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1.
Bone-Larson C Basu S Radel JD Liang M Perozek T Kapousta-Bruneau N Green DG Burmeister M Hankin MH 《Journal of neurobiology》2000,42(2):232-247
The or(J) allele of the murine ocular retardation mutation is caused by a premature stop codon in the homeodomain of the Chx10 gene. When expressed on an inbred 129/Sv strain, the or(J) phenotype is characterized by microphthalmia and a thin, poorly differentiated retina in which the peripheral portion is affected to a greater extent than the central portion. Such mutant retinae lack differentiated bipolar cells and the optic nerve typically fails to form, leading to blindness. Here, we show that progeny from an outcrossed backcross between 129/Sv-or(J) /or(J) and Mus musculus castaneus produce animals that are homozygous for the or(J) mutation and exhibit a much ameliorated eye phenotype. Although not of normal size, such modified or(J) eyes are significantly larger than those in 129/Sv-or(J) /or(J) mice, and contain a better organized retina which includes bipolar cells. Furthermore, optic nerves are frequently present, and the eyes show a degree of function as reflected by electroretinogram and pupillary response. As in 129/Sv-or(J) /or(J) mice, however, modified or(J) eyes show incomplete growth and a lack of cell differentiation in the periphery of the retina. The selective, and apparently nonmodifiable, effect of the ocular retardation phenotype on the periphery of the retina indicates that Chx10 plays an important role in the central-to-peripheral gradient of retinal development. These findings demonstrate that the ocular retardation phenotype can be greatly modified by the genetic background, and help to define a role for Chx10 in ocular development. 相似文献
2.
Yau-Sheng Tsai Avani Pendse Sheryl S. Moy Ikuko Mohri Antonio Perez Jacqueline N. Crawley Kinuko Suzuki Nobuyo Maeda 《Mammalian genome》2006,17(7):716-722
We observed severe ataxia in mice homozygous for modification of the Pparg locus. Genetic analysis and nucleotide sequencing revealed that ataxia is caused by a T692K substitution in plasma membrane
calcium ATPase 2 (Pmca2), which is tightly linked to Pparg, but not by modified PPARγ itself. We traced this mutation and found that it arose spontaneously during clonal expansion
of the targeted embryonic stem (ES) cells. Consistent with the deafwaddler phenotype in other Pmca2 mutants, homozygous T692K
Pmca2 mutants exhibit severe balance disorder, impaired neurologic reflexes, and motor coordination, and have profound hearing
loss. Heterozygous mutants have normal movement and motor function but are severely deficient in hearing. Our findings represent
a cautionary example since, although rare, spontaneous mutations do arise in ES cells during culture and hitchhike onto the
targeted gene mutation.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
This article contains a supplementary video. 相似文献
3.
Dalmatians, like humans, excrete uric acid in their urine. All other dogs and most mammals excrete allantoin, a water-soluble
compound that is further along the purine degradation pathway. Excretion of uric acid at high concentrations (hyperuricosuria)
predisposes Dalmatians to the formation of urinary urate calculi. Hyperuricosuria (huu) is found in all Dalmatians tested and is inherited as an autosomal recessive trait. A genome scan and linkage analysis performed
on a Dalmatian × Pointer interbreed backcross detected a single linked marker, REN153P03, located on CFA03. Haplotype analysis
of the region around this marker defined a 3.3-Mb interval flanked by single recombination events. This interval, which contains
the huu mutation, is estimated to include 24 genes.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users. 相似文献
4.
