Cholesterol deficiency carriers have lowered serum cholesterol and perform well at an elite cattle show

Basiel, Bailey L; Macrina, A.L.; Dechow, C.D.

doi:10.3168/jdsc.2020-18587

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…Our transcriptomic data from the differential expression analysis confirm that the ERV-K LTR insertion indirectly affects the regulation of cholesterol synthesis in addition to its direct effect on APOB transcription. Earlier studies identified that CDC animals show a decreased plasma cholesterol level 11 , 12 . Gross et al 12 suggested that this results from a lack of APOB protein with the consequence of building less HDL, LDL and/or VLDL complexes containing cholesterol.…”

Section: Discussionmentioning

confidence: 99%

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Allele-biased expression of the bovine APOB gene associated with the cholesterol deficiency defect suggests cis-regulatory enhancer effects of the LTR retrotransposon insertion

Becker

Weikard

Heimes

et al. 2022

Sci Rep

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The insertion of an endogenous retroviral long terminal repeat (LTR) sequence into the bovine apolipoprotein B (APOB) gene is causal to the inherited genetic defect cholesterol deficiency (CD) observed in neonatal and young calves. Affected calves suffer from developmental abnormalities, symptoms of incurable diarrhoea and often die within weeks to a few months after birth. Neither the detailed effects of the LTR insertion on APOB expression profile nor the specific mode of inheritance nor detailed phenotypic consequences of the mutation are undisputed. In our study, we analysed German Holstein dairy heifers at the peak of hepatic metabolic load and exposed to an additional pathogen challenge for clinical, metabolic and hepatic transcriptome differences between wild type (CDF) and heterozygote carriers of the mutation (CDC). Our data revealed that a divergent allele-biased expression pattern of the APOB gene in heterozygous CDC animals leads to a tenfold higher expression of exons upstream and a decreased expression of exons downstream of the LTR insertion compared to expression levels of CDF animals. This expression pattern could be a result of enhancer activity induced by the LTR insertion, in addition to a previously reported artificial polyadenylation signal. Thus, our data support a regulatory potential of mobile element insertions. With regard to the phenotype generated by the LTR insertion, heterozygote CDC carriers display significantly differential hepatic expression of genes involved in cholesterol biosynthesis and lipid metabolism. Phenotypically, CDC carriers show a significantly affected lipomobilization compared to wild type animals. These results reject a completely recessive mode of inheritance for the CD defect, which should be considered for selection decisions in the affected population. Exemplarily, our results illustrate the regulatory impact of mobile element insertions not only on specific host target gene expression but also on global transcriptome profiles with subsequent biological, functional and phenotypic consequences in a natural in-vivo model of a non-model mammalian organism.

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Section: Discussionmentioning

confidence: 99%

“…In addition to its molecular genetic background, also pathophysiological consequences of the CD mutation are controversially discussed 11 – 14 . Recent data challenge the recessive inheritance mode of CD.…”

Section: Introductionmentioning

confidence: 99%

Allele-biased expression of the bovine APOB gene associated with the cholesterol deficiency defect suggests cis-regulatory enhancer effects of the LTR retrotransposon insertion

Becker

Weikard

Heimes

et al. 2022

Sci Rep

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Interbreed differences in the cholesterol profile in cattle in Western Siberia

Sebezhko,

Konovalova,

Korotkevich

et al. 2023

Vestn. Novosib. gos. agrar. univ.

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The authors studied the leading indicators of the cholesterol profile of high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C) and total cholesterol (TC) in Black-and-White, Red Steppe and Holstein breeds of the second or third lactation, bred in large livestock farms—complexes on the territory of Western Siberia. Metabolism and concentration of lipid complexes of cholesterol status play a cardinal role in the homeostasis of cellular metabolic processes. The critical role of serum lipoproteins in cholesterol metabolism is well recognised, as is their role as predictors of cardiovascular disease. At the same time, the atherogenic effect of LRN-C is associated with the transfer of fatty acids, which act as energy substrates for ATP synthesis. Anti-atherogenic properties characterise HDL-C and have an antioxidant and anti-inflammatory effect. The concentration of HDL-C - was determined by the precipitation method of phosphotungstic acid with magnesium chloride; the level of LDL-C - by the enzymatic colourimetric direct method, total cholesterol - by the process of enzymatic hydrolysis and oxidation of CHOD-PAP using reagent kits “HDL-Cholesterol-Novo”, “LDLCholesterol-Novo-A”, “Cholesterol-Novo” (“Vector-Best, Russia. The content of OH and LDL-C in the blood serum of cows at the age of the second or third lactation bred in Western Siberia is higher than the generally accepted standard values, which reflects a different degree of adaptation to climatic conditions. Ranked series of breeds (p < 0.05) according to LDL-C: black-and-white → Holstein → red steppe, medians were 4.91; 2.77 and 2.24 mmol/l, respectively. Differences between the indicators of HDL-C and LDL-C in Black-and-White, Red Steppe and Holstein cows were established, which indicates the genetic determination of the level of lipoproteins in the blood serum. The strength of the influence of the cow breed factor on the level of HDL-C in blood serum was 29%, LDL-C - 17%.

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Investigation of hereditary cholesterol deficiency (CD) in Holstein Cattle at the state farms in Türkiye

Özbeyaz,

Özcan

2024

Ankara Üniversitesi Veteriner Fakültesi Dergisi

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Türkiye is exposed to international animal and semen movements. For this reason, Türkiye is very affected by diseases and hereditary disorders. State Farms is a state organization that raises and distributes breeding cattle. This study was aimed at investigating the presence and distribution of mutant alleles causing cholesterol deficiency (CD) disorder in Holstein cattle on state farms. For this purpose, blood and sperm samples were collected from 466 Holstein cattle. The real-time PCR method was used for genotyping. A total of seven cattle were found to be heterozygous. The frequency of the mutant allele was determined to be 0.75%. The kinship of four cattle carrying the mutant allele with Mauglin Storm, the bull in which this disease was first detected, was determined. The presence of cattle carrying the mutant allele in Türkiye is quite low compared to other countries. The Apolipoprotein-B (APOB) mutant allele was found at low frequencies and detected for the first time in Türkiye with this research. Therefore, it is necessary to develop control programs by screening other Holstein herds.

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Cholesterol deficiency carriers have lowered serum cholesterol and perform well at an elite cattle show

Cited by 3 publications

References 13 publications

Allele-biased expression of the bovine APOB gene associated with the cholesterol deficiency defect suggests cis-regulatory enhancer effects of the LTR retrotransposon insertion

Allele-biased expression of the bovine APOB gene associated with the cholesterol deficiency defect suggests cis-regulatory enhancer effects of the LTR retrotransposon insertion

Interbreed differences in the cholesterol profile in cattle in Western Siberia

Investigation of hereditary cholesterol deficiency (CD) in Holstein Cattle at the state farms in Türkiye

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