A periodic pattern of SNPs in the human genome

By surveying all validated SNPs in the human genome we have found that SNPs positioned 1, 2, 4, 6 or 8 bp apart are more frequent than SNPs 3, 5, 7 or 9 bp apart. This holds even when we correct for nucleotide frequencies and site dependencies in nucleotide usage in the genome. The observed pattern is not restricted to any of the genomic regions that might give sequencing or alignment errors; i.e. transposable elements (SINE, LINE and LTR), tandem repeats and large duplicated regions. However we can define periodic DNA, which virtually capture the entire pattern. Periodic DNA is defined as small DNA sequences (16.9 bp average length) with a high degree of periodicity in nucleotide usage. Periodic DNA is widely distributed in the genome, underrepresented in exons, widespread in transcripts and slightly overrepresented in tandem repeats. Furthermore periodic DNA has a 1.8 times higher SNP density than the rest of the genome.
A possible biological explanation of these observations is that during DNA replication small fragments of (periodic) DNA is copied to nearby positions, substituting the original sequence. If the copied fragment differs from the original sequence a new SNP is created. 
In conclusion these observations suggest that not all SNPs in the human genome are created by independent single nucleotide mutations.
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Hanstedgård : A Settlement Site from the Funnel Beaker Culture

Hanstedgård - A Settlement Site from the Funnel Beaker Cultur

Short Tandem Repeats in Human Exons: A Target for Disease Mutations

<p>Abstract</p> <p>Background</p> <p>In recent years it has been demonstrated that structural variations, such as indels (insertions and deletions), are common throughout the genome, but the implications of structural variations are still not clearly understood. Long tandem repeats (e.g. microsatellites or simple repeats) are known to be hypermutable (indel-rich), but are rare in exons and only occasionally associated with diseases. Here we focus on short (imperfect) tandem repeats (STRs) which fall below the radar of conventional tandem repeat detection, and investigate whether STRs are targets for disease-related mutations in human exons. In particular, we test whether they share the hypermutability of the longer tandem repeats and whether disease-related genes have a higher STR content than non-disease-related genes.</p> <p>Results</p> <p>We show that validated human indels are extremely common in STR regions compared to non-STR regions. In contrast to longer tandem repeats, our definition of STRs found them to be present in exons of most known human genes (92%), 99% of all STR sequences in exons are shorter than 33 base pairs and 62% of all STR sequences are imperfect repeats. We also demonstrate that STRs are significantly overrepresented in disease-related genes in both human and mouse. These results are preserved when we limit the analysis to STRs outside known longer tandem repeats.</p> <p>Conclusion</p> <p>Based on our findings we conclude that STRs represent hypermutable regions in the human genome that are linked to human disease. In addition, STRs constitute an obvious target when screening for rare mutations, because of the relatively low amount of STRs in exons (1,973,844 bp) and the limited length of STR regions.</p