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Simple Summary: Wuliangshan Black-bone chickens, an indigenous chicken breed in southwestern China, have characteristics of black skin, black bones, and black meat, and are suitable for rearing at high altitudes. After six generations of selection, the bodyweights of chickens have been greatly improved: cocks and hens have reached 2.0 kg and 1.5 kg weight at 126 days of age, respectively. The breast and thigh muscles are the main meat-producing parts of chicken; assessing and documenting the morphological features of breast and thigh muscle development and meat composition in Wuliangshan Black-bone chickens is very important in terms of their genetic breeding and also consumer interest. This study was conducted to illustrate the morphological features of the breast and thigh muscles at four developmental stages (1, 42, 84, and 126 days of age) of Wuliangshan Black-bone chickens and to compare the chemical composition, fatty acid, and amino acid contents of their meat at 126 days of age (D126). In total, 80 chickens (male, n = 40 and female, n = 40) in the sixth generation from the breeding farm were used in the experiment under free-range rearing conditions. The cross-sectional areas (CSA) of muscle fibers and meat composition were compared between different sex and different muscle types. The results showed that gender did not affect the CSA of the breast muscle fibers but did affect the CSA of the thigh muscle fibers at D42, D84, and D126 (p < 0.05). Muscle types affected the CSA of muscle fibers: male chickens exhibited significantly higher values than female chickens at D42, D84, and D126 (p < 0.05). The results of moisture, crude protein, and crude fat at D126 showed that moisture contents were higher in the thigh muscles than in the breast muscles in male and female chickens (p < 0.05). Gender affected the crude protein contents and crude fat contents: the breast muscle crude protein content was significantly higher than that in the thigh muscle, both in males and females (p < 0.05), whereas the crude fat contents were significantly higher in females than in males (p < 0.05); moreover, the thigh muscle fat contents were significantly higher than those of the breast muscles both in males and females (p < 0.05). Gender and muscle types also affected the fatty acid contents: the PUFA contents of the breast and thigh muscles were significantly higher in male than in female chickens (p < 0.05). Muscle types significantly influenced the total EAA, NEAA, and flavor amino acid contents. The total EAA contents of the breast muscles were significantly higher than those of the thigh muscles in males and females (p < 0.05), whereas the total NEAA and total flavor amino acid contents of the thigh muscles were significantly higher than those of the breast muscles (p < 0.05). Our results may lead to a better understanding of the effects of gender on the breast and thigh muscle development and meat composition of Wuliangshan Black-bone chicken. [ABSTRACT FROM AUTHOR]

Background: Traboulsi syndrome is an under-recognized syndromic form of ectopia lentis (EL) caused by the aspartate beta-Hydroxylase (ASPH) variant. The genotype-phenotype profile of ASPH-associated disease is poorly understood due to the rarity of the condition., Methods: We conducted targeted next-generation sequencing and bioinformatics analysis to identify potentially pathogenic ASPH variants in the cohort. Furthermore, we characterized the expression pattern of ASPH and major components of the zonules using single-cell RNA-sequencing (scRNA-seq) and evaluated the genotype-phenotype correlations by combining our data and those from the literature., Results: We identified a novel missense variant c.2075G > A (p.G692D) and a recurrent nonsense variant c.1126C > G (p.R376*) of ASPH in two pedigrees from a Chinese cohort of EL. Both probands were 5-year-old boys with canonical facial dysmorphisms and bilateral anteriorly-dislocated lenses. Other ocular comorbidities included microspherophakia, shallow anterior chamber, and narrow chamber angel. No cardiac involvements or filtering blebs were identified. The single-cell expression atlas of ciliary epithelium demonstrated the coexpression of ASPH with FBN1, FBN2, and LTBP2 in the non-pigmented ciliary epithelium cells. Furthermore, molecular modeling simulation of p.G692D revealed increased affinity to the cb EGF-like domain and a subsequent destabilized calcium-binding motif. The genotype-phenotype analysis demonstrated that patients with cardiac involvements all harbored biallelic truncation variants., Conclusions: The data from this study provide new insights into the genotype-phenotype profile of ASPH-associated disease and implicate the potential role of ASPH in the pathogenesis of EL., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK > 200 U / L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK > 200 U / L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF in vitro. Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH in vitro, and improve the rat ovarian function. Future studies may associate these results with female population. [ABSTRACT FROM AUTHOR]

