Escape from crossover interference increases with maternal age

Campbell, Christopher; Furlotte, Nicholas A.; Eriksson, Nick; Hinds, David A.; Auton, Adam

doi:10.1038/ncomms7260

Cited by 76 publications

(144 citation statements)

References 21 publications

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“…As the definition of an event is based solely on proximity of gene converted mpps, we cannot discern whether the gene converted mpps within the same long event occurred simultaneously in a single process or in several collocated processes. Crossover interference has recently been shown to decrease with maternal age 42 , possibly leading to double crossover recombination events which in our study design could be detected as long NCO events. The complex nature of long NCO events and their GC bias make it unlikely that crossover interference explains a large fraction of long NCO events (cf.…”

Section: Discussionmentioning

confidence: 79%

The rate of meiotic gene conversion varies by sex and age

et al. 2016

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Meiotic recombination involves a combination of gene conversion and crossover events that along with mutations produce germline genetic diversity. Here, we report the discovery of 3,176 SNP and 61 indel gene conversions. Our estimate of the non-crossover (NCO) gene conversion rate (G) is 7.0 for SNPs and 5.8 for indels per Mb per generation, and the GC bias is 67.6%. For indels we demonstrate a 65.6% preference for the shorter allele. NCO gene conversions from mothers are longer than those from fathers and G is 2.17 times greater in mothers. Notably, G increases with the age of mothers, but not fathers. A disproportionate number of NCO gene conversions in older mothers occur outside double strand break (DSB) regions and in regions with relatively low GC content. This points to age-related changes in the mechanisms of meiotic gene conversions in oocytes.

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Section: Discussionmentioning

confidence: 79%

The rate of meiotic gene conversion varies by sex and age

et al. 2016

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“…Moreover, the crossover rate appears to increase with advancing maternal age. Specifically, more crossovers are detected in children born to older mothers, implying that oocytes that give rise to viable offspring in older mothers tend to have more crossovers (Kong et al 2004;Coop et al 2008;Campbell et al 2015;Ottolini et al 2015). Extra crossovers are proposed to buffer against the effects of advancing maternal age, in particular, the erosion of sister-chromatid cohesion (discussed below).…”

Section: Clinical Significance Of Meiotic Recombinationmentioning

confidence: 99%

“…Thus, crossover rate may be under selection in human populations. Both common and rare human alleles have now been linked to heritable variation in crossover rate (Stefansson et al 2005;Kong et al 2008Kong et al , 2014Chowdhury et al 2009;Fledel-Alon et al 2011;Campbell et al 2015). These include alleles of genes known to regulate meiotic recombination: the crossover regulators, RNF212, HEI10 (CCNB1IP1), and MSH4 (described above); RAD21L and REC8, which encode meiosis-specific cohesin subunits (Uhlmann 2011); and the DSB regulator, PRDM9 .…”

