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PubMed2005

Genetic determinants of metabolic syndrome components in the stroke-prone spontaneously hypertensive rat.

OBJECTIVE: The metabolic syndrome is a complex multifactorial disease, which results from interactions between genes on multiple chromosomes and environmental factors. Animal models may facilitate genetic analysis of complex phenotypes by allowing complete control of environmental conditions and the ability to produce designer strains. METHODS: Stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rat strains were used to construct congenic (SP.WKYGla2a), consomic (SP.WKYGlaYw, WKY.SPGlaYs) and double-introgressed (SP.WKYGla2aYw) strains, which were characterized for metabolic syndrome phenotypes (systolic blood pressure, glucose tolerance and lipid profile) after feeding a 60% fructose diet for 14 days. RESULTS: The Y consomic strain (SP.WKYGlaYw) demonstrated that the WKY Y chromosome significantly lowered triglyceride levels (3.77 +/- 0.60 versus 9.09 +/- 1.47 mmol/l; P < 0.001) and improved glucose tolerance [area under the curve (AUC): 26.93 +/- 0.81 versus 31.47 +/- 0.89; P < 0.05] compared with SHRSP. The chromosome 2 congenic strain (SP.WKYGla2a) exhibited significantly improved glucose tolerance (AUC: 28.19 +/- 1.17 versus 31.47 +/- 0.89; P < 0.05) and lower systolic blood pressure (161.2 +/- 6.2 versus 179.7 +/- 3.9 mmHg; P < 0.05) compared with SHRSP. 2 x 2 factorial ANOVA identified a significant interaction for glucose metabolism (P = 0.004) in the double-introgressed strain (SP.WKYGla2aYw) between chromosome 2 and Y. CONCLUSIONS: These results identify novel interacting regions on chromosome 2 and the Y chromosome influencing a cluster of metabolic and cardiovascular phenotypes. Translation to clinical studies will facilitate genetic dissection of human metabolic syndrome.

Animals↗

PubMed2005

Selection in backcross programmes.

Backcrossing is a well-known and long established breeding scheme where a characteristic is introgressed from a donor parent into the genomic background of a recurrent parent. The various uses of backcrossing in modern genetics, particularly with the help of molecular markers, are reviewed here. Selection in backcross programmes is used to either improve the genetic value of plant and animal populations or fine map quantitative trait loci. Both cases are helpful in our understanding of the genetic bases of quantitative traits variation.

Animals↗

PubMedDate not supplied

Genomic contributions in livestock gene introgression programmes.

The composition of the genome after introgression of a marker gene from a donor to a recipient breed was studied using analytical and simulation methods. Theoretical predictions of proportional genomic contributions, including donor linkage drag, from ancestors used at each generation of crossing after an introgression programme agreed closely with simulated results. The obligate drag, the donor genome surrounding the target locus that cannot be removed by subsequent selection, was also studied. It was shown that the number of backcross generations and the length of the chromosome affected proportional genomic contributions to the carrier chromosomes. Population structure had no significant effect on ancestral contributions and linkage drag but it did have an effect on the obligate drag whereby larger offspring groups resulted in smaller obligate drag. The implications for an introgression programme of the number of backcross generations, the population structure and the carrier chromosome length are discussed. The equations derived describing contributions to the genome from individuals from a given generation provide a framework to predict the genomic composition of a population after the introgression of a favourable donor allele. These ancestral contributions can be assigned a value and therefore allow the prediction of genetic lag.

Animals↗

PubMed2004

High-resolution genetic mapping at the Bph15 locus for brown planthopper resistance in rice (Oryza sativa L.).

Resistance to the brown planthopper (BPH), Nilaparvata lugens Stal, a devastating sucking insect pest of rice, is an important breeding objective in rice improvement programs. Bph15, one of the 17 major BPH resistance genes so far identified in both cultivated and wild rice, has been identified in an introgression line, B5, and mapped on chromosome 4 flanked by restriction fragment length polymorphism markers C820 and S11182. In order to pave the way for positional cloning of this gene, we have developed a high-resolution genetic map of Bph15 by positioning 21 DNA markers in the target chromosomal region. Mapping was based on a PCR-based screening of 9,472 F(2) individuals derived from a cross between RI93, a selected recombinant inbred line of B5 bearing the resistance gene Bph15, and a susceptible variety, Taichung Native 1, in order to identify recombinant plants within the Bph15 region. Recombinant F(2) individuals with the Bph15 genotype were determined by phenotype evaluation. Analysis of recombination events in the Bph15 region delimited the gene locus to an interval between markers RG1 and RG2 that co-segregated with the M1 marker. A genomic library of B5 was screened using these markers, and bacterial artificial chromosome clones spanning the Bph15 chromosome region were obtained. An assay of the recombinants using the sub-clones of these clones in combination with sequence analysis delimited the Bph15 gene to a genomic segment of approximately 47 kb. This result should serve as the basis for eventual isolation of the Bph15 resistance gene.

