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A new Hessian fly resistance gene (H30) transferred from the wild grass Aegilops triuncialis to hexaploid wheat.

A new Hessian fly (Mayetiola destructor Say) resistance gene from Aegilops triuncialis and its transfer to hexaploid wheat via interspecific hybridisation is described. The transfer line TR-3531 (42 chromosomes), derived from the cross [(Triticum turgidum x Ae. triuncialis) x Triticum aestivum] and carrying the Heterodera avenae resistance gene Cre7, showed a high level of resistance to the M. destructor biotype prevailing in the SW of Spain. A single dominant gene (H30) seems to determine the Hessian fly resistance in this introgression line, and its linkage with an isozyme marker (Acph-U1) has also been studied. It has been demonstrated that the resistance gene H30 in the TR-3531 line is non-allelic with respect to the genes H3, H6, H9, H11, H12, H13, H18 and H21, present in wheat cultivars from the Uniform Hessian Fly Nursery (UHFN), as well as to H27, carried by the introgression line H-93-33. Advanced lines with the H30 gene were obtained by backcrossing the transfer line and different commercial wheats as recurrent parents. Several of them showed a high yield in tests carried out in the infested field. Electronic Supplementary Material is available if you access this article at http://dx.doi.org/10.1007/s00122-002-1182-z. On that page (frame on the left side), a link takes you directly to the supplementary material.

Animals↗

Genetics of growth habit (spring vs winter) in common wheat: confirmation of the existence of dominant gene Vrn4.

The number of dominant Vrn genes in common wheat, Triticum aestivum L., is estimated. Data were obtained supporting Pugsley's and Gotoh's data on the presence of a dominant gene Vrn4 in near-isogenic line 'Triple Dirk F'. The presence of a dominant gene Vrn4 in line 'Gabo-2' of cultivar 'Gabo', which was used by Pugsley as a donor of the gene Vrn4 for the near-isogenic line 'Triple Dirk F', was also confirmed. The Vrn2 and Vrn4 relationship and their chromosomal location are discussed. It was demonstrated that the dominant Vrn8 gene which was introgressed from Triticum sphaerococcum to common wheat by Stelmakh and Avsenin is allelic to Vrn4. While genes Vrn6(sc) and Vrn7(sc) which were introgressed from rye, Secale cereale L., by the above-mentioned authors are not allelic to the genes Vrn1, Vrn2, Vrn3 and Vrn4.

Alleles↗

Use of SSRs for establishing heterotic groups in subtropical maize.

Heterotic groups and patterns are of fundamental importance in hybrid breeding. The objectives of our research were to: (1) investigate the relationship of simple sequence repeats (SSR) based genetic distances between populations and panmictic midparent heterosis (PMPH) in a broad range of CIMMYT maize germplasm, (2) evaluate the usefulness of SSR markers for defining heterotic groups and patterns in subtropical germplasm, and (3) examine applications of SSR markers for broadening heterotic groups by systematic introgression of other germplasm. Published data of two diallels and one factorial evaluated for grain yield were re-analyzed to calculate the PMPH in population hybrids. Additionally, 20 pools and populations widely used in CIMMYT's breeding program were assayed with 83 SSR markers covering the entire maize genome. Correlations of squared modified Roger's distance (MRD(2)) and PMPH were mostly positive and significant, but adaption problems caused deviations in some cases. For intermediate- and early-maturity subtropical germplasm, two heterotic groups could be suggested consisting of a flint and dent composite. We concluded that the relationships between the populations obtained by SSR analyses are in excellent agreement with pedigree information. SSR markers are a valuable complementation to field trials for identifying heterotic groups and can be used to introgress exotic germplasm systematically.

Alleles↗

Mapping osmotic adjustment in an advanced back-cross inbred population of rice.

Osmotic adjustment is one of several characters putatively associated with drought tolerance in rice. Indica cultivars are known to have a greater capacity for osmotic adjustment than japonica cultivars. We developed an advanced back-cross population using an indica donor, IR62266-42-6-2, to introgress osmotic adjustment into an elite japonica cultivar, IR60080-46A. One hundred and fifty BC(3)F(3) families were genotyped using microsatellites and RFLP markers, and a few candidate genes. We evaluated osmotic adjustment in these lines under greenhouse conditions using the re-hydration technique. Using the composite interval mapping technique, we detected 14 QTLs located on chromosomes 1, 2, 3, 4, 5, 7, 8 and 10 that together explained 58% of the phenotypic variability. Most, but not all, of the alleles with positive effects came from the donor parent. On chromosome 8, two QTLs were associated in repulsion. The QTL locations were in good agreement with previous studies on this trait on rice and in other cereals. Some BC(3)F(3) lines carried the favorable alleles at the two markers flanking up to four QTLs. Intercrossing these lines followed by marker-aided selection in their progenies will be necessary to recover lines with levels of osmotic adjustment equal to the donor parent. The advanced back-cross strategy appeared to be an appropriate method to accelerate the process of introgressing interesting traits into elite material.

