Characterization of runs of homozygosity in Gyr cattle genome
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Data
2017-02-17
Autores
Peripolli, Elisa [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
As corridas de homozigose, do inglês “Runs of homozygosity” (ROH), são segmentos homozigóticos contínuos que estão presentes em indivíduos e populações. A habilidade desses segmentos em elucidar sobre eventos genéticos populacionais torna-os uma ferramenta capaz de prover informações valiosas a respeito da evolução demográfica de uma população ao longo do tempo. Além disso, informações amplas do genoma fornecem subsídios relevantes para compreender a constituição genética de um animal por meio da caracterização dos ROH, constituindo uma metodologia acurada para manter a diversidade genética em diversas populações animais. O objetivo deste estudo foi (i) acessar a autozigosidade do genoma de bovinos da raça Gir Leiteiro a fim de caracterizar os padrões de ROH; (ii) prospectar genes em ROH compartilhados por mais de 50% da população, e por fim (iii) comparar as estimativas de endogamia calculadas a partir da proporção genômica em homozigose (FROH), da matriz genômica de parentesco G (FGRM) e do pedigree tradicional (FPED). Animais da raça Gir Leiteiro foram genotipados com o BovineHD BeadChip (Illumina Inc., San Diego, CA, USA) que contêm 777.962 SNPs (n=582), BovineSNP50 BeadChip (Illumina Inc., San Diego, CA, USA) contendo 54.609 SNPs (n=1664) e GGP-LD Indicus (Geneseek® Genomic Profiler Indicus 30K) que contêm 27.533 SNPs (n=662). Todos os genótipos foram imputados para o painel BovineHD BeadChip (Illumina Inc., San Diego, CA, USA). SNPs sem posição definida ou mapeados nos cromossomos sexuais foram removidos do conjunto de dados. Após a edição, 2908 animais e 735,236 SNPs foram mantidos para as análises. Os ROH foram identificados por meio do software PLINK v1.07 considerando os seguintes parâmetros: uma janela deslizante de 50 SNPs, o número mínimo de SNPs consecutivos incluídos em um ROH foi 100, o comprimento mínimo de um ROH foi ajustado para 1 Mb, o intervalo máximo entre SNPs homozigóticos consecutivos foi de 500 kb, uma densidade de 1 SNP por 50 kb, cinco SNPs com genótipos faltantes e um genótipo heterozigoto. O FPED foi estimado por meio do software INBUPGF90. Para cada animal foi calculado um FROH (FROH1-2 Mb, FROH2-4 Mb, FROH4-8 Mb, FROH8-16 Mb e FROH>16 Mb) com base na distribuição de ROH a partir de cinco comprimentos (ROHj): 1-2, 2-4, 4-8, 8-16 e > 16 Mb, respectivamente. O FGRM foi calculado a partir da diagonal da matriz de relação genômica (G). Os ROH foram identificados em todos os animais, apresentando um número médio de 55,12±10,37 segmentos por animal e um comprimento médio de 3,17 Mb. Segmentos curtos (ROH1-2 Mb) foram abundantes nos genomas, representando cerca de 60% de todos os segmentos identificados, no entanto, cobriram apenas uma pequena proporção do genoma. Nossos resultados demonstraram que em média 7,01% (175,28 Mb) do genoma dessa população é autozigótico. As estimativas de FPED variaram de 0,000 a 0,327 e as de FROH de 0,001 a 0,201. Correlações baixas a moderadas foram observadas entre as estimativas de FPED-FROH e FGRM-FROH, com valores entre -0,16 e 0,59. As correlações entre FROH de diferentes comprimentos e FPED aumentaram com comprimento dos ROH. ROH compartilhados por mais de 50% das amostras foram classificados como ilhas de ROH. Quatorze ilhas de ROH foram identificadas e diversos genes contidos nessas ilhas foram associados com o teor de gordura do leite (DGAT1, CYP11B, EEF1D, INSIG2 e STAT1), involução da glândula mamária (IGFBP7), lactação (CHR e TRAPPC9) e adaptação ao calor (HSF1). Nossos resultados sugerem que (i) as baixas correlações (r<0.44) entre FPED-FROH para segmentos pequenos indicam que o FPED não é adequado para capturar eventos remotos de endogamia. As correlações moderadas (r>0.44) entre segmentos grandes indica que os níveis de autozigosidade derivados dos ROH podem ser utilizados como uma estimativa acurada dos níveis de endogamia; e (ii) ROH podem ser utilizados para identificar regiões genômicas sob seleção, uma vez que várias regiões compartilhadas estavam associadas com características de leite e adaptação.
