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Lama2 基因中影响脂肪沉积的同义单核苷酸多态性 (g.36417726C>A) 与摩拉水牛产后乏情期有关。

A synonymous single nucleotide polymorphism (g.36417726C > A) in the Lama2 gene influencing fat deposition is associated with post-partum anestrus interval in Murrah buffalo.

机构信息

Molecular Endocrinology, Functional Genomics & System Biology Laboratory, Animal Biochemistry Division, ICAR - National Dairy Research Institute (NDRI), Karnal, India.

Molecular Endocrinology, Functional Genomics & System Biology Laboratory, Animal Biochemistry Division, ICAR - National Dairy Research Institute (NDRI), Karnal, India.

出版信息

Gene. 2024 Feb 20;896:148032. doi: 10.1016/j.gene.2023.148032. Epub 2023 Nov 24.

Abstract

Postpartum absence of estrus exhibition known as postpartum anestrus interval (PPAI) for more than 90 days after calving is a concerning issue for dairy buffalo farmers' economy. The PPAI duration is influenced by both management practices and animal genetics. Investigating genetic markers associated with PPAI is crucial for incorporating them into marker-assisted selection programs. Towards this goal, our study focused on exploring potential genetic markers from early postpartum adipose tissue gene networks. We successfully identified 24 Single Nucleotide Polymorphisms (SNPs) within 9 candidate genes. In our initial analysis involving 100 buffaloes, we detected a significant association (P = 0.02267) between a specific synonymous SNP within the Lama2 gene (g.36417726C > A) and PPAI. This finding was subsequently validated (P = 0.02937) in a larger cohort of 415 buffaloes, where the SNP explained 1.36 % of the genetic variance. Intriguingly, buffaloes with the CC genotype of this SNP exhibited a PPAI that was 12.71 ± 3.21 days longer compared to buffaloes with AA and CA genotypes. To gain insight into the functional relevance of this SNP, a computational analysis was performed which indicated that the C allele of the SNP (g.36417726C > A) increased the stability of LAMA2 mRNA compared to the A allele. This computational prediction was corroborated by observing a significant increase (P = 0.01798) in Lama2 gene expression (greater than 8-fold) and higher fat percentage (P < 0.05) in adipose tissue of CC genotypes (48.78 ± 1.87 %) compared to AA genotypes (33.59 ± 4.5 %). Furthermore, we noted a significant (P < 0.05) upregulation of C/ebpβ, Pparγ, Fasn, C/ebpα, and Pnpla2 genes, along with the downregulation of Bmp2 and Ptch1 in CC genotypes as opposed to AA genotypes. This observation suggests the involvement of the Pparγ-mediated pathway in both adipogenesis and lipolysis within CC genotypes. In summary, our comprehensive analysis involving association and functional validation underscores the potential of the SNP (g.36417726C > A) within the Lama2 gene as a promising genetic marker against extended PPAI in Murrah buffalo.

摘要

产后乏情期(PPAI)是指奶牛产后 90 天以上仍无发情表现,这对奶农的经济造成了严重影响。PPAI 的持续时间受到管理实践和动物遗传因素的影响。研究与 PPAI 相关的遗传标记对于将其纳入标记辅助选择计划至关重要。为此,我们的研究侧重于从产后早期脂肪组织基因网络中探索潜在的遗传标记。我们成功鉴定了 Lama2 基因内 9 个候选基因中的 24 个单核苷酸多态性(SNP)。在最初涉及 100 头水牛的分析中,我们检测到 Lama2 基因内特定同义 SNP(g.36417726C > A)与 PPAI 之间存在显著关联(P = 0.02267)。这一发现在随后对 415 头水牛的更大队列中得到了验证(P = 0.02937),该 SNP 解释了 1.36%的遗传变异。有趣的是,该 SNP 的 CC 基因型水牛的 PPAI 比 AA 和 CA 基因型水牛长 12.71±3.21 天。为了深入了解该 SNP 的功能相关性,进行了计算分析,结果表明该 SNP 的 C 等位基因(g.36417726C > A)增加了 LAMA2 mRNA 的稳定性,而 A 等位基因则降低了 LAMA2 mRNA 的稳定性。这一计算预测得到了观察结果的支持,即与 AA 基因型(33.59±4.5%)相比,CC 基因型(48.78±1.87%)的 Lama2 基因表达显著增加(P = 0.01798)(大于 8 倍)和脂肪百分比更高(P < 0.05)。此外,我们注意到 CC 基因型中 C/ebpβ、Pparγ、Fasn、C/ebpα 和 Pnpla2 基因显著上调(P < 0.05),而 Bmp2 和 Ptch1 基因下调,而 AA 基因型则相反。这一观察结果表明,Pparγ 介导的途径参与了 CC 基因型的脂肪生成和脂肪分解。总之,我们的关联和功能验证综合分析强调了 Lama2 基因内 SNP(g.36417726C > A)作为一种有前途的遗传标记,可用于对抗穆拉水牛延长的 PPAI。

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