we demonstrated that the interstitial deletions including C3CER1 prevail over 3p14.2-pter losses in solid tumors.

Acid Anhydride Hydrolases↗

PubMed1996

De novo chromosome formations by large-scale amplification of the centromeric region of mouse chromosomes.

Chromosomes formed de novo which originated from the centromeric region of mouse chromosome 7, have been analysed. These new chromosomes were formed by apparently similar large-scale amplification processes, and are organized into amplicons of approximately 30 Mb. Centromeric satellite DNA was found to be the constant component of all amplicons. Satellite DNA sequences either bordered the large euchromatic amplicons (E-type amplification), or made up the bulk of the constitutive heterochromatic amplicons (H-type amplification). Detailed analysis of a heterochromatic megachromosome formed de novo by an H-type amplification revealed that it is composed of a tandem array of 10-12 large (approximately 30 Mb) amplicons each marked with integrated "foreign' DNA sequences at both ends. Each amplicon is a giant palindrome, consisting of two inverted doublets of approximately 7.5-Mb blocks of satellite DNA. Our results indicate that the building units of the pericentric heterochromatin of mouse chromosomes are approximately 7.5-Mb blocks of satellite DNA flanked by non-satellite sequences. We suggest that the formation de novo of various chromosome segments and chromosomes seen in different cell lines may be the result of large-scale E- and H-type amplification initiated in the pericentric region of chromosomes.

Animals↗

PubMed2004

Genetic variation in the multifunctional transcription factor Yy1 and type 1 diabetes mellitus in the BB rat.

Spontaneous diabetes in B(io)B(reeding) rats is complex, polygenic, and recessively inherited. Several crossing studies have demonstrated that beside the class II genes of the major histocompatibility complex (MHC, Iddm1) additional non-MHC genes are involved in diabetes development. One of them, Iddm4, was initially mapped on chromosome 6q32. To study the physiologic importance of Iddm4 a congenic BB.SHR rat strain (BB.6S) was established. The BB.6S is characterised by a drastic reduction of diabetes frequency (86 vs. 14%) indicating existence of diabetes protective genes of SHR on the exchanged chromosomal segment. One of the possible diabetes susceptibility candidate genes located within this exchanged region is the multifunctional transcription factor Yin yang 1 (Yy1). Yy1 was therefore sequenced in BB/OK and SHR rats. No genetic variation in exons between BB/OK and SHR was found. However, three single nucleotide polymorphisms (SNPs) were detected in intron 4. To determine the "wild type" allele, intron 4 of several diabetes-resistant inbred rat strains (DA, LEW, BN, and WOKW) and wild rats was sequenced. In addition, a congenic BB/OK strain was established by introgressing the same segment of chromosome 6 (D6Rat184-D6Rat3) of wild rats onto BB/OK background (BB.6W). The sequence analysis showed the SNP pattern of SHR (A/C/C) in all inbred rat strains studied whereas both unrelated wild rats showed the pattern of BB/OK rats (T/G/A). The congenic BB.6W rats developed diabetes in the same extent than BB/OK rats. This finding may support the assumption that the SNP pattern of BB/OK and wild rats favours and that of SHR suppresses diabetes development. Because of strong synteny between rat chromosome 6q32 and human 14q32, Yy1 may be also of interest in human type 1 diabetics showing significant linkage to markers on chromosome 14q32.

Animals↗

PubMed2000

The murine DSCR1-like (Down syndrome candidate region 1) gene family: conserved synteny with the human orthologous genes.

