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Results for “Genetic Introgression”

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PubMed1997

Chromosomal transmission bias in laboratory hybrids between wild strains of the two European subspecies of house mice.

Laboratory crosses between wild strains of the two European house mouse subspecies Mus musculus domesticus (2n = 34) and M. m. musculus (2n = 40) were performed to analyze the selective processes involved in the non-introgression of centromeric regions of Robertsonian (Rb) fusions in the Danish hybrid zone. The chromosomal analysis of 226 backcross progeny from 22 reciprocal crosses showed that the segregation of the three Rb fusions present did not significantly differ from Mendelian expectations. However, a significant negative correlation was found between Rb transmission rates and the average litter sizes of the F1 pairs. Among the different models of selection discussed, the most likely one supported the existence of two opposing selective factors resulting in an overall compensation of chromosomal types in the backcross progeny. A two-phase selective process involving embryo competition was postulated with non-Rb carriers being favored during pre-implantation but disadvantaged after implantation. Such balanced selective pressures acting on musculus non-Rb centromeres are compatible with the steep slope and off-centered position of the chromosomal cline observed in the Danish hybrid zone. These results suggested that these selective factors may be more related to centromere origin (musculus or domesticus) than to centromere structure (Rb or non-Rb).

Animals↗

PubMed2003

Congenic mapping and candidate sequencing of susceptibility genes for Type 1 diabetes in the NOD mouse.

Inheritance of type 1 diabetes is polygenic with a major susceptibility gene located in the major histocompatibility complex (MHC). In addition to MHC-linked susceptibility, a number of susceptibility genes have been mapped outside the MHC in both humans and animal models. In order to localize and identify susceptibility genes for type 1 diabetes, we have developed a series of congenic strains in which either susceptibility intervals from the NOD mouse, a mouse model of type 1 diabetes, were introgressed onto control background genes or protective intervals from control strains were introgressed onto NOD background genes. NOD. CTS-H-2 congenic mice, which possess recombinant MHC with NOD alleles at class II A and E genes, which are candidates for Idd1, revealed that Idd1 consists of multiple components, one in class II (Idd1) and the other adjacent to, but distinct from, Idd1 (Idd16). Phenotypes of NOD. IIS-Idd3 congenic mice, which share the same alleles at both Il2 and Il21 as the NOD mouse, were indistinguishable from the NOD parental strain, indicating that both Il2 and Il21 are candidates for Idd3. In contrast, NOD. IIS-Idd10 congenic mice, which share the same alleles at Fcgr1, a previous candidate for Idd10, as the NOD mouse, were protected from type 1 diabetes, suggesting that Fcgr1 may not be responsible for the Idd10 effect. These data suggest that the use of strain colony closely related to a disease model to find the same candidate mutation on different haplotypes and make congenic strains with this recombinant chromosome, termed ancestral haplotype congenic mapping, is an effective strategy for fine mapping and identification of genes responsible for complex traits.

Animals↗

PubMed2006

A chloroplast genealogy of myrmecophytic Macaranga species (Euphorbiaceae) in Southeast Asia reveals hybridization, vicariance and long-distance dispersals.

Macaranga (Euphorbiaceae) includes about 280 species with a palaeotropic distribution. The genus not only comprises some of the most prominent pioneer tree species in Southeast Asian lowland dipterocarp forests, it also exhibits a substantial radiation of ant-plants (myrmecophytes). Obligate ant-plant mutualisms are formed by about 30 Macaranga species and 13 ant species of the genera Crematogaster or Camponotus. To improve our understanding of the co-evolution of the ants and their host plants, we aim at reconstructing comparative organellar phylogeographies of both partners across their distributional range. Preliminary evidence indicated that chloroplast DNA introgression among closely related Macaranga species might occur. We therefore constructed a comprehensive chloroplast genealogy based on DNA sequence data from the noncoding ccmp2, ccmp6, and atpB-rbcL regions for 144 individuals from 41 Macaranga species, covering all major evolutionary lineages within the three sections that contain myrmecophytes. A total of 88 chloroplast haplotypes were identified, and grouped into a statistical parsimony network that clearly distinguished sections and well-defined subsectional groups. Within these groups, the arrangement of haplotypes followed geographical rather than taxonomical criteria. Thus, up to six chloroplast haplotypes were found within single species, and up to seven species shared a single haplotype. The spatial distribution of the chloroplast types revealed several dispersals between the Malay Peninsula and Borneo, and a deep split between Sabah and the remainder of Borneo. Our large-scale chloroplast genealogy highlights the complex history of migration, hybridization, and speciation in the myrmecophytes of the genus Macaranga. It will serve as a guideline for adequate sampling and data interpretation in phylogeographic studies of individual Macaranga species and species groups.

