Large family-based for chromosomal haplotype phasing. null

Inferring chromosome-level parental haplotypes and exact recombination sites is still a challenge. To date, no satisfying method has been reported to reach these goals. In this study, we whole genome sequenced a rabbit family with eight offspring. We processed the raw reads with standard pipelines using the OryCun3 reference genome sequence. After determining the SNPs, indels, and CNVs, we analyzed the inheritance of individual variations. Assuming the Mendelian inheritance laws, if one parent is a homozygous reference while the other is a homozygous alternate at a site, the children will be heterozygous. To investigate haplotypes and recombination sites, we studied sites where one parent is heterozygous (AB) while the other is homozygous (AA or BB, where A is the reference). Theoretically, half of the children will inherit the A allele, while the other half will inherit the B allele from the heterozygous parent. This means that if the homozygous parent had the reference (AA), we can divide the children into two groups according to their homozygous (AA) or heterozygous (AB) genotypes. These genotypes will also reflect the heterozygous parent’s haplotype. If we examine the next such (AB vs AA) variation along the chromosome, two cases can be observed: 1; precisely the same group of children are heterozygous than at the previous variation. 2; one child jumps from the heterozygous group into the homozygous group or vice versa. This means that a crossing-over event might have happened between the two examined variations in this child. In addition, at both cases, the consecutive inheritance of the group composition will determine the heterozygous parent’s haplotype. To deal with specific cases (badly called genotypes, homozygous ALT genotypes, etc.), we applied a window-based approach in our algorithm, which was implemented in the RecombiPos program (https://github.com/TravisCG/BUG/tree/main/recombipos). The RecombiPos program uses the VCF file of the parents and offspring to determine the crossing-over events in the children and the four parental haplotypes.