Was Charles Darwin's family adversely affected by inbreeding?

Question

I was reading the Wikipedia article on Inbreeding depression when I came across this:

Charles Darwin, through numerous experiments, was one of the first scientists to demonstrate the effects of inbreeding depression. Darwin had married his first cousin, Emma Wedgwood. He later became concerned that inbreeding within his own family would adversely affect the health of his own children. The Darwins had ten children, but three died before the age of ten. Of the surviving children, three of the six who had long-term marriages did not have any children.

The quote makes reference to the paper below:

"Was the Darwin/Wedgwood Dynasty Adversely Affected by Consanguinity?" Berra et al., Tim M.; Alvarez, Gonzalo; Ceballos, Francisco C. (2010) which is available in full via this link here.

The evidence for Darwin's concern is based solely on this quote:

“I have now six Boys!! & two girls; & it is the great drawback to my happiness, that they are not very robust; some of them seem to have inherited my detestable constitution” (Burkhardt and Smith 1991, p. 60).

So, here are my concerns about the quote above and also the multitude of news stories that were generated:

• Does this paper provide proof of an in-breeding depression in Darwin's family?
• Does the paper or any other reliable source provide proof that Darwin was concerned about the marriage to his cousin affecting the health of his children or descendants?
• Is there any proof to suggest that in-breeding caused Darwin or one of Darwin's descendants to be barren, have frequently ill children or to have children that were unfit so as to die prior to 10 years of age?

Answer 1

Related question with some general info about inbreeding: Does inbreeding cause severe birth defects?

Inbreeding is dangerous because it increases the chances of homozygosity, which means that for a particular gene, identical alleles of the gene are present on both homologous chromosomes. Those individuals result of the inbreeding have more chances of having recessive or deleterious traits.

In Darwin's case in particular, the authors calculated the coefficient of inbreeding for his children, which was F 5 0.0630 (more than 6% of their autosomal genome is expected to be homozygous). This is a moderate value. According to the letters and the genetic analysis of 25 Darwin/Wedgwood families belonging to four consecutive generations, there is a statistically significant positive association between child mortality (death at or before the age of 10 years) and inbreeding coefficient.

Three of Charles Darwin's six children with long-term marriage history suffered from infertility (Golubovsky). One of them died of tuberculosis, and it is suggested (Lyons) that inbreeding increases risk of tuberculosis infection as well as invasive bacterial diseases (cause of death of his last child, Charles Waring) in humans.

The high childhood mortality might be a result of increased homozygosity of deleterious recessive alleles produced by the consanguineous marriages within the Darwin/Wedgwood dynasty. Darwin's children had an increased risk of suffering the effects of detrimental recessive alleles.

Darwin's children had a relatively high coefficient of inbreeding, so the risk of negative traits was higher for them. The high child mortality in his family could most likely had been caused by detrimental recessive alleles product of inbreeding.