Animals↗

PubMed2005

Alien DNA introgression and wheat DNA rearrangements in a stable wheat line derived from the early generation of distant hybridization.

Polyploidy has been found to be common in plants. Bread or common wheat (Triticum aestivum L., 2n=42) is a good example of allopolyploid made up of three diploid genomes A, B and D. In recent years, by the study of mimicking the origination of common wheat, it was found that changes of DNA sequence and gene expression occurred at the early stages of artificial allohexaploid between tetraploid wheat and Aegilops tauschii, which was probably favorable to genetic diploidization of new synthetic hexaploid wheat. Common wheat 99L2 is a new line stable in genetic, which was derived from the early self-pollinated generation of wide hybrids between common wheat and rye. In this study, it was found that at least two rye DNA segments had been introgressed into 99L2. This result suggested that a mechanism of alien DNA introgression may exist, which was different from the traditional mechanism of chromosome pairing and DNA recombination between wheat and alien species. Meanwhile, during the introgression process of alien rye DNA segments, the changes in DNA sequences of wheat itself occurred.

Base Sequence↗

PubMed2006

Consomic strategies to localize genomic regions related to vascular reactivity in the Dahl salt-sensitive rat.

Chromosomal substitution strains afford the opportunity to discover regions of the rat genome that contain genes related to cardiovascular traits with the long-range goal of linking these genes to physiological function. PhysGen (Programs for Genomic Applications) created a consomic panel of rats derived from the introgression of a single chromosome (> or =95% of the BN chromosome, one at a time) of the Brown Norway (BN/NHsdMcwi) rat onto the homogeneous genetic background of the Dahl salt-sensitive rat (SS/JrHsdMcwi). For 3 wk before the experiment, the rats were maintained on a low-salt diet (0.4% NaCl). The dose response of aortic rings from each strain of rat to phenylephrine, acetylcholine, sodium nitroprusside, and three different levels of tissue bath hypoxia (10, 5, and 0% O2) was measured and compared with the parental SS rat. To maximize the possibility that differences among the strains would become apparent, each strain of rat including the parental SS and BN was also studied after being maintained on a high-salt diet (4.0% NaCl) for 3 wk. If the response of the aortic ring from a consomic strain to these vasoactive substances was different from that of the SS parental strain, it was concluded that the introgressed chromosome contained a gene or genes that contributed to that difference. Because the BN chromosome is removed from its native background and the SS rat loses a native chromosome, it is also necessary to consider the contribution of changes in gene-to-gene interaction.

Acetylcholine↗

PubMed2003

Paternal, maternal, and biparental molecular markers provide unique windows onto the evolutionary history of macaque monkeys.

We report the results of one of the first intrageneric analyses to simultaneously survey mitochondrial, Y-chromosomal, and autosomal loci from the same individuals representing the same taxa. Phylogenetic trees were constructed for each of these genetic systems from a pool of 63 macaques, representing all 19 recognized species in this genus, and eight outgroup taxa. The mitochondrial locus analyzed here (1.5 Kb) spans the 3' end of 12S rDNA, tRNA-VAL, and the 5' end of 16S rDNA; the Y chromosome dataset (3.1 Kb) consists of the genes SRY and TSPY; the two autosomal datasets include IRBP intron 3 (1.6 Kb) and the 5' half of C4 "long" intron 9 (3.3 Kb). A total of 1.35 million bases were read, revealing 682 variable sites within the genus Macaca. With regard to earlier unresolved issues of macaque evolution, a comparison of topologies reconstructed from each of the three genetic systems suggests: (1) four monophyletic species groups; (2) an initial bifurcation among Asian macaques between the silenus group progenitor and a M. fascicularis-like taxon, with the latter representing the probable common ancestor to all non-silenus group Asian macaques; (3) a possible hybrid origin of M. arctoides from proto-M. assamensis/thibetana and proto-M. fascicularis; and (4) contemporary introgression between M. mulatta and M. fascicularis in Indochina. Inferences 3 and 4 are of particular interest, because episodes of reticulate evolution often go undetected in analyses employing a single genetic system. Finally, divergence calculations suggest that, in female-philopatric taxa, mitochondrial bifurcations may typically predate Y-chromosomal divergences at the same node.

