A balanced reciprocal translocation t(5;7)(q14;q32) associated with autistic disorder: Molecular analysis of the chromosome 7 breakpoint

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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Genetic Studies of Autistic Disorder and Chromosome 7

Genomics ◽

10.1006/geno.1999.5968 ◽

1999 ◽

Vol 61 (3) ◽

pp. 227-236 ◽

Cited By ~ 136

Author(s):

A. Ashley-Koch ◽

C.M. Wolpert ◽

M.M. Menold ◽

L. Zaeem ◽

S. Basu ◽

...

Keyword(s):

Autistic Disorder ◽

Chromosome 7 ◽

Genetic Studies

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6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target

Molecular and Cellular Biology ◽

10.1128/mcb.8.1.441-451.1988 ◽

1988 ◽

Vol 8 (1) ◽

pp. 441-451

Author(s):

W S Pear ◽

G Wahlström ◽

S F Nelson ◽

H Axelson ◽

A Szeles ◽

...

Keyword(s):

Molecular Analysis ◽

Strong Correlation ◽

Chromosomal Translocation ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma ◽

Chromosome 7 ◽

Chromosome 6 ◽

Intron 1 ◽

Switch Regions ◽

Exon 1

Our previous studies have shown that spontaneously arising immunocytomas in the LOU/Ws1 strain of rats contain a t(6;7) chromosomal translocation in all seven tumors studied (F. M. Babonits, J. Spira, G. Klein, and H. Bazin, Int. J. Cancer 29:431-437, 1982). We have also shown that the c-myc is located on chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature (London) 306:497-499, 1983) and the immunoglobulin H cluster on chromosome 6 (W.S. Pear, G. Wahlström, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Immunogenetics 23:393-395, 1986). We now report a detailed cytogenetic and molecular analysis of nine additional rat immunocytomas. The t(6;7) chromosomal translocation is found in all tumors. Mapping of the c-myc breakpoints showed that in 10 of 14 tumors, the c-myc breakpoints are clustered in a 1.5-kilobase region upstream of exon 1. In contrast with sporadic Burkitt's lymphoma and mouse plasmacytoma, only 1 of 14 tumors contains the c-myc breakpoints in either exon 1 or intron 1. Analysis of the sequences juxtaposed to the c-myc show that immunoglobulin H switch regions are the targets in at least five tumors and that there is a strong correlation between the secreted immunoglobulin and the c-myc target. Unlike sporadic Burkitt's lymphoma and mouse plasmacytoma, at least two rat immunocytomas show recombination of the c-myc with sequences distinct from immunoglobulin switch regions.

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6;7 chromosomal translocation in spontaneously arising rat immunocytomas: evidence for c-myc breakpoint clustering and correlation between isotypic expression and the c-myc target.

Molecular and Cellular Biology ◽

10.1128/mcb.8.1.441 ◽

1988 ◽

Vol 8 (1) ◽

pp. 441-451 ◽

Cited By ~ 30

Author(s):

W S Pear ◽

G Wahlström ◽

S F Nelson ◽

H Axelson ◽

A Szeles ◽

...

Keyword(s):

Molecular Analysis ◽

Strong Correlation ◽

Chromosomal Translocation ◽

Burkitt’S Lymphoma ◽

Burkitt's Lymphoma ◽

Chromosome 7 ◽

Chromosome 6 ◽

Intron 1 ◽

Switch Regions ◽

Exon 1

Our previous studies have shown that spontaneously arising immunocytomas in the LOU/Ws1 strain of rats contain a t(6;7) chromosomal translocation in all seven tumors studied (F. M. Babonits, J. Spira, G. Klein, and H. Bazin, Int. J. Cancer 29:431-437, 1982). We have also shown that the c-myc is located on chromosome 7 (J. Sümegi, J. Spira, H. Bazin, J. Szpirer, G. Levan, and G. Klein, Nature (London) 306:497-499, 1983) and the immunoglobulin H cluster on chromosome 6 (W.S. Pear, G. Wahlström, J. Szpirer, G. Levan, G. Klein, and J. Sümegi, Immunogenetics 23:393-395, 1986). We now report a detailed cytogenetic and molecular analysis of nine additional rat immunocytomas. The t(6;7) chromosomal translocation is found in all tumors. Mapping of the c-myc breakpoints showed that in 10 of 14 tumors, the c-myc breakpoints are clustered in a 1.5-kilobase region upstream of exon 1. In contrast with sporadic Burkitt's lymphoma and mouse plasmacytoma, only 1 of 14 tumors contains the c-myc breakpoints in either exon 1 or intron 1. Analysis of the sequences juxtaposed to the c-myc show that immunoglobulin H switch regions are the targets in at least five tumors and that there is a strong correlation between the secreted immunoglobulin and the c-myc target. Unlike sporadic Burkitt's lymphoma and mouse plasmacytoma, at least two rat immunocytomas show recombination of the c-myc with sequences distinct from immunoglobulin switch regions.

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Genome imprinting phenomena on mouse chromosome 7

Genetics Research ◽

10.1017/s0016672300035333 ◽

1990 ◽

Vol 56 (2-3) ◽

pp. 237-244 ◽

Cited By ~ 75

Author(s):

Antony G. Searle ◽

Colin V. Beechey

Keyword(s):

Mouse Chromosome ◽

Genetic Markers ◽

Reciprocal Translocation ◽

Neonatal Death ◽

Reciprocal Cross ◽

The Other ◽

Chromosome 7 ◽

Chromosome 15 ◽

Wild Type ◽

Parental Transmission

SummaryHeterozygotes for the reciprocal translocation T(7;15)9H were intercrossed, with albino (c) and underwhite (uw) as genetic markers, in order to study genetic complementation in mouse chromosome 7. Chromosome 15 is known to show normal complementation. Neither reciprocal cross in which one parent was c/c and the other wild type yielded albino progeny at birth although about 17% would be expected, but albino foetuses were recovered when the mother was c/c and father wild type. These products of maternal duplication/paternal deficiency for distal 7 were markedly retarded with small placentae. No albino foetuses were found when the father was c/c and mother wild type, which suggested earlier lethality. Equivalent crosses with uw (chromosome 15) as proximal marker gave normal underwhite progeny when the mother was uw/uw but small placentae, retardation and neonatal death of presumptive underwhites in the reciprocal cross. These abnormal newborn would have had a maternal duplication/paternal deficiency for proximal 7. These and other findings indicate that one region of defective complementation probably lies distal to the breakpoint of T(7;18)50H at 7E2-F2, while another is between the centromere and 7B3. Examination of man-mouse homologies suggests that the loci for three pathological human conditions (Beckwith-Weidemann syndrome, dystrophia myotonia and rhabdomyosarcoma) with differential parental transmission may be located in homologous regions to those affected by imprinting phenomena on mouse chromosome 7.

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