chromosomal inversions in human populations
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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