Animals↗

PubMed1993

Co-transcription pattern of an introgressed operon in the maize chloroplast genome comprising four ATP synthase subunit genes and the ribosomal rps2.

Several examples of the introduction of a gene from one gene complex into another (introgression) are found when chloroplast RP gene clusters are compared to those in Escherichia coli or cyanobacteria. Here we describe the transcript pattern of one such cluster from maize (Zea mays) that includes the genes for 4 subunits of the thylakoid ATP synthase (atpI, H, F, A) and the rps2 gene. Twelve transcript species covering the size range from 7,000 to 800 nt were identified in RNA isolated from dark-grown and greening maize seedlings, and several of them were characterized by reverse transcription analysis. A major species of 6,200 nt, with its 5' end at 181 nt upstream of the initiating ATG of rps2, contained the transcripts of all the 5 genes. Two further sets of transcripts having their 5' ends ca. 120 and 50 nt upstream of the initiation codons of the atpI and atpH genes were also identified. Thus, this plastid gene cluster in maize is functionally organized as an operon with additional regulatory features to allow for increased accumulation of mRNAs for the thylakoid components.

Adenosine Triphosphatases↗

PubMed2006

Transgenics and vertebrate cloning as tools for species conservation.

It has been suggested that transgenics and vertebrate cloning have a role to play in conservation. Now is the time to evaluate their risks and benefits, before these technologies are widely implemented in our field. Direct risks of transgenics include escape and introgression of transgenes into wild populations; weedy invasion by transgenic organisms; toxicity or pathogenicity of engineered organisms and their products; and human error in the field testing and tracking of transgenic organisms. Indirect risks include environmental effects of increased herbicide use; the danger that engineered organisms may aid the development of bioweapons; the likelihood that gene patenting will lead to the privatization of natural resources; and the diversion of support from less glamorous forms of conservation. Formal risk assessments are commonly used to evaluate transgenic procedures, but our incomplete understanding of both ecosystem processes and the action of transgenes renders most of these assessments scientifically and socially unjustified. Nevertheless, a few, low-risk applications of transgenics may be possible: for example, "super-sterile" ornamental cultivars. Vertebrate cloning poses little risk to the environment, but it can consume scarce conservation resources, and its chances of success in preserving species seem poor To date, the conservation benefits of transgenics and vertebrate cloning remain entirely theoretical, but many of the risks are known and documented. Conservation biologists should devote their research and energies to the established methods of conservation, none of which require transgenics or vertebrate cloning.

Animals↗

PubMed1998

Paternal directional mating in two Amerindian subpopulations located at different altitudes in northwestern Argentina.