Volvariella volvacea (V. volvacea), commonly referred to as Chinese (paddy straw) mushroom, is a basidiomycete with a protein-rich volva and pileus. Selecting appropriate reference genes is a crucial step in the normalization of quantitative real-time PCR data. Therefore, 12 candidate reference genes were selected from the V. volvacea transcriptome based on previous studies and then BestKeeper, geNorm, and NormFinder were used to identify reference genes stably expressed during different developmental stages and conditions. Of the 12 candidate reference genes, SPRY domain protein (SPRYp), alpha-tubulin (TUBα), cyclophilin (CYP), L-asparaginase (L-asp), and MSF1-domain-containing protein (MSF1) were the most stably expressed under different experimental conditions, while 18S ribosomal RNA (18S), 28S ribosomal RNA (28S), and beta-actin (ACTB) were the least stably expressed. This investigation not only revealed potential factors influencing the suitability of reference genes, but also identified optimal reference genes from a pool of candidate genes under a wide range of conditions. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations of the actinin alpha 3 gene (ACTN3) R577X polymorphism with physical performance and frailty in an older Chinese population. Methods: Data from 1,463 individuals (57.8% female) aged 70-87 years from the Rugao Longevity and Ageing Study were used. The associations between R577X and timed 5-m walk, grip strength, timed Up and Go test, and frailty index (FI) based on deficits of 23 laboratory tests (FI-Lab) were examined. Analysis of variance and linear regression models were used to evaluate the genetic effects of ACTN3 R577X on physical performance and FI-Lab. Results: The XX and RX genotypes of the ACTN3 R557X polymorphism accounted for 17.1 and 46.9%, respectively. Multivariate regression analysis revealed that in men aged 70-79 years, the ACTN3 577X allele was significantly associated with physical performance (5-m walk time, regression coefficient (β) = 0.258, P = 0.006; grip strength, β = -1.062, P = 0.012; Up and Go test time β = 0.368, P = 0.019). In women aged 70-79 years, a significant association between the ACTN3 577X allele and the FI-Lab score was observed, with a regression coefficient of β = 0.019 (P = 0.003). These findings suggest an age- and gender-specific X-additive model of R577X for 5-m walk time, grip strength, Up and Go Test time, and FI-Lab score. Conclusion: The ACTN3 577X allele is associated with an age- and sex-specific decrease in physical performance and an increase in frailty in an older population. [ABSTRACT FROM AUTHOR]