A recently recognized gene family, conserved from yeast to humans, includes Down syndrome candidate region 1 gene (DSCR1), Adapt78 (recognized as the hamster ortholog of the DSCR1 isoform 4), ZAKI-4 (renamed DSCR1-like 1, DSCR1L1) and DSCR1L2 (a novel gene on human chromosome 1), along with yeast and C. elegans single members (Strippoli P., Lenzi L., Petrini M., Carinci P., Zannotti M., 2000. A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member. Genomics 64, 252-263). The proposed family labels were a putative single-strand nucleic acid binding domain similar to the RNA recognition motif, and a unique, highly-conserved serine-proline motif. We have used a bioinformatics-driven molecular biology approach to characterize the murine members of DSCR1-like gene family. Systematic expressed-sequence-tags (EST) database search and reverse-transcription polymerase chain rection (RT-PCR) product sequencing allowed identification of the murine DSCR1, DSCR1L1 and DSCR1L2. The sequences of the respective protein products are of 198, 197 and 241 amino acids, respectively, and are very similar to the corresponding human proteins. The very broad expression pattern of the murine DSCR1 genes is similar to that of the human genes. Using a radiation hybrid panel, we mapped the murine DSCR1-like family members. The murine DSCR1 ortholog is located on the chromosome 16, in a region corresponding to that on human chromosome 21 just upstream of the Down syndrome candidate region. DSCR1L1 and DSCR1L2 murine genes are also located in chromosomal segments of chromosome 17 and 4, respectively, exactly corresponding to those containing the respective human homologs on chromosomes 6 and 1. Description of the mouse orthologs for DSCR1-like genes will allow knockout mice to be obtained for specific family members.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Localization of a blood pressure QTL to a 2.4-cM interval on rat chromosome 9 using congenic strains.

A blood pressure (BP) quantitative trait locus (QTL) was previously found on rat chromosome 9 using Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats. A congenic strain, S.R(chr9), constructed by introgressing an R chromosomal segment into the S background, previously proved the existence of a BP QTL in a large 34.2-cM segment of chromosome 9. In the current work congenic substrains were constructed from the progenitor congenic strain, S.R(chr9). BP and heart weight comparisons between these congenic substrains and their S control localized the BP QTL to a 4.6-cM interval. Two solute carrier (Na(+)/H(+) exchanger) genes, Nhe2 and Nhe4, were excluded as candidates based on their map locations. A second iteration of congenic substrains was used to localize the QTL further to a 2.4-cM interval. Another solute carrier (Cl(-)/HCO3- exchanger) gene, Ae3, is in this reduced interval and was sequenced for both S and R strains, but no coding sequence variations were found. Ae3 mRNA was not differentially expressed in the kidney of congenic compared to S rats. Although the identity of the QTL remains unknown its map location has been reduced from an interval of 34.2 to 2.4 cM.

Animals↗

PubMed2003

Introgression of crown rust (Puccinia coronata) resistance from meadow fescue (Festuca pratensis) into Italian ryegrass (Lolium multiflorum) and physical mapping of the locus.

Resistance was found in the meadow fescue (Festuca pratensis) to crown rust (Puccinia coronata), originating from ryegrasses (Lolium spp). A backcrossing programme successfully transferred this resistance into diploid Italian ryegrass (Lolium multiflorum) and genomic in situ hybridisation (GISH) was used to identify the introgressed fescue chromosome segment. The resistant (R) plants in two BC3 lines all carried an introgressed segment on a single chromosome, which in one of the lines was confined to the short arm of the chromosome. Susceptible (S) plants either contained no introgressed chromosome segment or a segment which was physically smaller than the segments in resistant plants. Using GISH the resistance locus could be physically mapped to the midpoint of a short arm. Segregation ratios of the progeny of BC3 plants, when crossed as R x S and R x R, were in agreement with the hypothesis that the resistance was controlled by a single gene or very closely linked genes. No R plants were produced by crossing S x S plants.

Basidiomycota↗

PubMed2002

Linkage relationships of genes coding for alpha2-macroglobulin, C3 and C4 in the zebrafish: implications for the evolution of the complement and Mhc systems.

The alpha2-macroglobulin (A2M) and the complement components C3 and C4 are related proteins derived from a common ancestor. Theoretically, this derivation could have occurred either by tandem duplications of their encoding genes or by polyploidization involving chromosomal segments, a chromosome or the whole genome. In tetrapods the A2M-, C3- and C4-encoding genes are generally each located on a different chromosome. This observation has been interpreted as supporting their origin by polyploidization. We identified and mapped (with the help of a radiation hybrid panel of cell lines) the A2M, C3 and C4 loci in the zebrafish, Danio rerio. Each of the three types of loci is present in the zebrafish in multiple copies, but all of the identified copies of a given type map to the same region in linkage groups 1 (C3) and 15 (A2M, C4). The A2M and C4 loci are mapped in the same region not linked to any of the class I or class II major histocompatibility complex (Mhc) loci. These observations are interpreted as supporting the origin of the A2M family of genes by tandem duplications, followed by the dispersal of the copies to different chromosomes. It is also argued that the association of C4 with the class I/II loci in tetrapods is accidental and without functional significance.

