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1.
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
2.
Summary Spontaneous chlorate-resistant (CR) mutants have been isolated from Chlamydomonas reinhardtii wildtype strains. Most of them, 244, were able to grow on nitrate minimal medium, but 23 were not. Genetic and in vivo complementation analyses of this latter group of mutants indicated that they were defective either at the regulatory locus nit-2, or at the nitrate reductase (NR) locus nit-1, or at very closely linked loci. Some of these nit-1 or nit-2 mutants were also defective in pathways not directly related to nitrate assimilation, such as those of amino acids and purines. Chlorate treatment of wild-type cells resulted in both a decrease in cell survival and an increase in mutant cells resistant to a number of different chemicals (chlorate, methylammonium, sulphanilamide, arsenate, and streptomycin). The toxic and mutagenic effects of chlorate in minimal medium were not found when cells were grown either in darkness or in the presence of ammonium, conditions under which nitrate uptake is drastically inhibited. Chlorate was also able to induce reversion of nit
– mutants of C. reinhardtii, but failed to produce His
+ revertants or Arar mutants in the BA-13 strain of Salmonella typhimurium. In contrast, chlorate treatment induced mutagenesis in strain E1F1 of the phototrophic bacterium Rhodobacter capsulatus. Genetic analyses of nitrate reductase-deficient CR mutants of C. reinhardtii revealed two types of CR, to low (1.5 mM) and high (15 mM) chlorate concentrations. These two traits were recessive in heterozygous diploids and segregated in genetic crosses independently of each other and of the nit-1 and nit-2 loci. Three her loci and four lcr loci mediating resistance to high (HC) and low (LC) concentrations of chlorate were identified. Mutations at the nit-2 locus, and deletions of a putative locus for nitrate transport were always epistatic to mutations responsible for resistance to either LC or HC. In both nit
+ and nit
– chlorate-sensitive (CS) strains, nitrate and nitrite gave protection from the toxic effect of chlorate. Our data indicate that in C. reinhardtii chlorate toxicity is primarily dependent on the nitrate transport system and independent of the existence of an active NR enzyme. At least seven loci unrelated to the nitrate assimilation pathway and mediating CR are thought to control indirectly the efficiency of the nitrate transporter for chlorate transport. In addition, chlorate appears to be a mutagen capable of inducing a wide range of mutations unrelated to the nitrate assimilation pathway. 相似文献
3.
Adam H. Porter Remo Wenger Hansjürg Geiger Adolf Scholl Arthur M. Shapiro 《Evolution; international journal of organic evolution》1997,51(5):1561-1573
The pierid butterflies Pontia daplidice and P. edusa, parapatrically distributed in southern Europe, have very similar morphologies and life histories, but show fixed differences at four allozyme markers. We sampled these allozymes in a 28-population transect north of Genoa in Italy, through the hybrid zone where these taxa meet. We used the numerical techniques developed for hybrid zone analysis to study the patterns of genetic differentiation and their underlying evolutionary causes. The hybrid zone is characterized by a very short and steep central region, flanked by broad tails of introgression extended up to 100 km in either direction. From mean two-locus disequilibium of D = 0.148 (maximum-likelihood two-unit support limits 0.139-0.153), and after accounting for minor differences in the center locations of the single-locus clines, which act to bias the dispersal estimate, we estimated a dispersal rate of σ = 4.4 (3.7-5.5) km/gen1/2. The effective selection needed to maintain the steep central portion is strong, 0.47 < s? < 0.64, when combined over potential intrinsic (genetic background) and extrinsic (ecological) sources of selection. The clines in allozyme loci showed variation that was significantly different between the most divergent shapes, and the differences are attributable to different degrees of introgression on the edusa side of the zone. The average selection acting on individual allozyme loci was high at s???e 1.5%, but because of the narrowness of the central region of the cline, we suspect that this estimate is somewhat biased by selection on loci closely linked to the allozyme markers. A common question for taxa that show fixed allozyme differences in parapatry is whether or not they are genetically isolated. A fairly general measure of genetic isolation across hybrid zones is the time, T, that it takes a neutral allele to cross the hybrid zone and recombine into the opposite genetic background, given by T = (β/σ)2, where β is the barrier strength of the hybrid zone. Genetic isolation in the Pontia zone is weak, with T 25 generations for most allozyme markers. By this measure, populations of daplidice and edusa on opposite sides of the hybrid zone share more identical-by-descent alleles than do populations of phenotypically pure daplidice in, say, France and Morocco. Accordingly, we think it best for systematists to consider edusa as a well-marked subspecies of P. daplidice. 相似文献
4.
