Weighted single-step genome-wide association study for direct and maternal genetic effects associated with birth and weaning weights in sheep.

Body weight is an important economic trait for sheep meat production, and its genetic improvement is considered one of the main goals in the sheep breeding program. Identifying genomic regions that are associated with growth-related traits accelerates the process of animal breeding through marker-assisted selection, which leads to increased response to selection. In this study, we conducted a weighted single-step genome-wide association study (WssGWAS) to identify potential candidate genes for direct and maternal genetic effects associated with birth weight (BW) and weaning weight (WW) in Baluchi sheep. The data used in this research included 13,408 birth and 13,170 weaning records collected at Abbas-Abad Baluchi Sheep Breeding Station, Mashhad-Iran. Genotypic data of 94 lambs genotyped by Illumina 50K SNP BeadChip for 54,241 markers were used. The proportion of variance explained by genomic windows was calculated by summing the variance of SNPs within 1 megabase (Mb). The top 10 window genomic regions explaining the highest percentages of additive and maternal genetic variances were selected as candidate window genomic regions associated with body weights. Our findings showed that for BW, the top-ranked genomic regions (1 Mb windows) explained 4.30 and 4.92% of the direct additive and maternal genetic variances, respectively. The direct additive genetic variance explained by the genomic window regions varied from 0.31 on chromosome 1 to 0.59 on chromosome 8. The highest (0.84%) and lowest (0.32%) maternal genetic variances were explained by genomic windows on chromosome 10 and 17, respectively. For WW, the top 10 genomic regions explained 6.38 and 5.76% of the direct additive and maternal genetic variances, respectively. The highest and lowest contribution of direct additive genetic variances were 1.37% and 0.42%, respectively, both explained by genomic regions on chromosome 2. For maternal effects on WW, the highest (1.38%) and lowest (0.41%) genetic variances were explained by genomic windows on chromosome 2. Further investigation of these regions identified several possible candidate genes associated with body weight. Gene ontology analysis using the DAVID database identified several functional terms, such as translation repressor activity, nucleic acid binding, dehydroascorbic acid transporter activity, growth factor activity and SH2 domain binding.

Genes and Pathways Affecting Sheep Productivity Traits: Genetic Parameters, Genome-Wide Association Mapping, and Pathway Enrichment Analysis.

Ewe productivity is a composite and maternal trait that is considered the most important economic trait in sheep meat production. The objective of this study was the application of alternative genome-wide association study (GWAS) approaches followed by gene set enrichment analysis (GSEA) on the ewes' genome to identify genes affecting pregnancy outcomes and lamb growth after parturition in Iranian Baluchi sheep. Three maternal composite traits at birth and weaning were considered. The traits were progeny birth weight, litter mean weight at birth, total litter weight at birth, progeny weaning weight, litter mean weight at weaning, and total litter weight at weaning. GWASs were performed on original phenotypes as well as on estimated breeding values. The significant SNPs associated with composite traits at birth were located within or near genes RDX, FDX1, ARHGAP20, ZC3H12C, THBS1, and EPG5. Identified genes and pathways have functions related to pregnancy, such as autophagy in the placenta, progesterone production by the placenta, placental formation, calcium ion transport, and maternal immune response. For composite traits at weaning, genes (NR2C1, VEZT, HSD17B4, RSU1, CUBN, VIM, PRLR, and FTH1) and pathways affecting feed intake and food conservation, development of mammary glands cytoskeleton structure, and production of milk components like fatty acids, proteins, and vitamin B-12, were identified. The results show that calcium ion transport during pregnancy and feeding lambs by milk after parturition can have the greatest impact on weight gain as compared to other effects of maternal origin.

Genome-wide association study and pathway analysis identify NTRK2 as a novel candidate gene for litter size in sheep.