Animals↗

PubMed1998

Genetic diversity in porcine Oesophagostomum dentatum and O. quadrispinulatum and their delineation by isoenzyme analysis.

The genetic diversity in eight strains of Oesophagostomum dentatum and O. quadrispinulatum was investigated by the electrophoresis study of ten enzyme systems. The loci Idh-2, Fbp, Sdh, and Pgm were found to be diagnostic between the species examined. Both the proportion of fixed allelic differences (26.3%) and the genetic distance coefficient (D = 0.54) are well above the range for differentiation of valid species. Isoenzyme patterns of susceptible and resistant lines of O. dentatum showed at polymorphic loci a reduced genetic heterogeneity in the latter group. No qualitative difference in terms of the presence/absence of alleles was observed among susceptible and resistant isolates with the enzymes studied. The detection of one possible hybrid indicates that introgression in O. dentatum and O. quadrispinuatum may occur.

Alleles↗

PubMedDate not supplied

Self-administration of ethanol: towards the location of predisposing polygenes in quasi-congenic animal models.

Alcohol consumption by C57BL/6By background and BALB/cJ donor strains, and by two recently developed quasi-congenic QTL-introgression strains, which share about 96% of their genes with the background strain, was studied in a limited access paradigm. Alcohol and water were offered for 60 min per day using modified pipettes on a drinking cage. Increasing concentration of alcohol solutions, 3, 6, and 12%, were given for days 1-7, 8-14, and 15-22, respectively. Consumption of the 12% alcohol solution was highest in C57BL/6By (0.72 g/kg/h), lowest in BALB/cJ (0.14 g/kg/h). The B6.Cb4i5 beta 13 quasi-congenic strain, in spite of its genetic similarity to the C57BL/6By background strain, consumed significantly less alcohol (0.41 g/kg/h) than the background strain. The results suggest that polygenes that reduce alcohol consumption were introgressed from the BALB/cJ donor strain into the C57BL/6By background strain, and that the b4i5 series of the B6.C quasi-congenic QTL-introgression strains may be useful in mapping genes that influence alcohol-related behaviors. Locations of the introgressed candidate polygenes were tentatively identified by analyzing microsatellite maps of two of the quasi-congenic strains.

Animals↗

PubMed1987

Genetic control of a novel series of trypsin inhibitors in wheat and its relatives.

The aneuploids of Chinese Spring wheat have been used to locate the genes (Ti-2) coding for a novel series of trypsin inhibitors to the long arms of the homoeologous group 5 chromosomes. Three allelic variants at the 5D locus were detected in a limited survey among wheat varieties, but no variation at the loci on either chromosome 5A or chromosome 5B was detected. Homoeoloci were found in a number of alien relatives, and in the majority of cases, these were present on the group 5 homoeologue. However, in Aegilops umbellulata, the Ti-U2 locus was located on a chromosome presumed to belong to homoeologous group 1. No Hordeum vulgare or H. chilense Ti-2 gene was expressed in a wheat background. This new marker will be especially useful as a screening mechanism for nullisomy of chromosome 5B in work aimed at introgression of alien chromatin into wheat.

Chromosome Mapping↗

PubMed1999

Decreased ethanol sensitivity and tolerance development in gamma-protein kinase C null mutant mice is dependent on genetic background.

Initial sensitivity and tolerance development to the sedative-hypnotic and hypothermic effects of ethanol were investigated in gamma-protein kinase C (PKC) null mutant mice. Null mutants from a C57BL/6J x 129/SvJ mixed genetic background demonstrated decreased ethanol sensitivity and failed to develop chronic tolerance after 10 days of ethanol liquid diet. However, when the null mutation was introgressed onto a C57BL/6J background for six generations, the "no tolerance" phenotype for sedative-hypnotic and hypothermic effects of ethanol was no longer apparent Outcrossing the gamma-PKC null mutation to a C57BL/6J x 129/SvEvTac mixed background restored the "no tolerance" phenotype to ethanol-induced sedation after chronic ethanol diet; however, as measured by hypothermia, tolerance was still evident in the null mutant mice. These observations and the results of tests of chronic tolerance in the C57BL/6J, 129/SvJ, and 129/SvEvTac background inbred strains indicate that gamma-PKC plays an important role in initial sensitivity and tolerance to ethanol. However, the impact of gamma-PKC is modulated by the background genotype. These results stress the importance of including the effect of genetic background when evaluating the effects of single gene mutations on quantitative behavioral traits.