Daniel J. Becker Jay T. Myers Melissa M. Ruff Peter L. Smith Brenda W. Gillespie David W. Ginsburg John B. Lowe 《Mammalian genome》2003,14(2):130-139
The FX locus encodes an essential enzyme in the de novo pathway of GDP-fucose biosynthesis. Mice homozygous for a targeted mutation of the FX gene manifest a host of pleiotropic abnormalities including a lethal phenotype that is almost completely penetrant in heterozygous intercrosses on a mixed genetic background. Here we have investigated genetic suppression of FX-mediated lethality. Reduced recovery of heterozygous mice was observed while backcrossing the null FX allele to C57BL/6J (B6), but was less dramatic in an outcross to CASA/Rk and absent in an outcross to 129S1/SvImJ, indicating that genetic background modifies survival of FX+/- progeny. Substantial strain-specific differences in pre- and postnatal survival of FX-/- progeny were also detected in heterozygous crosses of C57BL/6J congenic, 129S1B6F1, and B6CASAF1 mice. Specifically, intrauterine survival of FX-/- mice was greatly increased during a heterozygous intercross on a uniform C57BL/6J genetic background compared with survival on a hybrid genetic background consisting of a mixture of C57BL/6J and 129S2/SvPas. In addition, statistically significant clustering of FX-/- progeny into litters and specific breeding cages was noted during a B6CASAF1 FX+/- intercross, suggesting a rare mechanism for modifier gene action in which parentally expressed genes define the phenotype, in this case the survival potential, of mutant offspring. Our results disclose that lethality in FX mutant mice is determined by one or more strain-specific modifier loci. 相似文献
5.
McLaughlin M Karim SA Montague P Barrie JA Kirkham D Griffiths IR Edgar JM 《Neurochemical research》2007,32(2):167-176
Mutations of the proteolipid protein gene (PLP1) cause Pelizaeus-Merzbacher disease (PMD) and Spastic paraplegia type 2 (SPG2). The rumpshaker mutation is associated with mild forms of PMD or SPG2 in man and the identical mutation occurs in mice, the phenotype depending
on genetic background. The mild phenotype in C3H mice becomes a lethal disease when expressed on the C57BL/6 background. rumpshaker PLP is synthesised at a similar rate to wild type but is rapidly degraded by the proteasome. We show that the rates of synthesis,
degradation and myelin incorporation of PLP/DM20 are similar in mutants on both backgrounds and therefore differences in PLP
processing are unlikely to be the basis of the phenotypic variation. An unfolded protein response (UPR) is activated in rumpshaker. Whereas activation of CHOP correlates with phenotypic severity, we find no difference in the response of BiP and X-box protein1
(Xbp1) between the two strains.
Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .
Special issue dedicated to Anthony Campagnoni. 相似文献
6.
CD23, the low affinity IgE receptor, is hypothesized to function as a negative regulator of IgE production. Upon discovering reduced CD23 surface levels in 129/SvJ inbred mice, we sought to further investigate 129/SvJ CD23 and to examine its influence on IgE levels. Five amino acid substitutions were found in 129/SvJ CD23. Identical mutations were also observed in CD23 from New Zealand Black and 129P1/ReJ mice. 129/SvJ B cells proliferated more rapidly than those from BALB/c after stimulation with IL-4 and CD40 ligand trimer. However, in vitro IgE levels in supernatants from stimulated 129/SvJ B cells were significantly reduced. Contrary to the in vitro findings, the 129/SvJ CD23 mutations correlated with a hyper IgE phenotype in vivo and 129/SvJ were able to clear Nippostrongylus brasiliensis infection more rapidly than either BALB/c or C57BL/6. Overall, this study further suggests that CD23 is an important regulatory factor for IgE production. 相似文献
7.
New quantitative trait loci that regulate wound healing in an intercross progeny from DBA/1J and 129×1/SvJ inbred strains of mice 总被引:1,自引:0,他引:1
Masinde GL Li R Nguyen B Yu H Srivastava AK Edderkaoui B Wergedal JE Baylink DJ Mohan S 《Functional & integrative genomics》2006,6(2):157-163
Wound healing/regeneration mouse models are few, and studies performed have mainly utilized crosses between MRL/MPJ (a good
healer) and SJL/J (a poor healer) or MRL/lpr (a good healer) and C57BL/6J (a poor healer). Wound healing is a complex trait
with many genes involved in the expression of the phenotype. Based on data from previous studies that common and additional
quantitative trait loci (QTL) were identified using different crosses of inbred strains of mice for various complex traits,
we hypothesized that a new cross would identify common and additional QTL, unique modes of inheritance, and interacting loci,
which are responsible for variation in susceptibility to fast wound healing. In this study, we crossed DBA/1J (DBA, a good
healer) and 129/SvJ (129, a poor healer) and performed a genome-wide scan using 492 (DBA×129) F2 mice and 98 markers to identify
QTL that regulate wound healing/regeneration. Four QTL on chromosomes 1, 4, 12, and 18 were identified which contributed toward
wound healing in F2 mice and accounted for 17.1% of the phenotypic variation in ear punch healing. Surprisingly, locus interactions
contributed to 55.7% of the phenotype variation in ear punch healing. In conclusion, we have identified novel QTL and shown
that minor interacting loci contribute significantly to wound healing in DBA×129 mice cross.
