Candidate genes associated with economically important traits in dairy goats

Abstract

Goats are important livestock species worldwide, due to their valuable commodities, including meat, milk, dairy products, fleece, and skin. Most of the economically important traits in dairy goats are complex quantitative traits, greatly influenced by polygenes and environmental factors. Hence, direct selection of these traits based on phenotypic data will not resulted a remarkable improvements in phenotypes of the traits, rather it needs to understand and include the molecular mechanisms controlling the traits in dairy goat breeding and trait selection. Consequently, following the advancement of molecular genetics and genotyping techniques, great quantities of candidate genes associated with economically important traits in different dairy goat breeds have been investigated by several scholars in the world. This review quantify candidate genes associated with the major economically important traits, including milk production, milk composition, reproduction, body conformation, environmental adaptations, and disease resistance traits in dairy goats by searching the available literature from different databases. As evidenced from literature, candidate genes have different functions on economically important traits, including regulating gene expression, protein functions, metabolism, physiological process, and expression of phenotype of the traits in dairy goats. The search of candidate genes associated with economically important traits, recognizing their genomic region, and physiological functions help breeders to identify marker-genes linked with economic traits used to attain faster selection response in dairy goat breeding. Therefore, quantifying candidate genes and their association with economically important traits will enhance the genetic improvement of dairy goats, which will improve nutritional security and the livelihoods of smallholder farmers.

Keywords:

• Candidate genes
• dairy goats
• economic traits
• physiological functions

PUBLIC INTEREST STATEMENT

Goat production is an acceptable business worldwide from the economic, socio-cultural, and environmental perspectives. Majority of the world goats are produced in tropical countries where many peoples have low per capita income and suffering by food shortage and malnutrition. In this areas, goats’ milk is a valuable part of the human diet sustaining life. Goats’ milk is also valued in developed countries, due to its nutritive and medicinal values. For enhanced milk production, genetics of the dairy goat breeds should be improved. But, economically important traits in dairy goats are multifaceted traits, traits influenced by polygenes and environmental factors, which makes difficult direct selection of the traits. Consequently, several scholars have been identified candidate genes associated with economically important traits in different dairy goat breeds. Hence, this review was intended to document candidate genes associated with economic traits in dairy goats, which would assist dairy goat breeding worldwide.

1. Introduction

Goats (Capra hircus) were among the first farm animals domesticated by man (Aldridge et al., 2018; Mazinani & Rude, 2020). As supported by archeological evidences, goat domestication took place around 10,000 years ago in the Zagros Mountain region of Iran (Nazari-Ghadikolaei et al., 2018). Today, about 1003 million heads of goats are found in the world (Pulina et al., 2018), which can be grouped into 576 distinct goat breeds, formed by natural and manmade selection together with other evolutionary forces (Gootwine, 2020). The majority of the world goat population is situated in developing countries, mostly occupying marginal lands with very harsh environmental conditions (Pardo et al., 2022). From the total goat population in the world, 388 (38.7%) million heads are found in Africa (Pulina et al., 2018). Ethiopia is home for 52.5 million heads of goats, mostly (99%) composed of the indigenous goat types (CSA, 2021). Phenotypically, Ethiopian indigenous goat population can be grouped into 14 goat types while, genetically they have been clustered into 7 distinct breeds (Tarekegn, 2016). Following domestication, goats have created symbolic relationships with humans (Muigai et al., 2018). Goats provide valuable commodities, including meat, milk, dairy products, fleece, and skin (Joshi et al., 2018), besides their unique socio-cultural values (Skapetas & Bampidis, 2016).

Most of the economically important traits in goats are quantitative traits, traits influenced by many genes, and environmental factors. Thus, improving the phenotypic expression of economically important traits in dairy goats needs comprehensive knowledge about the traits (Baenyi et al., 2020; Eusebi et al., 2020), including their genetic basis (Siddiki et al., 2020). Nowadays, advancement of molecular genetics and genotyping techniques give rise to the identification of great quantities of candidate genes associated with economically important traits in goats (Eusebi et al., 2020). This assists faster response to selection, and improvement of economic traits in goats (Raina et al., 2020; Sebastiani et al., 2022). Single nucleotide polymorphism, microsatellite markers, and genome-wide association studies are the commonly used molecular techniques to identify candidate genes associated with economically important traits in dairy goats. A candidate gene is a gene that is responsible for a substantial amount of genetic variation of a trait (Moioli et al., 2007; Siddiki et al., 2020). Currently, several scholars have been identified candidate genes related to economically important traits in dairy goats. Bringing and summarizing the information provides comprehensive knowledge for users. Hence, this review was aimed to summarize and document candidate genes associated with economically important traits in dairy goats to assist molecular breeding of dairy goats.

2. Candidate genes associated with economically important traits in dairy goats

2.1. Potential candidate genes regulating milk production/yield, milk composition and fertility traits

Goats should exhibit more productive traits related to milk production, meat production, prolificacy, environmental adaptability, disease resistance, and fitness traits, to remain important and best contribute to the economy of the producers (Baenyi et al., 2020). Accordingly, the milk production traits of dairy goats in terms of yield and quality, have great economic value in the dairy goat industry. These traits are influenced by genetics, environmental factors, and their interactions (Baenyi et al., 2020; Brzáková et al., 2021; Crepaldi et al., 2013; Kang et al., 2020). The quality of goats’ milk can be assessed using its chemical composition, and nutritional safety and organoleptic characteristics, aside of its technological and functional properties (Pilla et al., 2006). Similarly, García et al. (2014) were described the qualities of goats milk as its potential to tolerate different technological treatments to obtain products with the ability to satisfy consumer demand in terms of health, nutritional values, and sensory attributes. Aside from the feed types the animal consume (Shingfield et al., 2008), quality attributes of goats’ milk are controlled by candidate genes and genomic regions (QTL) in a different extent (Pilla et al., 2006).

The reproductive potential and success of the goats determines the amount of products obtained from them, namely, milk, meat, kids, and fiber and pelts. Because, livestock breeds including the goats with improved reproductive competence and increased fertility rate will produce more products in the farm and hence, maximizes the economic gain of the producers (Siddiki et al., 2020). In goats, fertility traits encompass the age at puberty, ovulation rate, age at first kidding, litter size, total numbers of kids born, and stillbirth (Gavran et al., 2021). The reproductive traits are fitness traits concerned with reproduction and viability (Joshi et al., 2018). The reproductive traits of goats such as litter size are complex, quantitative, and economically important traits, highly influenced by genetics and non-genetic factors (Bolacali et al., 2019; Mustefa et al., 2019; Suyadi et al., 2019; Tesema et al., 2020; Zarazaga et al., 2019). Multiple genes and factors are acting on the reproductive characteristics of goats (Ray et al., 2016). In this context, several scholars have been explored candidate genes associated with milk yield, milk composition, and fertility traits in different goat breeds around the world. Some of the reported candidate genes, which showed association with these traits, and their physiological functions are discussed in the following subsections.

2.1.1. Potential candidate genes regulating milk production/yield

In mammals, milk production is a physiological function controlled by many genes. To date, studies have been conducted to identify candidate genes, and genomic regions associated with milk production/yield in goats using the candidate gene approach (Ferreira et al., 2020; Talouarn et al., 2020). Some of the identified candidate genes associated with milk production/yield in different goat breeds are presented in Table 1. Recently, using genome wide association study, Massender (2022) identified three candidate genes named deoxycytidine kinase (DCK), OB kinase activator 1B (MOB1B), and ribosomal protein L8 (RPL8) genes, associated with milk production in Canadian Alpine and Saanen dairy goat breeds. The deoxycytidine kinase (DCK) gene is a positional candidate gene in Alpine, and Saanen goat breeds (Massender, 2022), that encodes deoxycytidine kinases, enzymes, which are involved in the nucleotide salvage pathway (Christiansen et al., 2015). According to Massender (2022), however, deoxycytidine kinase (DCK), and OB kinase activator 1B (MOBIB) genes were identified as positional candidate genes associated with milk production, and udder health traits in various dairy cattle populations, these genes are novel candidate genes associated with milk yield traits in goats.