Nonsyndromic orofacial clefts (NSOCs) are congenital newborn malformations. Myosin heavy chain 9 ( MYH9) is a candidate gene of NSOCs. To investigate the associations between single-nucleotide polymorphisms (SNPs) of MYH9 and NSOC susceptibility, a 2-stage case-control study was designed and 4 potentially functional SNPs of MYH9 (rs12107, rs2269529, rs9619601, rs5756130) were selected and genotyped by iPLEX Sequenom MassARRAY and TaqMan assay in the first stage (599 NSOC cases and 590 controls). The significant SNPs in the first stage were replicated in the second stage (676 NSOC cases and 705 controls) by TaqMan assay. Reverse transcription polymerase chain reaction, cell transfection, and luciferase assay were performed accordingly to explore their functionality. In stage I, rs12107 was nominally associated with NSOCs, whereas rs2269529 showed a significant association (rs12107: Phet = 0.028; rs2269529: Phet = 0.001). In stage II, rs12107 was nominally associated with NSOCs, and rs2269529 showed a significant association (rs12107: Phom = 0.014; rs2269529: Phet = 0.006). In combined stages, these 2 SNPs gained significant associations (rs12107: Pdom = 0.004; rs2269529: Pdom = 4.4 × 10-5). In subphenotype analysis, these 2 SNPs were associated with cleft lip only (CLO) and cleft lip with palate (CLP), and rs2269529 was also associated with cleft palate only (CPO). Haplotype analysis revealed associations between rs12107-G/rs2269529-T and NSOC susceptibility ( P = 0.011). Combined analysis of rs12107 and rs2269529 indicated the risk of NSOCs increased with the number of risk alleles (rs12107-G and rs2269529-T, P for trend = 0.008). MYH9 SNP rs12107 AG + GG and rs2269529 CT + TT were associated with higher MYH9 expression in lip tissues compared with their corresponding wild-type homozygote. For rs12107, higher luciferase activities of G allele than A allele were observed in the luciferase assay. MYH9 was downregulated when transfecting its putative binding target miR-196b-3p into human embryo plate mesenchyme (HEPM) and C2C12 cell lines. For rs2269529, C > T contributed to increased MYH9 messenger RNA. In conclusion, rs12107 and rs2269529 were associated with the expression of MYH9 and contributed to the susceptibility of NSOCs. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to report 6-year clinical prenatal diagnosis experience of Duchenne muscular dystrophy (DMD)-affected families evaluated at a single prenatal diagnosis center in China and establish a reliable and rational prenatal diagnosis procedure for DMD families.Methods: The prenatal diagnosis data of 146 at-risk pregnancies in 131 DMD families referred to our center from 2010 to 2016 were retrospectively reviewed.Results: The mutation detection rate of the probands was greater than 99%. In the 131 families, 50 mothers showed negative results during carrier testing, and de novo exon deletions arose in 51.1% of the probands. Of the 146 pregnancies, 91 were male fetuses, 34 of which were affected. Germline mosaicism was identified three times in this cohort, and recombination of the DMD gene was detected in nine cases.Conclusions: Accurate genetic diagnosis of the proband is important for preventing recurrence in at-risk families. The present results demonstrate the importance of considering maternal germline mosaicism in the genetic assessment. Prenatal diagnosis should be suggested to the parent with a DMD proband whether carrier testing found the causative mutation in the mother's blood or not. Finally, we have developed a prenatal diagnosis algorithm for dystrophinopathies that combines multiplex ligation-dependent probe amplification, quantitative PCR, sequencing and linkage analyses. © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: Hypertrophic cardiomyopathy (HCM) mainly results from autosomal-dominant inherited single heterozygous mutations in cardiac sarcomere genes. Contributions of multiple gene mutations to disease heterogeneity in a three-generation family were investigated.Methods: Clinical, electrocardiographic (ECG), and echocardiographic examination in members of a three-generation Chinese family was followed by exon and boarding intron analysis of 96 genes in the proband using second-generation sequencing. The identified mutations were confirmed by bi-directional Sanger sequencing in all family members and 300 healthy controls.Results: Four missense mutations were detected in the family. These were two novel MYH7-H1717Q and MYLK2-K324E mutations accompanied by the KCNQ1-R190W and TMEM70-I147T mutations. The proband carried all four mutations and showed overlapping HCM and LQT1 phenotypes. Five family members each carried two mutations. Subject II-2 only carried TMEM70-I147T. MYH7-H1717Q and TMEM70-I147T came from the paternal side, whereas KCNQ1-R190W and MYLK2-K324E came from the maternal side. Left ventricle mass indices in MYH7-H1717Q carriers were significantly higher than in non-H1717Q carriers (90.05 ± 7.33 g/m(2), 63.20 ± 4.53 g/m(2), respectively, P < 0.01). Four KCNQ1-R190W carriers showed QTc intervals that were significantly more prolonged than those in non-R190W carriers (472.25 ± 16.18 and 408.50 ± 7.66 ms, respectively, P < 0.05). All MYLK2-K324E carriers showed inverted ECG T waves. The subject with only a TMEM70-I147T mutation showed normal ECG and echocardiographs, suggesting that this had less pathological effects at least in this family.Conclusions: We demonstrate dual LQT1 and HCM phenotypes in this multiple LQT1- and HCM-related gene mutation carrier family for the first time and suggest that LQT-related gene mutations associate with QT interval prolongation and/or arrhythmia in HCM patients. [ABSTRACT FROM AUTHOR]

