Abstract #W56

# W56
Milk fatty acid profile of 32 inbred mice strains and in silico genome-wide association analysis to locate significant SNP associated with fatty acid variability.
C. I. Matamoros*1, K. E. Robinson1, D. L. Hadsell2,3, K. J. Harvatine1, 1Department of Animal Science, The Pennsylvania State University, University Park, PA, 2USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX.

Considerable variation in maternal ability and milk fat concentration has been reported between mouse strains (Mus musculus). Differences in milk fatty acid (FA) profile, including the FA synthesized de novo in the mammary gland, has not been well investigated. Our objective was to characterize the FA profile of different inbred strains and utilize genomic data to determine single nucleotide polymorphisms (SNP) that influence FA profile. For this objective, 32 mice strains from the mouse diversity panel were utilized and crossbred with CD-1 males. At 1 d postpartum litters were replaced with 10 one-day-old CD1 pups to standardize size and genetic background of litter and milk samples were collected at d 10. Milk FA were extracted with hexane:isopropanol, transmethylated with sodium methoxide, and quantified by GC. Distribution analysis was conducted in JMP Pro 13 and genome-wide association analysis was done in R (ver. 3.5.1) with EMMA package. Association analysis was conducted with 325,015 SNP that were filtered from the Broad2 and CGD-MDA1 data sets (minor allele frequency >0.05, no call rate <0.2, and removal of the Y chromosome and mitochondrial variants). Population structure effect was corrected by utilizing a kinship matrix of the strains in the association analysis. A genome-wide threshold of 1 × 10−6 was used to identify significant SNP. There was a wide distribution in the concentration of de novo [<16 C; mean = 29.92, 95% CI (30.45, 29.39), Range (15.88, 45.80)], mixed [16 C; mean = 28.51, 95% CI (28.92, 28.11), Range (19.58, 43.15)], and preformed FA [>16 C; mean = 38.53, 95% CI (38.97, 38.10), Range (54.22, 28.92)]. From 1,648 significant SNP, a strong signal (P = 5 × 10−9) in chromosome 2 associated with many de novo FA was identified in position 3–4 mbp. In-depth analysis shows that thioesterase II (Olah), an enzyme in mammary de novo lipogenesis, resides in that region. There is a wide variation in milk fat concentration between strains and differences in de novo FA are associated with specific genetic differences.

Key Words: milk fat, genome-wide association study (GWAS), Olah