Table 1. Candidate genes associated with milk production/yield traits of goats and their physiological functions from different goat breeds

Gene symbol	Gene name/description	Chr. no	Physiological functions and associated traits	Studied goat breeds	References
MDM1	Mdm1 nuclear protein	5	Regulating milk volume	French dairy goats	Talouarn et al. (2020)
ZNF232	Zinc finger protein 232	9
SCIMP	SLP adaptor & CSK interacting membrane protein	19
UCP2	Uncoupling protein 2	15	Regulating milk volume	Saanen & Alpine goats	Ferreira et al. (2020)
PPARG	Peroxisome proliferator activated receptor gamma	22
ACACA	Acetyl-CoA carboxylase alpha	19	Associated with daily milk yield	White Shorthaired, and Brown Shorthaired dairy goats	Brzáková et al. (2021)
BTN1A1	Butyrophilin subfamily 1 member A1	23
LPL	Lipoprotein lipase	8
SCD	Stearoyl-CoA desaturase	26
RPL3	Ribosomal Protein L3	5	Modulate energetic balance during lactation	Saanen goat	Zhang et al. (2018)
PRL	PROLACTIN protein	23	Involved in mammary gland tissue preparation before lactation and promotes milk production. Influence lactation performance	Alpine goat, and Liaoning cashmere goats	Le Provost et al. (1994); Wu et al. (2022)
IGF-1	Insulin-like growth factor 1	5	Control lactation milk yield	Damascus goat	Yakan et al. (2018)
CSN1S1	Casein alpha s1	6	Controlled total milk yield	Norwegian dairy goats	Dagnachew and Ådnøy (2014)
CSN2	Casein beta	6
AGPAT6	Glycerol-3-phosphate acyltransferase 4	27	Related with milk yield	Xinong Saanen goat Guanzhong goat	C. He et al. (2011)
ADAMTS20	ADAM metallopeptidase with thrombospondin type 1 motif 20	5	Involved in the differentiation of mammary cells, thus, regulates milk yield and its proteins content in goats	Alpine, Saanen, LaMancha, Nubian, and Toggenburg goats	Kang et al. (2020)
PAPPA2	Pappalysin 2	16	Regulates milk production or yield
DCK	Deoxycytidine kinase	6	Associated with milk production	Canadian Alpine and Saanen dairy goat breeds	Massender (2022)
MOB1B	OB kinase activator 1B	6
RPL8	Ribosomal protein L8	14
GH	Growth hormone	19	Associated with milk yield	Algarvia goat breed	Malveiro et al. (2001)

Note:—Chr. no = Chromosome number

In addition, by studding multiparous, intensively managed Saanen and Alpine goat breeds, Bagatoli et al. (2021) investigated the association between the apolipoprotein B (APOB) gene polymorphism and milk production in goats. According to the author, the AA genotypes of both the APOB/HaeIII, and APOB/SmaI polymorphisms are the most favorable genotypes for increased lactation length, and higher milk production. The link between the APOB gene polymorphism and milk yield and composition traits in goats may be due to the involvement of the APOB gene in energy metabolism of lactating ruminants, which intern affects the milk synthesis pathway (Bagatoli et al., 2021). However, in French Alpine and Saanen goats (Arnal et al., 2018), Polish White improved and Polish Fawn improved goats (Bagnicka et al., 2016), and Holstein-Friesian dairy cows (Haile-Mariam et al., 2003), a decrease in somatic cell score (SCS/SCC) was associated with increased milk production persistency. Besides, an experiment focused to investigate the association between growth hormone (GH) gene polymorphisms and milk production in Algarvia goats demonstrated that the growth hormone (GH) gene can be used as a candidate gene to undertake marker-assisted breeding in goat breeds to improve milk production traits (Malveiro et al., 2001).

Additionally, Talouarn et al. (2020) was explored three positional candidate genes, Mdm1 nuclear protein (MDM1), SLP adaptor and CSK interacting membrane protein (SCIMP), and zinc finger protein 232 (ZNF232) genes, associated with milk production/yield in the Saanen goat breeds; however, the study was not included functional analysis and hence, functional associations of the genes did not explored. Yakan et al. (2018) identified the association between the expression level of POU class 1 homeobox 1 (POU1F1), and insulin like growth factor 1 (IGF-1) genes with milk yield in Damascus goat breeds managed under pen (intensive) and pasture (extensive) based feeding systems. Due to embryonic differentiation, POU1F1 gene is with lifelong somatotropic, lactotropic, and thyroidropic influences, which is known to be related to milk yield with its lactotropic influence (Zhao et al., 2013). It is a part of the POU1F1 pathway, which plays a vital role in lactation, growth and development in mammal. Mutations of genes in this pathway resulted in combined pituitary hormone deficiency, a situation that may exposed the individual for decreased production of growth hormone (GH), and prolactin (PRL) (Zhao et al., 2013). Similarly, IGF-1 gene plays an important role for cell proliferations of every tissue, and organs involved in secret or activity of mammary glands, along with its metabolic impact on growth and development pathways (Curi et al., 2005).

Furthermore, a study conducted to investigate the impact of copy number variations on milk production traits in goats using the Caprine SNP50 array was identified two candidate genes, ADAM metallopeptidase with thrombospondin type 1 motif 20 (ADAMTS20), and pappalysin 2 (PAPPA2) genes associated with milk production in five dairy goat breeds (Kang et al., 2020). ADAMTS20 gene, member of secreted metalloproteases family, can secreted molecules and process a variety of extracellular matrix components involving in the differentiation of mammary cell, lactogenic activity of bovine mammary epithelial cells, and bovine mammosphere formation where genes involved in milk protein and fat biosynthesis were expressed (Riley et al., 2010). Instead, PAPPA2 gene is an insulin-like growth factor binding protein protease, which overlaps with CNV25 at its 5′ terminus, and can be used as a candidate gene associated with milk production and composition in goats (Kang et al., 2020). However, the PAPPA2 was showed associations with the reproduction and production traits in bovine (Wickramasinghe et al., 2011), egg production in chicken (Liu et al., 2019), and protein and fat synthesis in bovine (Sciascia et al., 2013). Moreover, Wu et al. (2022) reported the association of prolactin (PRL), and prolactin receptor (PRLR) genes with milk production performances in Liaoning Cashmere goat raised in China.

2.1.2. Potential candidate genes regulating milk contents/compositions

The composition/contents of goats milk, especially the fat and protein contents are controlled by the involvement of wide range of genes, including the αS1-casein, β-casein, diacylglycerol acetyl transferase-1, and β-lactoglobulin, that have a direct control over production of milk components (Moioli et al., 2007). This days, equally to the milk production traits, the candidate gene approach has been exploited in small ruminants focusing on the identification of the molecular mechanism, which make milks of different quality (Moioli et al., 2007). Consequently, many candidate genes associated with milk compositions have been identified in different goat breeds. Some of the identified candidate genes associated with milk composition/contents in goats and their physiological functions are presented in Table 2. Recently, candidate genes associated with milk composition such as acetyl-CoA carboxylase alpha (ACACA), butyrophilin subfamily 1 member A1 (BTN1A1), lipoprotein lipase (LPL), and stearoyl-CoA desaturase (SCD) genes have been explored in Czech national dairy goat breeds named White Shorthaired, Brown Shorthaired, and their crosses with other breeds, feed on grazing fields with supplementation of only organic feeds (Brzáková et al., 2021). Brzáková et al. (2021) reported significant association of the polymorphisms of formerly mentioned genes with protein and fat contents of goats’ milk however, polymorphisms of the ACACA gene didn’t associated with fat content of goats’ milk in the studied breeds. According to Brzáková et al. (2021), the only gene associated with milk somatic cell score in the studied goat breeds was butyrophilin subfamily 1 member A1 (BTN1A1) gene.

