October 3, 2004

October 3, 2004 – In a paper published today in the online edition of Nature Genetics, a deCODE-led team of scientists present the results of a large-scale population study linking recombination rate with maternal age and fertility. In the paper, entitled “Recombination rate and reproductive success in humans,” the deCODE team establish a novel and significant correlation between recombination – the shuffling of chromosomal material that takes place in the formation of eggs and sperm – and maternal age and fertility. Specifically, the average number of recombinations in eggs that go on to become successful live births tends to increase with the mother’s age, and mothers with a higher recombination rate in general also tend to have more children than do those with a lower recombination rate.

The authors conclude that the most likely explanation for this phenomenon is that recombination, which is one of the most important mechanisms for generating genetic diversity in sexually-reproducing organisms, is under selective pressure from the earliest stages of reproduction. In short, an egg with a higher recombination count – that is, in which a mother’s two sets of chromosomes have undergone a larger number of reshufflings to yield the one set that goes into an egg – has a better chance of becoming a live-born child than does an egg with a lower recombination count. Basic evolutionary theory holds that diversity provides the substrate or background upon which natural selection occurs, as slightly different versions of an organism come into contact with their environment and reproduce. But these findings suggest that there is a significant selective pressure putting a premium on the generation of diversity itself. The paper is published today in the online edition of Nature Genetics and can be accessed at www.nature.com/ng. It will be published in the November print edition of the journal.

This study is the largest of its kind ever undertaken. It was conducted utilizing deCODE’s nationwide genealogical database and genome-wide genotypic data from more than 23,000 Icelanders participating in deCODE’s gene discovery programs. It follows on the publication two years ago of deCODE’s recombination map of the human genome, which was used to complete the assembly of the sequence of the human genome. The recombination data employed to build that map confirmed on a highly detailed, genome-wide scale the findings of previous studies showing that women have a significantly higher recombination rate on average than do men, and that recombination rates vary substantially between women. It was also the first study to demonstrate significant variation in the maternal recombination rate of offspring of the same mother. The latter finding raised the question of whether this variation might be correlated with the mother’s age, the principal question addressed in the paper published today.

The data presented in the article published today demonstrate that the maternal recombination counts seen in children do indeed increase to a statistically significant degree in line with a mother’s age. The sample size of the study, which includes 5,463 families, is large enough to overcome the impact of reproductive choice in individual families. The authors note that recombination may be beneficial because, as other research suggests, a higher number of recombination events may protect against certain maternal-age related errors in the sorting of chromosomes as oocytes – the precursor cells to eggs – convert into eggs.