We used mitochondrial DNA (mtDNA) and Y-chromosome DNA polymorphisms to analyze the ethnic origin of maternal and paternal lineages in two Amerindian subpopulations from northwestern Argentina. One of the subpopulations was from San Salvador de Jujuy, located 1200 m above sea level. The second subpopulation inhabits the Quebrada de Humahuaca area at altitudes ranging from 2500 to 3500 m. Both subpopulations have the same ethnic background. All mtDNA haplotypes were identified as Amerindian with a frequency of 64.6% of the B form (9-bp deletion in mtDNA region V). Because all Central Andean Amerindian populations studied so far exhibit high frequencies of the B haplotype, we propose that they probably are derived from a common ancestral population that inhabited the Central Andes 6000-8000 years B.P. The presence of paternal directional mating (asymmetric contribution of one parental lineage to interethnic gene mixtures) was demonstrated by the finding of an average introgression of 40.5% Spanish Y chromosomes into our Amerindian sample. This introgression was more evident at low altitude than at high altitude, with frequencies of 64.3% in San Salvador de Jujuy (low altitude) and 27.6% in Quebrada de Humahuaca (high altitude) (p < 0.05). The San Salvador de Jujuy subpopulation also showed a significantly higher Y-chromosome gene variability than the Quebrada de Humahuaca subpopulation. These findings are in good agreement with historical reports indicating that the colonization of South America was undertaken by men who usually practiced polygamous unions with Amerindian women and that San Salvador de Jujuy was the main northwestern Argentinian region of European to Amerindian gene admixture. We found 16.7% of cases with Spanish Y chromosomes and Amerindian family names, and the same percentage with Amerindian Y chromosomes and Hispanic names. The former group probably is the result of unions between Hispanic men, who transmitted the Y chromosome, and Amerindian women, who transmitted the family name to the progeny. The latter group likely illustrates the practice of changing names from Amerindian to Hispanic during the baptism of native Americans in colonial times.

Adult↗

PubMed2006

Impact of chromosome 2 obesity loci on cardiovascular complications of insulin resistance in LDL receptor-deficient C57BL/6 mice.

Previous characterization of mouse chromosome 2 identified genomic intervals that influence obesity, insulin resistance, and dyslipidemia. For this, resistant CAST/Ei (CAST) alleles were introgressed onto a susceptible C57BL/6J background to generate congenic strains with CAST alleles encompassing 67-162 Mb (multigenic obesity 6 [MOB6]) and 84-180 Mb (MOB5) from mouse chromosome 2. To examine the effects of each congenic locus on atherosclerosis and glucose disposal, we bred each strain onto a sensitizing LDL receptor-null (LDLR(-/-)) C57BL/6J background to predispose them to hypercholesterolemia and insulin resistance. LDLR(-/-) congenics and controls were characterized for measures of atherogenesis, insulin sensitivity, and obesity. We identified a genomic interval unique to the MOB6 congenic (72-84 Mb) that dramatically decreased atherosclerosis by approximately threefold and decreased insulin resistance. This region also reduced adiposity twofold. Conversely, the congenic region unique to MOB5 (162-180 Mb) increased insulin resistance but had little effect on atherosclerosis and adiposity. The MOB congenic intervals are concordant to human and rat quantitative trait loci influencing diabetes and atherosclerosis traits. Thus, our results define a strategy for studying the poorly understood interactions between diabetes and atherosclerosis and for identifying genes underlying the cardiovascular complications of insulin resistance.

Alleles↗

PubMed2005

Chloroplast SSR polymorphisms in the Compositae and the mode of organellar inheritance in Helianthus annuus.

Because organellar genomes are often uniparentally inherited, chloroplast (cp) and mitochondrial (mt) DNA polymorphisms have become the markers of choice for investigating evolutionary issues such as sex-biased dispersal and the directionality of introgression. To the extent that organellar inheritance is strictly maternal, it has also been suggested that the insertion of transgenes into either the chloroplast or mitochondrial genomes would reduce the likelihood of gene escape via pollen flow from crop fields into wild plant populations. In this paper we describe the adaptation of chloroplast simple sequence repeats (cpSSRs) for use in the Compositae. This work resulted in the identification of 12 loci that are variable across the family, seven of which were further shown to be highly polymorphic within sunflower (Helianthus annuus). We then used these markers, along with a novel mtDNA restriction fragment length polymorphism (RFLP), to investigate the mode of organellar inheritance in a series of experimental crosses designed to mimic the initial stages of crop-wild hybridization in sunflower. Although we cannot rule out the possibility of extremely rare paternal transmission, our results provide the best evidence to date of strict maternal organellar inheritance in sunflower, suggesting that organellar gene containment may be a viable strategy in sunflower. Moreover, the portability of these markers suggests that they will provide a ready source of cpDNA polymorphisms for use in evolutionary studies across the Compositae.

