Gene-set enrichment analysis of selective sweeps reveals phenotypic traits in Nguni cattle

Adaptation of animals to different environments is typically associated with structural and functional genomic variations. High throughput SNP genotyping and next-generation sequencing (NGS) have made it possible to study positive selection footprints and adaptation traits. Nguni is a small frame-size breed, mostly horned, and well known for being adapted to diverse South African environmental conditions. This study used previously identified selective sweeps to perform functional analysis of genes related to phenotypic characteristics in Nguni. Two hundred and sixty-four candidate selective sweeps were used for gene-set enrichment analysis in molecular functional categories (KEGG pathways) using the database for annotation, visualization, and integrated discovery (DAVID). In total, 107 genes were identified across all the chromosomes with 74 genes associated with eight phenotype queries, including fat content, milk production, walking ability, heat tolerance, meat production, reproduction, and bone and muscle development. Gene CRHR2 was associated with meat quality (juiciness and flavour). The IRAK3 gene was associated with decreased body size, feed intake and fatness in cattle, and CARD15 with disease resistance. Gene annotation using phenotype queries identified four genes (SPI, YWHAZ, RGS4, and RGS5) that were associated with myometrial relaxation in cattle. Genes such as NOD2 and IL21R were associated with inflammatory bowel diseases in cattle, whereas CPLS gene was associated with fat content. These genes are important to the phenotypic and adaptive characteristics present in South African Nguni cattle and hold potential for selection for traits of economic importance.The Red Meat Research and Development of South Africa (RMRDSA) and the National Research Foundation (NRF).http://www.sasas.co.zaam2022Animal and Wildlife Science

Genome-wide SNP discovery in indigenous cattle breeds of South Africa

Single nucleotide polymorphism arrays have created new possibilities for performing genome-wide studies to detect genomic regions harboring sequence variants that affect complex traits. However, the majority of validated SNPs for which allele frequencies have been estimated are limited primarily to European breeds. The objective of this study was to perform SNP discovery in three South African indigenous breeds (Afrikaner, Drakensberger, and Nguni) using whole genome sequencing. DNA was extracted from blood and hair samples, quantified and prepared at 50 ng/ml concentration for sequencing at the Agricultural Research Council Biotechnology Platform using an Illumina HiSeq 2500. The fastq files were used to call the variants using the Genome Analysis Tool Kit. A total of 1,678,360 were identified as novel using Run 6 of 1000 Bull Genomes Project. Annotation of the identified variants classified them into functional categories. Within the coding regions, about 30% of the SNPs were non-synonymous substitutions that encode for alternate amino acids. The study of distribution of SNP across the genome identified regions showing notable differences in the densities of SNPs among the breeds and highlighted many regions of functional significance. Gene ontology terms identified genes such as MLANA, SYT10, and CDC42EP5 that have been associated with coat color in mouse, and ADAMS3, DNAJC3, and PAG5 genes have been associated with fertility in cattle. Further analysis of the variants detected 688 candidate selective sweeps (ZHp Z-scores 4) across all three breeds, of which 223 regions were assigned as being putative selective sweeps (ZHp scores 5). We also identified 96 regions with extremely low ZHp Z-scores ( 6) in Afrikaner and Nguni. Genes such as KIT and MITF that have been associated with skin pigmentation in cattle and CACNA1C, which has been associated with biopolar disorder in human, were identified in these regions. This study provides the first analysis of sequence data to discover SNPs in indigenous South African cattle breeds. The information will play an important role in our efforts to understand the genetic history of our cattle and in designing appropriate breed improvement programmes.The Red Meat Research and Development of South Africa (RMRDSA), South Africa Beef Genomic Project (BGP), and the National Research Foundation (NRF).http://www.frontiersin.org/Geneticsam2019Animal and Wildlife Science

Genome-wide marker discovery in three South African indigenous cattle breeds (Afrikaner Drakensberger and Nguni) using next generation sequencing

Afrikaner, Drakensberger, and Nguni are the South African (SA) landraces that played major roles in the social, cultural and economic history of SA. These breeds are valuable genetic resources for beef production and limited information is available for these breeds at the genome level. The aim of this study was to perform SNP discovery in these three breeds using whole genome sequencing. Ninety cattle representing the three breeds were used to identify more about 17.6 M putative variants including SNPs and Indels. DNA was extracted from blood and hair samples, quantified and prepared at 50ng/?l concentration for sequencing at the Agricultural Research Council Biotechnology Platform using an Illumina HiSeq 2000. The fastq files were used to call the variants using the Genome Analysis Tool Kit. A total of 4,369,879 (16% of the total SNPs) were identified as novel. Annotation of these variants classified them into functional categories. Within the coding regions, 43% of the SNPs were nonsynonymous substitutions that encode for alternate amino acids. Functional enrichment analysis of novel SNPs identified significant number of genes (p < 0.001) that were located within 5% of 1,481 100kb windows. Gene ontology terms identified genes such as MLANA and SYT10 that have been associated with coat colour and sense of smell in mouse, respectively, and the ADAMS3 gene has been associated with fertility in cattle. Furthermore, whole genome screening detected 688 candidate selective sweeps (ZHp Z-scores ? -4) across all three breeds, of which 223 regions were assigned as being putative selective sweeps (ZHp scores ? -5). We also identified 96 regions with extremely low ZHp Z-scores (? -6) in Afrikaner and Nguni. Several genes such as KIT and MITF that have been associated with skin pigmentation in cattle, and CACNA1C, which has been associated biopolar disorder in human were identified in these regions. Breed-specific SNPs (2,272,667) were identified across the breeds and only 186 of these SNPs were identified as putative breed-specific SNPs. These SNPs were further tested for their ability to assign individuals to a breed and need further validation. This study provides the first analysis of sequence data to discover SNPs in indigenous SA cattle breeds. These results provide insight into the genetic composition of the breeds and offer the potential for further applications in their genetic improvement.Thesis (PhD)--University of Pretoria, 2017.Animal and Wildlife SciencesPhDUnrestricte