Analysis of runs of homozygosity and their relationship with inbreeding in five cattle breeds farmed in Italy

Abstract

Increased inbreeding is an inevitable consequence of selection in livestock populations. The analysis of high-density single nucleotide polymorphisms (SNPs) facilitates the identification of long and uninterrupted runs of homozygosity (ROH) that can be used to identify chromosomal regions that are identical by descent. In this work, the distribution of ROH of different lengths in five Italian cattle breeds is described. A total of 4095 bulls from five cattle breeds (2093 Italian Holstein, 749 Italian Brown, 364 Piedmontese, 410 Marchigiana and 479 Italian Simmental) were genotyped at 54K SNP loci. ROH were identified and used to estimate molecular inbreeding coefficients (FROH ), which were compared with inbreeding coefficients estimated from pedigree information (FPED ) and using the genomic relationship matrix (FGRM ). The average number of ROH per animal ranged from 54 ± 7.2 in Piedmontese to 94.6 ± 11.6 in Italian Brown. The highest number of short ROH (related to ancient consanguinity) was found in Piedmontese, followed by Simmental. The Italian Brown and Holstein had a higher proportion of longer ROH distributed across the whole genome, revealing recent inbreeding. The FPED were moderately correlated with FROH > 1 Mb (0.662, 0.700 and 0.669 in Italian Brown, Italian Holstein and Italian Simmental respectively) but poorly correlated with FGRM (0.134, 0.128 and 0.448 for Italian Brown, Italian Holstein and Italian Simmental respectively). The inclusion of ROH > 8 Mb in the inbreeding calculation improved the correlation of FROH with FPED and FGRM . ROH are a direct measure of autozygosity at the DNA level and can overcome approximations and errors resulting from incomplete pedigree data. In populations with high linkage disequilibrium (LD) and recent inbreeding (e.g. Italian Holstein and Italian Brown), a medium-density marker panel, such as the one used here, may provide a good estimate of inbreeding. However, in populations with low LD and ancient inbreeding, marker density would have to be increased to identify short ROH that are identical by descent more precisely.

Genomic inbreeding estimation in small populations: evaluation of runs of homozygosity in three local dairy cattle breeds

“…In a previous study on Italian Holstein, Gaspa et al (2014) identified an interesting region of~2 Mb on BTA26 that harbors some genes involved in the metabolism of mammary gland. Similar values were reported by Marras et al (2014) in Italian Simmental and local Marchigiana cattle breeds.…”

“…Ferenčaković et al (2013a) found higher number of ROH in four analyzed cattle breeds probably because of the shorter length considered to define the ROH (>1 Mb). Similar results of F ROH > 4 Mb were reported by Ferenčaković et al (2013b) using a 50K panel for Pinzgauer (0.037) and Tyrol Grey (0.042) local cattle breeds, and by Marras et al (2014) in Marchigiana (0.046) beef cattle breed. Differences among breeds existed also for the ROH length.…”

“…In all breeds, most ROH segment coverage was in the shorter length categories (4 to 8 Mb), in particular Modicana (51%) and Italian Holstein (50%) ( Table 3). In fact, as reported in studies of ROH in human (Kirin et al, 2010) and cattle populations (Ferenčaković et al, 2013a;Marras et al, 2014) longer ROH were found less frequently than shorter ones. The expected length of autozygous segments that are IBD follows an exponential distribution with mean equal to 1/2g Morgans, where g is the number of generations since the common ancestor (Howrigan et al, 2011).…”

“…In fact, the same authors showed that allowing certain minimum numbers of heterozygous SNPs leads to inaccurate ROH calls, in particular at the ends of ROH. Marras et al (2014), in a study of ROH using medium-density chip, reported that when heterozygous SNPs were allowed, the number of longer ROH increased dramatically, and preferred not to use them in the ROH. Therefore, considering that in our study medium-density SNP data were used, and that the longest segment was below 2000 SNPs, only one heterozygous SNP was allowed in the ROH in order to avoid underestimation of long ROH.…”

“…In addition, chromosomal (BTA) F ROH (F ROHBTA ) values were also estimated for each breed, as F ROHBTA = L ROHBTA /L BTA (Silió et al, 2013), in which L ROHBTA is the total length of an individual's ROH in each BTA and L BTA is the length of each chromosome covered by the involved SNPs (Supplementary Table S1). ROH were classified into three classes (4 to 8, 8 to 16 and >16 Mb) using the same nomenclature reported by other authors (Ferenčaković et al, 2013a;Marras et al, 2014) except for two classes (<2 and 2 to 4 Mb), which were not considered in our study. The number and percentage of ROH within each ROH length category for breed were also determined.…”