Submit to Genes Review for Genes Propose a Special Issue

Journal Browser

► Journal Browser

Genome-Wide Association Analysis of Cattle

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Animal Genetics and Genomics".

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 32596

Share This Special Issue

Special Issue Editor

Prof. Dr. Ottmar Distl

E-Mail Website
Guest Editor

Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
Interests: cattle; domestication; ecotypes; selection signatures; resilience; climate change; genomics; breeding program; genomic evaluation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Genome-wide association studies (GWAS) using SNP chip data have significantly contributed to efforts in deciphering Mendelian and complex traits in many livestock species. Particularly, thousands of genetic variants and their potential role in Mendelian and complex traits were identified in cattle. However, there are many new phenotypic traits, mostly those difficult and cost-intensive to record, awaiting an in-depth analysis through genome-wide data. SNP chips cover bovine genes and genomes at a limited resolution, whereas genome-sequencing data offer a high coverage of genomes as well as a much high number of genetic and structural variants. These new analytical tools should increase the power of GWAS and open the possibility to target the mechanisms and genetic networks underlying complex traits as well as their interactions with the environment. Along with GWAS, new statistical analysis methods were developed to model population structure and relatedness among individuals—multiple simultaneous SNP analyses instead of SNP-by-SNP association studies, meta-analyses with large independent datasets, and methods to estimate and partition genetic variance due to segregating variants.

This Special Issue in Genes on “Animal Genetics and Genomics” will highlight the advances of understanding the biological consequences of variants tagging complex traits in order to improve animal health, welfare, and their interactions with efficiency of milk and beef cattle production. Research articles and short communications are invited to provide recent developments and the translation of GWAS discoveries into the biological understanding of complex traits.

Prof. Dr. Ottmar Distl
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cattle genomics
complex traits
health and functional keyword
genome-wide association
next-generation sequencing
network analysis
animal welfare

Published Papers (9 papers)

Download All Papers

Research

28 pages, 2323 KiB

Open AccessEditor’s ChoiceArticle

Genomewide Association Analyses of Lactation Persistency and Milk Production Traits in Holstein Cattle Based on Imputed Whole-Genome Sequence Data

by Victor B. Pedrosa, Flavio S. Schenkel, Shi-Yi Chen, Hinayah R. Oliveira, Theresa M. Casey, Melkaye G. Melka and Luiz F. Brito

Genes 2021, 12(11), 1830; https://doi.org/10.3390/genes12111830 - 19 Nov 2021

Cited by 38 | Viewed by 4187

Abstract

Lactation persistency and milk production are among the most economically important traits in the dairy industry. In this study, we explored the association of over 6.1 million imputed whole-genome sequence variants with lactation persistency (LP), milk yield (MILK), fat yield (FAT), fat percentage (FAT%), protein yield (PROT), and protein percentage (PROT%) in North American Holstein cattle. We identified 49, 3991, 2607, 4459, 805, and 5519 SNPs significantly associated with LP, MILK, FAT, FAT%, PROT, and PROT%, respectively. Various known associations were confirmed while several novel candidate genes were also revealed, including ARHGAP35, NPAS1, TMEM160, ZC3H4, SAE1, ZMIZ1, PPIF, LDB2, ABI3, SERPINB6, and SERPINB9 for LP; NIM1K, ZNF131, GABRG1, GABRA2, DCHS1, and SPIDR for MILK; NR6A1, OLFML2A, EXT2, POLD1, GOT1, and ETV6 for FAT; DPP6, LRRC26, and the KCN gene family for FAT%; CDC14A, RTCA, HSTN, and ODAM for PROT; and HERC3, HERC5, LALBA, CCL28, and NEURL1 for PROT%. Most of these genes are involved in relevant gene ontology (GO) terms such as fatty acid homeostasis, transporter regulator activity, response to progesterone and estradiol, response to steroid hormones, and lactation. The significant genomic regions found contribute to a better understanding of the molecular mechanisms related to LP and milk production in North American Holstein cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

16 pages, 2513 KiB

Open AccessArticle

Genome-Wide Association Studies for Milk Somatic Cell Score in Romanian Dairy Cattle

by Daniela Elena Ilie, Alexandru Eugeniu Mizeranschi, Ciprian Valentin Mihali, Radu Ionel Neamț, George Vlad Goilean, Ovidiu Ionuț Georgescu, Daniela Zaharie, Mihai Carabaș and Ioan Huțu

