Population validation of reproductive gene mutation loci and association with the litter size in Nubian goat.

Litter size is an important component trait of doe reproduction. By improving it, production efficiency and economic benefits can be significantly provided. Genetic marker-assisted selection (MAS) based on proven molecular indicators could enhance the efficacy of goat selection, as well as litter size trait. Many molecular markers have been identified that they can be used to improve litter size in different goat breeds. However, the presence and value of these markers vary among goat breeds. In the present study, we used the reported loci on other breeds of goat as candidate loci to detect whether these loci appear in this Nubian goat population; then we proceed to genotype and detect surrounding loci (50 bp) by multiplex PCR and sequencing technology. As a result, 69 mutations (59 SNPs and 10 indels) were screened out from 23 candidate genes in Nubian goat population, 12 loci were significantly associated with the litter size of first-parity individuals; 5 loci were significantly associated with the litter size of second-parity individuals; 3 loci were significantly associated with the litter size of third-parity individuals. In addition, five loci were significantly associated with the average litter size. The additive effect value of KITLG: g.18047318 G $>$ A in first parity, KITLG: g.18152042G $>$ A in third parity, KISS-1: g.1341674 C $>$ G in first parity, and GHR: g.32134187G $>$ A in second parity exceed more than 0.40, and the preponderant alleles are G, C, A and G, respectively. Further, linkage disequilibrium analysis of 21 mutation loci shows that 3 haplotype blocks are formed, and the litter size of combination type AACC in KISS-1 gene and AAGG in KITLG gene are significantly lower than that of other combinations genotype in first parity ( $P<0.05$ ). These findings can provide effective candidate DNA markers for selecting superior individuals in Nubian goat breeding.