Whole Genome Sequencing and Progress Toward Full Inbreeding of the Mouse Collaborative Cross Population

Author:

Shorter John R1,Najarian Maya L2,Bell Timothy A13,Blanchard Matthew1,Ferris Martin T1,Hock Pablo1,Kashfeen Anwica2,Kirchoff Kathryn E2,Linnertz Colton L1,Sigmon J Sebastian2,Miller Darla R1,McMillan Leonard2,Pardo-Manuel de Villena Fernando13

Affiliation:

1. Department of Genetics

2. Department of Computer Science, and

3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599

Abstract

Abstract Two key features of recombinant inbred panels are well-characterized genomes and reproducibility. Here we report on the sequenced genomes of six additional Collaborative Cross (CC) strains and on inbreeding progress of 72 CC strains. We have previously reported on the sequences of 69 CC strains that were publicly available, bringing the total of CC strains with whole genome sequence up to 75. The sequencing of these six CC strains updates the efforts toward inbreeding undertaken by the UNC Systems Genetics Core. The timing reflects our competing mandates to release to the public as many CC strains as possible while achieving an acceptable level of inbreeding. The new six strains have a higher than average founder contribution from non-domesticus strains than the previously released CC strains. Five of the six strains also have high residual heterozygosity (>14%), which may be related to non-domesticus founder contributions. Finally, we report on updated estimates on residual heterozygosity across the entire CC population using a novel, simple and cost effective genotyping platform on three mice from each strain. We observe a reduction in residual heterozygosity across all previously released CC strains. We discuss the optimal use of different genetic resources available for the CC population.

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology

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