Table 2. Candidate genes associated with constitutes/composition of goat’s milk and their physiological functions from different goat breeds

Gene symbol	Gene name/description	Chr. no	Physiological functions and associated traits	Studied goat breeds	References
AGPAT6	glycerol-3-phosphate acyltransferase 4	27	biosynthesis of triglyceride (milk fat), and related to milk protein	Xinong Saanen, Guanzhong, & Alpine Damascus goat	He et al. (2011); Bagatoli et al. (2021)
PPARγ	Peroxisome proliferator activated receptor gamma	22	Control milk fat yield.		Yakan et al. (2018)
CSN1S1	casein alpha s1	6	Linked with protein content of goats’ milk	Norwegian dairy goats, Saanen goats, and Alpine goats	Dagnachew and Ådnøy (2014); Martin et al. (2017)
CSN2	casein beta	6	Regulating protein, fat, FFA, and SCC content in goats’ milk
CSN3	casein kappa	6	Regulating protein content in goats’ milk
ACACA	acetyl-CoA carboxylase alpha	19	Involves in regulatory enzyme of fatty acid biosynthesis; hence, linked with milk protein, and milk fat content in goats	WSH and BSH dairy goats, and Alpine goats	Crepaldi et al. (2013); Brzáková et al. (2021)
BTN1A1	butyrophilin subfamily 1 member A1	23	Regulating protein, fat, and SCS content of goats’ milk
LPL	lipoprotein lipase	8	Regulating plasma triglyceride metabolism; hence, linked with protein, and fat contents
SCD	stearoyl-CoA desaturase	26	Regulating protein, and fat content
DGAT1	Diacylglycerol O Acyltransferase 1	14	Associated with fat content of milk	Saanen and Alpine goats	Martin et al. (2017)
SLC27A6	solute carrier family 27 member 6	7	Associated with lactose content of goats milk		Bagatoli et al. (2021)
APOB	apolipoprotein B	11	Associated with lactation length, and lactose content, and somatic cell score in goats milk
AGPAT6	glycerol-3-phosphate acyltransferase 4	27	Catalyzes acylation of lysophosphatidic acid to phosphatidic acid. link with fat & protein
PRL	PROLACTIN protein	23	Involves in synthesis of lactose and regulation of protein and fat content of milk	Liaoning cashmere goats	Wu et al. (2022)
LALBA	lactalbumin alpha	5	Associated with lactose content of goats milk, and affects renneting property in milk	Sarda breed	Dettori et al. (2015)
MTHFR	methylenetetrahydrofolate reductase	16	Has essential role in the milk protein synthesis pathway, and has an influence on it	Xinong Saanen, and Guanzhong dairy goats	An et al. (2015)
STAT5A	signal transducer and activator of transcription 5A	19	Associate with milk yield, and fat content of goats milk	Xinong Saanen, and Guanzhong dairy goats	An et al. (2013a)
SCAP	SREBP cleavage-activating protein	22	Play a central role in the regulation of milk fat synthesis, especially, the de novo synthesis of saturated FA. Influencing the short chain saturated FA, and unsaturated FA	Sirohi goat breed	Dixit et al. (2015)
PPARGC1A	Peroxisome proliferator-activated receptor gamma coactivator 1-alpha	6	Controlling energetic metabolism, adipogenesis and maintenance of the differentiated state. Related to FA contents of goats’ milk
OLR1	Oxidized low density lipoprotein (lectin-like) receptor 1	5	Involved in fatty acid transport and binds and degrades the oxidized form of low density lipoprotein. This gene associated with both saturated and unsaturated FA contents of milk in goats
FABP3	fatty acid binding protein 3	2	Is member of FABPs family that plays a role in fatty acid uptake, transport and metabolism; hence, linked with FA contents of goats milk like butyric and arachidic acids
PRL/prolactin	PROLACTIN protein	23	Involved in the synthesis of lactose and triacylglycerol as well as fatty acid uptake and lipogenesis; hence, influence FA contents of milk
GH	Growth hormone	19	Associated with milk protein and fat content	Algarvia Goat breed	Malveiro et al. (2001)
PAEP	progestagen-associated endometrial protein gene	11	Used to codes the β lactoglobulin precursor, whey protein in ruminants, and considered milk allergen. Associated with protein content	Saanen goat breeds	Martin et al. (2017)
ALOXE3	arachidonate lipoxygenase 3	19	Involved in metabolic pathway in formation of epidermal barrier, w/c includes, cell differentiation, cell proliferation and fat metabolism. Linked with FY, PY and SCS	Alpine, Nubia Saanen, Toggenburg, and crossbred goats	Scholtens et al. (2020)
KIF1C	kinesin family member 1C	19	Linked with FY and PY of goats’ milk

Note:—Chr. no = Chromosome number; FFA = Free fatty acids; SCC = Somatic cell count; WSH = whit shorthaired; BSH = Brown shorthaired; SCS = somatic cell score

The butyrophilin subfamily 1 member A1 (BTN1A1) gene is located on chromosome 23 in the goats’ genome, and has 8 exons and 3256 bp transcription length. This gene is a milk fat globule membrane protein that plays a vital role in lipid secretion and milk production (Qu et al., 2011). Similarly, Qu et al. (2011) explored the association of butyrophilin subfamily 1 member A1 (BTN1A1) and milk fat globule EGF and factor V/VIII domain containing (MFG-E8) genes with milk fat yield, total solid, solid-nonfat, and first milk yield traits in the Xinong Saanen and Guanzhong dairy goat breeds. Cecchinato et al. (2014) noted the essentiality of fatty acids in forming cell membranes and their use to synthesize fat that can be either stored in adipose tissue or secreted into milk by the mammary gland. The acetyl-CoA carboxylase alpha (ACACA) gene primarily regulated fatty acid biosynthesis, and catalyzes acetyl-CoA conversion to malonyl-CoA (Qu et al., 2011). In the mammary gland, stearoyl-CoA desaturase (SCD) gene plays a vital role in the cellular biosynthesis of monounsaturated fatty acids, as it regulates most conjugated linoleic acids synthesis (Crepaldi et al., 2013).

In addition, using the Amplified Fragment Length polymorphism (AFLP) sequencing technique, Bagatoli et al. (2021) explored candidate genes such as solute carrier family 27 member 6 (SLC27A6), glycerol-3-phosphate acyltransferase 4 (AGPAT6), and apolipoprotein B (APOB) genes associated with milk composition traits in multiparous Saanen and Alpine goat breeds. According to Bagatoli et al. (2021), APOB/HaeIII polymorphism of the apolipoprotein B (APOB) gene was associated with lactose content, and somatic cell score; whereas, the APOB/SmaI polymorphism of the same gene was associated with lactose percentage, total yield of solids non-fat, protein, and fat contents of milk in the aforementioned goat breeds. Additionally, SLC27A6/TspRI polymorphism of solute carrier family 27 member 6 (SLC27A6) gene, and AGPAT6/NcoI polymorphism of glycerol-3-phosphate acyltransferase 4 (AGPAT6) gene showed association with lactose content, and lactose, fat and protein contents of milk, respectively (Bagatoli et al., 2021). Unlike in goats, the association of solute carrier family 27 member 6 (SLC27A6) gene polymorphisms with milk fat content has been reported in bovine for instance, in Japanese Black cattle (Sasazaki et al., 2020).