Alpha-actinin-3 (ACTN3) is absent in 18% of healthy Caucasian individuals owing to homozygosity for a premature stop codon (X) at amino acid 577 (rs1815739). Previous studies have shown a strong association between ACTN3 genotype and human athletic performance. In a study of 452 young Chinese male soldiers, we examined the distribution of ACTN3 genotypes and alleles and analysed the association between ACTN3 genotypes and athletic performance. We found that the frequencies of the ACTN3 R577X genotype (RR 39.8%, RX 43.4%, and XX 16.8%) and R577X allele (R 61.5%, X 38.5%) in young Chinese males were not significantly different from those in Caucasians. We only observed a significant association (P = 0.025) between ACTN3 R577X genotypes and grip strength. Participants with the XX genotype displayed significantly lower handgrip strength than individuals with the RR genotype (P = 0.021), but the difference between XX and RX means (P = 0.258) and that between RR and RX means (P = 0.42) was not significant. We did not observe a strong association between the ACTN3 R577X genotypes and sprint phenotypes or endurance phenotypes. In conclusion, our results indicate that the ACTN3 R577X polymorphism is most strongly associated with grip strength in young Chinese male soldiers. [ABSTRACT FROM PUBLISHER]

Abstract: The pomfret, Pampus punctatissimus, is an important fisheries resource in China, but little is known about its amino acid and fatty acid compositions. Pomfret muscle contained 18.6% crude protein and 4.95% crude fat. Pomfret protein has a well-balanced amino acid composition, with high amounts of glutamic acid (114mg/g), lysine (82.8mg/g), leucine (76.7mg/g), and aspartic acid (76.0mg/g). Twenty two fatty acids were found in pomfret oil and saturated fatty acids were the most abundant (48.3%). Palmitic acid (16:0) was the dominant fatty acid, followed by oleic acid (18:1), DHA (22:6n-3), myristic acid (14:0) and stearic acid (18:0), with percentages of 30.5, 26.3, 12.2, 7.37 and 6.86, respectively. The ratio of n-3/n-6 polyunsaturated fatty acids (PUFAs) was 8.04; thus, pomfret muscle is rich in n-3 PUFA. [Copyright &y& Elsevier]

Myosin heavy chain 9, nonmuscle ( MYH9) and environmental factors have been shown to be associated with nonsyndromic cleft lip with or without cleft palate in several populations. Our study aimed to confirm the contribution of MYH9 and environmental factors to nonsyndromic orofacial cleft risk in western Han Chinese. Four single-nucleotide polymorphisms were investigated in 180 case trios and 224 normal peers in western China using transmission disequilibrium test, family-based association test analysis, and logistic regression models. Strong evidence of linkage disequilibrium was found between these markers and the disease by both single-nucleotide polymorphism analysis (G allele at rs2269529 and T allele at rs16996652) and haplotype analysis (G-T [for rs2269529 and rs16996652] and G-A-T [for rs2269529, rs3752462, and rs16996652] among others). Mothers' illness, medication, and passive smoking during the first trimester may increase the risk of nonsyndromic orofacial clefts, but mothers' vitamin (including folic acid) supplementation during the first trimester is a protective factor. Interactions between mothers' passive smoking during the first trimester and T/T genotype of rs16996652 had statistical significance. Risk factors identified in our study may provide a better understanding of the etiological role of MYH9 and influence of environmental factors in nonsyndromic orofacial cleft incidence. [ABSTRACT FROM AUTHOR]

Although food has been proposed as a possible factor on population regulation of small mammals, evidence of food restriction in field conditions is still lacking. Food restriction is generally thought to occur in high-density years of oscillating populations of small mammals. By using two body condition indices (muscle protein concentration and cleaned carcass index), we investigated variations of body condition of the greater long-tailed hamster (Tscherskia triton) and the striped hamster (Cricetulus barabensis) in the Raoyang County of the North China Plain during a population decline- and low-phase from 1998 to 2003. Our laboratory experiments showed that food restriction reduced muscle protein concentration and cleaned carcass index of greater long-tailed hamster. We found there were significant differences in body condition of hamsters over the six years. Both the muscle protein concentration and cleaned carcass index of T. triton were significantly and positively correlated with its yearly trap successes, which reflected yearly population densities. Muscle protein concentration of C. barabensis was positively correlated with the total yield of the wheat. This observation supported the hypothesis on the in-phase relation between food resources or availability and rodent abundances. During the four seasons, muscle protein concentration of two species was highest in autumn, and lowest in summer. These two body condition indices of wild T. triton in summer and in low phases were similar to 60% food restricted animals raised in the laboratory, but significantly lower than nonfood-restricted animals. Our results indicated that malnutrition occurred in summer when food was not abundant, and in low density years with low grain production (an index reflecting food abundance of rodents) in our study region. Therefore, we concluded that food limitation may play an important role in seasonal and inter-annual population fluctuation of these two hamster species. [ABSTRACT FROM AUTHOR]

