Friday, October 21, 2011

Antagonistic pleiotropy - the case for BRCA mutations

In a natural fertility population, these authors find that carriers of BRCA mutations have more children, shorter birth intervals, a later end to child-bearing, and "excess post-reproductive mortality risks".

Effects of BRCA1 and BRCA2 mutations on female fertility
Ken R. Smith, Heidi A. Hanson, Geraldine P. Mineau, and Saundra S. Buys
Proc. R. Soc. B
Abstract
Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly for BRCA1/2 mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played by BRCA1/2 mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.

7 comments:

Lim Leng Hiong said...

Very interesting study, thanks for the heads up.

Looks like the selection pressure is to preserve BRCA1/2 mutations.

Did the authors discuss any potential mechanism for the increased fertility?

Yann Klimentidis said...

They have a pretty lengthy and well-referenced discussion about potential mechanisms, focusing mostly on how BRCA may affect telomere length (i.e. mutations in BRCA protect telomeres) which may in turn increase fertility.

gaffa said...

"mutation carriers had approximately two more children (CEB) than controls. For example, controls born before 1930 had a mean CEB of 4.19 while carriers from the same era had 6.22."

Isn't that incredibly remarkable?? A single mutation gives you two more children than others? That's an enormous fitness difference.

Even stranger is that the previous research that they discuss towards the end (Pavard & Metcalf, 2007) supposedly shows that BRCA mutations have been under negative selection.

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