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1.
Transmission ratio distortion in offspring of mouse heterozygous carriers of a (7.18) Robertsonian translocation
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Transmission ratio distortion (TRD) is defined as a significant departure from expected Mendelian ratios of inheritance of an allele or chromosome. TRD is observed among specific regions of the mouse and human genome and is frequently associated with chromosome rearrangements such as Robertsonian (Rb) chromosomes. We intercrossed mice heterozygous for a (7.18) Rb translocation and genotyped chromosomes 7 and 18 in 1812 individuals, 47% of which were informative for chromosome segregation. We substantiated previous findings that females were less likely than expected to transmit the Rb chromosome to their offspring. Surprisingly, however, we report that heterozygous males transmitted the Rb translocation chromosome significantly more frequently than the acrocentrics. The transmission of the Rb chromosome was not significantly influenced by either the sex of the Rb grandparent or the strain of the Rb. 相似文献
2.
Sylvie Croteau Moises Freitas Andrade Fleur Huang Celia M.T. Greenwood Kenneth Morgan Anna K. Naumova 《Mammalian genome》2002,13(1):24-29
Deviations from Mendelian 1:1 transmission ratio have been observed in mice and humans. With few exceptions, the mechanism
leading to transmission-ratio distortion (TRD) remains obscure. We proposed that a genomic imprinting mechanism plays a key
role in the genesis of grandparental origin-dependent TRD (Naumova et al. 2001). To further test this hypothesis, we analyzed
the transmission of grandparental alleles at three imprinted regions of the mouse genome known to contain genes required for
embryo development. We found and replicated moderate (58%: 42%) TRD in favor of grandmaternal alleles in the imprinted region
of maternal distal Chromosome (Chr) 12 among female offspring. Comparison of transmission ratios at the distorted region of
Chr 12 among 3-week-old mice with those in embryos suggests that the distortion in favor of grandmaternal alleles is owing
to postimplantation embryo loss. The absence of grandparental origin-dependent TRD for maternal Chr 6 and 7 implies that the
relationship between TRD and imprinting is complex. Most likely, multiple conditions are required for TRD to occur.
Received: 20 June 2001 / Accepted: 28 August 2001 相似文献
3.
A fundamental principle of Mendelian inheritance is random segregation of alleles to progeny; however, examples of distorted transmission either of specific alleles or of whole chromosomes have been described in a variety of species. In humans and mice, a distortion in chromosome transmission is often associated with a chromosome abnormality. One such example is the fertile XO female mouse. A transmission distortion effect that results in an excess of XX over XO daughters among the progeny of XO females has been recognized for nearly four decades. Utilizing contemporary methodology that combines immunofluorescence, FISH, and three-dimensional confocal microscopy, we have readdressed the meiotic segregation behavior of the single X chromosome in oocytes from XO females produced on two different inbred backgrounds. Our studies demonstrate that segregation of the univalent X chromosome at the first meiotic division is nonrandom, with preferential retention of the X chromosome in the oocyte in approximately 60% of cells. We propose that this deviation from Mendelian expectations is facilitated by a spindle-mediated mechanism. This mechanism, which appears to be a general feature of the female meiotic process, has implications for the frequency of nondisjunction in our species. 相似文献
4.
We have observed maternal transmission ratio distortion (TRD) in favor of DDK alleles at the Ovum mutant (Om) locus on mouse chromosome 11 among the offspring of (C57BL/6 x DDK) F(1) females and C57BL/6 males. Although significant lethality occurs in this backcross ( approximately 50%), differences in the level of TRD found in recombinant vs. nonrecombinant chromosomes among offspring argue that TRD is due to nonrandom segregation of chromatids at the second meiotic division, i.e., true meiotic drive. We tested this hypothesis directly, by determining the centromere and Om genotypes of individual chromatids in zygote stage embryos. We found similar levels of TRD in favor of DDK alleles at Om in the female pronucleus and TRD in favor of C57BL/6 alleles at Om in the second polar body. In those embryos for which complete dyads have been reconstructed, TRD was present only in those inheriting heteromorphic dyads. These results demonstrate that meiotic drive occurs at MII and that preferential death of one genotypic class of embryo does not play a large role in the TRD. 相似文献
5.