Genes 2021, 12(10), 1495; https://doi.org/10.3390/genes12101495 - 24 Sep 2021

Cited by 7 | Viewed by 2890

Abstract

Mastitis is one of the most frequently encountered diseases in dairy cattle, negatively affecting animal welfare and milk production. For this reason, contributions to understanding its genomic architecture are of great interest. Genome-wide association studies (GWAS) have identified multiple loci associated with somatic cell score (SCS) and mastitis in cattle. However, most of the studies have been conducted in different parts of the world on various breeds, and none of the investigations have studied the genetic architecture of mastitis in Romanian dairy cattle breeds up to this point in time. In this study, we report the first GWAS for SCS in dairy cattle breeds from Romania. For GWAS, we used an Axiom Bovine v3 SNP-chip (>63,000 Single Nucleotide Polymorphism -SNPs) and 33,330 records from 690 cows belonging to Romanian Spotted (RS) and Romanian Brown (RB) cattle. The results found one SNP significantly associated with SCS in the RS breed and 40 suggestive SNPs with −log₁₀ (p) from 4 to 4.9 for RS and from 4 to 5.4 in RB. From these, 14 markers were located near 12 known genes (AKAP8, CLHC1, MEGF10, SATB2, GATA6, SPATA6, COL12A1, EPS8, LUZP2, RAMAC, IL12A and ANKRD55) in RB cattle, 3 markers were close to ZDHHC19, DAPK1 and MMP7 genes, while one SNP overlapped the HERC3 gene in RS cattle. Four genes (HERC3, LUZP2, AKAP8 and MEGF10) associated with SCS in this study were previously reported in different studies. The most significant SNP (rs110749552) associated with SCS was located within the HERC3 gene. In both breeds, the SNPs and position of association signals were distinct among the three parities, denoting that mastitis is controlled by different genes that are dependent according to parity. The current results contribute to an expansion in the body of knowledge regarding the proportion of genetic variability explained by SNPs for SCS in dairy cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

26 pages, 2298 KiB

Open AccessArticle

Genome-Wide Association Study Using Whole-Genome Sequence Data for Fertility, Health Indicator, and Endoparasite Infection Traits in German Black Pied Cattle

by Manuel J. Wolf, Tong Yin, Guilherme B. Neumann, Paula Korkuć, Gudrun A. Brockmann, Sven König and Katharina May

Genes 2021, 12(8), 1163; https://doi.org/10.3390/genes12081163 - 28 Jul 2021

Cited by 9 | Viewed by 3129

Abstract

This genome-wide association study (GWAS) aimed to identify sequence variants (SVs) and candidate genes associated with fertility and health in endangered German Black Pied cattle (DSN) based on whole-genome sequence (WGS) data. We used 304 sequenced DSN cattle for the imputation of 1797 genotyped DSN to WGS. The final dataset included 11,413,456 SVs of 1886 cows. Cow traits were calving-to-first service interval (CTFS), non-return after 56 days (NR56), somatic cell score (SCS), fat-to-protein ratio (FPR), and three pre-corrected endoparasite infection traits. We identified 40 SVs above the genome-wide significance and suggestive threshold associated with CTFS and NR56, and three important potential candidate genes (ARHGAP21, MARCH11, and ZNF462). For SCS, most associations were observed on BTA 25. The GWAS revealed 61 SVs, a cluster of 10 candidate genes on BTA 13, and 7 pathways for FPR, including key mediators involved in milk fat synthesis. The strongest associations for gastrointestinal nematode and Dictyocaulus viviparus infections were detected on BTA 8 and 24, respectively. For Fasciola hepatica infections, the strongest associated SVs were located on BTA 4 and 7. We detected 200 genes for endoparasite infection traits, related to 16 pathways involved in host immune response during infection. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

15 pages, 4419 KiB

Open AccessArticle

Gene Expression Analysis Provides New Insights into the Mechanism of Intramuscular Fat Formation in Japanese Black Cattle

by Shuji Ueda, Mana Hosoda, Ken-ichi Yoshino, Minoru Yamanoue and Yasuhito Shirai