Similarly, Ferreira et al. (2020) reported the association of polymorphisms in uncoupling protein 2 (UCP2), and peroxisome proliferator-activated receptor gamma (PPARG) genes with milk production and composition traits in multiparous Saanen and Alpine goat breeds. In the UCP2 gene, two polymorphisms, UCP2.29614171 G/A, and UCP2.29615319 G/A polymorphisms, were investigated where the former was associated with milk fat, milk protein and milk dry extract content while, the later was associated with breeding values for milk protein, milk dry extract and milk lactose content in the studied goat breeds (Ferreira et al., 2020). In addition, PPARG-A/B polymorphism in the peroxisome proliferator-activated receptor gamma (PPARG) gene associated with milk protein, dry extract, lactose yield, and milk lactose content Saanen and Alpine goat breeds (Ferreira et al., 2020).

The uncoupling protein 2 (UCP2) gene, which is located on goat’s chromosome 15, is a mitochondrial membrane transporter expressed in white adipose tissue. This gene regulates insulin secretion in pancreatic beta-cells. In addition, in adipose tissue, the same gene stimulates the secretion of adiponectin, a hormone that increases insulin sensitivity in the organism’s tissues (Chevillotte et al., 2007), and thereby slightly influence the fat and protein contents of milk (Mackle et al., 2000). Instead, the PPARG gene, which is located on goat’s chromosome 22, is used to stimulates the synthesis of monounsaturated fatty acids in dairy goat mammary epithelial cells by controlling stearoyl-coenzyme A desaturase (Shi et al., 2016).

2.1.3. Potential candidate genes regulating reproduction and fertility traits

Goats can provide valuable animal products such as milk, meat, leather, and manure (Luo et al., 2019). The production of these commodities depends on reproduction, and goats’ reproductive success (Gavran et al., 2021). In livestock breeds including the goats, reproductive traits are influenced by both genetic and non-genetic factors (Tesema et al., 2020; Zarazaga et al., 2019). These factors are categorized as intrinsic, and extrinsic factors, factors relate to the animal’s environment, and its genotype, respectively (Ajafar et al., 2022). According to Luo et al. (2019), the efficiency of dairy goat production is determined by goats’ fertility traits. However, the breed of goats, environment, and their interaction influences these traits (Miao et al., 2016). Reproductive traits such as litter size are complex economic traits that involves many aspects of reproduction such as hormone secretion, follicular growth, ovulation, fertilization, embryo implantation, and placenta and fetal development (Jun-jie et al., 2020) on which multiple genes and factors are involved (Ray et al., 2016).

Consequently, several studies have been conducted to identify genes and candidate genes associated with fertility traits in goats (Table 3). For instance, by studying the association of bone morphogenetic protein 15 (BMP15) gene with the prolific characteristics of Surti goats managed under the Farm and Field Condition, Dangar et al. (2022) identified two polymorphisms, one at 500 bp and another at 400 bp in female Surti goats. Dangar et al. (2022) suggested that the AB genotype of polymorphic region at 500 bp may be used as a marker genotype for early age selection for female Surti goat. In addition, the association of BMP15 gene with prolificacy/litter size was investigated in Jamunapari and crossbred goats (Shaha et al., 2021), in Haimen, Boer, and Huanghui goat breeds of China (Y. He et al., 2010), and Markhoz goats of Iran (Ghoreishi et al., 2019). Secondly, growth differentiation factor 9 (GDF9) is the most commonly explored gene associated with fecundity traits in different goat breeds comprising Jamunapari goats (Shaha et al., 2021), Haimen, Boer, Huanghui goats (Y. He et al., 2010), Jining gray goats (Jun-jie et al., 2020), Shaanbei white cashmere goats (Wang et al., 2018), and Markhoz/Iranian Angora goats (Ghoreishi et al., 2019). The BMP15, and GDF9 are genes located on the goats’ chromosome X and 5, respectively. These genes are the two members of the transforming growth factor-β (TGF-β) superfamily and are produced by the ovary and show intense effect on it, aside of their involvement in increasing the ovulation rate in goats (Knight & Glister, 2006), due to the role of these two genes in follicle growth and development at all stages of folliculogenesis in the females (Otsuka et al., 2011).

Table 3. Candidate genes that are associated with reproductive and fertility traits, and their physiological functions from different goat breeds

Gene symbol	Gene name/description	Chr. no	Physiological functions and associated traits	Studied goat breeds	References
CDC25C	cell division cycle 25C	7	Influence the ovarian development and hence, related with litter size in goats	Shaanxi Shaanbei White Cashmere goats	Wang et al. (2020b)
ENDOG	endonuclease G	11	enriched in the coiled coil process and related with litter size
NANOS3	nanos C2HC-type zinc finger 3	7	enriched in the coiled coil process and related with litter size
PSEN2	presenilin 2	16	Associated with litter size in goats	Laoshan dairy goat	Rui-Qian et al. (2018)
GDF9	Growth differentiation factor 9	5	Associated with litter size in goats	SWCG and Jamunapari goats	Wang et al. (2018); Shaha et al. (2021)
BMP15	bone morphogenetic protein 15	X	Associated with fecundity traits in goats	Jamunapari and crossbred goats	Shaha et al. (2021)
CSN1S1	casein alpha s1	6	Associated with litter size in goats	Jamunapari and goats	Shaha et al. (2021)
KDM6A	lysine demethylase 6A	X	Associated with litter size &fertility traits	SWCG	Cui et al. (2018)
YBOX2	Y-box Binding Protein 2	19	Associated with semen volume in bucks	French dairy goats	Talouarn et al. (2020)
POU1F1	POU class 1 homeobox 1 (Pit 1)	6	Associated with litter size and growth	Chengdu Brown, Jintang Black, and Tibetan Cashmere	Guo et al. (2019)
GDF9	growth differentiation factor 9	7	Enhances primary and preantral follicular growth, and hence, associated with fecundity	Haimen, Boer, Huanghui, Markhoz, and JGG goats	He et al. (2010); Feng et al. (2011); Ghoreishi et al. (2019); Jun-jie et al. (2020)
BMP15	bone morphogenetic protein 15	X	Enhances primary and preantral follicular growth, and hence, associated with fecundity/prolificacy and high kidding rate	Haimen, Boer, Huanghui, Markhoz, JGG, and Surti goats	He et al. (2010); Ghoreishi et al. (2019); Jun-jie et al. (2020); Dangar et al. (2022)
BMPR1B	bone morphogenetic protein receptor type 1B	6	Enhances primary and preantral follicular growth, and hence, associated with fecundity	Haimen, Boer, and Huanghui, and JGG goats	He et al. (2010); Jun-jie et al. (2020)
INHα	inhibin subunit alpha	2	Associated with fecundity traits in goats	Haimen, Boer, and Huanghui goats	He et al. (2010)
GnRHR	gonadotropin releasing hormone receptor	6	Linked with fecundity/ litter size through altering the concentration of LH and FSH	non-descript local goats of Sri Lanka	Ariyarathne et al. (2017)
NR6A1	nuclear receptor subfamily 6 group A member 1	11	Critically involve in embryonic development, hence, related to litter size	Dazu black goats	E et al. (2019)
STK3	serine/threonine kinase 3	14	promotes phosphorylation, and inhibit ovarian follicular development
IGF2BP2	insulin like growth factor 2 mRNA binding protein 2	1	Associated with reproductive process and reproduction in goats
AR	androgen receptor	X	Associated with development of ovaries, ovulation rate and vitality of sperm stores in the tests. It has an effect on average litter size
HMGA2	high mobility group AT-hook 2	5	Associated with litter size
NPTX1	neuronal pentraxin 1	19
ANKRD17	ankyrin repeat domain 17	6
PPP3CA	protein phosphatase 3 catalytic subunit alpha	6	Involved in neurodevelopmental disease and reproduction through stimulation of cell proliferation and signaling in fetal placental artery endothelial cells
PLCB1	phospholipase C beta 1	13	Involved in reproduction and litter size in goats
KISS1	KiSS-1 metastasis suppressor (kisspeptin)	16	Associated with litter size	Xinong, Saanen, and Guanzhong goat	An et al. (2013b)
SMAD2	SMAD family member 2	24	Associated with litter size	SWCG	Wijayanti et al. (2022)
NGF	Nerve Growth Factor	3	Have a significant influence on litter size via Enhancing folliculogenesis in goats	Malabari and Attappady Black goat breeds	Naicy et al. (2016)
SLAIN1	SLAIN motif family member 1	12	Expressed at thee stem cell, and play role in the development of the nervous system and morphogenesis of several embryonic structures	Abergelle goat	Berihulay et al. (2019)
NEK1	NIMA related kinase 1	8	Implication in ciliogenesis and DNA damaged response, and has essential role in meiosis
DSCAML1	Down syndrome cell adhesion molecule-like protein 1		Linked with sperm motility and density in male and first-birth litter size in female goats	Shaanbei White-Cashmere goat	Wang et al. (2020a)
CAMK2D	calcium/calmodulin dependent protein kinase II delta	6	Involved in protein serine/threonine kinase activity. Linked with embryo development	Begait goats	Berihulay et al. (2019)
NIN	ninein	10	Play significant roles in microtubule Stability. Linked with early embryo development
RSPH6A	radial spoke head 6 homolog A	18	Involved in acting on estrogen, which plays vital physiological functions the development and maintenance of reproductive organs linked with fertility traits
KISS1	KiSS-1 metastasis suppressor	16	Involves in the regulation of the gonadotropin-releasing hormone, which is in turn considered as gatekeeper of pubertal development and reproductive function. The gene is associated with litter size in goats	Jining Grey goat, Black Bengal goats, and Chinese Arbas Cashmere goat (Arbas high, and Arbas low goats)	Cao et al. (2010); Maitra et al. (2014); Islam et al. (2020)
WNT10B	Wnt family member 10B	5	Used for regulating the development of reproductive systems including, ovarian follicles, ovulation and luteinization of ovarian follicular cells. Linked with fecundity traits	Chinese Arbas Cashmere goat (Arbas high, and Arbas low)	Islam et al. (2020)
SETDB2	SET domain bifurcated histone lysine methyltransferase 2	12	This gene is a histone methyltransferase that plays an important role in the early stage of luteinization. Linked with fecundity traits
PPP3CA	protein phosphatase 3 catalytic subunit alpha	6	Involved in regulation of cell proliferation and signaling in fetal placental artery endothelial cells. The gene linked with fecundity/litter size

