Parental age in retinoblastoma

Summary In a review of information on 444 patients with sporadic retinoblastoma, a correlation with increased fathers'age was demonstrated and no correlation with was found in the unilateral form. These data favor the hypothesis that the bilateral form is caused by a germinal mutation and the unilateral form is due to somatic mutations.

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Zusammenfassung In einer Übersicht über 444 Patienten mit sporadischem Retinoblastom wurde eine Erhöhung des väterlichen Alters demonstriert. Bei den einseitigen Fällen wurde eine solche Erhöhung jedoch nicht gefunden. Die Daten sprechen dafür, daß die doppelseitige Form durch Keimzell-Mutation verursacht ist, während die einseitige form auf somatische Mutationen zurückgeht.

     

Parental age and seasonal variation in the births of children with sporadic retinoblastoma: a mutation-epidemiologic study

Summary Statistical analysis of parental age data from 225 sporadic cases of bilateral retinoblastoma, plus ten sporadic cases of chromosome deletion or translocation involving 13q14 that was identified as of paternal origin, revealed no evidence of paternal or maternal age effect. Parental exposure to ionizing radiation or chemical mutagens, the effect of which is accumulated with advancing age, does not seem to play a major role in the production of germinal mutations at the responsible (RB) locus. Furthermore, analysis of variation in the month of birth of 753 children with sporadic unilateral retinoblastoma did not show any significant deviation from the controls or a cyclic trend. The occurrence of nonheritable retinoblastoma is not likely to be associated with certain viruses such as human adenovirus 12 whose activity varies markedly with season. These results, together with the fairly uniform pattern in the incidence of this tumor among different populations, suggest that most, if not all, cases of sporadic retinoblastoma are caused by some intrinsic biological mechanisms, and not by environmental mutagens that may vary with respect to time and place.     

Parental origin of germ-line and somatic mutations in the retinoblastoma gene

Segregation analysis of polymorphic sites within the retinoblastoma (RB) gene and on chromosome 13, as well as the parental origin of the lost allele in the tumor, were analyzed in 24 families with RB patients. Four mutant alleles transmitted through the germ-line and seven de novo germ-line mutant alleles were identified in 11 patients with hereditary RB. Segregation analysis within the RB gene and on chromosome 13 was useful for DNA diagnosis of susceptibility to RB in relatives of hereditary patients, even if mutations were not identified. All seven de novo germ-line mutant alleles were paternally derived. The bias toward the paternal allele for de novo germ-line mutations of the RB gene was statistically significant. Seven paternal alleles and six maternal alleles were lost in 13 non-hereditary RB tumors with no bias in the parental origin of the somatic allele loss. These results suggest that the physical environment or a deficiency in DNA repair during spermatogenesis may be associated with significant risk factors for de novo germ-line mutations.     

Parental age difference and offspring count in humans

Preferences for certain age characteristics of partners are reported across cultures: men prefer mates who are younger and women prefer mates older than themselves. To examine whether these age preferences entail fitness effects for men and women, we investigated the association among age differences between partners and offspring count. On the basis of a sample of approximately 10,000 post-reproductive Swedish men and women who did not change their partner between the birth of their first and last child, we find maximum offspring count in men if their partner is approximately 6 years younger, and in women if their partner is approximately 4 years older. We further find that after separation, on average, both men and women shift to a partner younger than the first, albeit in women the new partner is still older than the female herself. We conclude that the age preference for the partner yields fitness benefits for both men and women and may thus be an evolutionarily acquired trait.     

Parental age and developmental stability inDrosophila melanogaster

Two strains ofDrosophila melanogaster, one outbred, recently derived from nature, and the other created by intensive directional selection on phototactic behavior for 19 years, were used to test the hypothesis that developmental stability is influenced by parental age. Three characters were examined: sternopleural bristle number, wing length, and wing area. The results do not support any relationship between parental age, either young or old, and developmental stability in offspring.     

Morphology of retinoblastoma and the age of the patient

A comparative histopathological analysis of 28 retinoblastomas was carried out in children of different age groups. The tumors in children under 1 year of age showed the fewest malignancy features and numerous Flexner-Wintersteiner's rosettes. In patients above 3 years of age particularly numerous pseudorosettes were seen.     

Parental age and the origin of trisomy 21

Summary Several studies have attempted to define the role of parental age in determining the prevalence of 47,+21 according to the origin of nondisjunction. This report analyzes the original data of 197 informative families from Italy and reviews the available literature (96 families from Denmark and 201 from other countries). Mothers whose gametes showed nondisjunction are treated as cases, and those with normal meiosis as controls within each study. To utilize the data fully, maternal age at birth of a 47,+21 individual is treated as a continuous variable in a nonparametric comparison. The combined evidence indicates that nondisjunction in the female is associated with a significant age difference between cases and controls which is mostly due to errors in the second meiotic division. It may be inferred that in the general population, aging enhances nondisjunction at both first and second division in the female, while aging in the male is presumably associated mostly (or only) with first division errors. Implications and alternative models are discussed.     

