Review: Genetic and protein variants of milk caseins in goats

The milk casein genes in goats, are highly polymorphic genes with numerous synonymous and non-synonymous mutations. So far, 20 protein variants have been reported in goats for alpha-S1-casein, eight for beta-casein, 14 for alpha-S2-casein, and 24 for kappa-casein. This review provides a comprehensive overview on identified milk casein protein variants in goat and non-coding DNA sequence variants with some affecting the expression of the casein genes. The high frequency of some casein protein variants in different goat breeds and geographical regions might reflect specific breeding goals with respect to milk processing characteristics, properties for human nutrition and health, or adaptation to the environment. Because protein names, alongside the discovery of protein variants, go through a historical process, we linked old protein names with new ones that reveal more genetic variability. The haplotypes across the cluster of the four genetically linked casein genes are recommended as a valuable genetic tool for discrimination between breeds, managing genetic diversity within and between goat populations, and breeding strategies. The enormous variation in the casein proteins and genes is crucial for producing milk and dairy products with different properties for human health and nutrition, and for genetic improvement depending on local breeding goals

Genetic Characterization of Indigenous Sudanese Cattle Using FSHR and LHR Genes

The aim of this study was to estimate the genotypic and allelic frequencies of the two polymorphisms located in the receptor of Follicle Stimulating Hormone (FSHR) and Luteinizing Hormone (LHR). One hundred and sixteen blood samples were collected from three native Sudanese dairy ecotypes. The studied samples include 32, 34 and 50 cows from Butana, Kenana and Erashy cattle types, respectively. The DNA was extracted following standard methods. The purified DNA was subjected to PCR-RFLP techniques to identify polymorphisms of the FSHR and LHR genes in the three Sudanese cattle ecotypes. The amplified fragments of FSHR (306 bp) were digested with restriction enzymes ALu resulting in 243 and 63 bp fragments. At exon10in the FSHR gene, all genotyped cows in the investigated native Sudanese population were homozygous for AA genotype. The restriction endonuclease Hhal allowed the identification of three genotypes of the LHR gene at exon 11 among the different cattle ecotypes: The TT, CT and the CC genotypes. The observed genotypic frequencies for LHR gene in Kenana were 33.3% for TT, 41.7% for CT and 25% for CC genotypes. In Butana cows, the frequencies were 18.7 for TT, 50% for CT and 31.3% for CC. In Erashy cattle the frequencies were 33.3% for TT, 50% for CT and 16.7% for CC. It was concluded that the allele of FSHR gene among the tested animals of Kenana, Butana and Erashy is monomorphic while the LHR allele is polymorphic

Validation of somatic cell score-associated SNPs from Holstein cattle in Sudanese Butana and Butana × Holstein crossbred cattle

The Bos indicus zebu cattle Butana is the most commonly used indigenous dairy cattle breed in Sudan. In the last years, high-yielding Holstein dairy cattle were introgressed into Butana cattle to improve their milk yield and simultaneously keep their good adaption to extreme environmental conditions. With the focus on the improvement of milk production, other problems arose such as an increased susceptibility to mastitis. Thus, genetic selection for mastitis resistance should be considered to maintain healthy and productive cows. In this study, we tested 10 single nucleotide polymorphisms (SNPs) which had been associated with somatic cell score (SCS) in Holstein cattle for association with SCS in 37 purebred Butana and 203 Butana × Holstein crossbred cattle from Sudan. Animals were genotyped by competitive allele-specific PCR assays and association analysis was performed using a linear mixed model. All 10 SNPs were segregating in the crossbred Butana × Holstein populations, but only 8 SNPs in Sudanese purebred Butana cattle. The SNP on chromosome 13 was suggestively associated with SCS in the Butana × Holstein crossbred population (rs109441194, 13:79,365,467, PBF = 0.054) and the SNP on chromosome 19 was significantly associated with SCS in both populations (rs41257403, 19:50,027,458, Butana: PBF = 0.003, Butana × Holstein: PBF = 6.2 × 10−16). The minor allele of both SNPs showed an increase in SCS. Therefore, selection against the disadvantageous minor allele could be used for genetic improvement of mastitis resistance in the studied populations. However, investigations in a bigger population and across the whole genome are needed to identify additional genomic loci

