A First-Generation Metric Linkage Disequilibrium Map of Bovine Chromosome 6

Khatkar, Mehar S.; Collins, Andrew; Cavanagh, Julie; Hawken, Rachel; Hobbs, Matthew; Zenger, Kyall R.; Barris, Wes; McClintock, Alexander E.; Thomson, Peter; Nicholas, F. W.; Raadsma, Herman W.

doi:10.1534/genetics.106.060418

Cited by 38 publications

(46 citation statements)

References 33 publications

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“…Linkage disequilibrium (LD) has been defined as the non-random association between alleles at different loci (Phillips et al 2003;Khatkar et al 2006bKhatkar et al , 2008Odani et al 2006). Information concerning the structure of LD at the population level is crucial for interpretation and application of the results of genome wide association studies (Meuwissen and Goddard 2000;Khatkar et al 2006a;Bohmanova et al 2010;Lu et al 2012) and for determination of the statistical doi: 10.17221/56/2017-CJAS power of association studies (Khatkar et al 2007;Kim and Kirkpatrick 2009).…”

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confidence: 99%

“…Characterization of the empirical patterns of LD across the genome is important to improve our understanding the biological pathway of recombinations and selection results in the bovine genome (Khatkar et al 2006a;Bohmanova et al 2010). Furthermore, understanding the genomic landscape of bovine LD and variation in recombination rates facilitates the efficient design and analysis of association studies and greatly improves inferences from DNA marker polymorphism data based on population studies (Khatkar et al 2006b). The construction of a high-resolution LD map for the bovine genome will provide further insights into the effects of selection and evolutionary forces upon the genomes of breeds which have been selected for different agricultural purposes (McKay et al 2007).…”

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confidence: 99%

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Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle

Salem¹,

Thompson²,

Chen³

et al. 2018

Czech J. Anim. Sci.

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Salem M.M.I., Thompson G., Chen S., Beja-Pereira A., Carvalheira J. (2018): Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle. Czech J. Anim. Sci., 63, 61-69.The objectives of this study were to estimate linkage disequilibrium (LD), describe and scan a haplotype block for the presence of genes that may affect milk production traits in Portuguese Holstein cattle. Totally 526 animals were genotyped using the Illumina BovineSNP50 BeadChip, which contained a total of 52 890 single nucleotide polymorphisms (SNPs). The final set of markers remaining after considering quality control standards consisted of 37 031 SNPs located on 29 autosomes. The LD parameters historical recombinations through allelic association (D') and squared correlation coefficient between locus alleles frequencies ( r 2 ) were estimated and haplotype block analyses were performed using the Haploview software. The averages of D' and r 2 values were 0.628 and 0.122, respectively. The LD value decreased with increasing physical distance. The D' and r 2 values decreased respectively from 0.815 and 0.283 at the distance of 0-30 kb to 0.578 and 0.090 at the distance of 401-500 kb. The identified total number of blocks was 969 and consisted of 4259 SNPs that covered 159.06 Mb (6.24% of the total genome) on 29 autosomes. Several genes inside the haplotype blocks were detected; CSN1S2 gene in haplotype block 51 on BTA 6, IL6 and B4GALT1 genes in haplotype blocks 6 and 33 on BTA 8, IL1B and ID2 genes in haplotype blocks 19 and 29 on BTA 11, and DGAT1 gene in haplotype block 1 on BTA 14. The extension of LD using BovineSNP50 BeadChip did not exceed 500 kb and its parameters r 2 and D' were less than 0.2 and 0.70, respectively, after 70-100 kb. Consequently, the 50K BeadChip would have a poor power in genome wide association studies at distances between adjacent markers lower than 70 kb.

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Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle

Salem¹,

Thompson²,

Chen³

et al. 2018

Czech J. Anim. Sci.