We consider the problem of testing for heterogeneity of K proportions when K is not small and the binomial sample sizes may not be large. We assume that the binomial proportions are normally distributed with variance σ2. The asymptotic relative efficiency (ARE) of the usual chi-square test is found relative to the likelihood-based tests for σ2=0. The chi-square test is found to have ARE = 1 when the binomial sample sizes are all equal and high relative efficiency for other cases. The efficiency is low only in cases where there is insufficient data to use the chi-square test. 相似文献
5.
Marie Lipoldová Helena Havelková Jana Badalová Jarmila Vojtíšková Lei Quan Magdaléna Krulová Yahya Sohrabi Alphons P. Stassen Peter Demant 《Cancer immunology, immunotherapy : CII》2010,59(2):203-213
Low infiltration of lymphocytes into cancers is associated with poor prognosis, but the reasons why some patients exhibit
a low and others a high infiltration of tumors are unknown. Previously we mapped four loci (Lynf1–Lynf4) controlling lymphocyte infiltration of mouse lung tumors. These loci do not encode any of the molecules that are involved
in traffic of lymphocytes. Here we report a genetic relationship between these loci and the control of production of IFNγ
in allogeneic mixed lymphocyte cultures (MLC). We found that IFNγ production by lymphocytes of O20/A mice is lower than by
lymphocytes of OcB-9/Dem mice (both H2
pz
) stimulated in MLC by irradiated splenocytes of C57BL/10SnPh (H2
b
) or BALB/cHeA (H2
d
) mice, or by ConA. IFNγ production in MLCs of individual (O20 × OcB-9)F2 mice stimulated by irradiated C57BL/10 splenocytes and genotyped for microsatellite markers revealed four IFNγ-controlling
loci (Cypr4-Cypr7), each of which is closely linked with one of the four Lynf loci and with a cluster of susceptibility genes for different tumors. This suggests that inherited differences in certain
lymphocyte responses may modify their propensity to infiltrate tumors and their capacity to affect tumor growth. 相似文献
6.
7.
PRASHIELA MANGA KIYOSHI SATO LIYAN YE FRIEDRICH BEERMANN M. LYNN LAMOREUX SETH J. ORLOW 《Pigment cell & melanoma research》2000,13(5):364-374
The albino (tyrosinase, Tyrc), brown (tyrosinase‐related protein 1, Tyrp1b) and slaty (tyrosinase‐related protein 2, tyrp2slt) loci are all involved in the regulation of melanogenesis. Phenotypes of inbred mice mutant at two or more of these loci are not always explicable by simple summation of the established or suspected catalytic functions of the gene products. These phenotypes suggest that relationships among the proteins extend beyond the obvious fact that they catalyze different steps in the same melanogenic pathway, and that they may also interact intimately in such a way that a mutation in one impacts the function of the other(s). Previous studies have attributed catalytic activities to each member of this trio; however, it has been difficult to study the proteins individually, either in vivo or in tissues or cells. Therefore, we undertook to transfect the genes, in revealing combinations, into COS‐7 cells (which have no melanogenic apparatus of their own) to clarify the interacting functions of their encoded proteins. Specifically, we attempted to evaluate the effects of Tyrp1 and Tyrp2 proteins on tyrosinase protein. We report evidence that Tyrp1 stabilizes tyrosinase, confirming previous observations, and, in addition, demonstrate that Tyrp1 decreases tyrosinase activity. By contrast, Tyrp2 increases tyrosinase activity by stabilizing the protein. We conclude that both Tyrp1 and Tyrp2, in addition to other catalytic functions they may possess, act together to modulate tyrosinase activity. 相似文献
8.
