Limits...
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

A three-generation family used for phasing haplotypes and inferring crossovers.We extracted 185,917 three-generation families, where the offspring, two parents and two grandsires were genotyped, from a large pedigree of Holstein cattle with over half million genotyped cattle maintained in USDA-AGIL (S1, S2 and S3 Tables). Depending on the number of genotyped granddams, we collected 67,690, 76,318 and 41,909 three-generation families respectively with two, one and zero genotyped granddams.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4634960&req=5

pgen.1005387.g001: A three-generation family used for phasing haplotypes and inferring crossovers.We extracted 185,917 three-generation families, where the offspring, two parents and two grandsires were genotyped, from a large pedigree of Holstein cattle with over half million genotyped cattle maintained in USDA-AGIL (S1, S2 and S3 Tables). Depending on the number of genotyped granddams, we collected 67,690, 76,318 and 41,909 three-generation families respectively with two, one and zero genotyped granddams.

Mentions: We extracted a total of 185,917 three-generation families that included one offspring, both parents, and two grandsires per family genotyped by various SNP chips ranging from 3K, 7K, to 770K SNPs from the large Holstein cattle pedigree with over half million genotyped cattle (Fig 1 and S1 Table). In each family, we phased the genotypes of the two parents and the offspring, and inferred recombination events for a paternal meiosis from the sire/offspring pair and for a maternal meiosis from the dam/offspring pair. In total, we inferred over 8.5 million paternal and maternal recombination events, which were used to estimate recombination rate between SNP intervals and individual-level recombination statistics. All the 185,917 paternal and maternal meioses were included in the GWAS of recombination rate, and only high-quality meioses from the 50K SNP data (70,715 paternal and 61,616 maternal) were used for the construction of recombination maps and GWAS of hotspot usage (S2 and S3 Tables). The sample sizes are the largest thus far available for studying cattle recombination. Even the sample size of high-quality meioses alone (paternal and maternal together) are already 13 times larger than the biggest sample size of previous cattle recombination studies [29,30]. To ensure data quality, we used the USDA Animal Genomics and Improvement Laboratory (AGIL) SNP coordinates and excluded the X chromosome from recombination calculation due to the poor quality of current genome assembly for the X chromosome [30,32,33].


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)

A three-generation family used for phasing haplotypes and inferring crossovers.We extracted 185,917 three-generation families, where the offspring, two parents and two grandsires were genotyped, from a large pedigree of Holstein cattle with over half million genotyped cattle maintained in USDA-AGIL (S1, S2 and S3 Tables). Depending on the number of genotyped granddams, we collected 67,690, 76,318 and 41,909 three-generation families respectively with two, one and zero genotyped granddams.
© Copyright Policy
Related In: Results  -  Collection

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

pgen.1005387.g001: A three-generation family used for phasing haplotypes and inferring crossovers.We extracted 185,917 three-generation families, where the offspring, two parents and two grandsires were genotyped, from a large pedigree of Holstein cattle with over half million genotyped cattle maintained in USDA-AGIL (S1, S2 and S3 Tables). Depending on the number of genotyped granddams, we collected 67,690, 76,318 and 41,909 three-generation families respectively with two, one and zero genotyped granddams.
Mentions: We extracted a total of 185,917 three-generation families that included one offspring, both parents, and two grandsires per family genotyped by various SNP chips ranging from 3K, 7K, to 770K SNPs from the large Holstein cattle pedigree with over half million genotyped cattle (Fig 1 and S1 Table). In each family, we phased the genotypes of the two parents and the offspring, and inferred recombination events for a paternal meiosis from the sire/offspring pair and for a maternal meiosis from the dam/offspring pair. In total, we inferred over 8.5 million paternal and maternal recombination events, which were used to estimate recombination rate between SNP intervals and individual-level recombination statistics. All the 185,917 paternal and maternal meioses were included in the GWAS of recombination rate, and only high-quality meioses from the 50K SNP data (70,715 paternal and 61,616 maternal) were used for the construction of recombination maps and GWAS of hotspot usage (S2 and S3 Tables). The sample sizes are the largest thus far available for studying cattle recombination. Even the sample size of high-quality meioses alone (paternal and maternal together) are already 13 times larger than the biggest sample size of previous cattle recombination studies [29,30]. To ensure data quality, we used the USDA Animal Genomics and Improvement Laboratory (AGIL) SNP coordinates and excluded the X chromosome from recombination calculation due to the poor quality of current genome assembly for the X chromosome [30,32,33].

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