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Comparative evaluation of genomic inbreeding parameters in seven commercial and autochthonous pig breeds
- G. Schiavo, S. Bovo, F. Bertolini, S. Tinarelli, S. Dall’Olio, L. Nanni Costa, M. Gallo, L. Fontanesi
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Single nucleotide polymorphism (SNP) genotyping tools, which can analyse thousands of SNPs covering the whole genome, have opened new opportunities to estimate the inbreeding level of animals directly using genome information. One of the most commonly used genomic inbreeding measures considers the proportion of the autosomal genome covered by runs of homozygosity (ROH), which are defined as continuous and uninterrupted chromosome portions showing homozygosity at all loci. In this study, we analysed the distribution of ROH in three commercial pig breeds (Italian Large White, n = 1968; Italian Duroc, n = 573; and Italian Landrace, n = 46) and four autochthonous breeds (Apulo-Calabrese, n = 90; Casertana, n = 90; Cinta Senese, n = 38; and Nero Siciliano, n = 48) raised in Italy, using SNP data generated from Illumina PorcineSNP60 BeadChip. We calculated ROH-based inbreeding coefficients (FROH) using ROH of different minimum length (1, 2, 4, 8, 16 Mbp) and compared them with several other genomic inbreeding coefficients (including the difference between observed and expected number of homozygous genotypes (FHOM)) and correlated all these genomic-based measures with the pedigree inbreeding coefficient (FPED) calculated for the pigs of some of these breeds. Autochthonous breeds had larger mean size of ROH than all three commercial breeds. FHOM was highly correlated (0.671 to 0.985) with FROH measures in all breeds. Apulo-Calabrese and Casertana had the highest FROH values considering all ROH minimum lengths (ranging from 0.273 to 0.189 and from 0.226 to 0.152, moving from ROH of minimum size of 1 Mbp (FROH1) to 16 Mbp (FROH16)), whereas the lowest FROH values were for Nero Siciliano (from 0.072 to 0.051) and Italian Large White (from 0.117 to 0.042). FROH decreased as the minimum length of ROH increased for all breeds. Italian Duroc had the highest correlations between all FROH measures and FPED (from 0.514 to 0.523) and between FHOM and FPED (0.485). Among all analysed breeds, Cinta Senese had the lowest correlation between FROH and FPED. This might be due to the imperfect measure of FPED, which, mainly in local breeds raised in extensive production systems, cannot consider a higher level of pedigree errors and a potential higher relatedness of the founder population. It appeared that ROH better captured inbreeding information in the analysed breeds and could complement pedigree-based inbreeding coefficients for the management of these genetic resources.
Invited review: Bioinformatic methods to discover the likely causal variant of a new autosomal recessive genetic condition using genome-wide data
- G. E. Pollott
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In animals, new autosomal recessive genetic diseases (ARGD) arise all the time due to the regular, random mutations that occur during meiosis. In order to reduce the effect of any damaging new variant, it is necessary to find its cause. To evaluate the best way of doing this, 34 papers which found the exact location of a new genetic disease in livestock were reviewed and found to require at least two stages. In the initial stage the commonly used χ2 method, applied in a case-control association analysis with single nucleotide polymorphism (SNP)-chip data, was found to have limitations and was almost always used in conjunction with a second method to locate the target region on the genome containing the variant. The commonly used methods had their drawbacks; so a new method was devised based on long runs of homozygosity, a common feature of new ARGD. This ‘autozygosity by difference’ method was found to be as good as, or better than, all the reviewed methods tested based on its ability to unambiguously find the shortest known target region in an already analysed data set. Mean target region length was found to be 4.6 megabases in the published reports. Success did not depend on the size of commercial SNP-chip used, and studies with as few as three cases and four controls were large enough to find the target region. The final stage relied on either sequencing the candidate genes found in the target region or using whole genome sequencing (WGS) on a small number of cases. Sometimes this latter method was used in conjunction with WGS on a number of control animals or resources such as the 1000 bull genomes data. Calculations showed that, in cattle, less than 15 animals would be needed in order to locate the new variant when using WGS data. This could be any combination of cases plus parents or other unrelated animals in the breed. Using WGS data, it would be necessary to search the three billion bases of the cattle genome for base positions which were homozygous for the same allele in all cases and heterozygous for that allele in parents, or not containing that homozygote in unrelated controls. This site could be confirmed on other healthy animals using much cheaper methods, and then a genetic test could be devised for that variant in order to screen the whole population and to devise a breeding programme to eliminate the disorder from the population.
Genomic inbreeding estimation in small populations: evaluation of runs of homozygosity in three local dairy cattle breeds
- S. Mastrangelo, M. Tolone, R. Di Gerlando, L. Fontanesi, M. T. Sardina, B. Portolano
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In the local breeds with small population size, one of the most important problems is the increase of inbreeding coefficient (F). High levels of inbreeding lead to reduced genetic diversity and inbreeding depression. The availability of high-density single nucleotide polymorphism (SNP) arrays has facilitated the quantification of F by genomic markers in farm animals. Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes and represent an estimate of the degree of autozygosity at genome-wide level. The current study aims to quantify the genomic F derived from ROH (FROH) in three local dairy cattle breeds. FROH values were compared with F estimated from the genomic relationship matrix (FGRM), based on the difference between observed v. expected number of homozygous genotypes (FHOM) and the genomic homozygosity of individual i (FMOL i). The molecular coancestry coefficient (fMOL ij) between individuals i and j was also estimated. Individuals of Cinisara (71), Modicana (72) and Reggiana (168) were genotyped with the 50K v2 Illumina BeadChip. Genotypes from 96 animals of Italian Holstein cattle breed were also included in the analysis. We used a definition of ROH as tracts of homozygous genotypes that were >4 Mb. Among breeds, 3661 ROH were identified. Modicana showed the highest mean number of ROH per individual and the highest value of FROH, whereas Reggiana showed the lowest ones. Differences among breeds existed for the ROH lengths. The individuals of Italian Holstein showed high number of short ROH segments, related to ancient consanguinity. Similar results showed the Reggiana with some extreme animals with segments covering 400 Mb and more of genome. Modicana and Cinisara showed similar results between them with the total length of ROH characterized by the presence of large segments. High correlation was found between FHOM and FROH ranged from 0.83 in Reggiana to 0.95 in Cinisara and Modicana. The correlations among FROH and other estimated F coefficients were generally lower ranged from 0.45 (FMOL i−FROH) in Cinisara to 0.17 (FGRM−FROH) in Modicana. On the basis of our results, recent inbreeding was observed in local breeds, considering that 16 Mb segments are expected to present inbreeding up to three generations ago. Our results showed the necessity of implementing conservation programs to control the rise of inbreeding and coancestry in the three Italian local dairy cattle breeds.