Genes 2021, 12(8), 1107; https://doi.org/10.3390/genes12081107 - 21 Jul 2021

Cited by 15 | Viewed by 3929

Abstract

Japanese Black cattle (Japanese Wagyu) have a unique phenotype in which ectopic intramuscular fat accumulates in skeletal muscle, producing finely marbled beef. However, the mechanism of intramuscular fat formation in Japanese Black cattle remains unclear. To investigate the key genes involved in intramuscular fat accumulation, we comprehensively analyzed mRNA levels in subcutaneous and intramuscular fat tissues using RNA sequence (RNA-seq) analysis, which detected 27,606 genes. We identified eight key genes, namely carboxypeptidase E, tenascin C, transgelin, collagen type IV alpha 5 (COL4A5), cysteine and glycine-rich protein 2, PDZ, and LIM domain 3, phosphatase 1 regulatory inhibitor subunit 14A, and regulator of calcineurin 2. These genes were highly and specifically expressed in intramuscular fat tissue. Immunohistochemical analysis revealed a collagen network, including COL4A5, in the basement membrane around the intramuscular fat tissue. Moreover, pathway analysis revealed that, in intramuscular fat tissue, differentially expressed genes are related to cell adhesion, proliferation, and cancer pathways. Furthermore, pathway analysis showed that the transforming growth factor-β (TGF-β) and small GTPases regulators RASGRP3, ARHGEF26, ARHGAP10, ARHGAP24, and DLC were upregulated in intramuscular fat. Our study suggests that these genes are involved in intramuscular fat formation in Japanese Black cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Graphical abstract

20 pages, 5777 KiB

Open AccessArticle

A Large-Scale Genome-Wide Association Study of Epistasis Effects of Production Traits and Daughter Pregnancy Rate in U.S. Holstein Cattle

by Dzianis Prakapenka, Zuoxiang Liang, Jicai Jiang, Li Ma and Yang Da

Genes 2021, 12(7), 1089; https://doi.org/10.3390/genes12071089 - 18 Jul 2021

Cited by 10 | Viewed by 3543

Abstract

Epistasis is widely considered important, but epistasis studies lag those of SNP effects. Genome-wide association study (GWAS) using 76,109 SNPs and 294,079 first-lactation Holstein cows was conducted for testing pairwise epistasis effects of five production traits and three fertility traits: milk yield (MY), fat yield (FY), protein yield (PY), fat percentage (FPC), protein percentage (PPC), and daughter pregnancy rate (DPR). Among the top 50,000 pairwise epistasis effects of each trait, the five production traits had large chromosome regions with intra-chromosome epistasis. The percentage of inter-chromosome epistasis effects was 1.9% for FPC, 1.6% for PPC, 10.6% for MY, 29.9% for FY, 39.3% for PY, and 84.2% for DPR. Of the 50,000 epistasis effects, the number of significant effects with log10(1/p) ≥ 12 was 50,000 for FPC and PPC, and 10,508, 4763, 4637 and 1 for MY, FY, PY and DPR, respectively, and A × A effects were the most frequent epistasis effects for all traits. Majority of the inter-chromosome epistasis effects of FPC across all chromosomes involved a Chr14 region containing DGAT1, indicating a potential regulatory role of this Chr14 region affecting all chromosomes for FPC. The epistasis results provided new understanding about the genetic mechanism underlying quantitative traits in Holstein cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

12 pages, 1683 KiB

Open AccessArticle

GWAS Hits for Bilateral Convergent Strabismus with Exophthalmos in Holstein Cattle Using Imputed Sequence Level Genotypes

by Anke Bögeholz, Clemens Falker-Gieske, Monika Guélat, Corinne Gurtner, Sibylle Hunziker, Anna Oevermann, Georg Thaller, Cord Drögemüller and Jens Tetens

Genes 2021, 12(7), 1039; https://doi.org/10.3390/genes12071039 - 04 Jul 2021

Cited by 2 | Viewed by 3567

Abstract

Bilateral convergent strabismus with exophthalmos (BCSE) is a malformation of the eyes and is recognized as a mild but progressive disorder that affects cattle in the first two years of life. This most likely inherited disorder is rarely described in cattle resembling autosomal dominantly inherited forms of human progressive external ophthalmoplegia (PEO). In German Braunvieh cattle, two linked genome regions were found that could be responsible for the development and/or progression of BCSE. The goal of this study was to phenotypically characterize BCSE in Holstein cattle from Germany and Switzerland as well as to identify associated genome regions by GWAS. The clinicopathological phenotype of 52 BCSE-affected Holstein cattle was in accordance with the phenotype described in German Braunvieh cattle, but in addition, signs of degeneration and cellular infiltration in the eye muscles were found. By using imputed sequence level genotype data, three genome-wide significant GWAS hits were revealed on different chromosomes that were not detected by initial GWAS based on high density SNP array data highlighting the usefulness of this approach for mapping studies. The associated genome regions include the ABCC4 gene as well as markers adjacent to the NCOR2 and DNAJC3 genes all illustrating possible functional candidate genes. Our results challenge a monogenic mode of inheritance and indicate a more complex inheritance of BCSE in Holstein cattle. Furthermore, in comparison to previous results from German Braunvieh cattle, it illustrates an obvious genetic heterogeneity causing BSCE in cattle. Subsequent whole genome sequencing (WGS)-based analyses might elucidate pathogenic variants in the future. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