Note:—Chr. no = Chromosome number; SWCG = Shaanbei white cashmere goats; JGG = Jining gray goat; Chr. Chromosome; LH = Luteinizing hormone; FSH = Follicle stimulating hormone. Chr. no = Chromosome number; SWCG = Shaanbei white cashmere goats; Chr. = Chromosome. Chr. no = Chromosome number

In addition, using whole-genome sequencing technique Wang et al. (2020b) investigated candidate genes, including cell division cycle 25C (CDC25C), endonuclease G (ENDOG), and nanos C2HC-type zinc finger 3 (NANOS3) associated with litter size in Shaanxi Shaanbei White Cashmere goats. Those candidate genes identified by Wang et al. (2020b) have a crucial role in follicular development and litter size in goats. Similarly, a study on selection signature of litter size using whole genome sequencing mixed pools strategy revealed candidate genes for example, NR6A1, STK3, IGF2BP2, AR, HMGA2, NPTX1, ANKRD17, DPYD, CLRB, PPP3CA, PLCB1, STK3 and HMGA2 associated with litter size in Dazu black goats (E et al., 2019). E et al. (2019) also investigated the involvement of some of the genes in biological process such as developmental, multiorganism, immune system, reproduction, and reproductive processes. Besides, the role of serine/threonine kinase 3 (STK3) gene to promote the phosphorylation of LATS1 that inhibits ovarian follicular development, and follicle selection during ovarian development has been reported (Lyu et al., 2016).

The nuclear receptor subfamily 6 group A member1 (NR6A1) gene is located on goats chromosome 11, and has 10 exons, and 2 transcripts. This gene is critical for embryonic development and has been found to be a transcriptional repressor by specifically binding to DR0 response elements. In addition, this gene can also plays a role in cultured ovaries to inhibit meiotic initiation and promote cell proliferation through estrogen (B. He et al., 2013). On the other hand androgen receptor (AR) gene, which is located on goats chromosome X, and has 8 exons, and 2 transcripts, is associated with the development of ovaries, and the vitality of sperm stores in the testes (Hara & Smith, 2015). In addition, androgen receptor (AR) gene showed associations with fecundity traits in Laoshan dairy goat populations (Lai et al., 2016).

Furthermore, Berihulay et al. (2019) explored positional and functional candidate genes associated with reproductive traits in Begait (CAMK2D, KANK4 NIN, RSPH6A, and UGT2A2 genes), and Abergelle goats (SLAIN1, and NEK1genes). The CAMK2D, and NIN genes, which are located on the goats’ chromosome 6, and 10, respectively, played critical roles in the early embryonic development. The NIN gene is the centrosome associated proteins that also plays an additional role in microtubule stability (Berihulay et al., 2019). The RSPH6A gene, which is located on goats’ chromosome 18, is found in a region that harbored UGT2A2 gene, which involves in capable of acting on estrogen, a hormone that plays a vital physiological functions in the development and maintenance of reproductive organs in females (Yaşar et al., 2017).

2.2. Potential candidate genes associated with body conformation, environmental adaptations, and disease resistance potential

2.2.1. Potential candidate genes regulating body conformation

Conformation traits of an animal refers to its anatomy and skeletal function, and how it impacts the animal’s health, adaptability, longevity, and productivity (Getaneh et al., 2022). These traits comprises the structure, balance, and soundness traits of the animals, which helps an animal to perform its functions successfully (Valencia-posadas et al., 2017). Castañeda-Bustos et al. (2014) noted that the heritability values of type traits in goats ranged from 0.16 to 0.33, which shows the presence of acceptable genetic variability allowing the traits to give good response to selection. Conformation traits are the interest of the breeders in any goat production enterprise, due to their influences on goats’ production, longevity, and profitability, beyond their descriptive nature (Despain et al., 2018; Sebastian et al., 2016). Hence, conformation and morphological traits of goats are the economically important traits for the goat meat and dairy businesses, due to their effect on phenotypes of traits with economic interest (Gu et al., 2022; Luigi-sierra et al., 2020). However, the genetic bases of those traits has not yet been widely examined (Luigi-sierra et al., 2020).

But, in recent years, some scholars have been trying to identify candidate genes associated with conformation traits in different goat breeds around the world. Some of the recognized candidate genes associated with goats’ conformation traits and their physiological functions are presented in Table 4. Firstly, in a genome wide association study of body conformation traits in Dazu Black goats using the whole genome sequencing techniques, Gu et al. (2022) explored 42 candidate genes associated with conformation traits, including body length (PSTPIP2), chest depth (SUN3, MANEA, CDKAL1, CDH9, CBLN4, and SOX4), and cannon circumferences (CCL19, SGCG, FIG9, CNTFR, RPP25L) traits. The proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) gene is located on the goats’ chromosome 24 and has 15 exons, and 2 transcripts. This gene associated with Body length in Dazu Black goats (Gu et al., 2022). According to Lukens et al. (2013) and Yao et al. (2019), proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) gene negatively regulates IL-1β, which plays a central role in osteomyelitis. This gene is highly expressed in the synovial cells, and inhibits the functions of fibroblastic synovial cells, and thereby, hinders the inflammatory response and reduces the number of osteoclasts (Gu et al., 2022). Besides, through regulating podosome assembly, PSTPIP2 gene can control the bone resorption process (Sztacho et al., 2016).