Adaptation, Psychological↗

Genetic diversity in the northernmost Oryza rufipogon populations estimated by SSR markers.

To estimate genetic diversity of the residual northern populations of Oryza rufipogon, a total of 232 individuals from six populations were analyzed using microsatellites (SSRs). The O. rufipogon populations with different status included three from Dongxiang (Jiangxi Province) and three from Chaling (Hunan Province) in China. The 23 rice SSR primer pairs selected from the RiceGenes Database detected a total of 115 alleles, indicating that all the SSR loci were polymorphic in this study. The total gene diversity was 0.919 in the six O. rufipogon populations, and the Donxiang populations showed higher diversity than the Chaling populations. More significant genetic differentiation and less gene flow were found among the Dongxiang populations than those from Chaling. The two putative introgressed populations showed relatively high genetic variation. One in situ conserved population from Dongxiang had the lowest level of genetic diversity. The re-introduced population from Chaling restored about 90% of the genetic variation, compared with the original source population. It is concluded from these results that a relatively high level of genetic variation resided in the northern O. rufipogon populations and continued efforts of conservation of these populations are needed; and that the conservation of some Chaling and Dongxiang populations has been effective in preventing gene flow from cultivated rice. Introgression of cultivated rice demonstrated significant impacts on genetic variability of the O. rufipogon populations, and should be carefully considered in conserving this wild rice. This study also suggested that re-introduction to its original habitats is an effective approach to restore O. rufipogon populations.

Base Sequence↗

Activation of a rice endogenous retrotransposon Tos17 in tissue culture is accompanied by cytosine demethylation and causes heritable alteration in methylation pattern of flanking genomic regions.

Tos17 is a copia-like, cryptic retrotransposon of rice, but can be activated by tissue culture. To study possible epigenetic mechanism controlling activity of Tos17, we subjected three rice lines (the parental line cv. Matsumae and two introgression lines, RZ2 and RZ35) that harbor different copies of the element to tissue culture. For each line, we investigated transcription and transposition of Tos17 in seed plants, calli and regenerated plants, cytosine-methylation status at CG and CNG positions within Tos17, effect of 5-azacytidine on methylation status and activity of Tos17, and cytosine-methylation states in genomic regions flanking original and some newly transposed copies of Tos17 in calli and regenerated plants. We found that only in introgression line RZ35 was Tos17 transcriptionally activated and temporarily mobilized by tissue culture, which was followed by repression before or upon plant regeneration. The activity and inactivity of Tos17 in calli and regenerated plants of RZ35 are accompanied by hypo- and hyper-CG methylation and hemi- and full CNG methylation, respectively, within the element, whereas immobilization of the element in the other two lines is concomitant with near-constant, full hypermethylation. Treatment with 5-azacytidine induced both CG and CNG partial hypomethylation of Tos17 in two lines (Matsumae and RZ35), which, however, was not accompanied by activation of Tos17 in any line. Heritable alteration in cytosine-methylation patterns occurred in three of seven genomic regions flanking Tos17 in calli and regenerated plants of RZ35, but in none of the five regions flanking dormant Tos17 in the other two lines.

Azacitidine↗

Arabidopsis thaliana chromosome III restores fertility in a cytoplasmic male-sterile Brassica napus line with A. thaliana mitochondrial DNA.