10 pages, 1085 KiB

Open AccessCommunication

Genetic Analyses and Genome-Wide Association Studies on Pathogen Resistance of Bos taurus and Bos indicus Cattle Breeds in Cameroon

by Babette Abanda, Markus Schmid, Archile Paguem, Hanna Iffland, Siegfried Preuß, Alfons Renz and Albert Eisenbarth

Genes 2021, 12(7), 976; https://doi.org/10.3390/genes12070976 - 26 Jun 2021

Viewed by 2096

Abstract

Autochthonous taurine and later introduced zebu cattle from Cameroon differ considerably in their resistance to endemic pathogens with little to no reports of the underlying genetic make-up. Breed history and habitat variations are reported to contribute significantly to this diversity worldwide, presumably in Cameroon as well, where locations diverge in climate, pasture, and prevalence of infectious agents. In order to investigate the genetic background, the genotypes of 685 individuals of different Cameroonian breeds were analysed by using the BovineSNP50v3 BeadChip. The variance components including heritability were estimated and genome-wide association studies (GWAS) were performed. Phenotypes were obtained by parasitological screening and categorised in Tick-borne pathogens (TBP), gastrointestinal nematodes (GIN), and onchocercosis (ONC). Estimated heritabilities were low for GIN and TBP (0.079 (se = 0.084) and 0.109 (se = 0.103) respectively) and moderate for ONC (0.216 (se = 0.094)). Further than revealing the quantitative nature of the traits, GWAS identified putative trait-associated genomic regions on five chromosomes, including the chromosomes 11 and 18 for GIN, 20 and 24 for TBP, and 12 for ONC. The results imply that breeding for resistant animals in the cattle population from Northern Cameroon might be possible for the studied pathogens; however, further research in this field using larger datasets will be required to improve the resistance towards pathogen infections, propose candidate genes or to infer biological pathways, as well as the genetic structures of African multi-breed populations. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

27 pages, 2910 KiB

Open AccessEditor’s ChoiceArticle

Meta-Analysis of Heifer Traits Identified Reproductive Pathways in Bos indicus Cattle

by Muhammad S. Tahir, Laercio R. Porto-Neto, Cedric Gondro, Olasege B. Shittu, Kimberley Wockner, Andre W. L. Tan, Hugo R. Smith, Gabriela C. Gouveia, Jagish Kour and Marina R. S. Fortes