Table 4. Candidate genes associated with body conformation traits and their physiological functions in different goat breeds

Gene symbol	Gene name/description	Chr. no	Physiological functions and associated traits	Studied goat breeds	References
PSTPIP2	proline-serine-threonine phosphatase interacting protein 2	24	Associated with body length measurement	Dazu black goats	Gu et al. (2022)
CCL19	C-C motif chemokine ligand 19	8	Associate with cannon circumference measurement
FGF9	fibroblast growth factor 9	12
SGCG	sarcoglycan gamma	12
FIGN	fidgetin, microtubule severing factor	2
CNTFR	ciliary neurotrophic factor receptor	8
RPP25L	ribonuclease P/MRP subunit p25 like
CCL21	C-C motif chemokine ligand 21
BRINP1	BMP/retinoic acid inducible neural specific 1
CDK5RAP2	CDK5 regulatory subunit associated protein 2
CBLN4	cerebellin 4 precursor	13	Associated with chest depth measurements
CDH9	cadherin	20
CDKAL1	CDK5 regulatory subunit associated protein 1 like 1	23
SOX4	SRY-box transcription factor 4	23
EDEM1	ER degradation enhancing alpha-mannosidase like protein 1	22
SIRT3	Sirtuin3	29	Associate with body conformation and growth traits	Malabari &Attappady Black goats	Silpa et al. (2020)
PRL	PROLACTIN protein	23	Associated with body size, body height, sacral height, chest width, hip bone width, shin circumference and waist height	Liaoning cashmere goats	Wu et al. (2022)
PRLR	prolactin receptor	20
LPGAT1	lysophosphatidylglycerol acyltransferase 1	16	Linked with MSL, TD, TP, UD traits	Murciano-Granadina goats	Luigi-sierra et al. (2020)
ATF3	Activating transcription factor 3	16	Modulate the synthesis of collagen I & II, and linked with MSL trait
PTH1R	parathyroid hormone 1 receptor	22	Acts as receptor for PTH & THrP, regulate ion homeostasis. is linked with goats ANG
APOB	apolipoprotein B	11	Associate with WH, RH, and BL traits	Karachai goats	Easa et al. (2022)
PTPRK	protein tyrosine phosphatase receptor type K	9	Related to chest perimeter
ADAMTS14	ADAM metallopeptidase with thrombospondin type 1 motif 14	28	Encode a procollagen N-proteinase, and associated with MSL of goats	Murciano-Granadina goats	Luigi-sierra et al. (2020)
WNT5A	Wnt family member 5A	22	Regulates planar cell polarity signaling during embryonic development, and linked with BD
CDH11	cadherin 11	18	Modulates postnatal bone growth and osteoblast differentiation. It is liked with RW
EPHA3	EPH receptor A3	1	Essential modulators of bone remodeling, ensure adequate coupling b/n bone resorption and formation. Linked with ANG trait
PIEZO2	piezo type mechanosensitive ion channel component 2	24	Involved in the etiology of digital arthrogryposis. This gene is linked with RLRV
SOCS7	suppressor of cytokine signaling 7	19	Inhibits prolactin, growth hormone, and leptin signaling. The gene also regulates mammary gland physiology. It is linked with TP
SPATA4	spermatogenesis-associated 4 gene	27	Involved in promoting osteoblast differentiation, and linked with RA
DNAH14	dynein axonemal heavy chain 14	16	Encodes an axonemal dynein heavy chain. Mutations in dynein genes can cause skeletal ciliopathies. It is linked with height (HT)
ECEL1	endothelin converting enzyme like 1		Regulating the neuropeptide and peptide hormone activity, and linked with MOT traits
ASGR2	asialoglycoprotein receptor 2	19	Involved in regulation of protein stability and lipid homeostasis, and hence, linked with UA	Mixed dairy goat breeds (composite of Saanen,	Mucha et al. (2018)
ALOXE3	arachidonate lipoxygenase 3	19	Involve in fat metabolism, cell differentiation, and proliferation. Associated with UD	Toggenburg, and Alpine goats)
ARHGEF15	Rho guanine nucleotide exchange factor 15	19	Encodes a protein annotated to be regulating stress fiber assembly. Linked with front legs
BCAR1	breast cancer anti-estrogen resistance1	18	Associated with chest width	Karachai goats	Easa et al. (2022)
AOAH	acyloxyacyl hydrolase	4	Associated with withers height and rump height
ASAH1	N-acylsphingosine amidohydrolase 1	27	Associated with rump height and body length

Note:—Chr. no = Chromosome number; MSL = medial suspensory ligament; TD = teat diameter; TP = teat placement; UD = udder depth; ANG = Angularity; PTH = parathyroid hormone; PTHrP = parathyroid-related peptide; WH = wither height; RH = rump height; BL = body length

Note:—Chr. no = Chromosome number; UA = Udder attachment; RW = Rump width; RA = Rump angle; BD = Body depth; MSL = medial suspensory ligament; TD = teat diameter; TP = teat placement; UD = udder depth; MOT = Mobility; RLRV = Rear legs rear view; ANG = Angularity; PTH = parathyroid hormone; PTHrP = parathyroid-related peptide

In addition, the association of Sirtuin3 (SIRT3) gene with body conformation and growth traits in Malabari and Attappady Black goat breeds has been explored (Silpa et al., 2020). According to Silpa et al. (2020) SIRT3 gene was significantly associated with goats’ body weight, and this gene is highly expressed in the muscle than uterus, liver and ovary, which indicates the involvement of Sirtuin3 (SIRT3) gene in the regulation of growth traits in goats. Sirtuin3 (SIRT3) gene is located on gaits’ chromosome 29, and has 8 exons and 2 transcripts. This gene is mainly localized in the mitochondria (Fu et al., 2014), and regulates various cellular processes, including regulation of the acetylation of several proteins, maintaining the homeostasis of mitochondrial reactive oxygen species by deacetylation of substrates of mitochondrial reactive oxygen species production, and modulate oxidative stress by deacetylation of superoxide dismutase in various tissues (Zhao et al., 2016).

Moreover, in a genome wide association analysis study for body, udder, and leg traits in Murciano-Granadina goats, Luigi-sierra et al. (2020) identified candidate genes associated with conformation and type traits in goats, including genes related to collagen synthesis (ATF3, ADAMTS14, and COL14A1), growth (CGGBP1), development (WNT5A and DNAH14), bon homeostasis and remodeling (PTH1R, CDH11, SPATA4, and EPHA3), limb development (ECEL1 and PIEZO2), and mammary physiology (SOCS7). The authors further stated that for Median Suspensory Ligament (MSL), they were identified two genome-wide significant associations namely, rs268273468 (CHI 16: 69,617,700), and rs268249346 (CHI 28: 18,321,523), which are located close to lysophosphatidylglycerol acyltransferase 1 (LPGAT1), and ADAM metallopeptidase with thrombospondin type 1 motif 14 (ADAMTS14) genes, respectively.

The lysophosphatidylglycerol acyltransferase 1 (LPGAT1) gene is located on chromosome 16 of the Caprine genome, and it has 12 exons, and 2 transcripts. The LPGAT1 gene is an sn-1 specific lysophosphatidylethanolamine acyltransferase that controls the stearate/palmitate homeostasis of phosphatidylethanolamine and its’ methylation pathway metabolites, thereby it regulates lipid biosynthesis associated with body fat content and longevity (Xu et al., 2022). In addition, the LPGAT1 gene encodes an enzyme involved in conversion of lysophosphatidylglycerol into phosphatidylglycerol (Yang et al., 2004). Likewise, the ADAM metallopeptidase with thrombospondin type 1 motif 14 ADAMTS14 gene is located on goats’ chromosome 28 and has 22 exons, and 2 transcripts. This gene is moderately produced by many types of cell, as mesenchymal cells and some immune cells (Dupont et al., 2022), and used for coding procollagen N-proteinase and regulating the immune response (Dupont et al., 2018).