K. Pecsenye K. Bokor L. P. Lefkovitch B. E. Giles A. Saura 《Molecular & general genetics : MGG》1997,255(3):258-268
The effects of environmental ethanol on larva-to-pupa survival and on the activities of four enzymes were investigated in
three Drosophila melanogaster strains. The strains had different allelic combinations at the Odh and Aldox loci on their third chromosomes, but they all carried the Adh
S
-Gpdh
F
allelic combination on the second chromosome. Replicates of each of the strains were exposed to three different ethanol treatments:
(i) no ethanol in the medium (control); (ii) 5% ethanol for a single generation (short-term exposure); (iii) 5% ethanol for
20 generations (long-term exposure). In all experiments, the activities of four enzymes (ADH, ODH, GPDH and AOX) were measured
in larvae, pupae and adults. The results showed that (i) the larval and adult metabolic responses to environmental ethanol
were different; (ii) enzyme activity changes under short-term exposure differed from those measured under long-term exposure;
(iii) the activities of the allozymes common to all strains (ADH-S and GPDH-F), differed depending on the genetic background.
Changes in larva-to-pupa survival were seen when the larvae of control and exposed lines of the three strains were confronted
with various concentrations of ethanol. In all three strains, the exposed lines had significantly higher initial survival
rate and ethanol tolerance than the control lines. Strain-specific differences were observed in the ethanol tolerance of both
types of line.
Received: 26 November 1996 / Accepted: 14 February 1997 相似文献
9.
Ocular retardation is a recessive murine mutation whose phenotypic expression is greatly affected by genetic background effects.
Mice of the inbred 129/SvJ background that are homozygous for the Chx10or-J mutation are blind and have a thin, poorly differentiated retina and no optic nerve. A backcross between 129/SvJ and Mus musculus castaneus (CASA/Rk) produced animals that were homozygous for the Chx10or-J mutation, yet showed a much milder phenotype. Such animals, when brother-sister mated and selected for mild phenotype for
several generations, resulted in partial recovery of visual function, including presence of an optic nerve and pupillary response.
In this article we report a genome scan of phenotypic extremes of the backcross to identify the genetic loci affecting this
phenotype modification. Our scan revealed significant loci on Chromosomes 6 and 14 where the CASA/Rk alleles are maintained
selectively. Markers were developed near candidate genes, but no candidate gene could be identified unequivocally.
Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. 相似文献
10.
Abraham B. Korol Valery M. Kirzhner Yeafim I. Ronin Eviatar Nevo 《Evolution; international journal of organic evolution》1996,50(4):1432-1441
The subject of this paper is polymorphism maintenance due to stabilizing selection with a moving optimum. It was shown that in case of two-locus additive control of the selected trait, global polymorphism is possible only when the geometric mean fitnesses of double homozygotes averaged over the period are lower than that of the single heterozygotes and of the double heterozygote (with a multiplier [1 – r]p, which depends on recombination rate r and period length p). But local stability of polymorphism cannot be excluded even if geometric mean fitnesses of all double homozygotes are higher than that of all heterozygotes. We proved, that for logarithmically convex fitness functions, cyclical changes of the optimum cannot help in polymorphism maintenance in case of additive control of the selected trait by two equal loci. However, within the same class of fitness functions, nonequal gene action and/or dominance effect for one or both loci may lead to local polymorphism stability with large enough polymorphism attracting domain. The higher the intensity of selection and closer the linkage between selected loci the larger is this domain. Note that even simple cyclical selection could result in two forms of polymorphic limiting behavior: (a) usually expected forced cycle with a period equal to that of environmental changes; and (b) “supercycles,” nondumping auto-oscillations with a period comprising of hundreds of forced oscillation periods. 相似文献
11.