Runs of homozygosity (ROH) are continuous homozygous segments that are common in individuals and populations. The ability of these segments to give insight into a population's genetic events makes them a useful tool to provide information about the demographic evolution of a population over time. Additionally, genome-wide information provides valuable information to comprehend the animal’s genome based on ROH, being and accurate tool to maintain diversity and fitness in livestock populations. The aim of this study was (i) to access genome-wide autozygosity to identify and characterize ROH patterns in Gyr dairy cattle genome; (ii) identify ROH islands for gene content and enrichment in segments shared by more than 50% of the samples, and (iii) compare estimates of molecular inbreeding calculated from ROH (FROH), GRM approach (FGRM), and from pedigree-based coefficient (FPED). Gyr dairy animals were genotyped with the BovineHD BeadChip (Illumina Inc., San Diego, CA, USA), that contains 777,962 bialleleic SNPs markers (n=582); the BovineSNP50 BeadChip (Illumina Inc., San Diego, CA, USA), containing 54,609 SNPs (n=1664); and with the GGP-LD Indicus (Geneseek® Genomic Profiler Indicus 30K), that contains 27,533 bialleleic SNPs markers (n=662). All genotypes were imputed to the BovineHD BeadChip (Illumina Inc., San Diego, CA, USA). SNPs unsigned to any chromosome and mapped to sexual chromosomes were removed from the dataset. After editing, 2908 animals and 735,236 SNPs were retained for the analyses. ROH were identified using PLINK v1.07 considering the following parameters: a sliding window of 50 SNPs, the minimum number of consecutive SNPs included in a ROH was 100, the minimum length of a ROH was set to 1 Mb, the maximum gap between consecutive homozygous SNPs was 500 kb, a density of 1 SNP per 50 kb, and a maximum of five SNPs with missing genotypes and up to one heterozygous genotype were allowed in a ROH. FPED was estimated through the software INBUPGF90. For each animal FROH (FROH1-2 Mb, FROH2-4 Mb, FROH4-8 Mb, FROH8-16 Mb, and FROH>16 Mb) was calculated based on ROH distribution of five minimum different lengths (ROHj): 1-2, 2-4, 4-8, 8-16, and >16 Mb, respectively. FGRM was calculated from the diagonal of the genomic relationship matrix (G). ROH were identified in all animals, with an average number of 55.12±10.37 segments and a mean length of 3.17 Mb. Short segments (ROH1-2 Mb) were abundant through the genomes, accounting for 60% of all segments identified, however, they just covered a small proportion of the genome. Our results suggest that on average 7.01% (175.28Mb) of the genome of this population is autozygous. FPED estimates ranged from 0.000 to 0.327 and FROH from 0.001 to 0.201. Low to moderate correlations were observed between FPED-FROH and FGRM-FROH, with values ranging from -0.16 to 0.59. Correlations between FROH from different lengths and FPED increased with ROH length. ROH shared by more than 50% of the samples were chosen as an indication of a possible ROH islands throughout the genome, and 14 regions were identified. Several genes inside those ROH islands were associated with milk fat content (DGAT1, CYP11B, EEF1D, INSIG2, and STAT1), mammary gland involution (IGFBP7), lactation (CHR and TRAPPC9), and heat adaptation (HSF1). Our results suggest that (i) low correlations (r<0.44) between FPED-FROH for small segments indicate that FPED estimates are not the most suitable method to capture ancient inbreeding. Moderate correlations (r>0.44) between larger ROH indicate that the levels of autozygosity derived from ROH can be used as an accurate estimator of individual inbreeding levels, and (ii) ROH might be used to identify genomic regions under selection as several overlapping regions were associated with dairy and adaptive traits.
