Centimorgan

In genetics, a centimorgan (abbreviated cM) or map unit (m.u.) is a unit for measuring genetic linkage. It is defined as the distance between chromosome positions (also termed loci or markers) for which the expected average number of intervening chromosomal crossovers in a single generation is 0.01. It is often used to infer distance along a chromosome. It is not a true physical distance however.

Relation to physical distance

The number of base-pairs to which it corresponds varies widely across the genome (different regions of a chromosome have different propensities towards crossover) and it also depends on if the meiosis where the crossing-over takes place is a part of oogenesis (formation of female gametes) or spermatogenesis (formation of male gametes).

One centimorgan corresponds to about 1 million base pairs in humans on average.^[1][2] The relationship is only rough as the physical chromosomal distance corresponding to one centimorgan varies from place to place in the genome, and also varies between men and women since recombination during gamete formation in females is significantly more frequent than in males. Morton et al. calculated that the female genome is 4782 centimorgans long, while the male genome is only 2809 centimorgans long.^[3] Plasmodium falciparum has an average recombination distance of ~15 kb per centimorgan: markers separated by 15 kb of DNA (15,000 nucleotides) have an expected rate of chromosomal crossovers of 0.01 per generation. Note that non-syntenic genes (genes residing on different chromosomes) are inherently unlinked, and cM distances have no meaning between them.

Relation to the probability of recombination

Because genetic recombination between two markers is detected only if there are an odd number of chromosomal crossovers between the two markers, the distance in centimorgans does not correspond exactly to the probability of genetic recombination. Assuming Haldane's map function, where the number of chromosomal crossovers is according to a Poisson distribution,^[4] a genetic distance of d centimorgans will lead to an odd number of chromosomal crossovers, and hence a detectable genetic recombination, with probability

$\Pr[{\text{recombination}}|{\text{linkage of }}d{\text{ cM}}]=\sum _{{k=0}}^{{\infty }}\Pr[2k+1{\text{ crossovers}}|{\text{linkage of }}d{\text{ cM}}]$

${}=\sum _{{k=0}}^{{\infty }}e^{{-d/100}}{\frac {(d/100)^{{2\,k+1}}}{(2\,k+1)!}}=e^{{-d/100}}\sinh(d/100)={\frac {1-e^{{-2d/100}}}{2}}\,,$

where sinh is the hyperbolic sine function. The probability of recombination is approximately d/100 for small values of d and approaches 50% as d goes to infinity.

The formula can be inverted, giving the distance in centimorgans as a function of the recombination probability:

$d=50\ln \left({{\frac {1}{1-2\Pr[{\text{recombination}}]}}}\right)\,.$

Etymology

The centimorgan was named in honor of geneticist Thomas Hunt Morgan by his student Alfred Henry Sturtevant. Note that the parent unit of the centimorgan, the Morgan, is rarely used today.

References

1. NIH ORDR - Glossary - C
2. Harvey Lodish; Arnold Berk; Paul Matsudaira; Chris A. Kaiser; Monty Krieger; Matthew P. Scott; Lawrence Zipursky; James Darnell (2004). Molecular Cell Biology, Fifth Edition. San Francisco: W. H. Freeman. p. 396. ISBN 0-7167-4366-3. ...in humans 1 centimorgan on average represents a distance of about 7.5x10E5 base pairs
3. Morton, NE (1 September 1991). "Parameters of the human genome.". Proceedings of the National Academy of Sciences of the United States of America. 88 (17): 7474–6. PMID 1881886. Evidence on genetic parameters includes chiasma counts and linkage maps corrected for failure to sample telomeres, giving an autosomal size of 2809 centimorgans in males and 4782 centimorgans in females.
4. "Mapping Functions". Department of Plant Sciences. Archived from the original on 26 Jan 2006.

Further reading

• Su X; Ferdig, MT; Huang, Y; Huynh, CQ; Liu, A; You, J; Wootton, JC; Wellems, TE (November 1999). "A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum". Science. 286 (5443): 1351–3. doi:10.1126/science.286.5443.1351. PMID 10558988.

See also

• Mutation rate