Hotspot (genetics)

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In genetics, a hotspot refers to areas in the DNA in which recombinations occur more frequently .

properties

The rate of recombination in a hotspot can be up to a thousand times higher than in the surrounding DNA sequences . The length of a hotspot is usually between 1.5 and 2 kilobases . There are over 25,000 hotspots in the human genome . In humans, a crossing-over occurs in a hotspot on average about every 1300 meioses ; in individual hotspots, recombination can take place every 110 meioses. Hotspots are more sensitive to DNA damage and partially defective DNA repair and may serve to increase the rate of recombination.

Presumably, the PRDM9 protein is a result of recombination in a mammalian hotspot.

aDNA

In aDNA research, a hotspot is a point at which post-mortem changes in the DNA strand are observed particularly frequently.

After the death of a living being , the autolysis (decomposition) of molecular cell components begins immediately , including the genetic material, the DNA . The decomposition processes do not always lead to complete dismantling of the DNA strands, but can also cause structural changes in individual bases or base pairs, which lead to reproduction errors in technical replication ( polymerase chain reaction , PCR) and thus indirectly to reading errors during sequencing . These structural changes are referred to as damage (German: "damage"). They can accumulate and occur in the vicinity of positions in the DNA molecule at which recombination errors ( point mutations ) also occur preferentially in the living organism ( mutational hotspots ). Such areas, which may be structurally more unstable, are called hotspots.

At these hotspots, it is not possible to completely differentiate between in vivo mutations and post-mortem changes using conventional processing and sequencing methods. Treatment of the samples with uracil-N-glycosylase prior to the PCR leads to the destruction of modified molecular residues. In addition, statistical methods are used to "clean up" aDNA sequences of post-mortem artifacts.

Individual evidence

  1. ↑ D. Burnouf, M. Bichara, C. Dhalluin, A. Garcia, R. Janel-Bintz, N. Koffel-Schwartz, I. Lambert, JF Lefèvre, JE Lindsley, G. Maenhaut-Michel, C. Milhé, R Lobo-Napolitano, P. Valladier-Belguise, RP Fuchs: Induction of frameshift mutations at hotspot sequences by carcinogen adducts. In: Recent results in cancer research. Advances in cancer research. Progrès dans les recherches sur le cancer. Volume 143, 1997, pp. 1-20, ISSN  0080-0015 . PMID 8912408 .
  2. ↑ Jeffreys AJ, Kauppi L, Neumann R: Intensely punctate meiotic recombination in the class II region of the major histocompatibility complex . In: Nat. Genet. . 29, No. 2, October 2001, pp. 217-22. doi : 10.1038 / ng1001-217 . PMID 11586303 .
  3. ↑ Myers S, Bottolo L, Freeman C, McVean G, Donnelly P: A fine-scale map of recombination rates and hotspots across the human genome . In: Science . 310, No. 5746, October 2005, pp. 321-4. doi : 10.1126 / science.1117196 . PMID 16224025 .
  4. ^ Myers S, Spencer CC, Auton A, et al. : The distribution and causes of meiotic recombination in the human genome . In: Biochem. Soc. Trans. . 34, No. Pt 4, August 2006, pp. 526-30. doi : 10.1042 / BST0340526 . PMID 16856851 .
  5. ^ Harris Bernstein, Carol Bernstein and Richard E. Michod (2011). Meiosis as an Evolutionary Adaptation for DNA Repair. Chapter 19 in DNA Repair. Inna Kruman editor. InTech Open Publisher. doi : 10.5772 / 25117 .
  6. ↑ Hochwagen A, Marais GA: Meiosis: a PRDM9 guide to the hotspots of recombination . In: Curr. Biol . 20, No. 6, March 2010, pp. R271-4. doi : 10.1016 / j.cub.2010.01.048 . PMID 20334833 .
  7. ↑ M. Hofreiter et al .: DNA sequences from multiple amplifications reveal artifacts induced by cytosine deamination in ancient DNA. In: Nucleic Acids Research 29, 2001, pp. 4793-4799.

literature

  • MTP Gilbert et al.: Post-mortem DNA damage hotspots in Bison (Bison bison) provide evidence for both damage and mutational hotspots in mitochondrial DNA. In: Journal of Archaeological Science 32, 2005, pp. 1053-1060.