Asteraceae↗

PubMed2006

Monitoring the escape of transgenic oilseed rape around Japanese ports and roadsides.

An investigation was carried out to monitor the escape and spread of oilseed rape (Brassica napus) transgenic plants and the introgression of transgenes to its closely related feral species in Japan. We screened a total of about 7500 feral B. napus, 300 B. rapa, and 5800 B. juncea seedlings from maternal plants in 143 locations at several ports, roadsides, and riverbanks. The presence of glufosinate-resistance or glyphosate-resistance transgenes in these seedlings was confirmed by means of herbicide treatments and also immunochemical and DNA analyses. B. napus plants with herbicide-resistant transgenic seeds were found at five of six major ports and along two of four sampled roadsides in the Kanto District. Transgenic oilseed rape plants have not been commercially cultivated in Japan, suggesting that the transgenes would probably have come from imported transgenic seeds that were spilled during transportation to oilseed processing facilities. No transgenes were detected in seeds collected from B. napus plants growing along riverbanks in the Kanto District or in seeds from closely related species (B. rapa and B. juncea). To our knowledge, this is the first published example of feral, transgenic populations occurring in a nation where the transgenic crop has not been cultivated commercially.

Aminobutyrates↗

PubMed2004

Introgression-mapping of genes for drought resistance transferred from Festuca arundinacea var. glaucescens into Lolium multiflorum.

Procedures for the transfer of genes for drought resistance from Festuca glaucescens (2n=4x=28) into Lolium multiflorum (2n=2x=14) are described. Following the initial hybridisation of a synthetic autotetraploid of L. multiflorum (2n=4x=28) with F. glaucescens, the F1 hybrid was backcrossed twice onto diploid L. multiflorum (2n=2x=14) to produce a diploid Lolium genotype with a single F. glaucescens introgression located distally on the nucleolar organiser region arm of chromosome 3. The transmission of F. glaucescens-derived amplified fragment length polymorphisms and a sequence-tagged-site (STS) marker was monitored throughout the breeding programme. Those genotypes of a mapping population of backcross 3 that survived combined severe drought and heat stress all contained the F. glaucescens-derived markers. The STS marker provided a prototype for a PCR-based system for high-throughput screening during cultivar development for the presence of the F. glaucescens-derived genes for drought resistance. The frequency of intergeneric recombination between L. multiflorum and F. glaucescens is described. During the initial stages of the breeding programme, preferential intraspecific chromosome pairing between Lolium homologues and Festuca homoeologues dominated with low frequencies of intergeneric chromosome associations. However, these increased in the backcross 1 due to the absence of opportunities for intraspecific chromosome pairing between homoeologous Festuca chromosomes following the loss of half of the Festuca chromosomes. Once transferred to Lolium, F. glaucescens sequences recombined with Lolium at high frequencies, thereby enabling the loss of potentially deleterious gene combinations that might reduce the forage quality of Lolium.

Acclimatization↗

PubMed1997

The plasmacytoma resistance gene, Pctr2, delays the onset of tumorigenesis and resides in the telomeric region of chromosome 4.

