Nondisjunction rates and abnormal embryonic development in a mouse cross between heterozygotes carrying a (7, 18) robertsonian translocation chromosome.

Abstract Mice bearing Robertsonian translocation chromosomes frequently produce aneuploid gametes. They are therefore excellent tools for studying nondisjunction in mammals. Genotypic analysis of embryos from a mouse cross between two different strains of mice carrying a (7,18) Robertsonian chromosome enabled us to measure the rate of nondisjunction for chromosomes 7 and 18. Embryos (429) were harvested from 76 litters of mice and the parental origin of each chromosome 7 and 18 determined. Genotyping these embryos has allowed us to conclude the following: (1) there were 96 embryos in which at least one nondisjunction event had taken place; (2) the rate of maternal nondisjunction was greater than paternal nondisjunction for teh chromosomes sampled in these mice; (3) a bias against chromosome 7 and 18 nullisomic gametes was observed, reflected in a smaller than expected number of uniparental disomic embryos; (4) nondisjunction events did not seem to occur at random throughout the 76 mouse litters, but were clustered into fewer than would be expected cy chance; and (5) a deficiency of paternal chromosome 18 uniparental disomic embryos was observed along with a higher than normal rate of developmental retardation at 8.5 days post coitum, raising the possibility that this chromosome has at least one imprinted gene.

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Molecular Analysis of Nondisjunction in Mice Heterozygous for a Robertsonian Translocation

Genetics ◽

10.1093/genetics/161.3.1219 ◽

2002 ◽

Vol 161 (3) ◽

pp. 1219-1224

Author(s):

Lara A Underkoffler ◽

Laura E Mitchell ◽

A Russell Localio ◽

Shannon M Marchegiani ◽

Justin Morabito ◽

...

Keyword(s):

Molecular Analysis ◽

Robertsonian Translocation ◽

Metacentric Chromosome ◽

Paternal Age ◽

Chromosome 7 ◽

Parental Origin ◽

Molecular Genotyping ◽

Factors Influencing ◽

Meiotic Nondisjunction ◽

Acrocentric Chromosomes

Abstract A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%.Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters.There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction.Strain background did not play an appreciable role in nondisjunction frequency.The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males.The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males. These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals.

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Parental origin effects in mice

Development ◽

10.1242/dev.97.supplement.137 ◽

1986 ◽

Vol 97 (Supplement) ◽

pp. 137-150

Author(s):

B. M. Cattanach

Keyword(s):

Embryonic Development ◽

Normal Development ◽

Full Term ◽

Nuclear Transplantation ◽

Parental Origin ◽

Paternal Chromosome ◽

Paternal Genome ◽

Maternal Genome ◽

Transplantation Experiments ◽

Hydatidiform Moles

Nuclear transplantation experiments in mice, reviewed elsewhere in this Symposium, have clearly demonstrated that the maternal and paternal genomes from which the embryo is formed are not functionally equivalent. The paternal genome appears to be essential for the normal development of extraembryonic tissues and the maternal genome for some stage of embryonic development. These findings provide some explanation for the observations that in mammals diploid parthenotes possessing two maternal genomes fail to survive (Markert, 1982) and that, in man, embryos with two paternal chromosome sets are inviable, forming hydatidiform moles (Kajii & Ohama, 1977). It has been proposed that a specific ‘imprinting’ of the paternal genomes occurs during gametogenesis so that the presence of both a female and male pronculeus is essential in an egg for full-term development (Barton, Surani & Norris, 1984; McGrath & Solter, 1984a; Surani, Barton & Norris, 1984).

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The H19 Differentially Methylated Region Marks the Parental Origin of a Heterologous Locus without Gametic DNA Methylation

Molecular and Cellular Biology ◽

10.1128/mcb.24.9.3588-3595.2004 ◽

2004 ◽

Vol 24 (9) ◽

pp. 3588-3595 ◽

Cited By ~ 29

Author(s):

Kye-Yoon Park ◽

Elizabeth A. Sellars ◽

Alexander Grinberg ◽

Sing-Ping Huang ◽

Karl Pfeifer

Keyword(s):

Dna Methylation ◽

Mouse Chromosome ◽

Germ Line ◽

Transcriptional Silencing ◽

Chromosome 7 ◽

Differentially Methylated Region ◽

Parental Origin ◽

Imprinted Genes ◽

Chromosome 5 ◽

The Third

ABSTRACT Igf2 and H19 are coordinately regulated imprinted genes physically linked on the distal end of mouse chromosome 7. Genetic analyses demonstrate that the differentially methylated region (DMR) upstream of the H19 gene is necessary for three distinct functions: transcriptional insulation of the maternal Igf2 allele, transcriptional silencing of paternal H19 allele, and marking of the parental origin of the two chromosomes. To test the sufficiency of the DMR for the third function, we inserted DMR at two heterologous positions in the genome, downstream of H19 and at the alpha-fetoprotein locus on chromosome 5. Our results demonstrate that the DMR alone is sufficient to act as a mark of parental origin. Moreover, this activity is not dependent on germ line differences in DMR methylation. Thus, the DMR can mark its parental origin by a mechanism independent of its own DNA methylation.

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IS THERE SPECIFICITY OF ACTION IN EXPERIMENTAL TERATOGENESIS?

