How we inherit acquired traits – all about non random mutations in the human genome

This is just a material collection for a forthcoming review. I am collecting links to studies showing an increased mutation rate in CpG islands that may possibly fix gene activation status.

PNAS 1997

In the P53 tumor suppressor gene, a remarkably large number of somatic mutations are found at methylated CpG dinucleotides.

Nature 2001

Indirect studies have suggested that nucleotide substitution is not uniform across mammalian genomes. By studying sets of repeat elements belonging to a common cohort, one can directly measure nucleotide substitution rates in different regions of the genome. We find strong evidence that the pattern of neutral substitution differs as a function of local GC content.

Nature 2009

G>T mutations at CpG dinucleotides were significantly more likely to be found outside CpG islands than expected by chance (…), suggesting that these transversions do indeed preferentially occur at methylated CpGs.

PLoS Biology 2009

… we show that there are highly nonrandom patterns of nucleotides that extend ~80 base pairs on either side of sites with coincident SNPs, suggesting that there are extensive and complex context effects. Finally, we estimate the level of variation needed to produce the excess of coincident SNPs and show that there is a similar, or higher, level of variation in the mutation rate associated with this cryptic process than there is associated with adjacent nucleotides, including the CpG effect.

Current Biology 2009 (the 1st direct NGS estimate!?)

The Y chromosomes of two individuals separated by 13 generations were flow sorted and sequenced by Illumina (Solexa) paired-end sequencing to an average depth of 11× or 20×, respectively [4]. Candidate mutations were further examined by capillary sequencing in cell-line and blood DNA from the donors and additional family members. Twelve mutations were confirmed in ∼10.15 Mb; eight of these had occurred in vitro and four in vivo.