Parental effect of DNA (Cytosine-5) methyltransferase 1 on grandparental-origin-dependent transmission ratio distortion in mouse crosses and human families
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Yang L Andrade MF Labialle S Moussette S Geneau G Sinnett D Belisle A Greenwood CM Naumova AK 《Genetics》2008,178(1):35-45
Transmission ratio distortion (TRD) is a deviation from the expected Mendelian 1:1 ratio of alleles transmitted from parents to offspring and may arise by different mechanisms. Earlier we described a grandparental-origin-dependent sex-of-offspring-specific TRD of maternal chromosome 12 alleles closely linked to an imprinted region and hypothesized that it resulted from imprint resetting errors in the maternal germline. Here, we report that the genotype of the parents for loss-of-function mutations in the Dnmt1 gene influences the transmission of grandparental chromosome 12 alleles. More specifically, maternal Dnmt1 mutations restore Mendelian transmission ratios of chromosome 12 alleles. Transmission of maternal alleles depends upon the presence of the Dnmt1 mutation in the mother rather than upon the Dnmt1 genotype of the offspring. Paternal transmission mirrors the maternal one: live-born offspring of wild-type fathers display 1:1 transmission ratios, whereas offspring of heterozygous Dnmt1 mutant fathers tend to inherit grandpaternal alleles. Analysis of allelic transmission in the homologous region of human chromosome 14q32 detected preferential transmission of alleles from the paternal grandfather to grandsons. Thus, parental Dnmt1 is a modifier of transmission of alleles at an unlinked chromosomal region and perhaps has a role in the genesis of TRD. 相似文献
6.
《PLoS genetics》2015,11(2)
Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 – 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, R2d) emerged as the strongest candidate for the causative allele. We mapped R2d sequences to two loci within the candidate interval. R2d1 is located near the proximal boundary, and contains a single copy of R2d in all strains tested. R2d2 maps to a 900 kb interval, and the number of R2d copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (R2d2WSBdel1) that eliminates the majority of the R2d2WSB copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for R2d2WSBdel1, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for R2d2WSBdel1, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in R2d2WSB heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the R2d2WSB transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system. 相似文献
7.
Pardo-Manuel de Villena F de la Casa-Esperon E Briscoe TL Malette JM Sapienza C 《Genetics》2000,154(1):351-356
F(1) backcrosses involving the DDK and C57BL/6 inbred mouse strains show transmission ratio distortion at loci on two different chromosomes, 11 and X. Transmission ratio distortion on chromosome X is restricted to female offspring while that on chromosome 11 is present in offspring of both sexes. In this article we investigate whether the inheritance of alleles at loci on one chromosome is independent of inheritance of alleles on the other. A strong nonrandom association between the inheritance of alleles at loci on both chromosomes is found among male offspring, while independent assortment occurs among female offspring. We also provide evidence that the mechanism by which this phenomenon occurs involves preferential cosegregation of nonparental chromatids of both chromosomes at the second meiotic division, after the ova has been fertilized by a C57BL/6 sperm bearing a Y chromosome. These observations confirm the influence of the sperm in the segregation of chromatids during female meiosis, and indicate that a locus or loci on the Y chromosome are involved in this instance of meiotic drive. 相似文献
8.
Transmission ratio distortion (TRD) occurs when one of the two alleles from either parent is preferentially transmitted to the offspring. This leads to a statistical departure from the Mendelian law of inheritance, which states that each of the two parental alleles is transmitted to offspring with a probability of 0.5. A number of mechanisms are thought to induce TRD such as meiotic drive, gametic competition, and embryo lethality. TRD has been extensively studied in animals, but the prevalence of TRD in humans remains largely unknown. Nevertheless, understanding the TRD phenomenon and taking it into consideration in many aspects of human genetics has potential benefits that have not been sufficiently emphasized in the current literature. In this review, we discuss the importance of TRD in three distinct but related fields of genetics: developmental genetics which studies the genetic abnormalities in zygotic and embryonic development, statistical genetics/genetic epidemiology which utilizes population study designs and statistical models to interpret the role of genes in human health, and population genetics which is concerned with genetic diversity in populations in an evolutionary context. From the perspective of developmental genetics, studying TRD leads to the identification of the processes and mechanisms for differential survival observed in embryos. As a result, it is a genetic force which affects allele frequency at the population, as well as, at the organismal level. Therefore, it has implications on genetic diversity of the population over time. From the perspective of genetic epidemiology, the TRD influence on a marker locus is a confounding factor which has to be adequately dealt with to correctly interpret linkage or association study results. These aspects are developed in this review. In addition to these theoretical notions, a brief summary of the empirical evidence of the TRD phenomenon in human and mouse studies is provided. The objective of our paper is to show the potentially important role of TRD in many areas of genetics, and to create an incentive for future research. 相似文献
9.