The authors Masinde, Li, and Nguyen contributed equally to this article. 相似文献
8.
Chee P Draye X Jiang CX Decanini L Delmonte TA Bredhauer R Smith CW Paterson AH 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(4):757-763
The current study is the first installment of an effort to explore the secondary gene pool for the enhancement of Upland cotton (Gossypium hirsutum L.) germplasm. We developed advanced-generation backcross populations by first crossing G. hirsutum cv. Tamcot 2111 and G. barbadense cv. Pima S6, then independently backcrossing F1 plants to the G. hirsutum parent for three cycles. Genome-wide mapping revealed introgressed alleles at an average of 7.3% of loci in each BC3F1 plant, collectively representing G. barbadense introgression over about 70% of the genome. Twenty-four BC3F1 plants were selfed to generate 24 BC3F2 families of 22–172 plants per family (totaling 2,976 plants), which were field-tested for fiber elongation and genetically mapped. One-way analysis of variance detected 22 non-overlapping quantitative trail loci (QTLs) distributed over 15 different chromosomes. The percentage of variance explained by individual loci ranged from 8% to 28%. Although the G. barbadense parent has lower fiber elongation than the G. hirsutum parent, the G. barbadense allele contributed to increased fiber elongation at 64% of the QTLs. Two-way analysis of variance detected significant (P<0.001) among-family genotype effects and genotype×family interactions in two and eight regions, respectively, suggesting that the phenotypic effects of some introgressed chromosomal segments are dependent upon the presence/absence of other chromosomal segments.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
9.
Neena B. Haider Weidong Zhang Ron Hurd Akihiro Ikeda Arne M. Nystuen Jürgen K. Naggert Patsy M. Nishina 《Mammalian genome》2008,19(3):145-154
The retinal degeneration 7 (rd7) mouse, lacking expression of the Nr2e3 gene, exhibits retinal dysplasia and a slow, progressive degeneration due to an abnormal production of blue opsin-expressing
cone cells. In this study we evaluated three strains of mice to identify alleles that would slow or ameliorate the retinal
degeneration observed in Nr2e3
rd7/rd7
mice. Our studies reveal that genetic background greatly influences the expression of the Nr2e3
rd7/rd7
phenotype and that the inbred mouse strains CAST/EiJ, AKR/J, and NOD.NON-H2
nb1
carry alleles that confer resistance to Nr2e3
rd7/rd7
-induced retinal degeneration. B6.Cg-Nr2e3
rd7/rd7
mice were outcrossed to each strain and the F1 progeny were intercrossed to produce F2 mice. In each intercross, 20–24% of the total F2 progeny were homozygous for the Nr2e3
rd7/rd7
mutation in a mixed genetic background; approximately 28–48% of the Nr2e3
rd7/rd7
homozygotes were suppressed for the degenerative retina phenotype in a mixed genetic background. The suppressed mice had
no retinal spots and normal retinal morphology with a normal complement of blue opsin-expressing cone cells. An initial genome
scan revealed a significant association of the suppressed phenotype with loci on chromosomes 8 and 19 with the CAST/EiJ background,
two marginal loci on chromosomes 7 and 11 with the AKR/J background, and no significant QTL with the NOD.NON-H2
nb1
background. We did not observe any significant epistatic effects in this study. Our results suggest that there are several
genes that are likely to act in the same or parallel pathway as NR2E3 that can rescue the Nr2e3
rd7/rd7
phenotype and may serve as potential therapeutic targets.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
Tomoji Mashimo Alexandra E. Erven Sarah L. Spiden Jean-Louis Guénet Karen P. Steel 《Mammalian genome》2006,17(8):841-850
Although recent progress in identifying genes involved in deafness has been remarkable, the genetic basis of progressive hearing
loss (or age-related hearing loss) is poorly understood because of the extreme difficulty in studying such a late-onset, complex
disease in human populations. Several inbred strains of mice such as 129P1/ReJ, C57BL/6J, DBA/2J, and BALB/cByJ have been
reported to exhibit age-related hearing loss and provide valuable models for human nonsyndromic progressive deafness. In this
article we show that 101/H mice also exhibit progressive deafness with early onset. Linkage analysis of F2 populations derived from crosses between the 101/H and the MAI/Pas and MBT/Pas wild-derived mice suggested at least two major
quantitative trait loci (QTLs) that influence progressive hearing loss. A first QTL, designated Phl1, was mapped with a maximum LOD score of 6.7 to the centromeric region of Chromosome 17, where no deafness-related QTL has
been mapped so far. A second QTL, designated Phl2, mapped to Chromosome 10 and exhibited a maximum LOD score of 5.3. The map position of Phl2 near the well-known QTL of age-related hearing loss (Ahl) suggested the possibility of allelism, although the Ahl mutation itself did not segregate in these crosses. Finally, we found some evidence of epistatic interaction between Phl1 and Phl2.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
Tomoji Mashimo, Alexandra E. Erven, and Sarah L. Spiden contributed equally to this work. 相似文献
11.