Genes 2021, 12(5), 768; https://doi.org/10.3390/genes12050768 - 18 May 2021

Cited by 28 | Viewed by 5426

Abstract

Fertility traits measured early in life define the reproductive potential of heifers. Knowledge of genetics and biology can help devise genomic selection methods to improve heifer fertility. In this study, we used ~2400 Brahman cattle to perform GWAS and multi-trait meta-analysis to determine genomic regions associated with heifer fertility. Heifer traits measured were pregnancy at first mating opportunity (PREG1, a binary trait), first conception score (FCS, score 1 to 3) and rebreeding score (REB, score 1 to 3.5). The heritability estimates were 0.17 (0.03) for PREG1, 0.11 (0.05) for FCS and 0.28 (0.05) for REB. The three traits were highly genetically correlated (0.75–0.83) as expected. Meta-analysis was performed using SNP effects estimated for each of the three traits, adjusted for standard error. We identified 1359 significant SNPs (p-value < 9.9 × 10⁻⁶ at FDR < 0.0001) in the multi-trait meta-analysis. Genomic regions of 0.5 Mb around each significant SNP from the meta-analysis were annotated to create a list of 2560 positional candidate genes. The most significant SNP was in the vicinity of a genomic region on chromosome 8, encompassing the genes SLC44A1, FSD1L, FKTN, TAL2 and TMEM38B. The genomic region in humans that contains homologs of these genes is associated with age at puberty in girls. Top significant SNPs pointed to additional fertility-related genes, again within a 0.5 Mb region, including ESR2, ITPR1, GNG2, RGS9BP, ANKRD27, TDRD12, GRM1, MTHFD1, PTGDR and NTNG1. Functional pathway enrichment analysis resulted in many positional candidate genes relating to known fertility pathways, including GnRH signaling, estrogen signaling, progesterone mediated oocyte maturation, cAMP signaling, calcium signaling, glutamatergic signaling, focal adhesion, PI3K-AKT signaling and ovarian steroidogenesis pathway. The comparison of results from this study with previous transcriptomics and proteomics studies on puberty of the same cattle breed (Brahman) but in a different population identified 392 genes in common from which some genes—BRAF, GABRA2, GABR1B, GAD1, FSHR, CNGA3, PDE10A, SNAP25, ESR2, GRIA2, ORAI1, EGFR, CHRNA5, VDAC2, ACVR2B, ORAI3, CYP11A1, GRIN2A, ATP2B3, CAMK2A, PLA2G, CAMK2D and MAPK3—are also part of the above-mentioned pathways. The biological functions of the positional candidate genes and their annotation to known pathways allowed integrating the results into a bigger picture of molecular mechanisms related to puberty in the hypothalamus–pituitary–ovarian axis. A reasonable number of genes, common between previous puberty studies and this study on early reproductive traits, corroborates the proposed molecular mechanisms. This study identified the polymorphism associated with early reproductive traits, and candidate genes that provided a visualization of the proposed mechanisms, coordinating the hypothalamic, pituitary, and ovarian functions for reproductive performance in Brahman cattle. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

13 pages, 2393 KiB

Open AccessArticle

Genetic and Genome-Wide Association Analysis of Yearling Weight Gain in Israel Holstein Dairy Calves

by Moran Gershoni, Joel Ira Weller and Ephraim Ezra

Genes 2021, 12(5), 708; https://doi.org/10.3390/genes12050708 - 10 May 2021

Cited by 4 | Viewed by 1979

Abstract

Yearling weight gain in male and female Israeli Holstein calves, defined as 365 × ((weight − 35)/age at weight) + 35, was analyzed from 814,729 records on 368,255 animals from 740 herds recorded between 1994 and 2021. The variance components were calculated based on valid records from 2008 through 2017 for each sex separately and both sexes jointly by a single-trait individual animal model analysis, which accounted for repeat records on animals. The analysis model also included the square root, linear, and quadratic effects of age at weight. Heritability and repeatability were 0.35 and 0.71 in the analysis of both sexes and similar in the single sex analyses. The regression of yearling weight gain on birth date in the complete data set was −0.96 kg/year. The complete data set was also analyzed by the same model as the variance component analysis, including both sexes and accounting for differing variance components for each sex. The genetic trend for yearling weight gain, including both sexes, was 1.02 kg/year. Genetic evaluations for yearling weight gain was positively correlated with genetic evaluations for milk, fat, protein production, and cow survival but negatively correlated with female fertility. Yearling weight gain was also correlated with the direct effect on dystocia, and increased yearling weight gain resulted in greater frequency of dystocia. Of the 1749 Israeli Holstein bulls genotyped with reliabilities >50%, 1445 had genetic evaluations. As genotyping of these bulls was performed using several single nucleotide polymorhphism (SNP) chip platforms, we included only those markers that were genotyped in >90% of the tested cohort. A total of 40,498 SNPs were retained. More than 400 markers had significant effects after permutation and correction for multiple testing (p_nominal < 1 × 10⁻⁸). Considering all SNPs simultaneously, 0.69 of variance among the sires’ transmitting ability was explained. There were 24 markers with coefficients of determination for yearling weight gain >0.04. One marker, BTA-75458-no-rs on chromosome 5, explained ≈6% of the variance among the estimated breeding values for yearling weight gain. ARS-BFGL-NGS-39379 had the fifth largest coefficient of determination in the current study and was also found to have a significant effect on weight at an age of 13–14 months in a previous study on Holsteins. Significant genomic effects on yearling weight gain were mainly associated with milk production quantitative trait loci, specifically with kappa casein metabolism. Full article

(This article belongs to the Special Issue Genome-Wide Association Analysis of Cattle)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Genome-Wide Association Analysis of Cattle

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (9 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI