1. CHROMOSOMAL INVERSIONS IN HUMAN POPULATIONS Andrea González Morales

2. Chromosomal Inversion Structural variation. A chromosomal segment changes its direction 180º. Balanced event. Segment genes form a ligament group – low recombination rate.

3. What causes them? Segmental duplications. –Are segments of DNA with near identical sequence. –They have been shown to be highly over- represented near sites of structural variation in the human genome.

4. What causes them? Retrotransposons. The amplification and dispersion of TE throughout the genome also generate an abundant substrate for subsequent rearrangements such as inversions. L-1 and Alu are the most abundant in human genome. L1 Alu

5. How they are produced? Non-allelic homologous recombination (NAHR) Segmental Duplication Retrotransposon

6. How can we study them? Sequencing and mapping. We create libraries and compair them with the reference genome. Paired-end mapping. Large-scale genome sequencing method to identify structural variants of at least 3 Kb. It needs the reference genome. Validated by: Sequencing and mapping FISH

7. How can we study them? HapMap data. Statistical method to detect large inversions where the inverted allele is high frecuency. Use of LD patterns – SNPs patterns. Validation: experimental methods

8. How can we study them? FISH Methaphase Interphase Assay Fiber

9. How can we study them? Directional genomic hybridization of chromatid painting. –When BrdU is incorporated during DNA synthesis, each nascent strand becomes photo-labile, allowing it to be selectively degraded. –This results in a metaphase chromosome whose sister chromatids are single-stranded and complementary. –Thanks to fluorescence we can see structural variation, even the small ones.

10. Sources Antonacci F et al. 2009. Characterization of six human disease- associated inversion polymorphims. Hum Mol Genet. 2009 Apr 21. Korbel JO et al. 2007. Paired-end mapping reveals extensive structural variation in the human genome. Science. 2007 Oct 19;318(5849):420-6. Epub 2007 Sep 27. Kidd JM et al. 2008. Mapping and sequencing of structural variation from eight human genomes. Nature. 2008 May 1;453(7191):56-64. Lee J et al. 2008. Chromosomal inversions between human and chimpanzee lineage caused by retrotransposons. PLoS ONE. 2008;3(12):e4047. Epub 2008 Dec 29. Bansal V et al. 2007. Evidence for large inversion polymorphism in the human genome from the HapMap data. Genome Res. 2007 Feb;17(2):219-30. Epub 2006 Dec 21. F.Andrew Ray et al. 2013. Directional genomic hybridization of chromatid painting. Springerlink.com 2013 April 10. http://www.ncbi.nlm.nih.gov http://www.genome.gov