Whole-Genome Sequencing Data Reveal New Loci Affecting Milk Production in German Black Pied Cattle (DSN)

German Black Pied (DSN) is considered an ancestral population of the Holstein breed. The goal of the current study was to fine-map genomic loci for milk production traits and to provide sequence variants for selection. We studied genome-wide associations for milk-production traits in 2160 DSN cows. Using 11.7 million variants from whole-genome sequencing of 304 representative DSN cattle, we identified 1980 associated variants (−log10(p) ≥ 7.1) in 13 genomic loci on 9 chromosomes. The highest significance was found for the MGST1 region affecting milk fat content (−log10(p) = 11.93, MAF = 0.23, substitution effect of the minor allele (ßMA) = −0.151%). Different from Holstein, DGAT1 was fixed (0.97) for the alanine protein variant for high milk and protein yield. A key gene affecting protein content was CSN1S1 (−log10(p) = 8.47, MAF = 049, ßMA = −0.055%) and the GNG2 region (−log10(p) = 10.48, MAF = 0.34, ßMA = 0.054%). Additionally, we suggest the importance of FGF12 for protein and fat yield, HTR3C for milk yield, TLE4 for milk and protein yield, and TNKS for milk and fat yield. Selection for favored alleles can improve milk yield and composition. With respect to maintaining the dual-purpose type of DSN, unfavored linkage to genes affecting muscularity has to be investigated carefully, before the milk-associated variants can be applied for selection in the small population.Federal Ministry of Food and Agriculture (BMEL)Peer Reviewe

Whole‐genome SNP genotyping unveils ancestral and recent introgression in wild and domestic goats

After the domestication of goats around 10,000 years before the present (BP), humans transported goats far beyond the range of their wild ancestor, the bezoar goat. This brought domestic goats into contact with many wild goat species such as ibex and markhor, enabling introgression between domestic and wild goats. To investigate this, while shedding light on the taxonomic status of wild and domestic goats, we analysed genome-wide SNP data of 613 specimens from 14 taxonomic units, including Capra hircus, C. pyrenaica, C. ibex (from Switzerland, Austria, Germany and Slovenia), C. aegagrus aegagrus, C. a. cretica, C. h. dorcas, C. caucasica caucasica, C. c. severtzovi, C. c. cylindricornis, C. falconeri, C. sibirica sibirica, C. s. alaiana and C. nubiana, as well as Oreamnos americanus (mountain goat) as an outgroup. To trace gene flow between domestic and wild goats, we integrated genotype data of local goat breeds from the Alps as well as from countries such as Spain, Greece, Türkiye, Egypt, Sudan, Iran, Russia (Caucasus and Altai) and Pakistan. Our phylogenetic analyses displayed a clear separation between bezoar-type and ibex-type clades with wild goats from the Greek islands of Crete and Youra clustered within domestic goats, confirming their feral origin. Our analyses also revealed gene flow between the lineages of Caucasian tur and domestic goats that most likely occurred before or during early domestication. Within the clade of domestic goats, analyses inferred gene flow between African and Iberian goats. The detected events of introgression were consistent with previous reports and offered interesting insights into the historical relationships among domestic and wild goats.Deutscher Akademischer Austauschdienst http://dx.doi.org/10.13039/501100001655Javna Agencija za Raziskovalno Dejavnost RS http://dx.doi.org/10.13039/501100004329Ministry of Science and Higher Education of the Russian Federation http://dx.doi.org/10.13039/501100012190Peer Reviewe