PEDIATRICS ◽

10.1542/peds.19.4.755 ◽

1957 ◽

Vol 19 (4) ◽

pp. 755-763

Author(s):

James G. Wilson

Keyword(s):

Embryonic Development ◽

Fetal Death ◽

Metabolic Process ◽

Teratogenic Effects ◽

Specific Effects ◽

Different Strains ◽

Time Specific

Time-specificity has been well established in numerous experiments in which a teratogenic agent has been shown to cause different malformations when applied at different times in development. These time-specific effects are related to definite stages or events in embryonic development which might be regarded as periods of special susceptibility. Excessive doses tend to obscure time-specificity by causing teratogenic effects at times other than during periods of special susceptibility. Recent experiments have indicated that, irrespective of time, many teratogenic agents seem to produce distinctive patterns of anomalies which differ qualitatively and quantitatively from those caused by other agents. The association of a particular group of malformations with a particular agent may be termed agent-specificity. Agent-specificity is not always readily apparent for reasons such as: a) elimination of certain types of abnormalities by fetal death of affected individuals, b) fluctuations in the pattern resulting from variations in dosage of the agent, c) variable reactions to the same agent in different species or even different strains, and d) varying interests and methods of study on the part of the investigator. When due allowance is made for such variables, distinctive patterns of malformations can often be associated with particular teratogenic agents. Although mechanisms of agent-specificity were not discussed in detail, it was suggested that each agent acts by interfering with a particular metabolic process in a specific way in the differentiating and growing embryo. Such action can be localized, generalized or selectively distributed, depending on the distribution within the embryo of the process concerned.

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Translocation chromosome karyotypes of the Robertsonian translocation carriers' embryos

Fertility and Sterility ◽

10.1016/j.fertnstert.2008.11.020 ◽

2010 ◽

Vol 93 (4) ◽

pp. 1061-1065 ◽

Cited By ~ 12

Author(s):

Huang Jin ◽

Liu Ping ◽

Qiao Jie ◽

Lian Ying ◽

Chen Yongjian

Keyword(s):

Robertsonian Translocation ◽

Translocation Chromosome

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Parental origin of Robertsonian translocation (15q22q) and Prader Willi syndrome associated with autism

Psychiatric Genetics ◽

10.1097/00041444-199421000-00009 ◽

1994 ◽

Vol 4 (1) ◽

pp. 63-66 ◽

Cited By ~ 8

Author(s):

I. Arrieta ◽

M. N. Lobato ◽

B. Martinez ◽

B. Criado

Keyword(s):

Robertsonian Translocation ◽

Parental Origin ◽

Prader Willi Syndrome

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The inheritance of germline-specific epigenetic modifications during development

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1993.0013 ◽

1993 ◽

Vol 339 (1288) ◽

pp. 165-172 ◽

Cited By ~ 14

Keyword(s):

Mouse Chromosome ◽

Germ Line ◽

Epigenetic Modification ◽

Embryonic Stem ◽

Epigenetic Inheritance ◽

Epigenetic Modifications ◽

Chromosome 7 ◽

Parental Origin ◽

Imprinted Genes ◽

Female Germline

Parental genomes in mammals are programmed in the germline with heritable epigenetic modifications that exert control on the expression of specific (imprinted) genes. DNA methylation is one form of epigenetic modification which shows marked genome-wide variations in the germline and during early development. Certain transgene loci also demonstrate (reversible) germline-specific methylation imprints that are heritable in somatic tissues during development. Recently, four endogenous genes have been identified whose expression is dependent on their parental origin. The mechanism of genomic imprinting and the role of imprinted genes during development is beginning to be analysed. Three of these genes map to the mouse chromosome 7. Human chromosomes 11p13, 11p15, and 15ql 1-13 are associated with disorders exhibiting parental origin effects in their patterns of inheritance. These regions share syntenic homology with mouse chromosome 7. The relationship between parental imprints, germ line-dependent epigenetic inheritance and totipotency is also under investigation using embryonic stem cells derived from the epiblast. These cells are pluripotent or totipotent and evidence indicates the presence of at least the primary parental imprints. However, imprints inherited from the paternal germline in androgenetic cells are apparently more stable than those from the female germline in parthenogenetic cells.

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Mechanism of imprinting on mouse distal chromosome 7

Genetics Research ◽

10.1017/s0016672398003565 ◽

1998 ◽

Vol 72 (3) ◽

pp. 237-245 ◽

Cited By ~ 7

Author(s):

JUSTIN F-X. AINSCOUGH ◽

ROSALIND M. JOHN ◽

M. AZIM SURANI

Keyword(s):

Chromosome 7 ◽

Parental Origin ◽

Imprinted Genes ◽

Critical Feature ◽

Male Germline ◽

Domain Type ◽

Distal Chromosome ◽

Type Mode ◽

Single Allele ◽

Female Germline

Genomic imprinting is an epigenetic mode of gene regulation that results in expression of the autosomal ‘imprinted’ genes from only a single allele, determined exclusively by parental origin. To date over 20 imprinted genes have been identified in mouse and man and these appear to lie in clusters in restricted regions on a subset of chromosomes. This may be a critical feature of imprinting suggesting a domain-type mode of regulation. Imprinted domains are replicated asynchronously, show sex-specific meiotic recombination frequencies and have CpG-rich regions that are differentially methylated, often associated with the imprinted genes themselves. Mouse distal chromosome 7 is one such domain, containing at least nine imprinted genes spanning over 1 Mb of DNA. For the maternally expressed p57Kip2 gene, passage through the female germline is essential to generate the active state, whereas passage through the male germline is needed to force the maternally expressed H19 gene into an inactive state. It is therefore possible that the mouse distal chromosome 7 imprinted domain is actually composed of two or more independently regulated subdomains.

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