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ObjectiveTo investigate the clinical and genetic characteristics of hereditary spherocythemia (HS) in Chinese children, and to analyze the potential genotypic/phenotypic associations.MethodsThe clinical data and gene test results of children with HS were collected. All patients were diagnosed by gene test results, and the laboratory results were obtained before splenectomy. The data of red blood cell (RBC), hemoglobin (HB), mean red blood cell volume (MCV), mean red blood cell hemoglobin (MCH), mean red blood cell hemoglobin concentration (MCHC), and hematocrit (HCT) were statistically analyzed according to different mutation genes. Statistical methods for comparison between groups Mann–Whitney test analysis, two-terminal p < 0.05 was considered significant difference.ResultsA total of 15 children were enrolled in our hospital, and 14 variants were found (nine variants have not been reported before), including 10 ANK1 mutations (seven ANK1 truncated mutations) and five SPTB mutations. Patients with ANK1 mutations had more severe anemia than those with SPTB mutations (significantly lower RBC, HB, MCHC, and HCT).ConclusionThis is one of the few studies on the genetic and clinical characteristics of children with HS in China. This study identified the unique genetic and clinical characteristics of Chinese children with HS and analyzed the pathogenic genotype–phenotypic association. The results confirmed that the anemia degree of HS patients caused by ANK1 was more serious than that of patients with SPTB deficiency. However, further study of the correlation between genotype and phenotype requires a larger sample size.

A genome-wide association study (GWAS) was conducted on 23 serum biochemical traits in Chinese Holstein cattle. The experimental population consisted of 399 cattle, each genotyped by a commercial bovine 50K SNP chip, which had 49,663 SNPs. After data cleaning, 41,092 SNPs from 361 Holstein cattle were retained for GWAS. The phenotypes were measured values of serum measurements of these animals that were taken at 11 days after parturition. Two statistical models, a fixed-effect linear regression model (FLM) and a mixed-effect linear model (MLM), were used to estimate the association effects of SNPs. Genome-wide significant and suggestive thresholds were set up to be 1.22E−06 and 2.43E−06, respectively. In the Chinese Holstein population, FLM identified 81 genome-wide significant (0.05/41,092 = 1.22E−06) SNPs associated with 11 serum traits. Among these SNPs, five SNPs (BovineHD0100005950, ARS-BFGL-NGS-115158, BovineHD1500021175, BovineHD0800028900, and BTB-00442438) were also identified by the MLM to have genome-wide suggestive effects on CHE, DBIL, and LDL. Both statistical models pinpointed two SNPs that had significant effects on the Holstein population. The SNP BovineHD0800028900 (located near the gene LOC101903458 on chromosome 8) was identified to be significantly associated with serum high-and low-density lipoprotein (HDL and LDL), whereas BovineHD1500021175 (located in 73.4Mb on chromosome 15) was an SNP significantly associated with total bilirubin and direct bilirubin (TBIL and DBIL). Further analyses are needed to identify the causal mutations affecting serum traits and to investigate the correlation of effects for loci associated with fatty liver disease in dairy cattle.

Menin, the protein encoded by the MEN1 gene, is abundantly expressed in the epithelial cells of mammary glands. Here, we found MEN1/menin expression slowly decreased with advancing lactation but increased by the end of lactation. It happened that the number of bovine mammary epithelial cells decreases since lactation, suggesting a role of menin in the control of mammary epithelial cell growth. Indeed, reduction of menin expression through MEN1-specific siRNA transfection in the bovine mammary epithelial cells caused cell growth arrest in G1/S phase. Decreased mRNA and protein expression of Cyclin D1 was observed upon MEN1 knockdown. Furthermore, menin was confirmed to physically bind to the promoter region of Cyclin D1 through a ChIP assay, indicating that menin plays a regulatory role in mammary epithelial cell cycle progression. Moreover, lower expression of MEN1/menin induced increased epithelial cell apoptosis and caused extracellular matrix remodeling by down-regulating its associated genes, such as DSG2 and KRT5, suggesting that menin’s role may also be involved in the control of cell–cell adhesion in normal mammary glands. Taken together, our data revealed an unknown molecular function of menin in epithelial cell proliferation, which may be important in the regulation of lactation behavior of mammary glands.Electronic supplementary materialThe online version of this article (10.1007/s10911-017-9385-8) contains supplementary material, which is available to authorized users.

MiR‐24‐3p, a broadly conserved, small, noncoding RNA, is abundantly expressed in mammary tissue. However, its regulatory role in this tissue remains poorly understood. It was predicted that miR‐24‐3p targets the 3′ untranslated region (3′‐UTR) of multiple endocrine neoplasia type 1 (MEN1), an important regulatory factor in mammary tissue. The objective of this study was to investigate the function of miR‐24‐3p in mammary cells. Using a luciferase assay in mammary epithelial cells (MAC‐T), miR‐24‐3p was confirmed to target the 3′‐UTR of MEN1. Furthermore, miR‐24‐3p negatively regulated the expression of the MEN1 gene and its encoded protein, menin. miR‐24‐3p enhanced proliferation of MAC‐T by promoting G1/S phase progression. MiR‐24‐3p also regulated the expression of key factors involved in phosphatidylinositol‐3‐kinase/protein kinase B/mammalian target of rapamycin and Janus kinase/signal transducer and activators of transcription signaling pathways, therefore controlling milk protein synthesis in epithelial cells. Thus, miR‐24‐3p appears to act on MAC‐T by targeting MEN1. The expression of miR‐24‐3p was controlled by MEN1/menin, indicating a negative feedback loop between miR‐24‐3p and MEN1/menin. The negatively inhibited expression pattern of miR‐24‐3p and MEN1 was active in mammary tissues at different lactation stages. The feedback mechanism is a new concept to further understand the lactation cycle of mammary glands and can possibly to be manipulated to improve milk yield and quality.