Animals↗

PubMed1996

Detection and evaluation of chromosomal aberrations induced by high doses of gamma-irradiation using immunogold-silver painting of prematurely condensed chromosomes.

We developed a method for detecting chromosomal aberrations after irradiation with high doses of gamma-rays. At high dose levels, few of the irradiated cells are able to enter mitosis so that it is difficult to obtain enough mitotic chromosomes using a conventional colcemid block. Therefore, okadaic acid was used to condense prematurely the chromosomes of interphase cells. Even after irradiation with doses > 40 Gy, okadaic acid was able to force sufficient numbers of cells to condense their chromosomes. Segments of chromosomes were then detected by chromosome painting using a gold-conjugated antibody followed by silver enhancement. This simple method allows highly damaged chromosomes to be detected with great sensitivity.

Cell Cycle↗

PubMed2006

Genetic regulation of plasma von Willebrand factor levels: quantitative trait loci analysis in a mouse model.

BACKGROUND: The genetic factors responsible for the wide variation in plasma von Willebrand factor (VWF) levels observed among individuals are largely unknown, although these genes are also likely to contribute to variability in the severity of von Willebrand disease (VWD) and other bleeding and thrombotic disorders. We have previously mapped two genes contributing to the regulation of plasma VWF levels in mice (Mvwf1 on chromosome 11 and Mvwf2 on chromosome 6). OBJECTIVE: To identify additional quantitative trait loci (QTL) contributing to the genetic regulation of murine plasma VWF levels. METHODS: To map genetic loci contributing to the > 7-fold difference in plasma VWF levels between two mouse strains (A/J and CASA/RkJ), high-density individual genotyping and R/qtl analyses were applied to a previously generated set of approximately 200 F2 mice obtained from an intercross of these two inbred lines. RESULTS: Genomic loci for two additional candidate VWF modifier genes were identified: Mvwf3 on chromosome 4 and Mvwf4 on chromosome 13. These loci demonstrate primarily epistatic effects when co-inherited with two CASA/RkJ Vwf alleles, although Mvwf4 may also exert a small, independent, additive effect. CONCLUSIONS: Mvwf3 and Mvwf4, combined with the effect of Mvwf2, explain approximately 45% of the genetic variation in plasma VWF level among the A/J and CASA/RkJ strains. Mvwf3 and Mvwf4 exhibit homology of synteny to three human chromosomal segments (on chromosomes 1, 5 and 6) previously reported by the Genetic Analysis of Idiopathic Thrombophilia (GAIT) study, suggesting that orthologs of Mvwf3 and Mvwf4 may also encode important VWF modifier genes in humans.

Animals↗

PubMed1996

Mouse euchromatin specific "genome-painting" with a LINE probe: a rapid method for identification and mapping of human chromosomes in mouse-human microcell hybrids by two-color FISH.

We describe the use of a long interspersed repetitive sequence (mCPE1.51) for mouse euchromatin specific "genome-painting". In fluorescence in situ hybridization (FISH) experiments, this probe was suitable for identification of the mouse genome and disclosure of translocations of mouse chromosome segments to chromosomes of different species without suppression hybridization. The euchromatin specificity of the probe allowed the discrimination between euchromatin and heterochromatin of mouse chromosomes. Simultaneous hybridization of the biotinylated mouse specific genome-painting probe and a digoxigenin-labeled human chromosome 3-specific cosmid probe to metaphase spreads of mouse-human microcell hybrid carrying a single deleted human chromosome 3 on a mouse fibrosarcoma background, allowed rapid identification and mapping of human chromosome 3.

Animals↗

PubMed2004

Wide-cross whole-genome radiation hybrid mapping of cotton (Gossypium hirsutum L.).

