Identification of candidate lethal haplotypes and genomic association with post-natal mortality and reproductive traits in Nellore cattle.

The wide use of genomic information has enabled the identification of lethal recessive alleles that are the major genetic causes of reduced conception rates, longer calving intervals, or lower survival for live-born animals. This study was carried out to screen the Nellore cattle genome for lethal recessive haplotypes based on deviation from the expected population homozygosity, and to test SNP markers surrounding the lethal haplotypes region for association with heifer rebreeding (HR), post-natal mortality (PNM) and stayability (STAY). This approach requires genotypes only from apparently normal individuals and not from affected embryos. A total of 62,022 animals were genotyped and imputed to a high-density panel (777,962 SNP markers). Expected numbers of homozygous individuals were calculated, and the probabilities of observing 0 homozygotes was obtained. Deregressed genomic breeding values [(G)EBVs] were used in a GWAS to identify candidate genes and biological mechanisms affecting HR, STAY and PNM. In the functional analyses, genes within 100 kb down and upstream of each significant SNP marker, were researched. Thirty haplotypes had high expected frequency, while no homozygotes were observed. Most of the alleles present in these haplotypes had a negative mean effect for PNM, HR and STAY. The GWAS revealed significant SNP markers involved in different physiological mechanisms, leading to harmful effect on the three traits. The functional analysis revealed 26 genes enriched for 19 GO terms. Most of the GO terms found for biological processes, molecular functions and pathways were related to tissue development and the immune system. More phenotypes underlying these putative regions in this population could be the subject of future investigation. Tests to find putative lethal haplotype carriers could help breeders to eliminate them from the population or manage matings in order to avoid homozygous.

Single nucleotide variants and InDels identified from whole-genome re-sequencing of Guzerat, Gyr, Girolando and Holstein cattle breeds.

Whole-genome re-sequencing, alignment and annotation analyses were undertaken for 12 sires representing four important cattle breeds in Brazil: Guzerat (multi-purpose), Gyr, Girolando and Holstein (dairy production). A total of approximately 4.3 billion reads from an Illumina HiSeq 2000 sequencer generated for each animal 10.7 to 16.4-fold genome coverage. A total of 27,441,279 single nucleotide variations (SNVs) and 3,828,041 insertions/deletions (InDels) were detected in the samples, of which 2,557,670 SNVs and 883,219 InDels were novel. The submission of these genetic variants to the dbSNP database significantly increased the number of known variants, particularly for the indicine genome. The concordance rate between genotypes obtained using the Bovine HD BeadChip array and the same variants identified by sequencing was about 99.05%. The annotation of variants identified numerous non-synonymous SNVs and frameshift InDels which could affect phenotypic variation. Functional enrichment analysis was performed and revealed that variants in the olfactory transduction pathway was over represented in all four cattle breeds, while the ECM-receptor interaction pathway was over represented in Girolando and Guzerat breeds, the ABC transporters pathway was over represented only in Holstein breed, and the metabolic pathways was over represented only in Gyr breed. The genetic variants discovered here provide a rich resource to help identify potential genomic markers and their associated molecular mechanisms that impact economically important traits for Gyr, Girolando, Guzerat and Holstein breeding programs.