Parental age and reproduction in the Marsh Tit Paras palustris

In the Marsh Tit Parus palustris , breeding performance improved with the age of both the male and the female parent—older birds produced larger clutches earlier in the season. The effect of male age, however, was mainly due to a positive association with the age of the female. When the effect of laying date was accounted for, there was no additional effect of female age on clutch-size. However, pairs with previous breeding experience laid larger clutches than newly formed pairs of the same age. There was some evidence that young females that laid late in the season were less likely to survive to breed again, leading to an age effect on reproductive performance. There was no evidence that individual birds laid earlier or produced larger clutches when they became older.     

Parental age influences developmental stability of the progeny in Drosophila

The stochastic nature of biochemical processes is a source of variability that influences developmental stability. Developmental instability (DI) is often estimated through fluctuating asymmetry (FA), a parameter that deals with within-individual variation in bilateral structures. A relevant goal is to shed light on how environment, physiology and genotype relate to DI, thus providing a more comprehensive view of organismal development. Using Drosophila melanogaster isogenic lines, we investigated the effect of parental age, parental diet and offspring heterozygosity on DI. In this work, we have uncovered a clear relationship between parental age and offspring asymmetry. We show that asymmetry of the progeny increases concomitantly with parental age. Moreover, we demonstrate that enriching the diet of parents mitigates the effect of age on offspring symmetry. We show as well that increasing the heterozygosity of the progeny eliminates the effect of parental age on offspring symmetry. Taken together, our results suggest that diet, genotype and age of the parents interact to determine offspring DI in wild populations. These findings provide us with an avenue to understand the mechanisms underlying DI.     

High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862–1994

We wished to determine the influence of parental age at the birth of a retinoblastoma patient on the risk of sporadic hereditary retinoblastoma. The parental age at birth of 941 patients of the Dutch retinoblastoma register (1862–1994) was identified and compared between sporadic hereditary and nonhereditary patients. In a subcohort (1936–1994), a comparison was made with parental age at birth in the general population, as obtained from the Central Bureau of Statistics. Missing birth dates of the parents of retinoblastoma patients were traced with the help of the municipal registries and the Central Bureau of Genealogy. The mean paternal age was 10.7 months higher and the mean maternal age was 11.0 months higher in the sporadic hereditary retinoblastoma patients than in parents of nonhereditary patients. In the subcohort, the mean paternal and maternal ages of sporadic hereditary patients were also higher (12.4 and 11.5 months, respectively) than those of the general population. All differences were statistically significant. This study shows that a high parental age is associated with an enhanced risk of sporadic hereditary retinoblastoma. Received: 10 November 1995 / Revised: 11 January 1996     

Hereditary retinoblastoma: Penetrance,expressivity and age of onset

Summary Analyses of family data published in Japan concerning 29 kindreds with 2 or more cases of retinoblastoma revealed that, in the children who received the gene from a carrier parent, both penetrance and expressivity increase with increasing degree of expressivity in the parent. The estimate for the average degree of penetrance varies from 0.7 to 0.9, depending upon the method employed. The value will be increased with increasing number of survivors of hereditary retinoblastoma. Data were presented to indicate that the hereditary form of retinoblastoma onset tends to be later in unilateral than in bilateral affection, though in the non-hereditary form onset will be further delayed. No effect of birth order was detected. It was suggested that suppressor genes at other loci play a significant role in manifestation of the major dominant gene for retinoblastoma. Implications of these findings were discussed.This work, contribution number 1093 from the National Institute of Genetics, was supported by grants-in-aid from the Ministry of Education and the Ministry of Health and Welfare.     

Parental age and the life-span of zygotes of Saccharomyces cerevisiae

Isolated cells of Saccharomyces cerevisiae were mated by micromanipulation and the reproductive capacity of the resulting zygotes was determined. The mating frequency was dependent on the age of the parents: conjugations between young cells and cells which had completed more than two thirds of their life-span were very rare events. The life-span of a zygote was very similar to the life-span of its shorter-lived parent. If one of the parent cells had budded several times prior to fusion, the life-span of the zygote was reduced correspondingly, i.e. there was no rescue by hybridization. In four crosses the distribution of buds on both of the parent cells was recorded. In three of these four crosses the buds were evenly distributed, and in one the -parent had three times as many buds as the a-parent.This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Bonn-Bad Godesberg).