The TNFα receptor TNFRSF1A and genes encoding the amiloride-sensitive sodium channel ENaC as modulators in cystic fibrosis 总被引:1,自引:0,他引:1
Stanke F Becker T Cuppens H Kumar V Cassiman JJ Jansen S Radojkovic D Siebert B Yarden J Ussery DW Wienker TF Tümmler B 《Human genetics》2006,119(3):331-343
The CFTR mutations in cystic fibrosis (CF) lead to ion transport anomalities which predispose to chronic infection and inflammation of CF airways as the major determinants for morbidity and mortality in CF. Discordant clinical phenotypes of siblings with identical CFTR mutations and the large variability of clinical manifestations of patients who are homozygous for the most common mutation F508del suggest that both environment and genes other than CFTR contribute substantially to CF disease. The prime candidates for genetic modifiers in CF are elements of host defence such as the TNFα receptor and of ion transport such as the amiloride-sensitive epithelial sodium channel ENaC, both of which are encoded side by side on 12p13 (TNFRSF1A, SCNN1A) and 16p12 (SCNN1B, SCNN1G). Thirty-seven families with F508del-CFTR homozygous siblings exhibiting extreme clinical phenotypes that had been selected from the 467 pairs of the European CF Twin and Sibling Study were genotyped at 12p13 and 16p12 markers. The ENaC was identified as a modulator of CF by transmission disequilibrium at SCNN1G and association with CF phenotype intrapair discordance at SCNN1B. Family-based and case-control analyses and sequencing of SCNN1A and TNFRSF1A uncovered an association of the TNFRSF1A intron 1 haplotype with disease severity. Carriers of risk haplotypes were underrepresented suggesting a strong impact of both loci on survival. The finding that TNFRSF1A, SCNN1B and SCNN1G are clinically relevant modulators of CF disease supports current concepts that the depletion of airway surface liquid and inadequate host inflammatory responses trigger pulmonary disease in CF.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
12.
Sehayek E Hagey LR Fung YY Duncan EM Yu HJ Eggertsen G Björkhem I Hofmann AF Breslow JL 《Journal of lipid research》2006,47(9):2020-2027
An intercross between C57BL/6J and CASA/Rk mice was used to study the genetics of biliary bile acid composition. In parental strains, male C57BL/6J mice had significantly higher cholic acid (CA; 14%) and lower beta-muricholic acid (betaMC; 27%) than CASA/Rk mice, whereas females did not differ. However, quantitative trait locus analysis of F2 mice revealed no significant chromosome 9 loci in males but loci in females on chromosome 9 for percentage CA (%CA) at 72 centimorgan (cM) [logarithm of the odds (LOD) 5.89] and %betaMC at 54 cM (LOD 4.09). Chromosome 9 congenic and subcongenic strains representing CASA/Rk intervals 38-73 cM (9KK) and 68-73 cM (9DKK) on the C57BL/6J background were made. In 9KK and 9DKK males, %CA was increased and %betaMC was unchanged, whereas in 9KK but not 9DKK females, %CA was increased and %betaMC was decreased. Sterol 12alpha-hydroxylase (Cyp8b1) channels bile acid precursors into CA and maps at chromosome 9 (73 cM). However, there was no significant difference in Cyp8b1 mRNA or enzymatic activity between parental mice, parental-congenic-subcongenic mice, or high-low biliary %CA F2 mice. In summary, two chromosome 9 loci control sexually dimorphic effects on biliary bile acid composition: a distal (68-73 cM) major determinant in males, and a more proximal (38-68 cM) major determinant in females. In this intercross, Cyp8b1, a strong candidate, does not appear to be responsible. 相似文献
13.
