DISCUSSION
InDel mutations related to economic traits have been investigated in
domestic animals such as pigs (Jung et al., 2020; Zhang et al., 2019),
cattle (Zhou et al., 2019; Xu et al., 2018), and sheep (Wu et al., 2020;
Zhao et al., 2018), indicating that InDel has a non-negligible role in
animal breeding. In this study, various candidate genes for economic
traits and adaptive traits of animals have been identified. In
particular, 94 candidate genes were found to be related to muscle
development (such as MEF2C , TCF4 , MAPK14 , andDDX17 ).
Myocyte enhancer factor 2C (MEF2C ) is widely involved in the
development of heart and skeletal muscle during the embryonic stage. The
synergistic action between MEF2C and the MYoD family
factors promote the development of skeletal muscle during the embryonic
process, and MEF2C can regulate cell proliferation by acting as
the endpoint of the intracellular signaling pathway regulated by various
growth factors (Black et al., 1998). MEF2C also exhibits DNA
binding activity in muscles and is highly expressed in muscle cells
during embryonic formation to regulate muscle development and
differentiation by interacting with muscle-derived bHLH protein, thyroid
hormone receptor, PEA3 , and PDP1 (Pozarska et al., 2016).
As a marker of muscle connective tissue fibroblasts, transcription
factor 4 (TCF4 ) can regulate the development of slow and fast
muscles and promote the conversion of fetuses to adult muscles (Mathew
et al., 2011). Tumor protein p73 (TP73 ) is involved in the
regulation of cell apoptosis (Stiewe et al., 2001), polyciliogenesis
(Fujitani et al., 2017), germ cell maturation (Santos et al., 2018), and
multiple biological processes (Nemajerova et al., 2019). Thus,TP73 plays an important role in animal development and
homeostasis maintenance.
DEAD box RNA helicase 17 (DEAD-box helicase 17, DDX17 ) regulates
gene expression and transcription factor activity (Bourgeois et al.,
2016). DDX17 is an activator of MyOD , which regulates
skeletal muscle development (Legerlotz et al., 2008). DDX17knockdown hinders skeletal muscle development and differentiation
(Caretti et al., 2006). Mitogen-activated protein kinase 14
(MAPK14 ) belongs to the MAP kinase family and is an important
factor in biological development. MAPK14 promotes cell
proliferation and activation by inhibiting the differentiation of
vascular smooth muscles during vascular injury. Pro-inflammatory gene
expression participates in the repair of blood vessels (Wu et al.,
2019). In addition, MAPK14 is involved in muscle atrophy by
direct phosphorylating and activating Bcl-2 family member Bax via
mitochondrial-dependent pathway, thus resulting in muscle fiber death
(Wissing et al., 2014).
This work also screened many candidate genes related to germ cell
development and reproductive hormone regulation, such as SRD5A1 ,FBXW11 , DMRT1 , CXADR , and RPTOR . Early
studies have isolated steroid 5 alpha-reductase 1 (SRD5A1 ) from
rat liver and found that it is one of the three forms of steroid
5α-reductase (Russell et al., 1994). SRD5A1 is involved in the
metabolism of estrogen and androgen. The catalytic substrates ofSRD5A1 include testosterone, progesterone, androstenedione,
epinephrine -T, cortisol, aldosterone, and deoxycorticosterone. This
enzyme catalyzes the conversion of testosterone into stronger androgen:
5α-di hydrotestosterone (DHT ). Therefore, SRD5A1 plays an
important role in mammalian stress, immune system regulation, and
reproduction (Han et al., 2021). F-box and WD repeat domain containing
11 (FBXW11 ), a member of the F-box protein family and a part of
the ubiquitin ligase complex, is important in the regulation of
ubiquitin-dependent spermatogenesis. The mRNA level of FBXW11 is
positively correlated with sperm motility (Liu et al., 2021).
Double sex and mab-3 related transcription factor 1 (DMRT1 ) is
involved in the sex determination of vertebrates. The functional lack ofDMRT1 in mice can lead to excessive proliferation of sertoli
cells without further differentiation in the testis, leading to germ
cell loss (Raymond et al., 2000). Knocking out the DMRT1 in the
sertoli cells in mice will activate FOXL2 , which in turn causes
the Sertoli cells to be reprogrammed into granular cells and the
testicular tissue to transform into an ovarian-like morphology (Matson
et al., 2011). As a member of the adhesion receptor tight junction
protein family, CXADR Ig-like cell adhesion molecule (CXADR )
plays an important role in embryonic development. Its absence causes
embryonic development to stagnate in morula (Kwon et al., 2015).
Regulatory associated protein of MTOR complex 1 (RPTOR ) encodes
the MTOR complex regulatory-related protein and is a part of the mTORC1
complex, which is important in the maintenance and renewal of mouse
spermatogonia (Serra et al., 2019).
Some candidate genes related to immune regulation were also identified.
CD200 molecule (CD200 ) is widely distributed on the surface of
myeloid immune cells, such as thymocytes, B cells, and macrophages
(Barclay et al., 1981). CD20 0 can combine with CD200R to
participate in immune regulation. The CD200 knockout in mice
increases the activity of macrophages and cell lineage and disrupts the
immune balance of body (Hoek et al., 2000). Serum/glucocorticoid
regulated kinase 1 (SGK1 ) plays an important role in cellular
stress response. SGK1 mediates the regulation of glucocorticoid
hormone and inhibits the proliferation of progenitor cells by increasing
glucocorticoid hormone receptor phosphorylation (Anacker et al., 2013).
Interleukin 17 receptor B (IL17RB ) exhibits immunomodulatory
activity, and its expression is up-regulated in patients with rhinitis
(Matsumoto et al., 2011). IL17RB also participates in the
regulation of inflammatory response by mediating NF-kappa B activation
and IL8 production (Ruskin et al., 2012).
In this study, many genes related to metabolism were observed (e.g.,INSR, STXBP3, H6PD, and APOE ). Insulin regulates the
body’s glucose, protein, and fat homeostasis. As the insulin receptor,INSR participates in insulin signaling pathway (Mukherjee et al.,
2009). When the INSR gene is knocked down, insulin cannot perform
function normally in the liver of mice, thus leading to the gradual
deterioration of liver function (Okamoto et al., 2005). Variations inINSR cause insulin resistance syndrome and Donohue syndrome in
multiple species (Reaven et al., 2005). The combination betweenSTXBP3 (syntaxin binding protein 3) and syntaxin 4 regulates
insulin in peripheral tissues (Jewell et al., 2010). Mice withSTXBP3 homozygous knockout cannot survive, whereas those withSTXBP3 heterozygous knockout exhibit reduced insulin secretion
and gradually become glucose intolerant when fed with a high-calorie
diet rich in fat and carbohydrates (Oh et al. 2005). Hexose-6-phosphate
dehydrogenase/glucose 1-dehydrogenase (H6PD ) is involved in cell
biochemical reactions and can mediate the regeneration of
glucocorticoids (Zhang et al., 2009). H6PD knockout in mice
reduces their sensitivity to glucocorticoids, which in turn increases
insulin sensitivity and glucose uptake in muscles, thus eventually
leading to severe skeletal myopathy (Lavery et al., 2008).
Apolipoprotein E (APOE ) encodes apolipoprotein and is one of the
transport carriers of chylomicrons. APOE mediates lipoprotein
catabolism and promotes the hydrolysis and clearance of soluble Aβ
protein (Jiang et al., 2008). Its abnormalities lead to endothelial cell
atherosclerosis (Nakashima et al., 1998) and central nervous system
defects (Masliah et al., 1995).