Transmission-Ratio Distortion through F(1) Females at Chromosome 11 Loci Linked to Om in the Mouse Ddk Syndrome 总被引:1,自引:0,他引:1
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FPM. de-Villena C. Slamka M. Fonseca A. K. Naumova J. Paquette P. Pannunzio M. Smith A. Verner K. Morgan C. Sapienza 《Genetics》1996,142(4):1299-1304
We determined the genotypes of >200 offspring that are survivors of matings between female reciprocal F(1) hybrids (between the DDK and C57BL/6J inbred mouse strains) and C57BL/6J males at markers linked to the Ovum mutant (Om) locus on chromosome 11. In contrast to the expectations of our previous genetic model to explain the ``DDK syndrome,' the genotypes of these offspring do not reflect preferential survival of individuals that receive C57BL/6J alleles from the F(1) females in the region of chromosome 11 to which the Om locus has been mapped. In fact, we observe significant transmission-ratio distortion in favor of DDK alleles in this region. These results are also in contrast to the expectations of Wakasugi's genetic model for the inheritance of Om, in which he proposed equal transmission of DDK and non-DDK alleles from F(1) females. We propose that the results of these experiments may be explained by reduced expression of the maternal DDK Om allele or expression of the maternal DDK Om allele in only a portion of the ova of F(1) females. 相似文献
10.
An open problem of some interest in the study of HLA has been the possible existence of transmission distortion in the human HLA complex. In this paper, transmission probabilities are estimated and tested using data on HLA A, B and DR loci genotypes of parents and offspring ascertained from the entire population of Finland (Childhood Diabetes in Finland Study) through one or more offspring diagnosed with insulin-dependent diabetes mellitus (IDDM) during the recruitment period from September 1986 to July 1989. First, we show how to get unbiased estimates of transmission probabilities from the family data collected in the disease registry of incident cases. This is accomplished by assuming that transmission of HLA genes to children in the general population is conditionally independent given the parents' genotypes, and the birth dates of all offspring. Based on the sampling (ascertainment) process in the study on Childhood Diabetes in Finland, younger siblings of the index child (the oldest proband) are independent of the ascertainment and therefore give rise to unbiased inference regarding allele transmission. The hypothesis of Mendelian transmission of alleles at each locus was tested using the standard chi(2) test. Goodness-of-fit of the Mendelian inheritance model to the individual locus data is calculated by maximizing the likelihood function over allele transmission intensities at each locus. The existence of a strong transmission distortion is not supported by this study at the loci considered. 相似文献
11.
Length of time in polymorphism is investigated as a possible evolutionary criterion for Mendel's laws in the case of two alleles at one locus and finite population. Deterministic models with constant and random segregation schemes are investigated. In deterministic models the optimum segregation system depends on the zygotic selection and is Mendelian only in symmetric models. In finite population models the initial gene frequencies interact with the segregation to determine mean time to fixation. In deterministic models with random distortion reduction of the variance of the distortion is more likely to produce polymorphism. 相似文献
12.
Segregation and linkage studies of allozyme loci in pair crosses of the oysterCrassostrea virginica 总被引:4,自引:0,他引:4
David W. Foltz 《Biochemical genetics》1986,24(11-12):941-956
The genetic control of 11 electrophoretically detected allozyme polymorphisms in the oyster Crassostrea virginica was investigated in 10 pair crosses. For nine allozyme loci, each offspring shared at least one band (electromorph) with each parent. For the remaining two loci (mannosephosphate isomerase and leucine aminopeptidase-2), some offspring failed to share a band with one or both parents. Several lines of evidence indicated that these anomalous results were due to transmission of null alleles. There was evidence of distorted segregation at 8 of the 11 loci. The departures from the Mendelian expectations within the pair crosses might be due either to viability selection in the offspring or to gametic selection in one or both parents, although the possibility that the distortion is due to a locus linked to the allozyme locus cannot be ruled out. However, there was no evidence that heterozygosity per se had an effect on viability of offspring within a cross. Linkage analysis revealed two linkage groups, one consisting of four allozyme loci and the other consisting of three loci. 相似文献
13.
We present a model of a primary locus subject to viability selection and an unlinked locus that causes sex-specific modification of the segregation ratio at the primary locus. If there is a balanced polymorphism at the primary locus, a population undergoing Mendelian segregation can be invaded by modifier alleles that cause sex-specific biases in the segregation ratio. Even though this effect is particularly strong if reciprocal heterozygotes at the primary locus have distinct viabilities, as might occur with genomic imprinting, it also applies if reciprocal heterozygotes have equal viabilities. The expected outcome of the evolution of sex-specific segregation distorters is all-and-none segregation schemes in which one allele at the primary locus undergoes complete drive in spermatogenesis and the other allele undergoes complete drive in oogenesis. All-and-none segregation results in a population in which all individuals are maximally fit heterozygotes. Unlinked modifiers that alter the segregation ratio are unable to invade such a population. These results raise questions about the reasons for the ubiquity of Mendelian segregation. 相似文献
14.