Peter C. Reifsnyder Jeffry C. Flynn Amanda L. Gavin Eric A. Simone John J. Sharp Lieselotte Herberg Edward H. Leiter 《Mammalian genome》1999,10(2):161-167
Recombinant Congenic Strains (RCS) are useful for dissecting complex polygenic traits. Here, we describe genetic and phenotypic
characterization of six new RCS generated from outcrosses between NOD/Shi and CBA/LsLt, followed by sib mating of first backcross
progeny (to CBA) for 20 generations, whereupon genetic and phenotypic analysis commenced. Four of the RCS were selected on
the basis of residual heterozygosity present at F20 in one of the three original RCS. Contrary to expectations for RCS developed
at first backcross, all derived at least 50% of the polymorphic markers typed from the NOD parental strain. Development of
autoimmune insulin-dependent diabetes mellitus (IDDM) in NOD is a strain-specific characteristic. The major genetic component
predisposing NOD mice to IDDM, their H2
g7
haplotype, was present in all RCS. Nevertheless, the presence of variable amounts of CBA genome at non-MHC loci conferred
complete resistance in all RCS to spontaneous IDDM development, and rendered them strongly resistant to cyclophosphamide-induced
IDDM. Although the RCS more resemble NOD in regard to certain strain-specific characteristics, such as prolificacy, an immunologic
phenotype that was significantly reduced when compared to both parental strains was the number of peripheral CD8+ T cells. Given the genetic characterization presented, these new RCS should prove valuable to investigators interested in
studying genes controlling differential susceptibilities distinguishing the NOD and CBA inbred strain backgrounds.
Received: 26 June 1998 / Accepted: 14 October 1998 相似文献
14.
Heike Weiss Tanja Arndt Anne Jörns Sigurd Lenzen Edwin Cuppen Hans J. Hedrich Markus Tiedge Dirk Wedekind 《Mammalian genome》2008,19(4):292-297
The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes mellitus (T1DM) with an autosomal recessive mode of inheritance. T1DM susceptibility
loci could be localized on chromosome (RNO) 20 in the major histocompatibility complex region (Iddm1) and on RNO1 (Iddm8, Iddm9) in a BN backcross cohort. In this study the impact of the different susceptibility regions on diabetes development was investigated
in a backcross population of the diabetes-resistant PAR strain. A cohort of 130 [(PAR × LEW.1AR1-iddm) × LEW.1AR1-iddm] N2 rats was monitored for blood glucose and analyzed by linkage analysis. Sixteen percent of the PAR backcross animals developed
T1DM. Genetic analysis revealed significant linkage to T1DM in the MHC region on RNO20p12. In contrast to the linkage analysis
of the BN backcross cohort, only one susceptibility locus for T1DM could be identified on RNO1. This susceptibility region
on RNO1 mapped to the telomeric end corresponding to Iddm8. Eighty-nine percent of diabetic PAR backcross animals were homozygous for Iddm8. The Iddm9 diabetes susceptibility region showed no linkage to diabetes in the PAR backcross cohort. The data of this study provide
evidence that the mutation leading to T1DM in the LEW.1AR1-iddm rat is located at the telomeric end of RNO1 corresponding to Iddm8.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
H. Weiss and T. Arndt contributed equally to this study. 相似文献
15.