Mouse plasmacytomas share pathogenetic features in common with both multiple myeloma and Burkitt's lymphoma in humans. Susceptibility to plasmacytoma induction by intraperitoneal pristane in mice is controlled by multiple genes. At least two of these genes reside on mouse chromosome 4 in regions of the genome sharing linkage homology with human chromosomes 9p21, 1p32, and 1p36. A series of congenic strains recombinant for regions of mouse chromosome 4 in the vicinity of the Pctr2 predisposition locus were created and typed for their tumor susceptibility/resistance phenotypes. These strains were derived by introgressively backcrossing alleles from resistant DBA/2 mice onto the susceptible BALB/cAnPt background. Six resistant and two susceptible strains were allelotyped for 10 genes and 49 random DNA markers to identify the smallest region of overlap in the resistant strains. These studies have determined that the Pctr2 locus resides in either a 500-kb interval proximal to Nppa, or in a 1- to 2-centiMorgan (cM) interval distal to Nppa. In these congenic strain analyses, the Nppa and Fv1 loci, in addition to genes within about 1 cM of these loci, have been excluded as candidates for the Pctr2 locus. A relevant locus that may reside in this interval is Rep2; it is associated with the efficiency of repairing X-ray induced DNA damage sustained during the G2 phase of the mitotic cycle. The Pctr2 locus acts in a codominant fashion. F1 hybrids between resistant and susceptible congenic strains exhibit a reduced tumor incidence and a significant delay in the onset of tumorigenesis. Identification and eventual cloning of the Pctr2 locus may assist in the identification of genes involved in many types of cancer showing aberrations in human chromosome 1p36.

Alleles↗

PubMed2006

Marker-free transgenic (MFT) near-isogenic introgression lines (NIILs) of 'golden' indica rice (cv. IR64) with accumulation of provitamin A in the endosperm tissue.

We have developed near-isogenic introgression lines (NIILs) of an elite indica rice cultivar (IR64) with the genes for beta-carotene biosynthesis from dihaploid (DH) derivatives of golden japonica rice (cv. T309). A careful analysis of the DH lines indicated the integration of the genes of interest [phytoene synthase (psy) and phytoene desaturase (crtI)] and the selectable marker gene (hygromycin phosphotransferase, hph) in two unlinked loci. During subsequent crossing, progenies could be obtained carrying only the locus with psy and crtI, which was segregated independently from the locus containing the hph gene during meiotic segregation. The NIILs (BC(2)F(2)) showed maximum similarity with the recurrent parent cultivar IR64. Further, progenies of two NIILs were devoid of any fragments beyond the left or right border, including the chloramphenicol acetyltransferase (cat) antibiotic resistance gene of the transformation vector. Spectrophotometric readings showed the accumulation of up to 1.06 microg total carotenoids, including beta-carotene, in 1 g of the endosperm. The accumulation of beta-carotene was also evident from the clearly visible yellow colour of the polished seeds.

Alkyl and Aryl Transferases↗

PubMed2000

Homoeoallelic gene Ncc-tmp of Triticum timopheevii conferring compatibility with the cytoplasm of Aegilops squarrosa in the tetraploid wheat nuclear background.

A nuclear gene, Ncc-tmp1A, of Triticum timopheevii is required for the nucleus-cytoplasm (NC) compatibility in tetraploid NC hybrids with the cytoplasm of Aegilops squarrosa. A euploid NC hybrid of T. durum was previously produced by introgressing the gene from chromosome 1A of T. timopheevii. To examine the possible presence of a functional homoeoallele in the G genome of T. timopheevii, segregation of seed viability was studied as a marker phenotype in BC1s involving the two types of NC hybrids, (Ae. squarrosa)-T. timopheevii and (Ae. squarrosa)-T. turgidum. The result of these test crosses suggested that the G genome possesses a functional homoeoallele Ncc-tmp1G. Segregation of two RAPD (random amplified polymorphic DNA) markers that were closely linked to Ncc-tmp1A was further studied among the viable BC1s obtained from a test cross of (Ae. squarrosa)-T. timopheevii x T. turgidum. Some viable BC1 segregants without the markers were obtained, suggesting a limited degree of transmission of chromosome 1G carrying Ncc-tmp1G. However, a similar RAPD analysis of BC1s obtained after backcrosses of reciprocal F1s of T. timopheevii/T. turgidum with T. turgidum showed random marker segregation. Thus, it was concluded that Ncc-tmp1A is not required for compatibility with its own cytoplasm. Southern blot analysis of the euploid NC hybrid using RFLP (restriction fragment length polymorphism) markers on the homologous group 1 chromosomes showed that Ncc-tmp1A locates in the centromeric region.

