Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

A. P. Jason de Koning, Wanjun Gu, Todd A. Castoe, Mark A. Batzer, David D. Pollock

Diego Halab Robles Programa de Doctorado en Ciencias Mdicas Unversidad Austral de Chile

Backround

RepeatMasker (RM) is a program that screens DNA sequences for interspersed repeats and low complexity DNA sequences Limitations; Not masking repeats per se Poor sensitivity Time consuming

Probability Clouds

Previous studies (Gu et al., 2008) on two human chromosomes indicated that a reasonably large fraction of the human genome is likely to be of repetitive origin, but not annotated by RM

Aim: to analyze the reliability of P-clouds and RM methods for identifying different sizes of fragments from two large and well-known families of human SINEs: Alu and MIR

Methods
P-Clouds algorithm
Oligonucleotide counts Clusters p-clouds Regions with high density of p-clouds

False positive assessment (oligos lenght = 16; cuttout distance = 3) Assessment of P-clouds annotation overlaps (BED, UCSC Browser)

P-clouds and RM detection capability for fragments of known elements; Alu ( 286 bp / 30, 40 and 50 bp) and MIR ( 260 bp / 30, 50, 80, 100, 150, and 200 bp) P-cloud = C10 80%
Element-specific P-clouds (ESPs) for specific annotation of novel Alu and MIR elements Validation of ESP predictions (BLAST)

Results

Average FP: 12.6 % Accuracy: 85.5 %

Weaknesses
Ausencia de un gold standard An es dbil detectando secuencias ms divergentes

Conclusions
Combined P-clouds and RM analysis of the human genome indicate that it consists of at least 6669% repetitive sequence P-clouds still probably provide underestimates of the true genomic TE content

References
A. de Koning, W. Gu, T. Castoe, et al., 2011. Repetitive elements may comprise over two-thirds of the human genome. PLoS genetics, 7(12), p.e1002384. W. Gu, T. Castoe, D. Hedges, et al., 2008. Identification of repeat structure in large genomes using repeat probability clouds. Analytical biochemistry, 380(1), pp.77-83.