According to Luigi-sierra et al. (2020), activating transcription factor 3 (ATF3), and suppressor of cytokine signaling 7 (SOCS7) genes are positional candidate genes showed associations with median suspensory ligament and teat position traits in the Murciano-Granadina goats, respectively. The ATF3 gene, which is located on the goats’ chromosome 16, has 5 exons, and 2 transcripts. This gene is responsible for controlling collagen I and III productions, beyond its role in regulating matrix metalloproteinases, which instead plays crucial role in ligaments development, renewal, and remodeling (Guenzle et al., 2017). While, the SOCS7 gene, which is located on the goats’ chromosome 19, has 10 exon counts, and 2 transcripts. This gene is members of SOCS gene families, which are negatively regulating cytokine and growth factor signaling, and mammary gland physiology (Luigi-sierra et al., 2020). Particularly, the SOCS7 gene hinders prolactin, growth hormone, and leptin signaling (Sutherland et al., 2007). Furthermore, Luigi-sierra et al. (2020) investigated 19 SNPs at the chromosome-wide level, which are significantly associated with angularity, rump angle, rump width, bone quality, chest width, height, and body depth in Murciano-Granadina goats. According to Luigi-sierra et al. (2020), many of the detected SNPs which have been significantly associated with conformation traits mentioned above are located near to genes regulating bone homeostasis, and skeletal development.

Besides, using genome-wide association study of milk yield and conformations of udder, teat, feet, and legs in Mixed dairy goats, composite breed of the Saanen, Toggenburg, and Alpine breeds, Mucha et al. (2018) detected three genome-wide significant SNPs for conformations of the udder attachment, udder depth, and front legs, which were located in the same genomic region of chromosome 19. In addition, Mucha et al. (2018) stated the polygenic inheritance of conformation traits in goats. Mucha et al. (2018) observed a significant SNP linked with udder attachment between exons 6 and 7 of the asialoglycoprotein receptor 2 (ASGR2) gene, which is located on the goats’ chromosome 19, and has 10 exons and 2 transcripts. Other reports presented the involvement of ASGR2 gene in regulating protein stability and lipid homeostasis, from which udder tissues are created (Mucha et al., 2018; Schrooten et al., 2000). Similarly, Mucha et al. (2018) also detected significant SNPs associated with udder depth, and front legs that were located near arachidonate lipoxygenase 3 (ALOX12), and Rho guanine nucleotide exchange factor 15 (ARHGEF15) genes, respectively. These genes are located on chromosome 19 in the goats’ genome. Moreover, arachidonate lipoxygenase 3 (ALOX12) gene is involved in fat metabolism, cell differentiation and proliferation while Rho guanine nucleotide exchange factor 15 (ARHGEF15) gene is involved in protein coding activities (Mucha et al., 2018).

2.2.2. Potential candidate genes regulating environmental adaptations

Following domestications, goats are undergone extensive natural and artificial selection, as they are adapting to various environmental weather conditions (Wang et al., 2016). Goats are using their behavioral, morphological, physiological, and genetic mechanisms to adapt themselves with the changing environment (Seixas et al., 2017). In goats, adaptation processes to environmental stressors is controlled by a complex network of genes acting together (Onzima et al., 2018). Knowledge on the genetic bases of environmental adaptation in goats help breeders to select animals that can survive and reproduce under adverse environmental weather conditions (Nejad et al., 2017). In this regard, several researches have been conducted to understand the molecular mechanisms of environmental adaptation in different goat breeds. Some of the identified candidate genes associated with environmental adaptation in goats are presented in Table 5.

Table 5. Candidate genes associated with environmental adaptations and their physiological functions from different breeds of goats

Gene symbol		Gene name/ description	Chr. no	Physiological function and associated traits	Studied goat breeds	References
LEPR		Leptin receptor	3	Associated with high-altitude and fitness traits	Tibetan goats	Jin et al. (2020)
LDB1		LIM domain binding 1	26	Associated with high-altitude adaptation
FGF2		Fibroblast growth factor 2	17
EGFR		Epidermal growth factor receptor	22
ADCY4		Adenylate cyclase 4	10	Involved in the regulation of the oxytocin and adrenergic signaling pathway, and insulin secretion	Cashmere goat	Li et al. (2017)
OXTR		oxytocin receptor	22	Involved in oxytocin signaling pathway, functionally related to skin development, fat metabolism, and ion homeostasis
ROCK1		Rho-associated protein kinase 1	24
ACNA1C		Calcium voltage-gated channel subunit alpha1 C	5
SLC24A4		Sodium/Potassium/Calcium Exchanger 4	21	Plays a role in hypoxia-related cellular responses
CACNA2D1		Calcium channel, voltage-dependent, alpha2/delta subunit 1	4	Involved in the renin secretion pathway
AGT		Angiotensinogen.	28
PTGER2		Prostaglandin E receptor 2	10
FGF2		Fibroblast growth factor 2	17	Influenced traits of adaptation to hot evn’t. through thermo-tolerance	Egyptian Barki goats	Kim et al. (2016)
GNAI3		G protein subunit alpha i3	3
PLCB1		Phospholipase C beta 1	13
MYH		mutY like protein	X	Involve in energy and digestive metabolism, and indirectly influenced adaptation to hot arid evn’t.
TRHDE		Thyrotropin releasing hormone degrading enzyme	5
ALDH1A3		Aldehyde dehydrogenase 1 family member A3	21
EPAS1		Endothelial PAS domain protein 1	11	Associated with high-altitude adaptation	Tibetan Cashmere goats	Guo et al. (2019)
KITLG		KIT ligand	5
DSG3		Desmoglein 3	24
RXFP2		Relaxin family peptide receptor 2	12
SOX6		SRY-box transcription factor 6	15
GMEB2		Glucocorticoid modulatory element binding protein 2	13	Associated with adaptation to different ecological environments	Nubian goats	Tarekegn et al. (2021)
ZBTB46		Zinc finger and BTB domain containing 46	13	Associated with adaptation to different ecological environments	Nubian goats	Tarekegn et al. (2021)
ARFRP1		ADP ribosylation factor related protein 1	13
STMN3		Stathmin 3	13
PCK1		Phosphoenolpyruvate carboxykinase 1	13	Associated with arid environment adaptations
CTCFL		CCCTC-binding factor like	13
SPO11		SPO11 initiator of meiotic double stranded breaks	13
BMP7		Bone morphogenetic protein 7	13
PLAGL2		PLAG1 like zinc finger 2	13	Associated with adaptation to oxidative stress
SR XN1		Sulfiredoxin 1	13
TDRD7		Tudor domain containing 7	8	Associated with mitochondrial homeostasis
CDK2		Cyclin-dependent kinase 2	5	Involved in hypoxia-induced apoptosis in Cardiomyocytes. Associated with high altitude adaptations	Tibetan goats	Wang et al. (2016)
SOCS2		Suppressor of cytokine signaling 2	5	Associated with high altitude adaptation
NOXA1		NADPH oxidase activator 1	11	Used to activate NOX1. Associated with high altitude adaption
ENPEP		Glutamyl aminopeptidase	6	Associated with high altitude adaptation
KITLG		KIT ligand	5	A coat color gene, associated with white colors
FGF5		Fibroblast growth factor 5	6	Involved in controlling of hair length in mammals. Associated with high altitude adaptation
HOXC13		Homeobox C13	5	Hair follicle differentiation, growth, and development by regulating the keratin differentiation-specific genes	Ugandan Sebei goats	Onzima et al. (2018)
PPP1R36		Protein phosphatase 1 regulatory subunit 36	10	Involved in tropical adaptation like thermo-tolerance and immune response	Ugandan Mubende goats
HSPA2		Heat shock protein A2	10
KPNA4		Karyopherin subunit alpha 4	1		Ugandan Karamojong goats
MTOR		Mechanistic target of rapamycin kinase	16

Note:—Chr. no = Chromosome number

For instance, Jin et al. (2020) investigated the association of LEPR, LDB1, FGF2, and EGFR genes with high-altitude adaptation, and fitness traits in Tibetan goats. The leptin receptor (LEPR) gene is located on the goats’ chromosome 3, and has 22 exons, and 2 transcripts. This gene is induce up-regulation of the hypoxic ventilatory response, a situation that increase hypoxia induced ventilation to allow the body to intake and process oxygen at higher rates. Besides, it is indicated in the literature that LEPR gene is associated with reproductive traits in Black Bengal goat (Alim et al., 2019). Instead, fibroblast growth factor 2 (FGF2) gene is located in chromosome 17 in the goats’ genome, and has 4 exons, and 2 transcripts. This gene is known member of the fibroblast growth factor families (FGFs), which plays a role in angiogenesis, one mechanism of high altitude adaptation (Presta et al., 2009). According to Jin et al. (2020), genes associated with high altitude adaptation are well expressed in the lungs of highland breeds than the lowland breeds however, they are expressed in a higher extent in the hearts of the lowland breeds. For example, LEPR, LDB1, and FGF2 genes have shown higher expression in the lungs of Tibetan goats than Huanghui goats.