Somatic Brassica napus (+) Arabidopsis thaliana hybrids with a cytoplasmic male sterility (CMS)-inducing cytoplasm were screened for fertility-restored plants. One line was selected and recurrently backcrossed with the maintainer line, B. napus, resulting in fertile/sterile segregating populations. Restriction fragment length polymorphism mapping showed the co-segregation of A. thaliana chromosome (chr) III markers with the fertility trait. As it was not possible to stabilise the fertility trait via selfings, a dihaploidisation strategy was assessed. Ninety haploid plants were regenerated and analysed with numerous simple sequence length polymorphism (SSLP) markers. Markers covering both arms of A. thaliana chr III were present in two plants, whereas no A. thaliana DNA could be detected in the other plants. Following colchicine-induced chromosome doubling only these two plants with A. thaliana DNA produced fertile offspring. In one of the two lines, however, the A. thaliana-specific DNA markers and fertility were lost in subsequent generations. The other line remained fertile after repeated selfings. Using genomic in situ hybridisation (GISH) we were able to demonstrate that this latter line possessed a disomic addition of the A. thaliana chromosome. The restored line was comparable to the maintainer line with respect to flower morphology, but the petals and stamens were slightly reduced in size. The homeotic conversion of stamens to pistil-like structures, which is typical for the CMS line, was reversed, and stamens with a normal appearance with viable pollen appeared. Flowering time was as in the CMS line-in both lines it was delayed in comparison to the maintainer line. The introgressed chromosome also contributes to several pleiotropic effects, such as reduced leaf crinkling and shorter stems. The ability to restore fertility through the introgression of nuclear genes from the main cytoplasmic donor species indicates that the CMS trait in this system mainly is due to B. napus/ A. thaliana alloplasmic incompatibility and not mitochondrial DNA rearrangements. Further exploitation of the material is discussed.

Arabidopsis↗

SSR marker and ITS cleaved amplified polymorphic sequence analysis of soybean x Glycine tomentella intersubgeneric derived lines.

Wild perennial Glycine species are an invaluable gene resource for the cultivated soybean [ Glycine max (L.) Merr., 2 n=40]. However, these wild species have been largely unexplored in soybean breeding programs because of their extremely low crossability with soybean and the need to employ in vitro embryo rescue methods to produce F(1) hybrids. The objective of this study was to develop molecular markers to identify gene introgression from G. tomentella, a wild perennial Glycine species, to soybean. A selection of 96 soybean simple sequence repeat (SSR) markers was evaluated for cross-specific amplification and polymorphism in G. tomentella. Thirty-two SSR markers (33%) revealed specific alleles for G. tomentella PI 483218 (2 n=78). These SSR markers were further examined with an amphidiploid line (2 n=118) and monosomic alien addition lines (MAALs), each with 2 n=40 chromosomes from soybean and one from G. tomentella. The results show that the use of SSR markers is a rapid and reliable method to detect G. tomentella chromosomes in MAALs. We also developed a cleaved amplification polymorphism sequence (CAPS) marker according to the sequences of internal transcribed spacer (ITS) regions in soybean and G. tomentella. Four MAALs that carry the ITS (rDNA) locus from G. tomentella were identified. The SSR and ITS-CAPS markers will greatly facilitate the introgression and characterization of gene transfer from G. tomentella to soybean.

Base Sequence↗

A genome-wide analysis of differentiation between wild and domesticated Phaseolus vulgaris from Mesoamerica.

Lack of introgression or divergent selection may be responsible for the maintenance of phenotypic differences between sympatric populations of crops and their wild progenitors. To distinguish between these hypotheses, amplified fragment length polymorphism markers were located on a molecular linkage map of Phaseolus vulgaris relative to genes for the domestication syndrome and other traits. Diversity for these same markers was then analyzed in two samples of wild and domesticated populations from Mesoamerica. Differentiation between wild and domesticated populations was significantly higher in parapatric and allopatric populations compared to sympatric populations. It was also significantly higher near genes for domestication compared to those away from these genes. Concurrently, the differences in genetic diversity between wild and domesticated populations were strongest around such genes. These data suggest that selection in the presence of introgression appears to be a major evolutionary factor maintaining the identity of wild and domesticated populations in sympatric situations. Furthermore, alleles from domesticated populations appear to have displaced alleles in sympatric wild populations, thus leading to a reduction in genetic diversity in such populations. These results also provide a possible experimental framework for assessing the long-term risk of transgene escape and the targeting of transgenes inside the genome to minimize the survival of these transgenes into wild populations following introduction by gene flow.

Chromosome Mapping↗

High-resolution mapping of a new brown planthopper (BPH) resistance gene, Bph18(t), and marker-assisted selection for BPH resistance in rice (Oryza sativa L.).

