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Broad-scale recombination patterns underlying proper disjunction in humans.

Fledel-Alon A, Wilson DJ, Broman K, Wen X, Ober C, Coop G, Przeworski M - PLoS Genet. (2009)

Bottom Line: Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale.We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference.These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.

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Related in: MedlinePlus

For each chromosome, the estimated fraction of bivalents that segregated properly without a chiasma, in male (blue) and female (red).See the legend of Figure 1 for additional details.
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pgen-1000658-g002: For each chromosome, the estimated fraction of bivalents that segregated properly without a chiasma, in male (blue) and female (red).See the legend of Figure 1 for additional details.

Mentions: We also assessed the stringency of the rule at the level of the entire chromosome. With these data, we can only test whether ichiasmatic bivalents can segregate properly for the smaller chromosomes, because for the larger chromosomes, they rarely occur (as the recombination rate is simply too high). Indeed, simulations suggest that, even if ichiasmatic chromosomes always segregated properly, we would have high power to detect their transmission only for the eight smallest chromosomes in males and for chromosomes 21 and 22 in females (see Supplementary Methods in Text S1). As expected, the larger chromosomes show no evidence of ichiasmatic transmissions to viable offspring (Figure 2). But among the smaller chromosomes, there are apparent exceptions. In males, we found evidence for proper segregation in the absence of a chiasma for two chromosomes: in over 0.1% (the lower 5%-tile) of cases for chromosome 12 (p = 0.0176), and in over 4.2% of cases for chromosome 18 (p = 0.0120). In females, in turn, we inferred that at least 7.3% (p = 0.0002) of chromosome 21 transmissions occur properly in the absence of a chiasma (Figure 3).


Broad-scale recombination patterns underlying proper disjunction in humans.

Fledel-Alon A, Wilson DJ, Broman K, Wen X, Ober C, Coop G, Przeworski M - PLoS Genet. (2009)

For each chromosome, the estimated fraction of bivalents that segregated properly without a chiasma, in male (blue) and female (red).See the legend of Figure 1 for additional details.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2734982&req=5

pgen-1000658-g002: For each chromosome, the estimated fraction of bivalents that segregated properly without a chiasma, in male (blue) and female (red).See the legend of Figure 1 for additional details.
Mentions: We also assessed the stringency of the rule at the level of the entire chromosome. With these data, we can only test whether ichiasmatic bivalents can segregate properly for the smaller chromosomes, because for the larger chromosomes, they rarely occur (as the recombination rate is simply too high). Indeed, simulations suggest that, even if ichiasmatic chromosomes always segregated properly, we would have high power to detect their transmission only for the eight smallest chromosomes in males and for chromosomes 21 and 22 in females (see Supplementary Methods in Text S1). As expected, the larger chromosomes show no evidence of ichiasmatic transmissions to viable offspring (Figure 2). But among the smaller chromosomes, there are apparent exceptions. In males, we found evidence for proper segregation in the absence of a chiasma for two chromosomes: in over 0.1% (the lower 5%-tile) of cases for chromosome 12 (p = 0.0176), and in over 4.2% of cases for chromosome 18 (p = 0.0120). In females, in turn, we inferred that at least 7.3% (p = 0.0002) of chromosome 21 transmissions occur properly in the absence of a chiasma (Figure 3).

Bottom Line: Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale.We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference.These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

ABSTRACT
Although recombination is essential to the successful completion of human meiosis, it remains unclear how tightly the process is regulated and over what scale. To assess the nature and stringency of constraints on human recombination, we examined crossover patterns in transmissions to viable, non-trisomic offspring, using dense genotyping data collected in a large set of pedigrees. Our analysis supports a requirement for one chiasma per chromosome rather than per arm to ensure proper disjunction, with additional chiasmata occurring in proportion to physical length. The requirement is not absolute, however, as chromosome 21 seems to be frequently transmitted properly in the absence of a chiasma in females, a finding that raises the possibility of a back-up mechanism aiding in its correct segregation. We also found a set of double crossovers in surprisingly close proximity, as expected from a second pathway that is not subject to crossover interference. These findings point to multiple mechanisms that shape the distribution of crossovers, influencing proper disjunction in humans.

Show MeSH
Related in: MedlinePlus