Base substitutions and deletions

According to Jim Crow”s 2006 article,  base substitutions are mostly (overwhelmingly) from males and increase with paternal age, but small deletions are contributed about equally by males and females, with no noticeable age effect. Probably the deletions happen during meiosis.

So, with a huge gene like those involved in Duchenne’s muscular dystrophy or neurofibromatosis I, which have many exons (79 for dystrophin), many of the mutations are caused by deletions. The paternal age effect is weaker for those syndromes (since less than half of the causal mutations are base substitutions)

Looking again at the loss-of-function paper in Science by whatisname, the Yoruba have about 42% more stop mutations than CEU (all base substitutions), while the number of large deletions is not higher in the Yoruba (26.6 for the Yoruba, 28.3 in CEU).  Smells like paternal age.

This pattern is obviously not brand new.  At least a couple of hundred years old, because you see it in both the Yoruba and African-Americans.  Obviously a good deal older than that.

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10 Responses to Base substitutions and deletions

  1. spandrell says:

    So what does maternal age cause? Nothing?

  2. The fourth doorman of the apocalypse says:

    This seems like a tin-foil hat brigade item: Gardasil potential cause of premature menopause in a 16-yo girl.

    However, it seems that the long-term effects of some of these vaccines are hard to test for.

  3. frost says:

    “paper in Science by whatisname”

    Was this a placeholder that wasn’t replaced or a joke?

  4. Mark says:

    So…. if mutational load is a significant cause of gaps in average intelligence between different population groups, what are the chances of proving those gaps have a genetic basis? If the gaps were just due to selection, it seems that once we identified genes that code for high intelligence, we could show how they differ in frequency between groups. But if the gaps are due to mutational load, would we expect it to be this simple?

  5. Kiwiguy says:

    fyi. New Steve Hsu post regarding NY Times article:

    “This NYTimes article discusses ideas similar to the ones in my BGA 2012 talk (slides): because of previous selection (e.g., over the last millions of years of hominid development), most rare alleles affecting intelligence will have slightly negative effect. That is, the alleles of large, positive effect will be found in every “normal” person, whereas alleles of small negative effect will still linger at low frequency. Being smarter is a consequence of having fewer of these rare deleterious variants.

    Note, deleterious variants are not all the result of recent mutations. Even after a long period of selection, (+) alleles are not necessarily fully fixed (Minor Allele Frequency = MAF > 0); instead one has a distribution of MAFs and (+) causal alleles for a selected trait will have a distribution peaked at 1 whereas (-) alleles will have a distribution peaked at 0. (See figures below.)…

    Here are some relevant figures from my slides showing the effect of selection on MAF distributions. Imagine millions of years of selection causing the distribution of alleles to change as shown in figures A and B. According to my estimates (based on actual data) most humans have (order of magnitude) 1000 rare (-) alleles for intelligence and height, and someone who is one standard deviation above average has (very roughly) 30 fewer (-) variants. (See slides for more details.) A human with none of the negative alleles might be 30 SD above average! Such a person has yet to exist in human history…”

    http://infoproc.blogspot.co.nz/2012/10/deleterious-variants-affecting-traits.html

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