International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Ms. Lara Underkoffler
Children's Hospital of Philadelphia
1004 ARC
34th St. and Civic Cntr. Blvd.
Philadelphia 19104

Co-Authors: 1) Mitchell,LE, 2) Oakey,RJ
Institutions: 1)University of Pennsylvania School of Medicine, Department of Biostatistics and Epidemiology, 2)Children's Hospital of Philadelphia, Genetics Division, Department of Pediatrics

A Robertsonian translocation results in a metacentric chromosome from the fusion of two acrocentric chromosomes.  The gametes of Rb heterozygote mice frequently undergo nondisjunction to produce aneuploid embryos providing a good model for studying nondisjunction in mammals.  We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1,927 embryos from 363 litters of mice with known parental origin, strain and age.  Nondisjunction events were scored in these mice and we then examined factors that influence the frequency of nondisjunction involving chromosomes 7 and 18.  This analysis allowed us to make a number of conclusions.  (1) The frequency of nondisjunction among 1,782 embryos, (3,564) meioses, was 16.5%.  (2) Nondisjunction events are distributed non-randomly among progeny.  This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all the litters.  (3) Strain background did not play an appreciable role in nondisjunction frequency.  (4) There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction.  (5) In males, but not females, the frequency of nondisjunction for chromosome 18 was significantly higher than for chromosome 7.  (6) In females the frequency of nondisjunction for chr 7 was significantly higher than for males, but there was no difference in chr 18 nondisjunction frequency between sexes.  These results show that molecular genotyping provides a valuable tool in understanding factors influencing nondisjunction in mammals.

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