Search

Copy number variations (CNVs) modify transcription levels mainly through changing genes and regulatory elements dosages. Hence, CNVs can contribute to the additive genetic variance of quantitative traits, which might not be fully captured by SNPs. Here, CNVs were mapped from 3,601 Holsteins and their contribution to complex traits was explored by i) quantitative trait loci (QTL) enrichment analysis, and ii) variance component analysis for metritis (1 = disease, 0 = no disease). The 4,113 CNVs derived from high-density (777k) genotypic information were compiled into 1,184 CNV regions (CNVRs) overlapping 7,832 QTLs reported in dairy cattle and available in the AnimalQTLdb. Fisher’s exact test was applied to perform the QTL enrichment analysis followed by False Discovery Rate (FDR) correction. Then, QTLs overlapping CNVRs were enriched for traits when the corrected P-value (PFDR) was lower than 0.05. For variance components estimation, genomic information from all CNVs loci was used to build the CNV-derived genomic relationship matrix (CNV_GRM). CNV loci showing double deletions, single deletions, and normal state in the population were coded as 0, 1, and 2, respectively, whereas CNV loci presenting normal state, single duplications, and double duplications were coded as 0, 1, and 2, respectively. Given that some CNVs presented both deletions and duplications at the same position in the population, these mixed-CNVs were treated as two distinct CNVs loci, one to represent deletions and the other to represent duplications. The variance components for metritis were estimated by fitting either only a SNP-derived GRM (SNP_GRM) or jointly SNP_GRM and CNV_GRM considering 3,272 cows in models that included the female category and farmyear-season as fixed effects. QTLs overlapped with CNVRs were enriched for milk (e.g., milk fat yield, milk yield, and milk protein percentage), reproduction (e.g., calving ease, non-return rate, and heat intensity), exterior (e.g., teat length, udder depth, and udder height), production (e.g., length of productive life, lifetime profit index, and net merit), and health traits (e.g., immune globulin G level, somatic cell, and bovine respiratory susceptibility). Regarding variance components, copy number variations were able to capture a fraction of the additive genetic variance not captured by SNPs alone, increasing the heritability estimate for metritis. In summary, our findings suggest that CNVs overlap QTLs associated with economically important traits more than only by chance and CNVs can capture additional additive genetic variance not fully captured by SNPs alone. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) represents an important source of genetic variation complementary to single nucleotide polymorphism (SNP) and provides valuable insights into the genetic architecture of complex traits in humans and livestock animals. However, many factors affect CNV detection, including sample size. Previous studies in Holstein cattle have only used hundreds of individuals. Therefore, in the present study, CNVs were identified from high-density genotype array data in 3,529 Holstein cows from 16 herds located in 7 U.S. states. CNVs were derived from 546,802 autosomal SNP markers with MAF > 0.05 and call rate > 0.90 using the intensity signals at each SNP position in a hidden Markov model implemented in PennCNV software. The log R ratio (LRR) values were corrected based on the guanine-cytosine content in the genomic regions located 500 kb upstream and downstream of each marker. After detection, CNVs presenting LRR = 0.30, B allele frequency drift < 0.01, waviness factor = 0.05, number of SNPs > 10 and length > 1 kb were merged into CNV regions (CNVR) using CNVRanger. A total of 1,881 non-redundant CNV events spanning the entire genome were identified in 1,771 cows, with a mean of 10 CNVs per individual and ranging from 1 to 27. The highest percentage of CNV calls was located on BTA7 (16%), while only 9 CNVs were identified on BTA9. The CNV calls were grouped into 685 CNVRs covering 3.07% of the bovine autosomal genome. The number of CNVRs with copy loss and gain were 356 and 310, and both types were observed in 19 regions. The chromosomal distribution of CNVR revealed that BTA7 harbors 38 CNVRs, while only 2 were detected on BTA28. These results will support further research on the contribution of CNVs and CNVRs to the genetic architecture of complex traits in Holstein cattle. [ABSTRACT FROM AUTHOR]

The article explains the role of lymphatic fluid in screening Mycobacterium avium subspecies paratumberculosis (MAP) in cattle. The study was performed on 58 cows, where lymph fluid was extracted from their udders to identify traces of MAP through nested polymerase chain reaction. Results revealed that MAP was identified in 43.1 percent of lymph samples, where it was discovered in 66.7 percent cows with clinical Johne's disease.

Subfertility represents one major challenge to enhancing dairy production and efficiency. Herein, we use a reproductive index (RI) expressing the predicted probability of pregnancy following artificial insemination (AI) with Illumina 778K genotypes to perform single and multi-locus genome-wide association analyses (GWAA) on 2,448 geographically diverse U.S. Holstein cows and produce genomic heritability estimates. Moreover, we use genomic best linear unbiased prediction (GBLUP) to investigate the potential utility of the RI by performing genomic predictions with cross validation. Notably, genomic heritability estimates for the U.S. Holstein RI were moderate (h2 = 0.1654 ± 0.0317-0.2550 ± 0.0348), while single and multi-locus GWAA revealed overlapping quantitative trait loci (QTL) on BTA6 and BTA29, including the known QTL for the daughter pregnancy rate (DPR) and cow conception rate (CCR). Multi-locus GWAA revealed seven additional QTL, including one on BTA7 (60 Mb) which is adjacent to a known heifer conception rate (HCR) QTL (59 Mb). Positional candidate genes for the detected QTL included male and female fertility loci (i.e. spermatogenesis and oogenesis), meiotic and mitotic regulators, and genes associated with immune response, milk yield, enhanced pregnancy rates, and the reproductive longevity pathway. Based on the proportion of the phenotypic variance explained (PVE), all detected QTL (n = 13; P ≤ 5e - 05) were estimated to have moderate (1.0% < PVE ≤ 2.0%) or small effects (PVE ≤ 1.0%) on the predicted probability of pregnancy. Genomic prediction using GBLUP with cross validation (k = 3) produced mean predictive abilities (0.1692-0.2301) and mean genomic prediction accuracies (0.4119-0.4557) that were similar to bovine health and production traits previously investigated., Competing Interests: Conflicts of interest The authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)