Paternal Age and De Novo Nonrecurrent Translocations

: J Med Genet. 2009 Jul 27. [Epub ahead of print]
De novo apparently balanced translocations in man are predominantly paternal in origin and associated with a significant increase in paternal age.Thomas NS, Morris JK, Baptista J, Ng BL, Crolla JA, Jacobs PA.
Salisbury District Hospital, United Kingdom.

BACKGROUND: Congenital chromosome abnormalities are relatively common in our species and among structural abnormalities the most common class is balanced reciprocal translocations. Determining the parental origin of de novo balanced translocations may provide insights into how and when they arise. While there is a general paternal bias in the origin of non-recurrent unbalanced rearrangements, there are few data on parental origin of non-recurrent balanced rearrangements. METHODS: The parental origin of a series of de novo balanced reciprocal translocations was determined using DNA from flow sorted derivative chromosomes and linkage analysis. RESULTS: Of 27 translocations, we found 26 to be of paternal origin and only one of maternal origin. We also found the paternally derived translocations to be associated with a significantly increased paternal age (p<0.008). CONCLUSION: Our results suggest there is a very marked paternal bias in the origin of all non-recurrent reciprocal translocations and that they may arise during one of the numerous mitotic divisions that occur in the spermatogonial germ cells prior to meiosis.

PMID: 19638350 [PubMed - as supplied by publisher]

Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages

Psychol Med. 2009 Jul 23:1-9. [Epub ahead of print]
Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring.
Menezes PR, Lewis G, Rasmussen F, Zammit S, Sipos A, Harrison GL, Tynelius P, Gunnell D.
Department of Preventive Medicine, University of Sao Paulo, Brazil.
BACKGROUND: A consistent association between paternal age and their offspring's risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring's risk of BPAD, whereas maternal age is not.MethodThis population-based cohort study was conducted with individuals born in Sweden during 1973-1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox's proportional hazard regression. RESULTS: After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (CI) 1.11-1.48], but this fell to 1.20 (95% CI 0.97-1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08-1.56) before adjustment for paternal age, HR 1.12 (95% CI 0.86-1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01-1.57) and it was 1.45 (95% CI 1.16-1.81) if both parents were >30 years. CONCLUSIONS: Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.
PMID: 19627644 [PubMed - as supplied by publisher]
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Data Converges About Older Fathers

Data Converges About Older Fathers
A recent post in the New York Times presents some evidence that men who become fathers at a later age have unhealthier children. It is well recognized that men retain their reproductive potential longer, and lose it in a more gradual manner, than do women. Whereas women's fertility declines sharply after age 35 or so, men retain their ability to father children, albeit to a diminished degree, for several decades longer. Recently, some evidence has been presented in the scientific literature that suggests that children conceived with sperm from an older male may have cognitive or psychological challenges compared to those fathered by younger males. A recent study performed by Australian scientists concluded that older dads have children with slightly lower IQs. Others have shown increased rates of schizophrenia, bipolar disorder, and autism in children fathered by older vs. younger men. This evidence suggests that men are susceptible to age-related effects on reproductive ability. This should not surprise anyone. However, the effects of reproductive ageing appear to be expressed differently in males than in females. Dr. Dolores Malaspina, a professor of psychiatry at New York University Medical Center, puts it this way: “It turns out the optimal age for being a mother is the same as the optimal age for being a father.”