Searching for new loci and candidate genes for economically important traits through gene-based association analysis of Simmental cattle

Xia, Jiangwei; Fan, Huizhong; Chang, Tianpeng; Xu, Lingyang; Zhang, Wengang; Song, Yifu; Zhu, Bo; Zhang, Lupei; Gao, Xue; Chen, Yan; Li, Junya; Gao, Huijiang

doi:10.1038/srep42048

Cited by 44 publications

(49 citation statements)

References 62 publications

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“…); LAP3 and FAM184B, both reported as candidate genes for carcass or growth traits in cattle (Xia et al . ); LAP3, also associated with milk production traits (Zheng et al . ); NCAPG, related to fetal growth, body frame size (Eberlein et al .…”

Section: Resultsmentioning

confidence: 99%

Runs of homozygosity reveal genome‐wide autozygosity in Italian sheep breeds

et al. 2018

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Summary 18The availability of dense single-nucleotide polymorphism (SNP) assays allows for the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 F o r P e e r R e v i e wThe abundance of single-nucleotide polymorphisms (SNPs) throughout the genome and the 44 availability of dense SNP assays, makes these markers particularly suitable for the detection of 45 genomic regions where a reduction in heterozygosity occurred (Kim et al. 2013). Runs of 46 homozygosity (ROH) are contiguous segments of homozygous genotypes that are present in an 47 individual due to parents transmitting identical haplotypes to their offspring (Gibson et al. 2006). 48In animal genetics, ROH are used as predictors of whole genome inbreeding levels (Purfield et 49 al. 2012; Marras et al. 2015; Mastrangelo et al. 2016), to characterize the genomic distribution of 50 inbreeding depression on a phenotype (Biscarini et al. 2014; Pryce et al. 2014), and to identify 51 genes associated with traits of economic interest present in these regions (Zhang et al. 2015; 52 Szmatola et al. 2016; Purfield et al. 2017). Selection pressure and mating schemes can be 53 disentangled by ROH; therefore, ROH detection can also be used to minimize inbreeding and to 54 improve mating systems (Bosse et al. 2012; Zhang et al. 2015 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Runs of homozygosity definition 106Runs of homozygosity were estimated for each animal using PLINK (Purcell et al. 2007). No where L ROH is the total length of all ROH in the genome of an individual, and L aut the specified 118 length of the autosomal genome covered by SNPs on the chip (2 452.06 Mb). 119Each ROH was categorized based on its physical length into 1 to <5 Mb, 5 to <10 Mb, 10 to <15 and averaging this per breed. 123The genomic inbreeding coefficient based on the difference between observed vs. expected 124 number of homozygous genotypes (F HOM ) was also estimated using PLINK (Purcell et al. 2007). 125Pearson's correlation between the two measures of inbreeding was calculated. 127Detection of common runs of homozygosity 128To identify the genomic regions most commonly associated with ROH for the meta-population, 129and for groups on the basis of production purposes (milk, meat, wool and "milk and meat"), the 136Genomic coordinates for all the identified ROH islands were used for the annotation of genes 137 that were fully or partially contained within each selected region using the UCSC Genome 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59...

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Section: Resultsmentioning

confidence: 99%

Runs of homozygosity reveal genome‐wide autozygosity in Italian sheep breeds

et al. 2018

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“…Considering our previous GWAS results for bone weight (Xia et al., ), four genes have been identified associated with bone weight. Some of our results ( LCORL and LAP3 ) confirmed previously reported associations with genes related to bone weight.…”

Section: Discussionmentioning

confidence: 99%

Multimarker and rare variants genomewide association studies for bone weight in Simmental cattle

Miao

Wang

Bao³

et al. 2018

J Animal Breeding Genetics

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Bone weight, defined as the total weight of the bones in all the forequarter and hindquarter joints, can reflect somebody conformation traits and skeletal diseases. To gain a better understanding of the genetic determinants of bone weight, we used a composite strategy including multimarker and rare-marker association to perform genomewide association studies (GWAS) for that character in Simmental cattle. Our strategy consisted of three models: (i) A traditional linear mixed model (LMM) was applied (Q+K-LMM); (ii) single nucleotide polymorphisms (SNPs) with p-values less than .05 from the LMM were selected to undergo the least absolute shrinkage and selector operator (Lasso) in the second stage (LMM-Lasso); (iii) genes containing two or more rare SNPs were examined by performing the sequence kernel association test (gene-based SKAT). A total of 1,225 cattle were genotyped with an Illumina BovineHD BeadChip containing 770,000 SNPs. After the quality-control procedures, 1,217 individuals with 608,696 common SNPs and 105,787 rare SNPs (with 0.001 < minor allele frequency [MAF] <0.05) remained in the sample for analysis. A traditional LMM successfully mapped three genes associated with bone weight, while LMM-Lasso identified nine genes, which included all genes found by traditional LMM. Only a single gene, EPHB3, surpassed the significance threshold after Bonferroni correction in gene-based SKAT. In conclusion, based on functional annotation and results from previous endeavours, we believe that LCORL, RIMS2, LAP3, PRKAR2B, CHSY1, MAP2K6 and EPHB3 are candidate genes for bone weight. In general, such a comprehensive strategy for GWAS may be useful for researchers seeking to probe the full genetic architecture underlying economic traits in livestock.

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“…For each group (protein of transcript) of oligopeptides, we constructed principal components (PCs) according to the following rules [14]. We treated each oligopeptide (kmer) within a group as a single variable, and calculated the variance-covariance matrix.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Numerous strategies and statistical approaches have been developed to meet the technical challenges and the great opportunities provided by GWAS [4,14,15]. One of such approaches is gene-based GWAS analysis [14]. In GWAS analysis, gene-based association analysis could combine the significance of all SNPs in a gene and effectively assess the association between gene and phenotype traits in hundreds or thousands of individuals.…”

Section: Introductionmentioning

confidence: 99%

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A Whole-Genome Association Approach for Large-scaled Inter-species Trait

Fan

Chen

et al. 2018

Preprint

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1Genome wide association studies (GWAS) have provided an avenue for the association between 2 common genetic variants and complex traits. However, using SNP as a genetic marker, GWAS has 3 been confined to detect genetic basis traits only for within species but not for the large-scale 4 inter-species traits. Here, we propose a practical statistical approach that is using kmer frequencies 5 as the genetic markers to associate genetic variants with large scale inter-species traits. We applied 6 this new approach to the trait of chromosome number in 96 mammalian proteomes, and we 7 prioritized 130 genes including TP53 and BAD, of which 6 were candidate genes. These genes 8 were proved to be associated with cellular reaction of DNA double-strand breaks caused by 9 chromosome fission/fusion. Our study provides a new effective genomic strategy to perform 1 0 association studies for large-scaled inter-species traits, using the chromosome number as a case. 1 1We hope this approach could provide exploration for broadly widely traits. 1 2 1 3

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Searching for new loci and candidate genes for economically important traits through gene-based association analysis of Simmental cattle

Cited by 44 publications

References 62 publications

Runs of homozygosity reveal genome‐wide autozygosity in Italian sheep breeds

Runs of homozygosity reveal genome‐wide autozygosity in Italian sheep breeds

Multimarker and rare variants genomewide association studies for bone weight in Simmental cattle

A Whole-Genome Association Approach for Large-scaled Inter-species Trait

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