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“…Additionally, until recently most studies have focused on bovine populations from developed 1 countries where they are subjected to intensive breeding, such as the Holstein breed, and these studies have suggested that significant LD among markers extends over several megabases (Farnir et al 2000;Tenesa et al 2003;Khatkar et al 2006;Thevenon et al 2007). As part of the whole bovine genome sequencing project, significant efforts are currently being carried out to identify a large number of SNPs by comparing hundreds of thousands of random sequences originating from a small set of individuals belonging to different populations with a reference sequence.…”

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Genetic and Haplotypic Structure in 14 European and African Cattle Breeds

et al. 2007

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To evaluate and compare the extent of LD in cattle, 1536 SNPs, mostly localized on BTA03, were detected in silico from available sequence data using two different methods and genotyped on samples from 14 distinct breeds originating from Europe and Africa. Only 696 SNPs could be validated, confirming the importance of trace-quality information for the in silico detection. Most of the validated SNPs were informative in several breeds and were used for a detailed description of their genetic structure and relationships. Results obtained were in agreement with previous studies performed on microsatellite markers and using larger samples. In addition, the majority of the validated SNPs could be mapped precisely, reaching an average density of one marker every 311 kb. This allowed us to analyze the extent of LD in the different breeds. Decrease of LD with physical distance across breeds revealed footprints of ancestral LD at short distances (,10 kb). As suggested by the haplotype block structure, these ancestral blocks are organized, within a breed, into larger blocks of a few hundred kilobases. In practice, such a structure similar to that already reported in dogs makes it possible to develop a chip of ,300,000 SNPs, which should be efficient for mapping purposes in most cattle breeds.

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“…A following step has been the construction of LD maps for the human (Maniatis 2002) and animal genomes (e.g., Khatkar et al 2006). LD maps are based on: (a) estimation of a linkage disequilibrium parameter, r, which has the same maximum absolute value as the statistics D9 of Lewontin (1964), and (b) use of a model of decay of disequilibrium leading to equations of Malecot's model for isolation by distance (Malecot 1964).…”

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confidence: 99%

“…If the bias depends upon the distance between the adjacent SNPs as shown here then inferences on population structure and the evolution of the cattle population may not be fully correct. Khatkar et al (2006) carried out a LD map of bovine chromosome 6 using bulls from the Australian Holstein-Friesian. They estimated average coancestry by 0.012 using available pedigree information.…”

Section: Discussionmentioning

confidence: 99%

Maximum Likelihood Estimation of Linkage Disequilibrium in Half-Sib Families

Gomez‐Raya

2012

Genetics

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Maximum likelihood methods for the estimation of linkage disequilibrium between biallelic DNA-markers in half-sib families (half-sib method) are developed for single and multifamily situations. Monte Carlo computer simulations were carried out for a variety of scenarios regarding sire genotypes, linkage disequilibrium, recombination fraction, family size, and number of families. A double heterozygote sire was simulated with recombination fraction of 0.00, linkage disequilibrium among dams of d= 0.10, and alleles at both markers segregating at intermediate frequencies for a family size of 500. The average estimates of d were 0.17, 0.25, and 0.10 for Excoffier and Slatkin (1995), maternal informative haplotypes, and the half-sib method, respectively. A multifamily EM algorithm was tested at intermediate frequencies by computer simulation. The range of the absolute difference between estimated and simulated d was between 0.000 and 0.008. A cattle half-sib family was genotyped with the Illumina 50K BeadChip. There were 314,730 SNP pairs for which the sire was a homo-heterozygote with average estimates of r 2 of 0.115, 0.067, and 0.111 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. There were 208,872 SNP pairs for which the sire was double heterozygote with average estimates of r 2 across the genome of 0.100, 0.267, and 0.925 for half-sib, Excoffier and Slatkin (1995), and maternal informative haplotypes methods, respectively. Genome analyses for all possible sire genotypes with 829,042 tests showed that ignoring half-sib family structure leads to upward biased estimates of linkage disequilibrium. Published inferences on population structure and evolution of cattle should be revisited after accommodating existing half-sib family structure in the estimation of linkage disequilibrium.

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A First-Generation Metric Linkage Disequilibrium Map of Bovine Chromosome 6

Cited by 38 publications

References 33 publications

Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle

Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle

Genetic and Haplotypic Structure in 14 European and African Cattle Breeds

Maximum Likelihood Estimation of Linkage Disequilibrium in Half-Sib Families

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