We report the development and characterization of a "wide-cross whole-genome radiation hybrid" (WWRH) panel from cotton (Gossypium hirsutum L.). Chromosomes were segmented by gamma-irradiation of G. hirsutum (n = 26) pollen, and segmented chromosomes were rescued after in vivo fertilization of G. barbadense egg cells (n = 26). A 5-krad gamma-ray WWRH mapping panel (N = 93) was constructed and genotyped at 102 SSR loci. SSR marker retention frequencies were higher than those for animal systems and marker retention patterns were informative. Using the program RHMAP, 52 of 102 SSR markers were mapped into 16 syntenic groups. Linkage group 9 (LG 9) SSR markers BNL0625 and BNL2805 had been colocalized by linkage analysis, but their order was resolved by differential retention among WWRH plants. Two linkage groups, LG 13 and LG 9, were combined into one syntenic group, and the chromosome 1 linkage group marker BNL4053 was reassigned to chromosome 9. Analyses of cytogenetic stocks supported synteny of LG 9 and LG 13 and localized them to the short arm of chromosome 17. They also supported reassignment of marker BNL4053 to the long arm of chromosome 9. A WWRH map of the syntenic group composed of linkage groups 9 and 13 was constructed by maximum-likelihood analysis under the general retention model. The results demonstrate not only the feasibility of WWRH panel construction and mapping, but also complementarity to traditional linkage mapping and cytogenetic methods.

DNA Primers↗

PubMedDate not supplied

Mutagenicity and carcinogenicity of N-methyl-N'-nitro-N-nitrosoguanidine I. Induction of chromosome aberrations and mitotic anomalies in Chinese hamster ovary cells.

Cultured chinese hamster ovary (CHO) cells were exposed to different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for either 24 hr or 6 days. For cytological consequences of MNNG exposure, CHO cells were treated for 24 hr and allowed a 24 hr recovery period prior to analysis; for the estimation of cytotoxicity of MNNG, cells were treated for 6 days followed by a 6 day recovery period. The cytotoxic effect of MNNG based on the colony-forming ability of treated cells showed a semi-logarithmic decrease in the number of colonies formed with an increase in MNNG concentration. The data on the cytological effect of MNNG on CHO cells demonstrate that the chemical causes both structural and numerical chromosomal anomalies and that the incidence of each aberration type is influenced by MNNG concentration. Karyomorphological analysis of CHO cells treated for 24 hr and fixed after four cell cycles showed a varied chromosome constitution ranging from 18 to 54. Chromosomal structural changes arising from breaks and/or exchanges were of chromatid types. Distribution of breaks along the length of the chromosomes and among chromosomes showed that no chromosome segment or chromosome was preferentially susceptible to the clastogenic effect of MNNG. MNNG-induced chromosomal rearrangements, such as ring configurations, exchanges, and dicentrics, exceeded such cytological errors as fragments and pulverizations. In a descending order of magnitude the induced structural rearrangements were ring chromosomes, triradials, quadriradials, and dicentrics.

Animals↗

PubMed1968

Chromosomal DNA synthesis in Drosophila melanogaster.

Analysis of labeling patterns in three chromosome segments of Drosophila melanogaster has shown that the replicative activity within chromosomes is temporally ordered. Moreover, specific labeling patterns on one chromosome occur with specific patterns on another chromosome with a very high degree of correlation. This circumstance leads to the conclusion that DNA synthesis among all the regions in the three chromosome segments studied is coordinated. The various labeling patterns observed in any one chromosome and the combinations of labeling patterns observed in all three chromosome segments can be arranged in ordered arrays, if one assumes that the DNA synthesis in each chromosome region will go to completion without stopping once it has started. Such arrays can serve as models for the temporal order of DNA synthesis among chromosome regions. They predict that in any one chromosome DNA replication begins and ends at very few loci and that synthesis at a larger number of points occurs at an intermediate time.

Autoradiography↗

PubMed1984

An extra segment in chromosome 1 of wild Mus musculus: a C-band positive homogeneously staining region.

An extra segment in chromosome 1 between bands C5 and D has been found in wild mouse populations. Its size varies between 6.1% and 30.1% of the length of a standard chromosome 1. It differs among individuals and populations but is constant in a genetically homogeneous line. According to its staining properties and variation in length it is a homogeneously staining region (HSR), a kind of segment otherwise found only in cell lines under strong selection and in tumor cells. G-banding gives a homogeneous staining of medium intensity. With C-banding, staining is positive, though lighter than that of centromeric heterochromatin. Fluorescence is dull with Hoechst 33258 and bright with mithramycin. The extra segment does not contain mouse satellite DNA sequences in any quantity detectable by in situ hybridization. Such an extra segment was found in several European populations of mice from Spain to Russia. It is carried through the germ line. It has been introduced into a laboratory mouse strain, and, by recombination, inserted into a Robertsonian metacentric chromosome for easier handling and identification.

Animals↗