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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

The total recombination rate per chromosome, in males and females, as predicted by an obligate chiasma per bivalent (i.e, an intercept at 0.5 crossovers per gamete) and the physical length of the chromosome.In red are the observed values for females and in blue the ones for males; circles denote metacentric chromosomes and diamonds acrocentric ones. The regression line is shown for each sex separately. In both cases, there is an excellent fit of this simple model to the data (R2 = 0.94 for females; R2 = 0.95 for males).
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pgen-1000658-g005: The total recombination rate per chromosome, in males and females, as predicted by an obligate chiasma per bivalent (i.e, an intercept at 0.5 crossovers per gamete) and the physical length of the chromosome.In red are the observed values for females and in blue the ones for males; circles denote metacentric chromosomes and diamonds acrocentric ones. The regression line is shown for each sex separately. In both cases, there is an excellent fit of this simple model to the data (R2 = 0.94 for females; R2 = 0.95 for males).

Mentions: Our statistical analysis indicates that human crossovers are not regulated on the scale of an arm but on that of an entire chromosome (as found also in another mammal, shrews, using a cytogenetic approach [29]). In fact, the genetic length of a chromosome is extremely well predicted by a model that incorporates only two features: the need for one event and the length of the chromosome [19],[30] (see also Figure 5). The tight fit of the model further suggests that there are few chromosome-specific factors affecting the total recombination rate per chromosome and that beyond one event, additional crossovers occur in rough proportion to physical length.


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)

The total recombination rate per chromosome, in males and females, as predicted by an obligate chiasma per bivalent (i.e, an intercept at 0.5 crossovers per gamete) and the physical length of the chromosome.In red are the observed values for females and in blue the ones for males; circles denote metacentric chromosomes and diamonds acrocentric ones. The regression line is shown for each sex separately. In both cases, there is an excellent fit of this simple model to the data (R2 = 0.94 for females; R2 = 0.95 for males).
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000658-g005: The total recombination rate per chromosome, in males and females, as predicted by an obligate chiasma per bivalent (i.e, an intercept at 0.5 crossovers per gamete) and the physical length of the chromosome.In red are the observed values for females and in blue the ones for males; circles denote metacentric chromosomes and diamonds acrocentric ones. The regression line is shown for each sex separately. In both cases, there is an excellent fit of this simple model to the data (R2 = 0.94 for females; R2 = 0.95 for males).
Mentions: Our statistical analysis indicates that human crossovers are not regulated on the scale of an arm but on that of an entire chromosome (as found also in another mammal, shrews, using a cytogenetic approach [29]). In fact, the genetic length of a chromosome is extremely well predicted by a model that incorporates only two features: the need for one event and the length of the chromosome [19],[30] (see also Figure 5). The tight fit of the model further suggests that there are few chromosome-specific factors affecting the total recombination rate per chromosome and that beyond one event, additional crossovers occur in rough proportion to physical length.

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