Animals↗

PubMed1993

Allozyme variability in the Italian wolf (Canis lupus) population.

Multilocus protein electrophoresis was used to estimate genetic variability in a sample of 38 Italian wolves (Canis lupus). Percentage of polymorphic loci was p = 10.0 per cent (four polymorphic loci out of 40 examined), and average observed heterozygosity was Ho = 0.028. Genotypes were in Hardy-Weinberg equilibrium. Electrophoretic analysis does not indicate a significant reduction of genetic variability at nuclear gene loci following at least one century of isolation from other European populations and demographic fluctuations suggested by recent range contraction and expansion. These findings are compared with published allozyme and mitochondrial DNA data for dogs, Canadian wolves, and introgressed wolf x coyote populations from Minnesota and Isle Royale (U.S.A.).

Animals↗

PubMed1995

[Genetic structure and origin of the tetraploid toad Bufo danatensis Pisanetz, 1978 (Amphibia, Bufonidae) from Central Asia. Biochemical polymorphism and comparison of the level of heterozygosity of diploid species with tetraploid species].

Comparison of individual variation at 24 biochemical loci in members of the species complex of Palearctic green toads showed that the heterozygosity of the tetraploid species Bufo danatensis (Hobs + 0.45) was significantly higher than that of the diploid species B. viridis, B. sp., and B. raddei (Hobs = 0.009 - 0.103). Such difference can be explained only by a hybrid origin of the tetraploid species. Individual electrophoretic variability of the polyploid toad species is associated with an allelic variation that is manifested in constantly heterozygous spectra as the gene dosage effect. At the population level, this phenomenon found in Pamir toads is caused by irregular meiosis in founders of the population or by directional changes in gene regulation. Genotypic distributions in zones of contact of the diploid and tetraploid taxons demonstrate the possibility of restricted introgressive hybridization.

Animals↗

PubMed2001

Mitochondrial DNA variation and GIS analysis confirm a secondary origin of geographical variation in the bushcricket Ephippiger ephippiger (Orthoptera: Tettigonioidea), and resurrect two subspecies.

Geographic variation within species can originate through selection and drift in situ (primary variation) or from vicariant episodes (secondary variation). Most patterns of subspecific variation within European flora and fauna are thought to have secondary origins, reflecting isolation in refugia during Quaternary ice ages. The bushcricket Ephippiger ephippiger has an unusual pattern of geographical variability in morphology, behaviour and allozymes in southern France, which has been interpreted as reflecting recent primary origins rather than historical isolation. Re-analysis of this variation using Geographical Information Systems (GIS) suggests a possible zone of hybridization within a complex pattern of geographical variation. Here we produce a genetic distance matrix from restriction fragment length polymorphism (RFLP) bandsharing of an approximately 4.5 kb fragment of mitochondrial DNA (mtDNA), and compare this with predictions resulting from the GIS analysis. The mtDNA variation supports a postglacial origin of geographical variation. Partial Mantel test comparisons of genetic distances with matrices of geographical distance, relevant environmental characteristics and possible refugia show refugia to be the best predictors of genetic distance. There is no evidence to support isolation by distance. However, environmental contrasts do explain significant variation in genetic distance after allowing for the effect of refugial origin. Also, a neighbour-joining tree has a major division separating eastern and western forms. We conclude that the major source of variation within the species is historical isolation in glacial refugia, but that dispersal, hybridization and selection associated with environmental features has influenced patterns of mtDNA introgression. At least two valid subspecies can be defined.

Animals↗

PubMed2001

The zone of sympatry and hybridization of Mytilus edulis and M. galloprovincialis, as described by intron length polymorphism at locus mac-1.