γ-Glutamyl Cyclotransferase: A New Genetic Polymorphism in the Mouse (MUS MUSCULUS) Linked to LYT–2
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Electrophoretically variant forms of gamma-glutamyl cyclotransferase have been identified in red cells of inbred mouse strains. Each inbred strain exhibited a major band of activity and a minor band that migrated more anodally. The polymorphism affects the migration of both the major and minor bands in a similar way. F1 hybrids between strains with fast forms (A/J) and strains with the slow forms (C57BL/6J) exhibited a four-banded pattern consistent with co-dominant inheritance. The patterns observed in backcross and F2 mice were consistent with the segregation of a pair of autosomal co-dominant alleles. Recombinant inbred strains and a congenic strain were used to show that the locus controlling gamma-glutamyl cyclotransferase (Ggc) is linked to Lyt-2, a lymphocyte alloantigen locus on chromosome 6, with an estimated map distance of 5.0 +/- 2.5 centimorgans. 相似文献
15.
Laboratory and wild-derived mice with multiple loci for production of xenotropic murine leukemia virus. 总被引:2,自引:1,他引:1
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Mendelian segregation analysis was used to define genetic loci for the induction of infectious xenotropic murine leukemia virus in several laboratory and wild-derived mice. MA/My mice contain two loci for xenotropic virus inducibility, one of which, Bxv -1, is the only induction locus carried by five other inbred strains. The second, novel MA/My locus, designated Mxv -1, is unlinked to Bxv -1 and shows a lower efficiency of virus induction. The NZB mouse carries two induction loci; both are distinct from Bxv -1 since neither is linked to the Pep-3 locus on chromosome 1. Finally, one partially inbred strain derived from the wild Japanese mouse, Mus musculus molossinus, carries multiple (at least three) unlinked loci for induction of xenotropic virus. Although it is probable that inbred strains inherited xenotropic virus inducibility from Japanese mice, our data suggest that none of the induction loci carried by this particular M. m. molossinus strain are allelic with Bxv -1. 相似文献
16.
Background
The Sb supergene in the fire ant Solenopsis invicta determines the form of colony social organization, with colonies whose inhabitants bear the element containing multiple reproductive queens and colonies lacking it containing only a single queen. Several features of this supergene — including suppressed recombination, presence of deleterious mutations, association with a large centromere, and “green-beard” behavior — suggest that it may be a selfish genetic element that engages in transmission ratio distortion (TRD), defined as significant departures in progeny allele frequencies from Mendelian inheritance ratios. We tested this possibility by surveying segregation ratios in embryo progenies of 101 queens of the “polygyne” social form (3512 embryos) using three supergene-linked markers and twelve markers outside the supergene.Results
Significant departures from Mendelian ratios were observed at the supergene loci in 3–5 times more progenies than expected in the absence of TRD and than found, on average, among non-supergene loci. Also, supergene loci displayed the greatest mean deviations from Mendelian ratios among all study loci, although these typically were modest. A surprising feature of the observed inter-progeny variation in TRD was that significant deviations involved not only excesses of supergene alleles but also similarly frequent excesses of the alternate alleles on the homologous chromosome. As expected given the common occurrence of such “drive reversal” in this system, alleles associated with the supergene gain no consistent transmission advantage over their alternate alleles at the population level. Finally, we observed low levels of recombination and incomplete gametic disequilibrium across the supergene, including between adjacent markers within a single inversion.Conclusions
Our data confirm the prediction that the Sb supergene is a selfish genetic element capable of biasing its own transmission during reproduction, yet counterselection for suppressor loci evidently has produced an evolutionary stalemate in TRD between the variant homologous haplotypes on the “social chromosome”. Evidence implicates prezygotic segregation distortion as responsible for the TRD we document, with “true” meiotic drive the most likely mechanism. Low levels of recombination and incomplete gametic disequilibrium across the supergene suggest that selection does not preserve a single uniform supergene haplotype responsible for inducing polygyny.17.
