1. Chromosome inversions in human populations Kallie Rivers

2. What is an inversion? An inversion is a chromosome rearrangement which occurs when a chromosome breaks at two points and the segment bounded by the breakpoints is reinserted in the reversed orientation. An inversion occurs when a single chromosome undergoes breakage and rearrangement within itself. Inversions are of two types: paracentric and pericentric.

3. Mechanisms by which inversions occur  Double stranded breaks  Hotspots  Non allelic homologous recombination  Non-homologous end joining  Fork stalling and template switching.

4. How and why do chromosomal inversions evolve? Figure 2. Schematic showing the suppression of recombination in an inversion heterozygote. Two loci segregate for the alleles (A, a) and (B, b). An individual that is heterozygous at both loci and for the inversion does not produce the recombinant gametes A/b and a/B.

5. Recombination

6. Evolution  Selection: structural problems with meiosis, a breakpoint can disrupt an open reading frame or alter gene expression, adaptive mutation.  Underdominance, overdominance and ‘‘associative overdominance.’’

7. Speciation

8. Disease

9. How are inversions detected?  FISH  Pair end sequencing  Genome assembly.  HapMap Project.

10. Conclusion  Inversion definition- paracentric and pericentric  Mechanisms- Double stranded breaks, Hotspots, Non allelic homologous recombination, Non-homologous end joining, Fork stalling and template switching  Recombination  Evolution  Speciation  Disease  Detection- FISH, Pair end sequencing, Genome assembly, HapMap Project.

11. References  https://classconnection.s3.amazonaws.com/807/flashcards/1471807/png/inversions1335480280395.png  https://www.youtube.com/watch?v=kzQBXTV_nIsm (GENETICS 3: CHROMOSOMES: PERICENTRIC, PARACENTRIC INVERSIONS) https://www.youtube.com/watch?v=kzQBXTV_nIsm  Sturtevant AH (1921) A case of rearrangement of genes in Drosophila. Proc Natl Acad Sci U S A 7: 235–237  Feuk L, MacDonald JR, Tang T, Carson AR, Li M, et al. (2005) Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genet 1: e56. doi:10.1371/journal.pgen.0010056  Castermans D, Vermeesch JR, Fryns JP, Steyaert JG, Van de Ven WJM, et al. (2007) Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism. Eur J Hum Genet 15: 422–431.  White MJD (1973) Animal cytology and evolution. Cambridge: Cambridge University Press.  Lande R (1979) Effective deme sizes during long-term evolution estimated from rates of chromosomal rearrangement. Evolution 33: 234–251.  Sturtevant AH, Mather K (1938) The interrelations of inversions, heterosis and recombination. Am Nat 72: 447–452  Lahn BT, Page DC (1999) Four evolutionary strata on the human X chromosome. Science 286: 964–967  Bachtrog D (2006) A dynamic view of sex chromosome evolution. Current Opinion Genet Dev 16: 578–585.  White MJD (1978) Modes of speciation. San Francisco, CA: W.H. Freeman  Maarit Jaarola, Rene´e H. Martin, and Terry Ashley. Direct Evidence for Suppression of Recombination within Two Pericentric  Inversions in Humans: A New Sperm-FISH Technique. Am. J. Hum. Genet. 63:218–224, 1998

12. References  Speciation and inversions: chimps and humans. Jody Hey. BioEssays 25:825–828, 2003. 2003 Wiley Periodicals, Inc.  Human inversions and their functional consequences Marta Puig, So` nia Casillas, Sergi Villatoro and Mario Ca´ceres. Briefings in Functional Genomics, 2015, 1–11  http://flystocks.bio.indiana.edu/Fireworks/Balancer_figs/balfig2.png http://flystocks.bio.indiana.edu/Fireworks/Balancer_figs/balfig2.png  The human Y chromosome, in the light of evolution, Bruce T. Lahn, Nathaniel M. Pearson & Karin Jegalian, Nature Reviews Genetics 2, 207-216 (March 2001) doi:10.1038/35056058  http://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome http://ghr.nlm.nih.gov/condition/wolf-hirschhorn-syndrome  http://www.ninds.nih.gov/disorders/sotos/sotos.htm http://www.ninds.nih.gov/disorders/sotos/sotos.htm  http://www.angelman.org/understanding-as/medical-info/ http://www.angelman.org/understanding-as/medical-info/  http://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy http://ghr.nlm.nih.gov/condition/emery-dreifuss-muscular-dystrophy  Bansal V, Bashir A, Bafna V. Evidence for large inversion polymorphisms in the human genome from HapMap data 2007:219–30.  Lee J, Han K, Meyer TJ, Kim H-S, Batzer M a. Chromosomal inversions between human and chimpanzee lineages caused by retrotransposons. PLoS One. 2008;3:e4047.  http://www.genome.jp/kegg/pathway/ko/ko03450.png http://www.genome.jp/kegg/pathway/ko/ko03450.png  https://sangerinstitute.wordpress.com/2014/04/30/non-allelic-homologous-recombination- inheritance-or-chance/ https://sangerinstitute.wordpress.com/2014/04/30/non-allelic-homologous-recombination- inheritance-or-chance/  http://www.researchgate.net/figure/260119504_fig4_Mechanistic-model-of-fork-stalling-and- template-switching.-(A)-The-replication-fork http://www.researchgate.net/figure/260119504_fig4_Mechanistic-model-of-fork-stalling-and- template-switching.-(A)-The-replication-fork  https://era7bioinformatics.com/en/page.cfm?id=1626&title=paired-end-and-mate-pair-sequencing:- what-is-it-and-how-is-it-done?

13. Any questions?