Multicolor FISH studies of male non-disjunction: Evidence for a paternal age effect
- Case Western Reserve Univ., Cleveland, OH (United States); and others
Approximately 5-10% of autosomal trisomies and the majority of sex chromosome aneuploidies are paternally derived, thus paternal non-disjunction is an important contributor to human chromosomal syndromes. We have been using multicolor FISH to screen for aneuploidy in sperm of normal males and to determine whether there is, among individuals or among chromosomes, variation in the likelihood of non-disjunction. Our initial studies based on analysis of 5000 sperm scored per chromosome in nine males identified significant differences in disomy rates for chromosomes 16, 18 and the sex chromosomes. We have now extended those analyses to a new series of 10 donors aged 22 to 45 to confirm or refute our observations of chromosome-specific differences in rates of disomy; to determine if the size of the centromeric (alpha satellite) sequences is related to non-disjunction frequency; and to determine if there is a paternal as well as a maternal age effect on non-disjunction. For these studies, we have used 3 color FISH for chromosomes 18 and the X and Y chromosomes to now score {approximately}20,000 sperm for each of 10 new donors. Our results provide little evidence for an effect of the size of the Y chromosome centromere on the frequency of sex chromosome disomy. However, we have found considerable variation in rates of disomy among individuals and have confirmed significant differences among chromosomes in the likelihood of non-disjunction; i.e., the rate of non-disjunction of the sex chromosomes is 3.5 -4 times greater than that of chromosome 18 and meiosis II errors are significantly more likely for the Y chromosome than for the X chromosome. Specifically, we have identified increases in the frequency of disomy 18 and both meiosis I (XY) and meiosis II (XX and YY) sex chromosome disomy although the effect is only significant for total sex chromosome disomy.
- OSTI ID:
- 133438
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
Similar Records
The relationship between paternal age, sex ratios, and aneuploidy frequencies in human sperm, as assessed by multicolor FISH
Reliability of aneuploidy estimates in human sperm: Results of fluorescence in situ hybridization studies using two different scoring criteria
Related Subjects
BASIC STUDIES
AGE DEPENDENCE
ANEUPLOIDY
CENTROMERES
CHROMOSOMAL ABERRATIONS
DNA HYBRIDIZATION
DNA SEQUENCING
FLUORESCENCE
GENETICS
HEREDITARY DISEASES
HETEROCHROMOSOMES
HUMAN CHROMOSOME 16
HUMAN CHROMOSOME 18
HUMAN CHROMOSOMES
MALES
MEIOSIS
NON-DISJUNCTION
SEX DEPENDENCE
SPERMATOZOA