Brown planthopper (BPH) is a destructive insect pest of rice in Asia. Identification and the incorporation of new BPH resistance genes into modern rice cultivars are important breeding strategies to control the damage caused by new biotypes of BPH. In this study, a major resistance gene, Bph18(t), has been identified in an introgression line (IR65482-7-216-1-2) that has inherited the gene from the wild species Oryza australiensis. Genetic analysis revealed the dominant nature of the Bph18(t) gene and identified it as non-allelic to another gene, Bph10 that was earlier introgressed from O. australiensis. After linkage analysis using MapMaker followed by single-locus ANOVA on quantitatively expressed resistance levels of the progenies from an F2 mapping population identified with marker allele types, the Bph18(t) gene was initially located on the subterminal region of the long arm of chromosome 12 flanked by the SSR marker RM463 and the STS marker S15552. The corresponding physical region was identified in the Nipponbare genome pseudomolecule 3 through electronic chromosome landing (e-landing), in which 15 BAC clones covered 1.612 Mb. Eleven DNA markers tagging the BAC clones were used to construct a high-resolution genetic map of the target region. The Bph18(t) locus was further localized within a 0.843-Mb physical interval that includes three BAC clones between the markers R10289S and RM6869 by means of single-locus ANOVA of resistance levels of mapping population and marker-gene association analysis on 86 susceptible F2 progenies based on six time-point phenotyping. Using gene annotation information of TIGR, a putative resistance gene was identified in the BAC clone OSJNBa0028L05 and the sequence information was used to generate STS marker 7312.T4A. The marker allele of 1,078 bp completely co-segregated with the BPH resistance phenotype. STS marker 7312.T4A was validated using BC2F2 progenies derived from two temperate japonica backgrounds. Some 97 resistant BC2F2 individuals out of 433 screened completely co-segregated with the resistance-specific marker allele (1,078 bp) in either homozygous or heterozygous state. This further confirmed a major gene-controlled resistance to the BPH biotype of Korea. Identification of Bph18(t) enlarges the BPH resistance gene pool to help develop improved rice cultivars, and the PCR marker (7312.T4A) for the Bph18(t) gene should be readily applicable for marker-assisted selection (MAS).

Alleles↗

Identification and confirmation of three neutral alleles conferring wide compatibility in inter-subspecific hybrids of rice (Oryza sativa L.) using near-isogenic lines.

Wide-compatibility varieties (WCVs) are a special class of rice germplasm that is able to produce fertile hybrids when crossed to both indica and japonica subspecies. Previous studies determined 'Dular' and 02428 as two WCVs and identified a number of QTLs as having large effects on fertility of inter-subspecific hybrids. In this study, we developed five near-isogenic lines (NILs) for three of the QTLs, f5, f6 and S5, by backcrossing and marker-assisted selection, using "Dular" and 02428 as the donors and "Zhenshan 97" as the recipient. Three of the NILs each carried one introgressed allele, and two NILs each carried two introgressed alleles in combinations. The NILs were testcrossed to an indica tester "Nanjing 11" and a japonica tester "Balilla". The results showed that the f5 allele from "Dular"(f5-Du) is a neutral allele conferring wide compatibility, with a large effect on both pollen and spikelet fertility, and the f6 allele from "Dular" (f6-Du) is a neutral allele for spikelet fertility with smaller effect. The S5 allele from 02428 (S5-08) was confirmed to be a neutral allele for spikelet fertility. It is likely that f6 and S5 are the same locus as deduced by their genomic locations and effects. The results also showed that even in combination, two neutral alleles of different loci were not able to produce normal fertility hybrids in typical indica-japonica crosses. The implications of the findings in rice breeding programs are discussed.

Alleles↗

QTL analysis of yield traits in an advanced backcross population derived from a cultivated Andean x wild common bean (Phaseolus vulgaris L.) cross.

Advanced backcross QTL analysis was used to identify quantitative trait loci (QTL) for agronomic performance in a population of BC2F(3:5) introgression lines created from the cross of a Colombian large red-seeded commercial cultivar, ICA Cerinza, and a wild common bean accession, G24404. A total of 157 lines were evaluated for phenological traits, plant architecture, seed weight, yield and yield components in replicated trials in three environments in Colombia and genotyped with microsatellite, SCAR, and phaseolin markers that were used to create a genetic map that covered all 11 linkage groups of the common bean genome with markers spaced at an average distance of every 10.4 cM. Segregation distortion was most significant in regions orthologous for a seed coat color locus (R-C) on linkage group b08 and two domestication syndrome genes, one on linkage group b01 at the determinacy (fin) locus and the other on linkage group b02 at the seed-shattering (st) locus. Composite interval mapping analysis identified a total of 41 significant QTL for the eight traits measured of which five for seed weight, two for days to flowering, and one for yield were consistent across two or more environments. QTL were located on every linkage group with b06 showing the greatest number of independent loci. A total of 13 QTL for plant height, yield and yield components along with a single QTL for seed size showed positive alleles from the wild parent while the remaining QTL showed positive alleles from the cultivated parent. Some QTL co-localized with regions that had previously been described to be important for these traits. Compensation was observed between greater pod and seed production and smaller seed size and may have resulted from QTL for these traits being linked or pleiotropic. Although wild beans have been used before to transfer biotic stress resistance traits, this study is the first to attempt to simultaneously obtain a higher yield potential from wild beans and to analyze this trait with single-copy markers. The wild accession was notable for being from a unique center of diversity and for contributing positive alleles for yield and other traits to the introgression lines showing the potential that advanced backcrossing has in common bean improvement.