Epilepsy is a common neurological disorder affecting approximately 1% of the population. Mutations in voltage‐gated sodium channels are responsible for several monogenic epilepsy syndromes. More than 800 mutations in the voltage‐gated sodium channel SCN1A have been reported in patients with generalized epilepsy with febrile seizures plus and Dravet syndrome. Heterozygous loss‐of‐function mutations in SCN1A result in Dravet syndrome, a severe infant‐onset epileptic encephalopathy characterized by intractable seizures, developmental delays and increased mortality. A common feature of monogenic epilepsies is variable expressivity among individuals with the same mutation, suggesting that genetic modifiers may influence clinical severity. Mice with heterozygous deletion of Scn1a (Scn1a+/?) model a number of Dravet syndrome features, including spontaneous seizures and premature lethality. Phenotype severity in Scn1a+/? mice is strongly dependent on strain background. On the 129S6/SvEvTac strain Scn1a+/? mice exhibit no overt phenotype, whereas on the (C57BL/6J × 129S6/SvEvTac)F1 strain Scn1a+/? mice exhibit spontaneous seizures and early lethality. To systematically identify loci that influence premature lethality in Scn1a+/? mice, we performed genome scans on reciprocal backcrosses. Quantitative trait locus mapping revealed modifier loci on mouse chromosomes 5, 7, 8 and 11. RNA‐seq analysis of strain‐dependent gene expression, regulation and coding sequence variation provided a list of potential functional candidate genes at each locus. Identification of modifier genes that influence survival in Scn1a+/? mice will improve our understanding of the pathophysiology of Dravet syndrome and may suggest novel therapeutic strategies for improved treatment of human patients. 相似文献
16.
A linkage map of mouse Chromosome 1 using an interspecific cross segregating for the gld autoimmunity mutation 总被引:6,自引:0,他引:6
Mark L. Watson Peter D'Eustachio Beverly A. Mock Alfred D. Steinberg Herbert C. Morse III Rebecca J. Oakey Thad A. Howard Julie M. Rochelle Michael F. Seldin 《Mammalian genome》1992,2(3):158-171
An interspecific backross was used to define a high resolution linkage map of mouse Chromosome (Chr) 1 and to analyze the segregation of the generalized lymphoproliferative disease (gld) mutation. Mice homozygous for gld have multiple features of autoimmune disease. Analysis of up to 428 progeny from the backcross [(C3H/HeJ-gld x Mus spretus)F1 x C3H/HeJ-gld] established a map that spans 77.6 cM and includes 56 markers distributed over 34 ordered genetic loci. The gld mutation was mapped to a less than 1 cM segment on distal mouse Chr 1 using 357 gld phenotype-positive backcross mice. A second backcross, between the laboratory strains C57BL/6J and SWR/J, was examined to compare recombination frequency between selected markers on mouse Chr 1. Significant differences in crossover frequency were demonstrated between the interspecific backcross and the inbred laboratory cross for the entire interval studied. Sex difference in meiotic crossover frequency was also significant in the laboratory mouse cross. Two linkage groups known to be conserved between segments of mouse Chr 1 and the long arm of human Chrs 1 and 2 where further defined and a new conserved linkage group was identified that includes markers of distal mouse Chr 1 and human Chr 1, bands q32 to q42. 相似文献
17.
Mutations in the voltage-gated sodium channels SCN1A and SCN2A are responsible for several types of human epilepsy. Variable expressivity among family members is a common feature of these
inherited epilepsies, suggesting that genetic modifiers may influence the clinical manifestation of epilepsy. The transgenic
mouse model Scn2aQ54 has an epilepsy phenotype as a result of a mutation in Scn2a that slows channel inactivation. The mice display progressive epilepsy that begins with short-duration partial seizures that
appear to originate in the hippocampus. The partial seizures become more frequent and of longer duration with age and often
induce secondary generalized seizures. Clinical severity of the Scn2aQ54 phenotype is influenced by genetic background. Congenic C57BL/6J.Q54 mice exhibit decreased incidence of spontaneous seizures,
delayed seizure onset, and longer survival in comparison with [C57BL/6J × SJL/J]F1.Q54 mice. This observation indicates that strain SJL/J carries dominant modifier alleles at one or more loci that determine
the severity of the epilepsy phenotype. Genome-wide interval mapping in an N2 backcross revealed two modifier loci on Chromosomes 11 and 19 that influence the clinical severity of of this sodium channel-induced
epilepsy. Modifier genes affecting clinical severity in the Scn2aQ54 mouse model may contribute to the variable expressivity seen in epilepsy patients with sodium channel mutations. 相似文献
18.
