Effect of sex, age and genetics on crossover interference in cattle

Abstract

Crossovers generated by homologous recombination ensure proper chromosome segregation during meiosis. Crossover interference results in chiasmata being more evenly distributed along chromosomes, but the mechanism underlying crossover interference remains elusive. Based on large pedigrees of Holstein and Jersey cattle with genotype data, we extracted three-generation families, including 147,327 male and 71,687 female meioses in Holstein, and 108,163 male and 37,008 female meioses in Jersey, respectively. We identified crossovers in these meioses and fitted the Housworth-Stahl “interference-escape” model to study crossover interference patterns in the cattle genome. Our result reveals that the degree of crossover interference is stronger in females than in males. We found evidence for inter-chromosomal variation in the level of crossover interference, with smaller chromosomes exhibiting stronger interference. In addition, crossover interference levels decreased with maternal age. Finally, sex-specific GWAS analyses identified one locus near the NEK9 gene on chromosome 10 to have a significant effect on crossover interference levels. This locus has been previously associated with recombination rate in cattle. Collectively, this large-scale analysis provided a comprehensive description of crossover interference across chromosome, sex and age groups, identified associated candidate genes, and produced useful insights into the mechanism of crossover interference.

Variation in recombination frequency and distribution across eukaryotes: patterns and processes

“…In Arabadopsis thaliana , paternal recombination rate (cM/Mb) measured at nine genomic intervals was stable in five of these regions, but increased with age in the other four [ 99 ]. In cattle and humans, CO interference, which can set a minimum distance between neighbouring COs, decreases with maternal age, which may explain observed increases in recombination frequency [ 106 , 108 ].…”

A Genomic Region Containing REC8 and RNF212B Is Associated with Individual Recombination Rate Variation in a Wild Population of Red Deer (Cervus elaphus)

“…These genes are involved in with chromatin binding and structure ( SP16H , TOX4 ), histone binding ( CHD8 , SUPT16H ), nucleosome organization ( SP16H ) and cell cycle transition ( TOX4 ). One of these genes, SUPT16H , interacts with NIMA related kinase 9 ( NEK9 ), which is involved with meiotic spindle organization, chromosome alignment and cell cycle progression in mice ( Yang et al 2012 ) and is a strong candidate locus for crossover interference in cattle ( Wang et al 2016 ). The SNP cela1_red_10_26005249 was 825kb from Cyclin B1 Interacting Protein 1 ( CCNB1IP1 ), also known as Human Enhancer Of Invasion 10 ( HEI10 ), which interacts with RNF212 to allow recombination to progress into crossing-over in mice ( Qiao et al 2014 ) and Arabidopsis ( Chelysheva et al 2012 ); this locus is also associated with recombination rate variation in humans ( Kong et al 2014 ).…”

The Genomic Landscape of Crossover Interference in the Desert Tree Populus euphratica

“…A reduction in CO interference can result from a lack of DNA-damage-response-kinase Tel1/ATM (Anderson et al, 2015). Links between CO interferences and sex differences (Jan et al, 2007; Szatkiewicz et al, 2013), stress-induced adaptation (Yant et al, 2013; Aggarwal et al, 2015), and aging (Campbell et al, 2015; Wang Z. et al, 2016) have been discovered, highlighting the multifaceted role of COs in mediating biological processes. As an evolutionary phenotype, CO interference varies with biotic and abiotic environmental parameters, such as sex, age, and stress.…”

“…As an evolutionary phenotype, CO interference varies with biotic and abiotic environmental parameters, such as sex, age, and stress. For example, in mice and cattle, interference is stronger in females than in males (Szatkiewicz et al, 2013; Wang Z. et al, 2016). However, the opposite is found in humans, where interference is stronger in males than in females, although this pattern varies by chromosome (Campbell et al, 2015).…”