Intron-size variation at the actin gene locus mac-1 was used to characterize mussel, Mytilus spp., populations in the approximately 2000-km wide zone of contact and hybridization ('hybrid zone') between M. edulis and M. galloprovincialis in western Europe. Twenty-five samples were collected in 1995-99 in locations within the hybrid zone and from reference populations of each species. We used correspondence analysis on the matrix of allelic frequencies to determine which alleles are characteristic of each species, and to characterize samples along the genetic gradient between M. edulis and M. galloprovincialis. In the hybrid zone, some samples exhibited mac-1 allele frequencies that were typical of M. edulis; other samples were distributed along the M. edulis/M. galloprovincialis gradient and displayed variable levels of intergradation that were not correlated with geography. Some of the latter samples exhibited significant heterozygote deficiencies. The simple admixture hypothesis (Wahlund effect) could not be rejected for two-fifths of the samples. The hybrid zone thus appeared as a mosaic of populations which are either pure M. edulis, or hybrid between M. galloprovincialis and M. edulis, or a mixture of the foregoing with M. galloprovincialis individuals. These results were consistent with published allozyme data, suggesting that they can be extended to the entire nuclear genome. M. edulis mac-1 alleles were present at moderate frequency in Atlantic M. galloprovincialis, and at significantly lower frequency in some Mediterranean samples. This pattern was homogeneous over a broad geographical range within each basin. It was not evident that introgression of M. edulis into M. galloprovincialis presently occurs south of the zone of contact. We propose that the distinctness of the Atlantic M. galloprovincialis population results from past introgression by M. edulis alleles.

Actins↗

PubMed2005

An ancestral oomycete locus contains late blight avirulence gene Avr3a, encoding a protein that is recognized in the host cytoplasm.

The oomycete Phytophthora infestans causes late blight, the potato disease that precipitated the Irish famines in 1846 and 1847. It represents a reemerging threat to potato production and is one of >70 species that are arguably the most devastating pathogens of dicotyledonous plants. Nevertheless, little is known about the molecular bases of pathogenicity in these algae-like organisms or of avirulence molecules that are perceived by host defenses. Disease resistance alleles, products of which recognize corresponding avirulence molecules in the pathogen, have been introgressed into the cultivated potato from a wild species, Solanum demissum, and R1 and R3a have been identified. We used association genetics to identify Avr3a and show that it encodes a protein that is recognized in the host cytoplasm, where it triggers R3a-dependent cell death. Avr3a resides in a region of the P. infestans genome that is colinear with the locus containing avirulence gene ATR1(NdWsB) in Hyaloperonospora parasitica, an oomycete pathogen of Arabidopsis. Remarkably, distances between conserved genes in these avirulence loci were often similar, despite intervening genomic variation. We suggest that Avr3a has undergone gene duplication and that an allele evading recognition by R3a arose under positive selection.

Agrobacterium tumefaciens↗

PubMed2000

The origin of the domestic pig: independent domestication and subsequent introgression.

The domestic pig originates from the Eurasian wild boar (Sus scrofa). We have sequenced mitochondrial DNA and nuclear genes from wild and domestic pigs from Asia and Europe. Clear evidence was obtained for domestication to have occurred independently from wild boar subspecies in Europe and Asia. The time since divergence of the ancestral forms was estimated at approximately 500,000 years, well before domestication approximately 9,000 years ago. Historical records indicate that Asian pigs were introduced into Europe during the 18th and early 19th centuries. We found molecular evidence for this introgression and the data indicated a hybrid origin of some major "European" pig breeds. The study is an advance in pig genetics and has important implications for the maintenance and utilization of genetic diversity in this livestock species.

Animals↗

PubMed2002

Phylogeography of Lake Malawi cichlids of the genus Pseudotropheus: significance of allopatric colour variation.

One of the most compelling features of the cichlid fishes of the African Great Lakes is the seemingly endless diversity of male coloration. Colour diversification has been implicated as an important factor driving cichlid speciation. Colour has also been central to cichlid taxonomy and, thus, to our concept of species diversity. We undertook a phylogeographical examination of several allopatric populations of the Lake Malawi cichlid Pseudotropheus zebra in order to reconstruct the evolutionary history of the populations, which exhibit one of two dorsal fin colours. We present evidence that populations with red dorsal fins (RT) are not monophyletic. The RT population defining the northern limit of the distribution has evidently originated independently of the southern RT populations, which share a common ancestry. This evidence of species-level colour convergence is an important discovery in our understanding of cichlid evolution. It implies that divergence in coloration may accompany speciation, and that allopatric populations with similar coloration cannot be assumed to be conspecific. In addition to this finding, we have observed evidence for introgression, contributing to current evidence that this phenomenon may be extremely widespread. Thus, in species-level phylogenetic reconstructions, including our own, consideration must be given to the potential effects of introgression.

Alleles↗