Chromosome Mapping↗

Fine mapping of a quantitative trait locus for grain number per panicle from wild rice (Oryza rufipogon Griff.).

SIL040, an introgression line (IL) developed by introgressing chromosomal segments from an accession of Oryza rufipogon into an indica cultivar Guichao 2, showed significantly less grains per panicle than the recurrent parent Guichao 2. Quantitative trait locus (QTL) analysis in F2 and F3 generations derived from the cross between SIL040 and Guichao 2 revealed that gpa7, a QTL located on the short arm of chromosome 7, was responsible of this variation. Alleles from O. rufipogon decreased grains per panicle. To fine mapping of gpa7, a high-resolution map with 1,966 F2 plants derived from the cross between SIL040 and Guichao 2 using markers flanking gpa7 was constructed, and detailed quantitative evaluation of the structure of main panicle of each of F3 families derived from recombinants screened was performed. By two-step substitution mapping, gpa7 was finally narrowed down to a 35-kb region that contains five predicted genes in cultivated rice. The fact that QTLs for five panicle traits (length of panicle, primary branches per panicle, secondary branches per panicle, grains on primary branches and grains on secondary branches) were all mapped in the same interval as that for gpa7 suggested that this locus was associated with panicle structure, showing pleiotropic effects. The characterizing of panicle structure of IL SIL040 further revealed that, during the domestication from common wild allele to cultivated rice one at gpa7, not only the number of branches and grains per panicle increased significantly, more importantly, but also the ratio of secondary branches per panicle to total branches per panicle and the ratio of grains on secondary branches per panicle to total grains per panicle increased significantly. All these results reinforced the idea that gpa7 might play an important role in the regulation of grain number per panicle and the ratio of secondary branches per panicle during the domestication of rice panicle.

Alleles↗

Strong linkage disequilibrium near the selected Yr17 resistance gene in a wheat experimental population.

Dynamic management (DM) is a method of genetic resources conservation that aims at maintaining evolutionary process in subdivided populations cultivated in contrasted environments. Such populations are often submitted to strong natural selection as it was the case for experimental wheat populations maintained under DM. Understanding impacts of selection on genetic diversity around selected genes is necessary for the middle-term maintenance of genetic variability in DM populations. Evolution of diversity at six neutral markers located near the yellow rust resistance gene Yr17 has been studied for the parental lines and for generations 1, 5, 10 and 17 in one of the DM populations. Yr17 provided complete resistance to yellow rust in France until 1997 and thus was suspected to be under strong selection. The gene is located on a fragment introgressed in winter wheat from a wild species. The presence of the gene was estimated using a marker closely related to the gene. We showed that the Yr17 gene has been selected between generations 5 and 10. Generally, selection tends to reduce diversity around selected genes, generating linkage disequilibrium (LD) between a gene and adjacent markers. Here, the major effect of the Yr17 gene selection was a reduction of multilocus diversity and the maintenance of strong pre-existing LD in the zone surrounding the gene for a distance of 20 cM. As expected, the presence of the exogenous introgression was responsible for restrictions to recombination which contributed to the maintenance of strong correlations between loci. However, we found a noticeable number of recombinations around the gene indicating a progressive incorporation of the fragment into the wheat genome.

Alleles↗

Utility of barley and wheat simple sequence repeat (SSR) markers for genetic analysis of Hordeum chilense and tritordeum.

A selection of 36 wheat and 35 barley simple sequence repeat markers (SSRs) were studied for their utility in Hordeum chilense. Nineteen wheat and nineteen barley primer pairs amplified consistent H. chilense products. Nine wheat and two barley SSRs were polymorphic in a H. chilense mapping population, producing codominant markers that mapped to the expected homoeologous linkage groups in all but one case. Thirteen wheat and 10 barley primer pairs were suitable for studying the introgression of H. chilense into wheat because they amplified H. chilense products of distinct size. Analysis of wheat/ H. chilense addition lines showed that the H. chilense products derived from the expected homoeologous linkage groups. The results showed that wheat and barley SSRs provide a valuable resource for the genetic characterization of H. chilense, tritordeums and derived introgression lines.