Age-related CpG (AR-CpG) sites are currently the most promising molecular markers for forensic age estimation. However, the AR-CpG sites of Han Chinese population remains to be systematically characterized. In this study, we performed genome-wide methylation analyses on 42 whole blood DNA from healthy Han Chinese volunteers (aged from 18 to 62 years) using the Illumina MethylationEPIC BeadChip microarray. As expected, both known and novel AR-CpG sites were identified. Considering the sex difference in aging rate, we then separately selected AR-CpG candidates and built pyrosequencing-based multiple linear regression models for age estimation of males and females. The model constructed from the male sample group (n = 167, aged from 1.50 to 85.71 years) explained 95.22% of variation in age using five AR-CpG sites (chr6:11044864 ELOVL2, chr1:207997068 C1orf132, cg19283806 CCDC102B, cg17740900, and chr10:73740306 CHST3) and yielded a mean absolute error (MAE) of 2.79 years. The model constructed from the female sample group (n = 141, aged from 3.33 to 80.38 years) explained 94.90% of variation in age with six AR-CpG sites (chr6:11044867 ELOVL2, chr1:207997060 C1orf132, chr2:106015757 FHL2, cg26947034, chr16: 67184108 B3GNT9, and chr20:44658203 SLC12A5) and yielded an MAE of 2.53 years. Besides, the estimated age was highly correlated with the actual age (R > 0.97). The robustness of these AR-CpG markers was demonstrated by 10-fold cross-validations. In conclusion, we updated the AR-CpG sites of Han Chinese population and provided two sets of AR-CpG sites for accurate age estimation., (© 2021 Wiley-VCH GmbH.)

Tetralogy of Fallot (TOF) is a common congenital heart defect (CHD). However, the genetic causes are largely unknown. Blood vessel epicardial substance (BVES) is postulated to play a role in embryonic development, and we previously found that the expression of BVES is upregulation in patients with congenital septal defect and that BVES participates in cardiocyte differentiation. We hypothesized that BVES is a candidate gene of TOF. In the present study, the entire coding sequence and splice junctions of BVES were sequenced in 114 unrelated patients with TOF and 400 unrelated healthy individuals used as controls. The functional effects of the exon mutant BVES were characterized in contrast to its wild-type counterpart using a luciferase reporter assay system. Four novel BVES mutations (c.166T>C, c.909C>T, c.540-80C>T, c.958+30A>G) were identified in patients with TOF but not in the 400 controls. Functional analysis indicated that the c.166T>C mutation of BVES was associated with an increased transcriptional activity. This finding suggests that BVES as a novel TOF gene may provide further insight into the molecular mechanisms involved in TOF.

Background & Aims: Hepatocellular carcinoma (HCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. We used an integrative approach to identify HCC driver genes, defined as genes whose copy numbers associate with gene expression and cancer progression., Methods: We combined data from high-resolution, array-based comparative genomic hybridization and transcriptome analysis of HCC samples from 76 patients with hepatitis B virus infection with data on patient survival times. Candidate genes were functionally validated using in vitro and in vivo models., Results: Unsupervised analyses of array comparative genomic hybridization data associated loss of chromosome 8p with poor outcome (reduced survival time); somatic copy number alterations correlated with expression of 27.3% of genes analyzed. We associated expression levels of 10 of these genes with patient survival times in 2 independent cohorts (comprising 319 cases of HCC with mixed etiology) and 3 breast cancer cohorts (637 cases). Among the 10-gene signature, a cluster of 6 genes on 8p, (DLC1, CCDC25, ELP3, PROSC, SH2D4A, and SORBS3) were deleted in HCCs from patients with poor outcomes. In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene DLC1., Conclusions: We used an unbiased approach to identify 10 genes associated with HCC progression. These might be used in assisting diagnosis and to stage tumors based on gene expression patterns., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)