Alleles↗

PubMed2006

Molecular analysis, cytogenetics and fertility of introgression lines from transgenic wheat to Aegilops cylindrica host.

Natural hybridization and backcrossing between Aegilops cylindrica and Triticum aestivum can lead to introgression of wheat DNA into the wild species. Hybrids between Ae. cylindrica and wheat lines bearing herbicide resistance (bar), reporter (gus), fungal disease resistance (kp4), and increased insect tolerance (gna) transgenes were produced by pollination of emasculated Ae. cylindrica plants. F1 hybrids were backcrossed to Ae. cylindrica under open-pollination conditions, and first backcrosses were selfed using pollen bags. Female fertility of F1 ranged from 0.03 to 0.6%. Eighteen percent of the sown BC1s germinated and flowered. Chromosome numbers ranged from 30 to 84 and several of the plants bore wheat-specific sequence-characterized amplified regions (SCARs) and the bar gene. Self fertility in two BC1 plants was 0.16 and 5.21%, and the others were completely self-sterile. Among 19 BC1S1 individuals one plant was transgenic, had 43 chromosomes, contained the bar gene, and survived glufosinate treatments. The other BC1S1 plants had between 28 and 31 chromosomes, and several of them carried SCARs specific to wheat A and D genomes. Fertility of these plants was higher under open-pollination conditions than by selfing and did not necessarily correlate with even or euploid chromosome number. Some individuals having supernumerary wheat chromosomes recovered full fertility.

Breeding↗

PubMed1996

Genomic incompatibilities in the hybrid zone between house mice in Denmark: evidence from steep and non-coincident chromosomal clines for Robertsonian fusions.

The pattern of chromosomal variation is investigated in house mice from the Danish hybrid zone between the translocation-prone Mus musculus domesticus and the chromosomally conservative M. m. musculus. The cytogenetic analysis confirmed the non-introgression of three pairs of Robertsonian (Rb) fusions from M. m. domesticus into the M. m. musculus genome. The geographic distribution of two of these Rb fusions was shown to follow staggered chromosomal clines which increased in steepness the closer they were to the centre of the hybrid zone as defined by allozymes. Analysis of alternate hypotheses suggests that chromosomal differentiation of the Danish domesticus occurred after contact was established with musculus. The staggering of the clines would reflect the order of arrival of the Rb fusions into the hybrid zone. Several models with different processes of underdominance of the chromosomal heterozygotes are discussed to account for the difference in width between clines. A selective model with increasing levels of genomic underdominance due to interaction with a progressively enriched musculus genome provides the best fit for the observed pattern. Selection against Rb fusions with little effect on the recombination of linked allozyme markers supports the view that no reduction in gene flow due to chromosomal heterozygosity is yet apparent through the hybrid zone and that only the centromeric segments of the Rb fusions are incompatible with the musculus genome.

Animals↗

PubMed2001

Cytotaxonomic characteristics of the genus Glyptotendipes Kieffer (Chironomidae, Diptera) from fish and retention ponds (Silesia, southern Poland).

The cytotaxonomic characteristics of species of the genus Glyptotendipes (Chironomidae): G. glaucus Meigen, G. paripes Edwards, and G. barbipes (Staeger) are described. The studied material was collected from a fish pond at Gołysz and a sewage retention pond at Chybie in Silesia. All the studied species have the chromosome set 2n = 8, but with many specific structural and functional changes. The cytogenetic data of G. glaucus showed that the studied specimens of this species have been produced by the introgressive hybridization of two sibling species: G. glaucus x G. pallens, and subsequent crossing-over in the hybrid chromosome CD. Owing to this process, the band pattern of chromosome arm D coincided with those of G. pallens. New aberrations (homo- and heterozygous deletions in arm G as well as heterozygous inversions in chromosome arm B) were detected in G. glaucus. Specific band sequences were discovered in chromosomes of G. paripes. The band patterns established in chromosomes AB and G of this species were identical with those of Siberian populations. The banding patterns of the polytene chromosomes of G. barbipes do not differ from the standard. However, high frequency of pericentric inversion of chromosome AB was established. Many new puffs were found in the polytene chromosomes of all the studied species. Their nucleolar organizer was very sensitive to environmental changes. In G. glaucus it appeared in three different states: very active, slightly active, and heterozygous state. The organic pollution existing in the sewage retention pond may contribute to possible mutations and chromosomal damage in Glypotendipes species. Structural and functional rearrangements of the polytene chromosomes of these species mobilized their genomes and provide for survival under polluted conditions.