More recently, Tarekegn et al. (2021) has been reported genes linked with adaptation to diverse ecologies, arid environment, oxidative stress, and mitochondrial homeostasis in Nubian goats raised in the Ethiopian lowlands. Noticeably, more genes and candidate genes associated with environmental adaptation have been explored in Cashmere goats (Li et al., 2017), Egyptian Barki goats (Kim et al., 2016), Tibetan Cashmere goats (Guo et al., 2019), Tibetan goats (Wang et al., 2016), and Ugandan goat (Onzima et al., 2018) breeds.

Chr. no = Chromosome number

1. Potential candidate genes regulating disease resistance

Disease in goats can be divided in to two main groups i.e. infectious and non-infectious/ metabolic diseases. In the case of infectious disease, the word infection refers to the colonization of a host by disease causing organisms such as viruses, bacteria, protozoa, helminths and ecto-parasites, while the word disease refers to the pathogenic consequence of infection (Bishop & Morris, 2007). Commonly, the term disease resistance refers to the host’s ability to resist infection, and its disease consequence (Bishop & Morris, 2007). The animal factor, environmental factor, client factor, and rarely veterinarian’s factor are the four basic factors predisposing animals to diseases. Within the animal factor, species, breed, pedigree, and unique genetic composition of an animal determines its disease resistance, and susceptibility to disease (Biobaku & Amid, 2018). This is because, genetic variation between animals in the form of SNPs, CNV, gene, whole gene, or whole chromosomal rearrangement have effects on gene expression and protein function (Mandal et al., 2018).

In addition, it is worthily noted that similar to production traits, explorations of genes, and candidate genes associated with diseases resistance in goats is helpful for breeders to select goats for enhanced resistance to a variety of disease (Mandal et al., 2018). Accordingly, different researches have been identified genes and candidate genes regulating disease resistance potential in different goat breeds (Table 6). For instance, a study in Egyptian Barki goats that are indigenous to the hot-arid environment showed the association of GRIA1, IL2, IL7, IL21, and IL1R1, genes with the nervous and autoimmune response (Kim et al., 2016). The glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) gene, which is located on goats’ chromosome 7, has 17 exons and 2 transcripts. The GRIA1 gene encodes neurotransmitter receptor protein that plays a crucial role in the long-term memory formation (Khalkhkali‑Evrigh et al., 2022). Instead, IL2, IL7, IL21, and IL1R1 are genes that involved in enhancing host defense mechanisms such as the immune and the inflammatory responses through encoding cytokine receptors (Kim et al., 2016).

Table 6. Candidate genes that are associated with disease resistance potential and their physiological functions from different goat breeds

Gene symbol	Gene name/description	Chr. no	Physiological function and associated traits	Studied goat breeds	References
LTF	Lactoferrin	22	Inhibits proinflammatory cytokines. Liked with Mastitis resistance somatic cell count	Damascus goat	Yakan et al. (2018)
ATP2A3	ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3	19	Associated with fecal egg count (FEC)	Yichang White (YCW), Nanjiang Yellow (NJY), and their cross with Enshi Black goats (ESB)	Alam et al. (2019)
HSPA8	Heat shock protein family A (Hsp70) member 8	15	Associated with fecal egg count (FEC) and involve in the resistance of Haemonchus contortus
ESYT1	Extended synaptotagmin 1	5
SERPING1	Serpin family G member 1	15
GRIA1	Glutamate ionotropic receptor AMPA type subunit 1	7	Involved in nervous and autoimmune response	Egyptian Barki goats	Kim et al. (2016)
IL2	Interleukin 2	17	Involved in cytokine receptors that participate in host defense mechanisms, including immune and inflammatory responses. Associate with the nervous and autoimmune response
IL7	Interleukin 7	14
IL21	Interleukin 21	17
IL1R1	Interleukin 1 receptor type 1	11
IRF4	Interferon regulatory factors	23	Hampers PPR virus replication	India native goats	Manjunath et al. (2015)
IRF5		23
TRIM56	Tripartite motif protein	25	Hampers PPR virus replication, and involved in the restriction of bovine viral diarrhea
PPP4R3B	Protein phosphatase 4 regulatory subunit 3B	11	Involved in gluconeogenesis, lipid metabolism. Related with Metabolic syndrome (MetS)	Abergelle goats	Berihulay et al. (2019)
PNPT1	Polyribonucleotide nucleotidyltransferase 1	11	Implicated with multiple metabolic RNA processing-related genes
RARA	Retinoic acid receptor alpha	19	Regulates the expression of target genes conditioned mastitis resistance, and is involved in various biological processes. Associated with response to intramammary infections	French dairy goats (Saanen and Alpine breeds)	Martin et al. (2018)
STAT3	Signal transducer and activator of transcription 3	19	Belongs to the Janus kinase signaling pathway. Influence response to intramammary infection	French dairy goats (Saanen breed)
DGKB	Diacylglycerol kinase beta	14	Regulating innate and adaptive immunity	Small East African	Onzima et al. (2018)
IL10RB	Interleukin 10 receptor subunit beta	1	Involved in type III Interferon Signaling Pathway, and enhance immunity	Kigezi goats
IFNLR1	Interferon lambda receptor 1	1

Note:—Chr. no = Chromosome number

Moreover, in a genome-wide association mapping study for type and mammary health traits in French dairy goats, candidate genes, (RARA, STAT3, STAT5A, and STAT5B) linked with somatic cell count, and intramammary infection has been explored (Martin et al., 2018). The RARA, and STAT3 are genes located on goats’ chromosome 19, which have 12 exons and 2 transcripts, and 24 exons and 2 transcripts, respectively. These genes regulates various physiological process such as the inflammatory and immune response (Suarez et al., 2018).

3. Conclusion

In dairy goats, traits with economic importance, are quantitative traits, which are controlled by many genes and environmental factors, as well as by their interactions and hence, follows a polygenic inheritance pattern. Thus, genetic improvement of dairy goats is critical for enhanced expression of traits with economic significance. This can be done using selective breeding schemes, which depend on phenotypes and estimated breeding value of the traits; but, will not notably improve the traits. Hence, breeders explore candidate genes associated with economically important traits in different dairy goat breeds, and this lead towards new selection paradigm in dairy goat breeding and trait selection. Knowing the genetic bases of economic traits in dairy goat breeds enhances selection accuracy, and accelerate the response to selection. However, in developing countries where numbers of goat population with diversified gene pool are found, exploration of candidate genes associated with economically important traits in dairy goats is almost negligible. Therefore, future researches in these areas should be focused on quantifying candidate genes associated with economically important traits such as milk yield, milk quality, and fertility traits in dairy goat breeds.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

There was no any funding for this work.

Notes on contributors

Mezgebu Getaneh

Mezgebu Getaneh is a Ph.D. student in the department of Animal Genetics and Breeding at Bahir Dar University, Ethiopia

Kefyalew Alemayehu is a professor of Animal Genetics and Breeding at Bahir Dar University, Ethiopia