Identification of candidate lethal haplotypes and recombination events in Nellore cattle

• Ano de defesa: 2020
• Autor(a) principal: Schmidt, Patrícia Iana
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Universidade Estadual Paulista (Unesp)
• Palavras-chave em Português: beef cattle; expected frequencies; haplotype phasing; homozygous individuals; paternal meiosis
• Link de acesso: http://hdl.handle.net/11449/193374

With genomic data, lethal recessives may be discovered from haplotypes that are common in the population but are never homozygous in live animals. In addition, it also allows the characterization of patterns and rates of recombination that are important for the understanding of genetic diversity throughout the genome. The objectives of the present study were to identify lethal haplotypes, based on expected population frequencies and to build a recombination map for identify the hotspots regions for the understanding of genetic diversity of this Nellore cattle population. Pedigree information comprised 2,688,124 animals and the conflict.f90 software was used to correct Mendelian errors and fill missing SNP using parental genotypes. A total of 4,447 Nellore animals were genotyped with a high-density panel (777,962 SNP markers) and 4,041 with a panel containing 74,677 markers. Map locations are from the ARS-UCD1.2 Bos taurus genome assembly. The haplotypes were constructed using the sliding windows method implemented in findhap.f90 software v3. Expected numbers of homozygous individuals were calculated through two methods: Simple - assuming random mating and using the number of individuals genotyped divided by 4 and multiplied by the square of the carrier frequency; and Mating - using the actual mating pattern for calculating the number of carrier service sire × carrier maternal grandsire matings divided by 4. Recombination rates were measured by an indirect method, extracting progeny-sire pairs from pedigree of Nellore cattle. Both, sire and offspring were genotyped and phased in order to infer about recombination events for a paternal meiosis. Hotspot regions were defined as SNP intervals with recombination rate > 2.5 standard deviations above the mean. Twenty-six haplotypes had high expected frequency but no homozygotes observed. Two haplotypes on chromosome 1:56,408,787-56,947,331 and on 21:22,003,502- 22,770,526 overlaps with previously known defects: Deficiency of Uridine Monophosphate Synthase and Brachyspina syndrome, respectively. Furthermore, the candidate lethal haplotypes on chromosome 7:52,418,587-53,136,816 and on chromosome 12:27,930,543-28,993,509 match with potential signatures of selection found previously in a similar population of Nellore cattle. For the functional analyses, we used SIFT scores to classify mutations as deleterious or tolerant. We found 55 candidate genes responsible for harboring the deleterious mutations and 11 genes with tolerant mutations. We extracted 21,391 crossover events and 659 paternal meiosis with an average number of crossovers per meiosis of 32.4 for Nellore males. There were found 520 hotspots regions, especially in chromosomes 1, 6 and 11, with the highest recombination rates. We have found 52 candidate genes underlying hotspot regions and associated GO terms related pathways. Some pathways as Lysine degradation, Pyruvate metabolism, Viral myocarditis, Basal transcription factors and GO terms related to transcription and translation processes, were found. The detection of lethal haplotypes, as well as the characterization of recombination events in a population, provide important information regarding genetic diversity throughout the genome for a further improvement of genetic gain.