Adaptation, Physiological↗

PubMed2002

Partial hybridization in wide crosses between cultivated sunflower and the perennial Helianthus species H. mollis and H. orgyalis.

To obtain introgressed sunflower lines with improved disease resistance, interspecific crosses were performed with foreign perennial species. We report on several unusual features displayed by these hybrid plants. The methods used to produce the kernels affected yield and genotypes of progeny. Phenotypic traits and DNA markers were investigated in 97 plants derived from cross-pollination between annual diploid cultivated sunflower (Helianthus annuus) and the perennial diploid species H. mollis or H. orgyalis, and the reverse reciprocal crosses. The level of hybridization in progeny was determined using RAPD and RFLP markers. Hybridization was performed by leaving embryos to develop normally on the head (classical crossing) or using embryo rescue. All observed plants derived from H. mollis were diploid (2n = 34). Phenotypes were predominantly similar to the female when cultivated sunflower was the female parent. Progeny from crosses using a wild species as the female parent resembled that parent. Thus, reciprocal crosses led to different progeny. F1 sister progeny shared different sets of molecular markers representing a few of those of the wild species used as the pollen donor. Our results indicate mechanisms leading to the unusual event of partial hybridization. Possible mechanisms behind these unusual events and their possible impact on evolution are discussed.

Chromosome Segregation↗

PubMed2000

Mapping of quantitative trait loci for hypnotic sensitivity to ethanol in crosses derived from the C57BL/6 and DBA/2 mouse strains.

BACKGROUND: Acute ethanol sensitivity is thought to be a predisposing factor toward the development of alcoholism. Accumulated evidence suggests that this characteristic may be at least partly heritable. A widely accepted approach for identifying genes thought to contribute to alcoholism is to map quantitative trait loci (QTLs) for various ethanol-related behaviors in rodent models. METHODS: Ethanol sensitivity QTLs were interval-mapped in a C57BL/6 (B6) X DBA/2 (D2) F2 intercross that contained 391 mice. Sensitivity was measured as the duration of loss of righting reflex (LORR) after 4.1 g/kg ip. LORR also was evaluated in a chromosome 1 marker-assisted congenic strain that had an approximately 30 centiMorgan (cM) portion of D2 DNA from the distal end of chromosome 1 introgressed onto a B6 background. RESULTS: A suggestive QTL was mapped on chromosome 1 (LOD = 3.3; approximately 80 cM) and a provisional QTL on chromosome 5 (LOD = 2.3; approximately 26 cM). The provisional chromosome 5 QTL was found to be sex-specific (LOD = 2.5 for males; LOD < 1 for females) with the D2 allele increasing LORR. The chromosome 1 D2 allele decreased LORR. Consistent with the F2 QTL mapping, congenic mice heterozygous for the chromosome 1 interval (B6/D2) had a significantly different mean (+/- SEM) LORR of 74.0 +/- 4.9 min (n = 36) compared with 90.8 +/- 6.2 min (n = 33) for their homozygous (B6/B6) littermates (p = 0.02). Blood ethanol concentration at regain of righting reflex was 377 +/- 10 mg% for the B6/D2 and 368 +/- 10 mg% (p = NS) for the B6/B6. CONCLUSIONS: LORR results in the chromosome 1 congenic mice were consistent with and very similar to what was predicted from the QTL analysis in the B6 X D2 F2 population. These results support a suggestive LORR QTL on the distal end of mouse chromosome 1. The results also indicate that there is a provisional sex-specific LORR QTL on chromosome 5.

Alcoholism↗