CHROMOSOMAL INVERSIONS IN HUMAN

POPULATIONS

Andrea González Morales

Chromosomal Inversion

• Structural variation. A chromosomal segment changes its direction 180º.

• Balanced event. • Segment genes form a

ligament group – low recombination rate.

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.

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

How they are produced?

Non-allelic homologous recombination (NAHR)

Segmental Duplication

Retrotransposon

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

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

How can we study them?

• FISH

•Methaphase

•Interphase

•Assay

•Fiber

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.

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