QTLs and epistasis for aluminum tolerance in rice (Oryza sativa L.) at different seedling stages 总被引:11,自引:0,他引:11
P. Wu C. Y. Liao B. Hu K. K. Yi W. Z. Jin J. J. Ni C. He 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2000,100(8):1295-1303
To investigate the genetic background for aluminum (Al) tolerance in rice, a recombinant inbred (RI) population, derived from
a cross between an Al-sensitive lowland indica rice variety IR1552 and an Al-tolerant upland japonica rice variety Azucena, was used in culture solution. A molecular linkage map, together with 104 amplified fragment length
polymorphism (AFLP) markers and 103 restriction fragment length polymorphism (RFLP) markers, was constructed to map quantitative
trait loci (QTLs) and epistatic loci for Al tolerance based on the segregation for relative root length (RRL) in the population.
RRL was measured after stress for 2 and 4 weeks at a concentration of 1mM of Al3+ and a control with a pH 4.0, respectively. Two QTLs were detected at both the 2nd and the 4th weeks on chromosomes 1 and
12 from unconditional mapping, while the QTL on chromosome 1 was only detected at the 2nd stress week from conditional mapping.
The effect of the QTL on chromosome 12 was increased with an increase of the stress period from 2 to 4 weeks. The QTL on chromosome
1 was expressed only at the earlier stress, but its contribution to tolerance was prolonged during growth. At least one different
QTL was detected at the different stress periods. Mean comparisons between marker genotypic classes indicated that the positive
alleles at the QTLs were from the Al-tolerant upland rice Azucena. An important heterozygous non-allelic interaction on Al
tolerance was found. The results indicated that tolerance in the younger seedlings was predominantly controlled by an additive
effect, while an epistatic effect was more important to the tolerance in older seedlings; additionally the detected QTLs may
be multiple allelic loci for Al tolerance and phosphorus-uptake efficiency, or for Al and Fe2+ tolerance.
Received: 29 July 1999 / Accepted: 13 October 1999 相似文献
12.
Thomas Le Voyer Zichun Lu James Babb Traci Lifsted Max Williams Kent Hunter 《Mammalian genome》2000,11(10):883-889
Previous studies from our laboratory demonstrated that the latency, tumor growth, and metastatic progression of polyoma middle
T-induced mammary tumor in an FVB/NJ inbred mouse background could be significantly altered by the introduction of different
genetic backgrounds. In this study we extend these findings by mapping a number of interacting quantitative trait loci responsible
for the changes in phenotype. Introduction of the I/LnJ inbred genetic background into the FVB/NJ-PyMT animal significantly
accelerated the appearance of the primary tumor (35 vs. 57 days postnatal, p < 10−7). A backcross mapping panel was established, and loci responsible for the tumor acceleration were detected on Chrs 15 and
9. Examination of the genotype/phenotype correlation revealed that the FVB/NJ but not the I/LnJ allele of the Chr 15 locus
was associated with tumor acceleration and was conditional on the presence of I/LnJ allele on Chr 9. These loci, designated
Apmt1 and Apmt2, map to homologous regions associated with LOH in human breast cancer. These results suggest that allelic variants of genes
in these regions may contribute to age of onset in human breast cancer.
Received: 2 March 2000 / Accepted: 4 May 2000 相似文献
13.
This article develops mathematical models describing the evolutionary dynamics of both asexually and sexually reproducing
populations of diploid unicellular organisms. The asexual and sexual life cycles are based on the asexual and sexual life
cycles in Saccharomyces cerevisiae, Baker’s yeast, which normally reproduces by asexual budding, but switches to sexual reproduction when stressed. The mathematical
models consider three reproduction pathways: (1) Asexual reproduction, (2) self-fertilization, and (3) sexual reproduction.
