The acceleration in genome sequencing capacity is just incredible. In May 2010, I posted on the sequencing of the complete genomes of two parents and two of their kids. Now in August of 2012 we have the results on the complete genomes of 78 parent children trios, along with 1,859 complete sequences from the same population, for comparison.
To get you started here’s the first post:
My family breeds about as fast as sequoias. A cousin had a child at 46 who is presently burning up Columbia. My brother had a child at 48, also doing OK. But we do know that the older the parents, the more likely a kid is to have genetic problems (Sarah Palin & Trig). So what are the odds and how do they change with age?
We don’t really know, but in the next five to ten years, we’ll have a good idea. The first human genome project sequenced most of the 3,200,000,000 positions in our DNA. It cost billions and took years. DNA sequencing technology marches on at an incredible pace. A recent paper rated only 4 pages [ Science vol. 328 pp. 636 – 639 ’10 ]. The complete genome sequence of 2 parents and 2 of their children was performed (to 1/100,000 accuracy yet). There was known genetic disease in the family and the authors were looking for its cause. The genome sequences of the parents and their children were compared position by position (using computers of course). If the base (adenine, thymine, guanosine, cytosine) at a given position differed from that of the parent supplying the surrounding DNA, a mutation had taken place between the generations. Since they had looked at the entire genome, they could count the number of mutations they found. The rate of mutation was 1.1 per 100 million positions, making about 30 new mutations between generations.
So this isn’t by guess and by gosh, but an actual mutation rate and a count. While medical science marches on, our biology has not. We’ll soon be able to give the numbers of the mutations occurring between parents and progeny at a variety of parental ages, when enough of this sort of thing is done. And it definitely will be done as only 10 years separates the incredibly laborious first human genome project from this paper.
Interestingly, the authors didn’t mention anything about this application in their paper, so this may be (gasp) an original idea.
This brings us to [ Nature vol. 488 pp. 439, 467 – 468 (editorial) and 471 – 475 (the actual paper) ]. Some 78 trios (momma poppa and baby) had their entire genomes sequenced, looking for changes found in the baby, not present in either parent. The paper is from Iceland, which has a small population (317,000), and complete genealogical records going back 10 generations (thanks to National Censuses and Parish records). In addition, to find out what a normal Icelandic genome was, they completely sequenced the genomes of 1,859 more. The more times a single genome is sequenced, the more accurate it is, and 78 trios were sequenced to 30x coverage — making it quite accurate. Knowing both the father’s genome and the mothers (which are of course different), any change in the baby from a carbon copy could be definitively linked to the parent providing the mutated sperm or egg.
The bottom line is that mothers contribute 15 mutations to the baby regardless of age, while fathers transmit more (25 to 65). The most important point, is that the older the father, the greater the number of mutations transmitted. Why do men transmit more than women — because they are continually producing new sperm, while the eggs each woman possesses were present at birth. Anyone who has ever played the telephone game knows that messages get distorted when copied. Nonetheless, the accuracy of the copying is incredible (around 1 error per 100 million bases copied).
Should you be worried about this? Possibly, but look who they studied — of the 78 children studied 44 had autism spectrum disorder and 21 were schizophrenic. They don’t say anything about the other 13.
I can’t fault the authors for looking for genetic information to help us all understand autism and schizophrenia, but remember these weren’t normal kids. This work may not generally apply. The study definitely needs to be repeated with normal progeny before getting too excited.
As usual, even though there 4,933 mutations were discovered in this population, none were found more than once. This has been discussed before. For details see https://luysii.wordpress.com/2010/04/25/tolstoy-was-right-about-hereditary-diseases-imagine-that/ and