Hi-C for the detection and characterization of chromosomal rearrangements in cattle
Résumé
Recently, a new approach has been developed to detect inter-chromosomal rearrangements in cattle. This method is based on the detection of abnormal linkage disequilibrium patterns between markers located on different chromosomes in large paternal half-sib families genotyped as part of routine genomic evaluations (Jourdain et al., Genome Res. 2023 Jun; 33(6)). This method allowed to identify 12 inter-chromosomal rearrangements including, for the first time in cattle, an insertional translocation between the BTA4 and BTA8. In order to characterize this rearrangement more precisely, Hi-C experiments were carried out on a heterozygous carrier using the Arima kit. Examination of the entire Hi-C matrix revealed ectopic interactions between BTA4 and BTA8 confirming the translocation of a part of BTA4 into BTA8. The BTA4 Hi-C matrix showed an increase in interactions of regions flanking the translocated segment indicating a deletion of this segment. Analysis of the BTA8 matrix showed a decrease in chromosomal interactions compared to a normal individual at the breakpoint position confirming the insertion of BTA4 material into this region.
More unexpectedly, analysis of the BTA8 matrix revealed a characteristic butterfly pattern indicating a heterozygous inversion of a 17Mb region (breakpoints located around 11,250kb and 27,900kb). This inversion was not previously detected by the interchromosomal linkage disequilibrium analysis.
Our results demonstrate the interest of the Hi-C for the detection and characterization of chromosomal rearrangements. Further analysis (capture-HiC and phasing) are planned to study the impact of this abnormality on the 3D organization and function of the genome