Litter size is one of the most important economic traits in sheep. Identification of gene variants that are associated with the prolificacy rate is an important step in breeding program success and profitability of the farm. So, to identify genetic mechanisms underlying the variation in litter size in Iranian Baluchi sheep, a two-step genome-wide association study (GWAS) was performed. GWAS was conducted using genotype data from 91 Baluchi sheep. Estimated breeding values (EBVs) for litter size calculated for 3848 ewes and then used as the response variable. Besides, a pathway analysis using GO and KEGG databases were applied as a complementary approach. A total of three single nucleotide polymorphisms (SNPs) associated with litter size were identified, one each on OAR2, OAR10, and OAR25. The SNP on OAR2 is located within a novel putative candidate gene, Neurotrophic receptor tyrosine kinase 2. This gene product works as a receptor which is essential for follicular assembly, early follicular growth, and oocyte survival. The SNP on OAR25 is located within RAB4A which is involved in blood vessel formation and proliferation through angiogenesis. The SNP on OAR10 was not associated with any gene in the 1Mb span. Moreover, gene-set analysis using the KEGG database identified several pathways, such as Ovarian steroidogenesis, Steroid hormone biosynthesis, Calcium signaling pathway, and Chemokine signaling. Also, pathway analysis using the GO database revealed several functional terms, such as cellular carbohydrate metabolic, biological adhesion, cell adhesion, cell junction, and cell-cell adherens junction, among others. This is the first study that reports the NTRK2 gene affecting litter size in sheep and our study of this gene functions showed that this gene could be a good candidate for further analysis.

Genome-Wide Identification of Microsatellites and Transposable Elements in the Dromedary Camel Genome Using Whole-Genome Sequencing Data.

Transposable elements (TEs) along with simple sequence repeats (SSRs) are prevalent in eukaryotic genome, especially in mammals. Repetitive sequences form approximately one-third of the camelid genomes, so study on this part of genome can be helpful in providing deeper information from the genome and its evolutionary path. Here, in order to improve our understanding regarding the camel genome architecture, the whole genome of the two dromedaries (Yazdi and Trodi camels) was sequenced. Totally, 92- and 84.3-Gb sequence data were obtained and assembled to 137,772 and 149,997 contigs with a N50 length of 54,626 and 54,031 bp in Yazdi and Trodi camels, respectively. Results showed that 30.58% of Yazdi camel genome and 30.50% of Trodi camel genome were covered by TEs. Contrary to the observed results in the genomes of cattle, sheep, horse, and pig, no endogenous retrovirus-K (ERVK) elements were found in the camel genome. Distribution pattern of DNA transposons in the genomes of dromedary, Bactrian, and cattle was similar in contrast with LINE, SINE, and long terminal repeat (LTR) families. Elements like RTE-BovB belonging to LINEs family in cattle and sheep genomes are dramatically higher than genome of dromedary. However, LINE1 (L1) and LINE2 (L2) elements cover higher percentage of LINE family in dromedary genome compared to genome of cattle. Also, 540,133 and 539,409 microsatellites were identified from the assembled contigs of Yazdi and Trodi dromedary camels, respectively. In both samples, di-(393,196) and tri-(65,313) nucleotide repeats contributed to about 42.5% of the microsatellites. The findings of the present study revealed that non-repetitive content of mammalian genomes is approximately similar. Results showed that 9.1 Mb (0.47% of whole assembled genome) of Iranian dromedary's genome length is made up of SSRs. Annotation of repetitive content of Iranian dromedary camel genome revealed that 9,068 and 11,544 genes contain different types of TEs and SSRs, respectively. SSR markers identified in the present study can be used as a valuable resource for genetic diversity investigations and marker-assisted selection (MAS) in camel-breeding programs.

Genetic variants analysis of three dromedary camels using whole genome sequencing data.

Whole genome wide identification and annotation of genetic variations in camels is in its first steps. The aim of this study was the identification of genome wide variants, functional annotations of them and enrichment analysis of affected genes using whole genome sequencing data of three dromedary camels. The genomes of two Iranian female dromedary camels that mostly used to produce meat and milk were sequenced to 41.9-fold and 38.6-fold coverage. A total of 4,727,238 single-nucleotide polymorphisms (SNPs) and 692,908 indels (insertions and deletions) were found by mapping raw reads to the dromedary reference assembly (GenBank Accession: GCA_000767585.1). In-silico functional annotation of the discovered variants in under study samples revealed that most SNPs (2,305,738; 48.78%) and indels (339,756; 49.03%) were located in intergenic regions. A comparison of the identified SNPs with those of the African camel (BioProject Accession: PRJNA269274) indicated that they had 993,474 SNPs in common. We found 15,168 non-synonymous SNPs in the shared variants of the three camels that could affect gene function and protein structure. Obtained results revealed that there were 7085, 6271 and 4688 non-synonymous SNPs among the 3436, 3058 and 2882 genes in the specific gene sets of Yazd dromedary, Trod dromedary and African dromedary, respectively. The list of genes predicted to be affected by non-synonymous variants in different individuals was subjected to gene ontology (GO) enrichment analysis.