S. Gregorová M. Mňuková-Fajdelová Z. Trachtulec J. Čapková M. Loudová M. Hoglund R. Hamvas H. Lehrach V. Vincek J. Klein J. Forejt 《Mammalian genome》1996,7(2):107-113
We have generated a high-resolution genetic map, 0.071 cM per backcross animal, of the 13 cM T–H2 region of the mouse Chromosome (Chr) 17. The map contains two phenotypic loci, T and Hst1, 12 RFLP markers, and 24 microsatellite loci. The Hst1 gene was mapped to a chromosomal interval contained within a single 580-kb YAC clone. The FFEH11 YAC is 0.44 cM long and
carries, besides the Hst1 gene, five polymorphic DNA markers and recombination breakpoints of six backcross animals. Two candidate genes for Hst1 were identified based on their location and testicular expression. These are Tbp and D17Ph4e. The sub-milliMorgan map of the T–H2 region revealed significant clustering of (CA)n loci. The clustering, if shown to be a common feature in the mouse genome, may cause gaps in the physical map of the mouse
genome.
Received: 11 September 1995 / Accepted: 9 October 1995 相似文献
19.
Sledge MK Ray IM Jiang G 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(5):980-992
A genetic map constructed from a population segregating for a trait of interest is required for QTL identification. The goal
of this study was to construct a molecular map of tetraploid alfalfa (Medicago sativa.) using simple sequence repeat (SSR) markers derived primarily from expressed sequence tags (ESTs) and bacterial artificial
chromosome (BAC) inserts of M. truncatula. This map will be used for the identification of drought tolerance QTL in alfalfa. Two first generation backcross populations
were constructed from a cross between a water-use efficient, M. sativa subsp. falcata genotype and a low water-use efficient M. sativa subsp. sativa genotype. The two parents and their F1 were screened with 1680 primer pairs designed to amplify SSRs, and 605 single dose alleles (SDAs) were amplified. In the
F1, 351 SDAs from 256 loci were mapped to 41 linkage groups. SDAs not inherited by the F1, but transmitted through the recurrent parents and segregating in the backcross populations, were mapped to 43 linkage groups,
and 44 of these loci were incorporated into the composite maps. Homologous linkage groups were joined to form eight composite
linkage groups representing the eight chromosomes of M. sativa. The composite maps consist of eight composite linkage groups with 243 SDAs from M. truncatula EST sequences, 38 SDAs from M. truncatula BAC clone sequences, and five SDAs from alfalfa genomic SSRs. The total composite map length is 624 cM, with average marker
density per composite linkage group ranging from 1.5 to 4.4 cM, and an overall average density of 2.2 cM. Segregation distortion
was 10%, and distorted loci tended to cluster on individual homologues of several linkage groups.
Electronic Supplementary Material Supplementary material is available for this article at 相似文献
20.
Elisabetta Giuffra Gary Evans Anna Törnsten Richard Wales Andy Day Holger Looft Graham Plastow Leif Andersson 《Mammalian genome》1999,10(12):1132-1136
A white belt is a common coat color phenotype in pigs and is determined by a dominant allele (Be). Here we present the result of a genome scan performed using a Hampshire (Belt)/Pietrain (non-Belt) backcross segregating
for the white belt trait. We demonstrate that Belt maps to the centromeric region of pig Chromosome (Chr) 8 harboring the
Dominant white (I/KIT) locus. Complete cosegregation between Belt and a single nucleotide polymorphism in the KIT gene was observed. Another potential candidate gene, the endothelin receptor type A gene (EDNRA), was excluded as it was assigned to a different region (SSC8q21) by FISH analysis. We argue that Belt is a regulatory KIT mutation on the basis of comparative data on mouse KIT mutants and our previous sequence analysis of the KIT coding sequence from a Hampshire pig. Quantitative PCR analysis revealed that Belt is not associated with a KIT duplication, as is the case for the Patch and Dominant white alleles. Thus, Belt is a fourth allele at the Dominant white
locus, and we suggest that it is denoted I
Be
.
Received: 5 May 1999 / Accepted: 3 August 1999 相似文献