Section: Clinical Significance Of Meiotic Recombinationmentioning

confidence: 99%

Meiotic Recombination: The Essence of Heredity

Hunter

2015

Cold Spring Harb Perspect Biol

673

869

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The study of homologous recombination has its historical roots in meiosis. In this context, recombination occurs as a programmed event that culminates in the formation of crossovers, which are essential for accurate chromosome segregation and create new combinations of parental alleles. Thus, meiotic recombination underlies both the independent assortment of parental chromosomes and genetic linkage. This review highlights the features of meiotic recombination that distinguish it from recombinational repair in somatic cells, and how the molecular processes of meiotic recombination are embedded and interdependent with the chromosome structures that characterize meiotic prophase. A more in-depth review presents our understanding of how crossover and noncrossover pathways of meiotic recombination are differentiated and regulated. The final section of this review summarizes the studies that have defined defective recombination as a leading cause of pregnancy loss and congenital disease in humans. MEIOSIS AND THE ROOTS OF RECOMBINATION RESEARCHT he concept of recombination emerged during the early 20th century, following the post-Mendel era of heredity research. Thomas Hunt Morgan's formal theory of gene linkage and crossing-over (Morgan 1913) was a synthesis of three key concepts: "the chromosome theory of inheritance," imparted by Wilhelm Roux, Walther Flemming, Theodor Boveri, and Walter Sutton; "gene linkage," an exception to Mendel's law of independent assortment, first reported by Carl Correns; and the "chiasmatype theory," derived from Frans Janssens' cytological observations of meiotic chromosomes. The first proof of the crossover theory came from Harriet Creighton and Barbara McClintock (Creighton and McClintock 1931), who were able to correlate cytological and genetic exchanges in maize.Experiments aimed at understanding the mechanism of meiotic recombination became dominated by fungal genetics because of the huge advantage afforded by being able to recover all four meiotic products. These elegant studies culminated in four key concepts that formed the foundation of molecular models of recombination: gene conversion, an exception to Mendel's principle of segregation, signaled a local nonreciprocal transfer of genetic information (Winkler 1930;Lindergren 1953;Mitchell 1955); postmeiotic segregation (PMS) indicated the presence of heteroduplex DNA (Olive 1959;Kitani et al. 1962) (Lissouba and Rizet 1960;Murray 1960); and the strong correlation between gene conversion/ PMS events and crossing-over led to the proposal that these processes were mechanistically linked (Kitani et al. 1962;Perkins 1962;Whitehouse 1963). MOLECULAR MODELS OF MEIOTIC RECOMBINATIONHolliday's classic model reconciled gene conversion, PMS, and crossing-over into a single mechanism with the key features of hybrid (heteroduplex) DNA formed via strand exchange, mismatch correction of hybrid DNA to yield gene conversion, and a four-way exchange junction that could be resolved to yield either crossover or noncrossover duplex products (Holliday...

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“…Conversely, the influence of age on male meiotic recombination remains controversial. Some human studies reported decreased recombination rates in older men compared to younger ones [Sun et al, 2006], but comparable analyses in mice revealed opposite results [Vrooman et al, 2014], or an absence of effect Shi et al, 2002;Sun et al, 2005;Campbell et al, 2015]. For practical reasons, all these results were obtained by comparing samples from different individuals of different ages.…”

Section: Intraindividual Variation Of Meiotic Recombination Parametermentioning

confidence: 94%

“…Aging is a factor likely to influence intraindividual variation of meiotic recombination. The influence of age on aneuploidy has been thoroughly studied in humans [Hassold and Hunt, 2001;Campbell et al, 2015], as well as in mice [Vrooman et al, 2014]. In these species, an increasing risk of aneuploidy related to aging has been unequivocally demonstrated in female meiosis, which might be explained by a decreased recombination in older females.…”

Section: Intraindividual Variation Of Meiotic Recombination Parametermentioning

confidence: 99%

Intraindividual Variation of Meiotic Recombination Parameters in Pig Spermatocytes: A Preliminary Study

Mary

Barasc

Calgaro

et al. 2018

Cytogenet Genome Res

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Meiotic recombination parameters like crossover (CO) rate or synaptonemal complex (SC) length are known to vary strongly between individuals and between cells from the same individual. The origins of this variability remain elusive, and little is known about the variations that might occur between different samples and/or over time within the same individual. To document this question, pachytene cells from 3 boars of the Large White breed were analyzed twice, at a 1-year interval, using immunocytological techniques. CO rate, SC length, and MLH1 inter-foci distances varied significantly between the 3 individuals. CO rate and SC length differed significantly between the 2 sampling periods for 1 individual. However, no significant differences were observed between the 2 samples for CO distribution and inter-foci distances in the 3 boars studied.

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Escape from crossover interference increases with maternal age

Cited by 76 publications

References 21 publications

The rate of meiotic gene conversion varies by sex and age

The rate of meiotic gene conversion varies by sex and age

Meiotic Recombination: The Essence of Heredity

Intraindividual Variation of Meiotic Recombination Parameters in Pig Spermatocytes: A Preliminary Study

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