Journal Article↗

Heteroplasmy suggests paternal co-transmission of multiple genomes and pervasive reversion of maternally into paternally transmitted genomes of mussel (Mytilus) mitochondrial DNA.

Marine mussels of the genus Mytilus have two types of mitochondrial DNA with separate paternal and maternal inheritance. Females are homoplasmic for an F genome that is transmitted to all offspring, whereas males are heteroplasmic for this F genome and for a highly diverged (> 20%) M genome that is transmitted only to sons. Here we provide phylogenetic evidence based on lrRNA sequence data that most of the paternal genomes in European M. trossulus have an introgressive female M. edulis origin and are nearly indistinguishable in sequence from F types of M. trossulus. This observation is best explained by the hypothesis that introgressed F type molecules have recently invaded the paternal route and have assumed the role of M molecules, then resetting to zero the time of sequence divergence between M and F lineages. European M. trossulus shows a high prevalence of males heteroplasmic for three different mitochondrial DNA types all having the same two paternal types and the same maternal type, consistent with paternal co-transmission of multiple genomes. Co-transmission of the same genomes must apparently operate uninterruptedly for several generations in spite of the very different evolutionary origin of the specific molecules that are transmitted paternally and maternally in European M. trossulus.

Animals↗

Association of misexpression with sterility in hybrids of Drosophila simulansand D. mauritiana.

Recent studies have identified genes associated with hybrid sterility and other hybrid dysfunctions, but the consequences of introgressions of these "speciation genes" are often poorly understood. Previously, we identified a panel of genes that are underexpressed in sterile male hybrids of Drosophila simulans and D. mauritiana relative to pure species. Here, we build on this reverse-genetics approach to demonstrate that the underexpression of at least five of these genes in hybrids is associated with hybrid sterility and that these five genes are coordinately regulated. We map one upstream regulator of these genes to a region previously shown to harbor one or more factors causing hybrid sterility. Finally, we show that the genes underexpressed in hybrids are often highly conserved, as might be predicted for downstream targets of the genetic changes that cause hybrid sterility. This approach integrates forward genetics with reverse genetics to show a proximate consequence of the introgression of particular hybrid sterility-conferring regions between species: underexpression of genes necessary for normal spermatogenesis.

Animals↗

Genetic dissection of collagen-induced arthritis in Chromosome 10 quantitative trait locus speed congenic rats: evidence for more than one regulatory locus and sex influences.

Rat Chromosome 10 (RNO10) harbors Cia5, a non-MHC quantitative trait locus (QTL) that regulates the severity of type II collagen-induced arthritis (CIA) in DAxF344 and DAxBN F2 rats. CIA is an animal model with many features that resemble rheumatoid arthritis. To facilitate analysis of Cia5 independently of the other CIA regulatory loci on other chromosomes, DA recombinant QTL speed congenic rats, DA.F344(Cia5), were generated. These QTL congenic rats have a large chromosomal segment containing Cia5 (interval size < or =80.1 cM) from CIA-resistant F344 rats introgressed into their genome. Phenotypic analyses of these rats for susceptibility and severity of CIA confirmed that Cia5 is an important disease-modifying locus. CIA severity was significantly lower in the Cia5 congenic rats than in DA controls. We also generated DA Cia5 speed sub-congenic rats, DA.F344(Cia5a), which had a smaller segment of the F344 genome, Cia5a, comprising only the distal q-telomeric end (interval size < or = 22.5 cM) of Cia5, introgressed into their genome. DA.F344(Cia5a) sub-congenic rats also exhibited reduced CIA disease severity compared with the parental DA rats. The regulatory effects in both congenic strains were sex influenced. The disease-ameliorating effect of the larger fragment, Cia5, was greater in males than in females, but the effect of the smaller fragment, Cia5a, was greater in females. We also present an improved genetic linkage map covering the Cia5/Cia5a region, which we have integrated with two rat radiation hybrid maps. Comparative homology analysis of this genomic region with mouse and human chromosomes was also undertaken. Regulatory loci for multiple autoimmune/inflammatory diseases in rats (RNO10), mice (MMU11), and humans (HSA17 and HSA5q23-q31) map to chromosomal segments homologous to Cia5 and Cia5a.

Animals↗