Runs of homozygosity (ROH) are continuous homozygous segments that are common in individuals and populations. The ability of these segments to give insight into a population's genetic events makes them a useful tool to provide information about the demographic evolution of a population over time. Additionally, genome-wide information provides valuable information to comprehend the animal’s genome based on ROH, being and accurate tool to maintain diversity and fitness in livestock populations. The aim of this study was (i) to access genome-wide autozygosity to identify and characterize ROH patterns in Gyr dairy cattle genome; (ii) identify ROH islands for gene content and enrichment in segments shared by more than 50% of the samples, and (iii) compare estimates of molecular inbreeding calculated from ROH (FROH), GRM approach (FGRM), and from pedigree-based coefficient (FPED). Gyr dairy animals were genotyped with the BovineHD BeadChip (Illumina Inc., San Diego, CA, USA), that contains 777,962 bialleleic SNPs markers (n=582); the BovineSNP50 BeadChip (Illumina Inc., San Diego, CA, USA), containing 54,609 SNPs (n=1664); and with the GGP-LD Indicus (Geneseek® Genomic Profiler Indicus 30K), that contains 27,533 bialleleic SNPs markers (n=662). All genotypes were imputed to the BovineHD BeadChip (Illumina Inc., San Diego, CA, USA). SNPs unsigned to any chromosome and mapped to sexual chromosomes were removed from the dataset. After editing, 2908 animals and 735,236 SNPs were retained for the analyses. ROH were identified using PLINK v1.07 considering the following parameters: a sliding window of 50 SNPs, the minimum number of consecutive SNPs included in a ROH was 100, the minimum length of a ROH was set to 1 Mb, the maximum gap between consecutive homozygous SNPs was 500 kb, a density of 1 SNP per 50 kb, and a maximum of five SNPs with missing genotypes and up to one heterozygous genotype were allowed in a ROH. FPED was estimated through the software INBUPGF90. For each animal FROH (FROH1-2 Mb, FROH2-4 Mb, FROH4-8 Mb, FROH8-16 Mb, and FROH>16 Mb) was calculated based on ROH distribution of five minimum different lengths (ROHj): 1-2, 2-4, 4-8, 8-16, and >16 Mb, respectively. FGRM was calculated from the diagonal of the genomic relationship matrix (G). ROH were identified in all animals, with an average number of 55.12±10.37 segments and a mean length of 3.17 Mb. Short segments (ROH1-2 Mb) were abundant through the genomes, accounting for 60% of all segments identified, however, they just covered a small proportion of the genome. Our results suggest that on average 7.01% (175.28Mb) of the genome of this population is autozygous. FPED estimates ranged from 0.000 to 0.327 and FROH from 0.001 to 0.201. Low to moderate correlations were observed between FPED-FROH and FGRM-FROH, with values ranging from -0.16 to 0.59. Correlations between FROH from different lengths and FPED increased with ROH length. ROH shared by more than 50% of the samples were chosen as an indication of a possible ROH islands throughout the genome, and 14 regions were identified. Several genes inside those ROH islands were associated with milk fat content (DGAT1, CYP11B, EEF1D, INSIG2, and STAT1), mammary gland involution (IGFBP7), lactation (CHR and TRAPPC9), and heat adaptation (HSF1). Our results suggest that (i) low correlations (r<0.44) between FPED-FROH for small segments indicate that FPED estimates are not the most suitable method to capture ancient inbreeding. Moderate correlations (r>0.44) between larger ROH indicate that the levels of autozygosity derived from ROH can be used as an accurate estimator of individual inbreeding levels, and (ii) ROH might be used to identify genomic regions under selection as several overlapping regions were associated with dairy and adaptive traits.
Descrição
Palavras-chave
Autozigosidade, Bos indicus, Diversidade genética, Endogamia, Autozygosity, Bos indicus, Genetic diversity, Inbreeding