# Survey of SNPs Associated with Total Number Born and Total Number Born Alive in Pig
## 4 Potential Candidate Genes for Litter Traits of Pig
Thus, rs80927364 (intron variant _DDAHI_) on SSC4, rs81434499 (intergenic variant) on SSC12, rs81447100 (intron variant _CLSTN2_) on SSC13 showed significant associations with TNB and NBA in the studies of [PERSON] et al. [8] and [PERSON] et al. [28] respectively. The _DDAHI_ gene (dimethylarginine dimethylaminohydrolase 1), along with other _DDAH_ genes, is involved in the metabolic control of asymmetric dimethylarginine (ADMA), contributes to the maintenance of vascular homeostasis due to the expansion of blood vessels, suppression of inflammation and inhibiting vascular smooth muscle cells, adhesion and aggregation of platelets [51; 52; 53]. Data onthe metabolic control of ADMA by _DDAH_ genes and their effect on endothelial cells were obtained in animal studies. Transgenic mice with overexpression of _DDAH1_ showed a twofold decrease of ADMA in plasma, associated with a twofold increase of NOS activity in tissue [54]. Conversely, the _DDAH1_ Knock Out Mice exhibited increased pulmonary endothelial permeability as a result of increased ADMA, which was prevented by over-expression of _DDAH1_ and _DDAH2_ in endothelial cells [55]. _CLSTN2_ (calsintenin 2) is associated with obesity in mammals, especially in the process of increasing adipocytes in visceral tissues and in subcutaneous fat [56]. [PERSON] et al. [57] defined _CLSTN2_ as a candidate gene associated with ultrasound-derived measurements of the rib-eye area, backfat thickness and rumpfat thickness in Nellore cattle. Adipose tissue is an active endocrine organ and proteins involved in forming adipose tissue is increasingly attracting attention as mammalian reproduction markers [58; 59]. We can also note SNPs rs81463092 (intergenic variant) and rs81289648 (intergenic variant) defined in the works of [PERSON] et al. [8] and [PERSON] et al. [28], localized on SSC16 and lying in close proximity to each other (68 kb). The table shows the intervals between neighboring SNPs (add file 1). Hence, we can note a number of closely related SNPs identified in various studies. For example, rs55618224 (3 prime UTR variant) and rs81388947 (intergenic variant) on SSC6 are defined by [PERSON] et al. [33] and [PERSON] et al. [27] and the interval between them is 140 kb. SNP rs336670754 (synonymous variant _ARIDIA_) and SNP rs329711941 (intron variant _ZDHHC18_) are located at a distance of about 39 kb from each other, defined on SSC6 by [PERSON] et al., (2019) and [PERSON] et al. [29] respectively. On the whole, we can note that SNPs presented in PigQTLdb as associations with TNB and NBA are more localized in genes (intron variant 60%). Wherein that, 15% are intergenic variants and this can be considered as an evidence of significance for intergenic variants in the genetic architecture of reproductive traits (add file 2). In conclusion, we wanted to estimate the gene-based protein-protein interactions obtained with the studied SNPs being localized. The total number of genes was 127, but only 40 genes formed some pairs or chains (Figure 1). It is interesting that some chains are composed of genes (SNPs) identified in only one study (add file 3). For example, _RBP7_, _LRRK1_, _UBE4B_, _TRPC5_, _LHFPL1_ genes were identified by [PERSON] et al. [26]; _DLC1_, _SEMA3A_, _DPYSL3_, _NRPI_ by [PERSON] et al. [8] similarly. However, the other chains includes genes identified in various studies such as _GRIA4_[8], _CLSTN2_[8], _GRIP1_[28], _GABRA5_[22], _UBE3A_[22], _COPG2_[22], _ANKRD40_[8], _MYO10_[7], _SHISA9_[8]. The presented review shows that most SNPs annotated from genome-wide studies are found in chromosome regions where candidate genes or QTLs have already been identified. Future research will be aimed at annotating sequences and analyzing these data, which can contribute to better understanding the mechanisms of reproductive traits formation. However, the main problem in summarizing the results is the design of the experiment (consideration of traits, features of the studied populations, etc.).