Although mouse t haplotypes carry recessive mutations causing male sterility and embryonic lethality, they persist in wild mouse populations via male transmission ratio distortion (TRD). Genetic evidence suggests that at least five t-haplotype-encoded loci combine to cause TRD. One of these loci, called the t complex responder (Tcr), is absolutely required for any deviation from Mendelian segregation to occur. A candidate for the Tcr gene has previously been identified. Evidence that this gene represents Tcr is its localization to the appropriate genomic subregion and testis-specific expression pattern. Here, we report the molecular cloning of the region between recombinant chromosome breakpoints defining the Tcr locus. These results circumscribe Tcr to a 150- to 220-kb region of DNA, including the 22-kb candidate responder gene. This gene and two other homologs were created by large genomic duplications, each involving segments of DNA 10-fold larger than the individual genes. 相似文献
18.
We have shown previously that the progeny of crosses between heterozygous females and C57BL/6 males show transmission ratio distortion at the Om locus on mouse chromosome 11. This result has been replicated in several independent experiments. Here we show that the distortion maps to a single locus on chromosome 11, closely linked to Om, and that gene conversion is not implicated in the origin of this phenomenon. To further investigate the origin of the transmission ratio distortion we generated a test using the well-known effect of recombination on maternal meiotic drive. The genetic test presented here discriminates between unequal segregation of alleles during meiosis and lethality, based on the analysis of genotype at both the distorted locus and the centromere of the same chromosome. We used this test to determine the cause of the transmission ratio distortion observed at the Om locus. Our results indicate that transmission ratio distortion at Om is due to unequal segregation of alleles to the polar body at the second meiotic division. Because the presence of segregation distortion at Om also depends on the genotype of the sire, our results confirm that the sperm can influence segregation of maternal chromosomes to the second polar body. 相似文献
19.
Jules Hernández-Sánchez Dave Waddington Pamela Wiener Chris S. Haley John L. Williams 《Mammalian genome》2002,13(3):164-168
A genome-wide search for markers associated with BSE incidence was performed by using Transmission-Disequilibrium Tests (TDTs).
Significant segregation distortion, i.e., unequal transmission probabilities of alleles within a locus, was found for three
marker loci on Chromosomes (Chrs) 5, 10, and 20. Although TDTs are robust to false associations owing to hidden population
substructures, it cannot distinguish segregation distortion caused by a true association between a marker and bovine spongiform
encephalopathy (BSE) from a population-wide distortion. An interaction test and a segregation distortion analysis in half-sib
controls were used to disentangle these two alternative hypotheses. None of the markers showed any significant interaction
between allele transmission rates and disease status, and only the marker on Chr 10 showed a significant segregation distortion
in control individuals. Nevertheless, the control group may have been a mixture of resistant and susceptible but unchallenged
individuals. When new genotypes were generated in the vicinity of these three markers, evidence for an association with BSE
was confirmed for the locus on Chr 5.
Subscribers can view a supplementary table for this article at url:http:// link.springer-ny/link/service/journals/OO335/contents/01/3068/paper/
index.html. 相似文献
20.
The evolution of sex-independent transmission ratio distortion involving multiple allelic interactions at a single locus in rice 总被引:1,自引:0,他引:1
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Koide Y Ikenaga M Sawamura N Nishimoto D Matsubara K Onishi K Kanazawa A Sano Y 《Genetics》2008,180(1):409-420
Transmission ratio distortion (TRD) is frequently observed in inter- and intraspecific hybrids of plants, leading to a violation of Mendelian inheritance. Sex-independent TRD (siTRD) was detected in a hybrid between Asian cultivated rice and its wild ancestor. Here we examined how siTRD caused by an allelic interaction at a specific locus arose in Asian rice species. The siTRD is controlled by the S(6) locus via a mechanism in which the S(6) allele acts as a gamete eliminator, and both the male and female gametes possessing the opposite allele (S(6)(a)) are aborted only in heterozygotes (S(6)/S(6)(a)). Fine mapping revealed that the S(6) locus is located near the centromere of chromosome 6. Testcross experiments using near-isogenic lines (NILs) carrying either the S(6) or S(6)(a) alleles revealed that Asian rice strains frequently harbor an additional allele (S(6)(n)) the presence of which, in heterozygotic states (S(6)/S(6)(n) and S(6)(a)/S(6)(n)), does not result in siTRD. A prominent reduction in the nucleotide diversity of S(6) or S(6)(a) carriers relative to that of S(6)(n) carriers was detected in the chromosomal region. These results suggest that the two incompatible alleles (S(6) and S(6)(a)) arose independently from S(6)(n) and established genetically discontinuous relationships between limited constituents of the Asian rice population. 相似文献