We also consider two forms of genome organization. In the first case, we assume that the genome consists of two multi-gene
chromosomes, whereas in the second case, we consider the opposite extreme and assume that each gene defines a separate chromosome,
which we call the multi-chromosome genome. These two cases are considered to explore the role that recombination has on the
mutation-selection balance and the selective advantage of the various reproduction strategies. We assume that the purpose
of diploidy is to provide redundancy, so that damage to a gene may be repaired using the other, presumably undamaged copy
(a process known as homologous recombination repair). As a result, we assume that the fitness of the organism only depends
on the number of homologous gene pairs that contain at least one functional copy of a given gene. If the organism has at least
one functional copy of every gene in the genome, we assume a fitness of 1. In general, if the organism has l homologous pairs that lack a functional copy of the given gene, then the fitness of the organism is κ
l
. The κ
l
are assumed to be monotonically decreasing, so that κ0 = 1 > κ1 > κ2 > ⋯ > κ∞ = 0. For nearly all of the reproduction strategies we consider, we find, in the limit of large N, that the mean fitness at mutation-selection balance is max{2 e-m-1, 0} ,\hbox{max}\{2 e^{-\mu}-1, 0\} , where N is the number of genes in the haploid set of the genome, ε is the probability that a given DNA template strand of a given
gene produces a mutated daughter during replication, and μ = Nε. The only exception is the sexual reproduction pathway for the multi-chromosomed genome. Assuming a multiplicative fitness
landscape where κ
l
= α
l
for α ∈ (0, 1), this strategy is found to have a mean fitness that exceeds the mean fitness of all the other strategies.
Furthermore, while other reproduction strategies experience a total loss of viability due to the steady accumulation of deleterious
mutations once μ exceeds ln2 ,\ln 2 , no such transition occurs in the sexual pathway. Indeed, in the limit as α → 1 for the multiplicative landscape, we can show
that the mean fitness for the sexual pathway with the multi-chromosomed genome converges to e
−2μ, which is always positive. We explicitly allow for mitotic recombination in this study, which, in contrast to previous studies
using different models, does not have any advantage over other asexual reproduction strategies. The results of this article
provide a basis for understanding the selective advantage of the specific meiotic pathway that is employed by sexually reproducing
organisms. The results of this article also suggest an explanation for why unicellular organisms such as Saccharomyces cerevisiae (Baker’s yeast) switch to a sexual mode of reproduction when stressed. While the results of this article are based on modeling
mutation-propagation in unicellular organisms, they nevertheless suggest that, in more complex organisms with significantly
larger genomes, sex is necessary to prevent the loss of viability of a population due to genetic drift. Finally, and perhaps
most importantly, the results of this article demonstrate a selective advantage for sexual reproduction with fewer and much
less restrictive assumptions than those of previous studies. 相似文献
14.
Jun-ichi Suto Saori Matsuura Kenkichi Imamura Harumichi Yamanaka Kenji Sekikawa 《Mammalian genome》1998,9(7):506-510
KK mouse is known as a polygenic model for non-insulin-dependent diabetes mellitus with moderate obesity. To identify the
quantitative trait loci (QTLs) responsible for the body weight in KK, linkage analysis with 97 microsatellite markers was
carried out into 192 F2 progeny, comprising 93 mice with a/a genotype at agouti locus and 99 mice with A
y
/a genotype, of a cross between C57BL/6J female and KK-Ay (Ay congenic) male, thereby the influence of A
y
allele on the quantitative regulation of body weight was also examined. In F2
a/a mice, we identified a QTL on Chromosome (Chr) 4, and two loci with suggestive linkage on Chrs 15 and 18. In F2
A
y
/a mice, a QTL was identified on Chr 6, and two loci with suggestive linkage were identified on Chrs 4 and 16. That the QTL
on Chr 4 was held in common between F2
a/a and F2
A
y
/a progenies implies that this locus may be a primary component regulating body weight in KK and KK-Ay. These results suggest that the body weight in KK is controlled by multiple genes, and the different combination of loci
is involved in the presence of A
y
allele. The QTL on Chr 6 seemed to determine the body weight by controlling fat deposition, because the linkage was identified
on body weight and adiposity, and is suggested to be a component involved in the metabolic pathway in obesity caused by the
A
y
allele.
Received: 16 December 1997 / Accepted: 16 March 1998 相似文献
15.
