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Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

Ma L, O'Connell JR, VanRaden PM, Shen B, Padhi A, Sun C, Bickhart DM, Cole JB, Null DJ, Liu GE, Da Y, Wiggans GR - PLoS Genet. (2015)

Bottom Line: Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes.Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only.Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

No MeSH data available.


Related in: MedlinePlus

Manhattan plot of the GWAS of genome-wide recombination rates for males (A) and females (B).Different colors were used to distinguish the 29 chromosomes. The genome-wide significance level of 1.6×10−7 was shown by the horizontal dotted line. USDA-AGIL SNP coordinates were used for plotting, which placed PRDM9-linked SNPs to the end of Chromosome 1. Note that UMD3.1 assembly placed PRDM9 near the middle of Chromosome 1.
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pgen.1005387.g005: Manhattan plot of the GWAS of genome-wide recombination rates for males (A) and females (B).Different colors were used to distinguish the 29 chromosomes. The genome-wide significance level of 1.6×10−7 was shown by the horizontal dotted line. USDA-AGIL SNP coordinates were used for plotting, which placed PRDM9-linked SNPs to the end of Chromosome 1. Note that UMD3.1 assembly placed PRDM9 near the middle of Chromosome 1.

Mentions: A total of thirteen loci were identified to have significant effects on recombination rate, four loci on male recombination rate and nine loci on female recombination rate, among which three loci were shared between the two sexes (Table 1 and Fig 5 and S5 Fig). The three shared loci (one on chromosome 6 and two on chromosome 10) were among the strongest associations (Table 1 and Fig 5). The top SNP at the chromosome 6 locus, rs110253089 (Pfemale = 2.95×10−51; Pmale = 7.34×10−30), was located in the intron of the CPLX1 gene, which was associated with genome-wide recombination rate in humans [39]. Using this SNP as a covariate in a conditional analysis, other originally associated SNPs at the same locus were no longer significantly associated with recombination rate, suggesting a potential single underlying QTL at this locus. We found two significantly associated loci on chromosome 10. The associations at the first locus peaked at SNP rs137264867 (Pfemale = 2.62×10−51; Pmale = 1.07×10−16), which was located downstream of PABPN1. A conditional analysis identified four independently associated SNPs at this locus, spanning a 9-Mb window that consisted of several meiosis-related genes, including REC8, REC114, and FMN1 (Table 1). The REC8 gene has been previously reported to associate with recombination rate in cattle [29]. The top associated SNP at the second locus on chromosome 10 was rs43640523 (Pfemale = 8.96×10−23; Pmale = 9.10×10−13). This SNP was located 10 kb downstream of NEK9 that was related to spindle organization and cell cycle progression during mouse oocyte formation [40]. A conditional analysis adjusting for the top SNP in this locus indicated a single underlying QTL in this region.


Cattle Sex-Specific Recombination and Genetic Control from a Large Pedigree Analysis.

Ma L, O'Connell JR, VanRaden PM, Shen B, Padhi A, Sun C, Bickhart DM, Cole JB, Null DJ, Liu GE, Da Y, Wiggans GR - PLoS Genet. (2015)

Manhattan plot of the GWAS of genome-wide recombination rates for males (A) and females (B).Different colors were used to distinguish the 29 chromosomes. The genome-wide significance level of 1.6×10−7 was shown by the horizontal dotted line. USDA-AGIL SNP coordinates were used for plotting, which placed PRDM9-linked SNPs to the end of Chromosome 1. Note that UMD3.1 assembly placed PRDM9 near the middle of Chromosome 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4634960&req=5

pgen.1005387.g005: Manhattan plot of the GWAS of genome-wide recombination rates for males (A) and females (B).Different colors were used to distinguish the 29 chromosomes. The genome-wide significance level of 1.6×10−7 was shown by the horizontal dotted line. USDA-AGIL SNP coordinates were used for plotting, which placed PRDM9-linked SNPs to the end of Chromosome 1. Note that UMD3.1 assembly placed PRDM9 near the middle of Chromosome 1.
Mentions: A total of thirteen loci were identified to have significant effects on recombination rate, four loci on male recombination rate and nine loci on female recombination rate, among which three loci were shared between the two sexes (Table 1 and Fig 5 and S5 Fig). The three shared loci (one on chromosome 6 and two on chromosome 10) were among the strongest associations (Table 1 and Fig 5). The top SNP at the chromosome 6 locus, rs110253089 (Pfemale = 2.95×10−51; Pmale = 7.34×10−30), was located in the intron of the CPLX1 gene, which was associated with genome-wide recombination rate in humans [39]. Using this SNP as a covariate in a conditional analysis, other originally associated SNPs at the same locus were no longer significantly associated with recombination rate, suggesting a potential single underlying QTL at this locus. We found two significantly associated loci on chromosome 10. The associations at the first locus peaked at SNP rs137264867 (Pfemale = 2.62×10−51; Pmale = 1.07×10−16), which was located downstream of PABPN1. A conditional analysis identified four independently associated SNPs at this locus, spanning a 9-Mb window that consisted of several meiosis-related genes, including REC8, REC114, and FMN1 (Table 1). The REC8 gene has been previously reported to associate with recombination rate in cattle [29]. The top associated SNP at the second locus on chromosome 10 was rs43640523 (Pfemale = 8.96×10−23; Pmale = 9.10×10−13). This SNP was located 10 kb downstream of NEK9 that was related to spindle organization and cell cycle progression during mouse oocyte formation [40]. A conditional analysis adjusting for the top SNP in this locus indicated a single underlying QTL in this region.

Bottom Line: Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes.Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only.Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America.

ABSTRACT
Meiotic recombination is an essential biological process that generates genetic diversity and ensures proper segregation of chromosomes during meiosis. From a large USDA dairy cattle pedigree with over half a million genotyped animals, we extracted 186,927 three-generation families, identified over 8.5 million maternal and paternal recombination events, and constructed sex-specific recombination maps for 59,309 autosomal SNPs. The recombination map spans for 25.5 Morgans in males and 23.2 Morgans in females, for a total studied region of 2,516 Mb (986 kb/cM in males and 1,085 kb/cM in females). The male map is 10% longer than the female map and the sex difference is most pronounced in the subtelomeric regions. We identified 1,792 male and 1,885 female putative recombination hotspots, with 720 hotspots shared between sexes. These hotspots encompass 3% of the genome but account for 25% of the genome-wide recombination events in both sexes. During the past forty years, males showed a decreasing trend in recombination rate that coincided with the artificial selection for milk production. Sex-specific GWAS analyses identified PRDM9 and CPLX1 to have significant effects on genome-wide recombination rate in both sexes. Two novel loci, NEK9 and REC114, were associated with recombination rate in both sexes, whereas three loci, MSH4, SMC3 and CEP55, affected recombination rate in females only. Among the multiple PRDM9 paralogues on the bovine genome, our GWAS of recombination hotspot usage together with linkage analysis identified the PRDM9 paralogue on chromosome 1 to be associated in the U.S. Holstein data. Given the largest sample size ever reported for such studies, our results reveal new insights into the understanding of cattle and mammalian recombination.

No MeSH data available.


Related in: MedlinePlus