This gene encodes a CTL protein, and the A polymorphism is correlated with an increased dystocia rate in the calving female. Here, we demonstrate that cows with high birth weights carry an A polymorphism in the 5′ untranslated region (UTR) of solute carrier family 44, member 5 ( SLC44A5). It remains unclear, however, how each choline transporter is involved in proliferation. Hemicholinium-3 (HC-3) is one of the strongest CHT inhibitors and has been shown to inhibit cell proliferation in human colon cancer, and lung cancer cells. There are three systems for choline transport: (i) polyspecific organic cation transporters (OCTs) with low affinities for choline (ii) high-affinity choline transporters (CHTs), and (iii) intermediate-affinity choline transporter-like (CTL) proteins.
Choline deficiency reduces cell proliferation and increases apoptosis, suggesting that choline transporters are important for regulating cell proliferation. Birth weight is a quantitative trait that is controlled by many genes, and an additional whole-genome scan is warranted.Ĭholine is a component of the major phospholipids of cell membranes. However, this method has identified only one gene, which encodes for non-SMC condensin I complex, subunit G, as a genetic factor that modulates fetal growth in cattle. Whole-genome scans for quantitative trait loci (QTL) associated with birth weight or dystocia have been previously conducted. Therefore, selecting for cows with a smaller birth size would prevent dystocia and be beneficial for farmers. Moreover, high milk production in the dam predisposes it to give birth to a smaller calf, and a lower birth size does not have any subsequent adverse effects on milk productivity. The probability of dystocia increases by 13% for each kg increase in birth weight. Selective breeding has resulted in larger cows that have a higher milk production potential, but these larger cows also tend to induce dystocia in the calving female. One study estimated that the cost of dystocia with extremely difficult labor was nearly $400 per incident. This study provides novel insights into the molecular mechanisms that control birth weight in Holsteins and suggests that SLC44A5 may serve as a potential target for preventing dystocia.ĭystocia has a major economic impact on the dairy cattle industry. Taken together, our results suggest that calves with reduced SLC44A5 expression are larger due to enhanced cell proliferation.
Furthermore, cell viability assays indicated that SLC44A5 knockdown increased cell proliferation, whereas SLC44A5 overexpression repressed proliferation. Uptake studies in HeLa cells demonstrated that SLC44A5 knockdown reduces choline efflux, whereas SLC44A5 overexpression resulted in the opposite effect. SLC44A5 encodes a choline transporter-like protein, and choline is a component of the major phospholipids of cell membranes. Luciferase assays and quantitative polymerase chain reaction (QPCR) assays revealed that SLC44A5 transcripts with the A polymorphism are expressed at lower levels than those carrying the G polymorphism. Cows with higher birth weights carried the A polymorphism in the SLC44A5 5′ UTR, and the presence of the A polymorphism correlated with a high rate of dystocia. To identify genes that regulate birth weight, we conducted a genome-wide association study using 1151 microsatellite markers and identified a single nucleotide polymorphism (SNP) associated with birth weight: A-326G in the 5′ untranslated region (UTR) of solute carrier family 44, member 5 ( SLC44A5). Because smaller birth size does not adversely affect subsequent milk production, selecting for cows with a smaller birth size would reduce dystocia rates and be beneficial for both the cattle and the farmers. Dystocia is a major problem for the dairy cattle industry, and the observed high rates of this condition stem from genetic selection to increase subsequent milk production of the calving female.
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