Haplotype analysis and linkage disequilibrium for DGAT1

This study focused on haplotype effects and linkage disequilibrium (LD) for the K232A locus and the promoter VNTR in the DGAT1 gene. Analyses were carried out in three German Holstein Frisian populations (including 492, 305, and 518 animals) for milk yield, milk fat and protein yield, and milk fat and protein content. We found that effects of the promoter VNTR were not significant and explain only a small amount of the variation of the QTL on BTA14. Haplotype effects were less significant than the K232A locus by itself, but the haplotype containing the A allele of the K232A locus and allele 3 with five repeats of the promoter VNTR showed negative effects on protein content when paternally inherited, whereas the haplotype with the A allele and VNTR allele 2 (with six repeats) increased the protein content. Significant differences between these two haplotypes occurred for protein yield as well, pointing to a linked effect that is picked up by the haplotypes rather than a direct effect of the VNTR. The linkage disequilibrium, estimated by D', showed values between 0.29 and 0.59 which is unexpectedly low for a distance of ~10 kb. Only a very low correlation between the two loci was observed due to the almost similar frequencies of haplotypes containing the A or K allele of the K232A locus

Genetic Variants of Candidate Genes Influencing Milk Yield, Composition and Somatic Cell Score in German Holstein Cows

The aims of this study were to estimate the genotype and allele frequencies and genotype effects located in the Acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1), Leptin (Lep/ob),Growth hormone receptor (GHR), Prolactin receptor (PRLR), and Kappa casein (CSN3) genes on milk yield, composition and somatic cell score (SCS) in German Holstein cows. The association analyses were based on data from 1380 German Holstein cows. The allele frequencies of the DGAT1 K232A were 44.2% and 55.8% for the Lysine and Alanine variant, respectively. The allele substitution effect for the Lysine variant was significantly increased the fat (0.30%,

Capture Sequencing to Explore and Map Rare Casein Variants in Goats

Genetic variations in the four casein genes CSN1S1, CSN2, CSN1S2, and CSN3 have obtained substantial attention since they affect the milk protein yield, milk composition, cheese processing properties, and digestibility as well as tolerance in human nutrition. Furthermore, milk protein variants are used for breed characterization, biodiversity, and phylogenetic studies. The current study aimed at the identification of casein protein variants in five domestic goat breeds from Sudan (Nubian, Desert, Nilotic, Taggar, and Saanen) and three wild goat species [Capra aegagrus aegagrus (Bezoar ibex), Capra nubiana (Nubian ibex), and Capra ibex (Alpine ibex)]. High-density capture sequencing of 33 goats identified in total 22 non-synonymous and 13 synonymous single nucleotide polymorphisms (SNPs), of which nine non-synonymous and seven synonymous SNPs are new. In the CSN1S1 gene, the new non-synonymous SNP ss7213522403 segregated in Alpine ibex. In the CSN2 gene, the new non-synonymous SNPs ss7213522526, ss7213522558, and ss7213522487 were found exclusively in Nubian and Alpine ibex. In the CSN1S2 gene, the new non-synonymous SNPs ss7213522477, ss7213522549, and ss7213522575 were found in Nubian ibex only. In the CSN3 gene, the non-synonymous SNPs ss7213522604 and ss7213522610 were found in Alpine ibex. The identified DNA sequence variants led to the detection of nine new casein protein variants. New variants were detected for alpha S1 casein in Saanen goats (CSN1S1∗C1), Bezoar ibex (CSN1S1∗J), and Alpine ibex (CSN1S1∗K), for beta and kappa caseins in Alpine ibex (CSN2∗F and CSN3∗X), and for alpha S2 casein in all domesticated and wild goats (CSN1S2∗H), in Nubian and Desert goats (CSN1S2∗I), or in Nubian ibex only (CSN1S2∗J and CSN1S2∗K). The results show that most novel SNPs and protein variants occur in the critically endangered Nubian ibex. This highlights the importance of the preservation of this endangered breed. Furthermore, we suggest validating and further characterizing the new casein protein variants.Peer Reviewe