Genome-wide association study for female fertility in Nordic Red cattle

Background: The Nordic Red Cattle (NRC) consists of animls belonging to the Danish Red, Finnish Ayrshire, and Swedish Red breeds. Compared to the Holstein breed, NRC animals are smaller, have a shorter calving interval, lower mastitis incidence and lower rates of stillborn calves, however they produce less milk, fat and protein. Female fertility is an important trait for the dairy cattle farmer. Selection decisions in female fertilty in NRC are based on the female fertility index (FTI). FTI is a composite index including a number of sub-indices describing aspects of female fertility in dairy cattle. The sub-traits of FTI are: number of inseminations per conception (AIS) in cows (C) and heifers (H), the length in days of the interval from calving to first insemination (ICF) in cows, days from first to last insemination (IFL) in cows and heifers, and 56-day non-return rate (NRR) in cows and heifers. The aim of this study was first to identify QTL for FTI by conducting a genome scan for variants associated with fertility index using imputed whole genome sequence data based on 4207 Nordic Red sires, and subsequently analyzing which of the sub-traits were affected by each FTI QTL by associating them with the sub-traits. Results: A total 17,388 significant SNP markers (-log(10)(P) > 8.25) were detected for FTI distributed over 25 chromosomes. The chromosomes with the most significant markers were tested for associations with the underlying sub-traits: BTA1 (822 SNP), BTA2 (220 SNP), BTA3 (83 SNP), BTA5 (195 SNP), two regions on BTA6 (503 SNP), BTA13 (980 SNP), BTA15 (23 SNP), BTA20 (345 SNP), and BTA24 (104 SNP). The fertility traits underlying the FTI peak area were: BTA1 (IFLC, IFLH), BTA2 (AISH, IFLH, NRRH), BTA3 (AISH, NRRH), BTA5 (AISC, AISH, IFLH), BTA6 (region 1: AISH, NRRH; region 2: AISH, IFLH), BTA13 (IFLH, IFLC), BTA15 (IFLC, NRRH), and BTA24 (AISH, IFLH). For BTA20 all sub-traits had SNP markers with a -log10(P) > 10. Furthermore the genes assigned to the most significant SNP for FTI were located on BTA6 (GPR125), BTA13 (ANKRD60), BTA15 (GRAMD1B), and BTA24 (ZNF521). Conclusion: This study 1) shows that many markers within FTI QTL regions were significantly associated with both AISH and IFLH, and 2) identified candidate genes for FTI located on BTA6 (GPR125), BTA13 (ANKRD60), BTA15 (GRAMD1B), and BTA24 (ZNF521). It is not known how the genes/variants identified in this study regulate female fertility, however the majority of these genes were involved in protein binding, 3) a SNP in a QTL region for FTI on BTA20 was previously validated in three cattle breeds.