Linkage disequilibrium (LD) is the nonrandom association of alleles at two markers. Patterns of LD have biological implications as well as practical ones when designing association studies or conservation programs aimed at identifying the genetic basis of fitness differences within and among populations. However, the temporal dynamics of LD in wild populations has received little empirical attention. In this study, we examined the overall extent of LD, the effect of sample size on the accuracy and precision of LD estimates, and the temporal dynamics of LD in two populations of bighorn sheep (Ovis canadensis) with different demographic histories. Using over 200 microsatellite loci, we assessed two metrics of multi‐allelic LD, D′, and χ′2. We found that both populations exhibited high levels of LD, although the extent was much shorter in a native population than one that was founded via translocation, experienced a prolonged bottleneck post founding, followed by recent admixture. In addition, we observed significant variation in LD in relation to the sample size used, with small sample sizes leading to depressed estimates of the extent of LD but inflated estimates of background levels of LD. In contrast, there was not much variation in LD among yearly cross‐sections within either population once sample size was accounted for. Lack of pronounced interannual variability suggests that researchers may not have to worry about interannual variation when estimating LD in a population and can instead focus on obtaining the largest sample size possible. 相似文献
16.
Novel genes influencing the expression of the yellow locus and mdg4 (gypsy) in Drosophila melanogaster 总被引:9,自引:0,他引:9
Summary We used a system with a mobilized Stalker transposable element, sometimes in combination with P-M hybrid dysgenesis, in the search for new mutations interfering with the y
2 mutation induced by mdg4 (gypsy) insertion into the yellow locus. A novel gene, modifier of mdg4, was detected in chromosome 3. The mutation mod(mdg4) either enhanced or suppressed phenotypic changes in different mutations induced by mdg4 insertions. Thus, mod(mdg4) seems to be involved in the control of mdg4 expression. Six other loci designated as enhancers of yellow were also detected. The e(y)
n
(with n from 1–6) mutations enhanced the expression of several y mutations induced by different insertions into the yellow locus. The major change is a damage of bristle and hair pigmentation which is not suppressed by su(Hw) mutations. On the other hand, e(y)
n
alleles do not interact with mdg4 induced mutations in other loci. All e(y)
n
genes are located in different regions of the X chromosome. One may speculate that e(y)
n
genes are involved in trans-regulation of the yellow locus and possibly of some other loci. 相似文献
17.
Several experimental in vivo systems exist that generate reciprocal translocations between engineered chromosomal loci of yeast or Drosophila, but not without previous genome modifications. Here we report the successful induction of chromosome translocations in unmodified yeast cells via targeted DNA integration of the KANR selectable marker flanked by sequences homologous to two chromosomal loci randomly chosen on the genome. Using this bridge-induced translocation system, 2% of the integrants showed targeted translocations between chromosomes V-VIII and VIII-XV in two wild-type Saccharomyces cerevisiae strains. All the translocation events studied were found to be non-reciprocal and the fate of their chromosomal fragments that were not included in the translocated chromosome was followed. The recovery of discrete-sized fragments suggested multiple pathway repair of their free DNA ends. We propose that centromere-distal chromosome fragments may be processed by a break-induced replication mechanism ensuing in partial trisomy. The experimental feasibility of inducing chromosomal translocations between any two desired genetic loci in a eukaryotic model system will be instrumental in elucidating the molecular mechanism underlying genome rearrangements generated by DNA integration and the gross chromosomal rearrangements characteristic of many types of cancer.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
18.
19.
20.
We explore the potential for the biologically based two-stage clonal expansion model to make statements about the influence
of genetic factors on the steps in the model. We find evidence that the different susceptibility of BALB/C and CBA/Ca mice
to bone cancer after 227Thorium injection may be mostly due to different promotional responses to radiation. In BALB/C × CBA/Ca back-crossed mice,
we analyzed the specific contribution of two individual loci in the carcinogenic process. This analysis suggests that the
two high- or low-risk alleles are acting on promotion or on the background parameters, but not on radiation-induced initiation.
Taken together with the comparison of CBA/Ca and BALB/C mice, this hints at the possibility that the two loci are candidates
for modifying radiation-induced promotion. 相似文献