ABSTRACT
Rare diseases are usually chronically debilitating or even life-threatening with diagnostic and therapeutic challenges in current clinical practice. It has been estimated that 80% of rare diseases are genetic in origin, and thus genome sequencing-based diagnosis offers a promising alternative for rare-disease management. In this study, 79 individuals from 16 independent families were performed for whole-genome sequencing (WGS) in an effort to identify the causative mutations for 16 distinct rare diseases that are largely clinically intractable. Comprehensive analysis of variations, including simple nucleotide variants (SNVs), copy-number variations (CNVs), and structural variations (SVs), was implemented using the WGS data. A flexible analysis pipeline that allowed a certain degree of misclassification of disease status was developed to facilitate the identification of causative variants. As a result, disease-causing variants were identified in 10 of the 16 investigated diseases, yielding a diagnostic rate of 62.5%. Additionally, new potentially pathogenic variants were discovered for two disorders, including IGF2/INS-IGF2 in mitochondrial disease and FBN3 in Klippel-Trenaunay-Weber syndrome. Our WGS analysis not only detected a CNV associated with 3p deletion syndrome but also captured a simple sequence repeat (SSR) variation associated with Machado-Joseph disease. To our knowledge, this is the first time the clinical WGS analysis of short-read sequences has been used successfully to identify a causative SSR variation that perfectly segregates with a repeat expansion disorder. After the WGS analysis, we confirmed the initial diagnosis for three of 10 established disorders and modified or corrected the initial diagnosis for the remaining seven disorders. In summary, clinical WGS is a powerful tool for the diagnosis of rare diseases, and its diagnostic clarity at molecular levels offers important benefits for the participating families.
Subject(s)
Asian People/genetics , Rare Diseases/diagnosis , Rare Diseases/genetics , Undiagnosed Diseases/diagnosis , Undiagnosed Diseases/genetics , Whole Genome Sequencing , Base Sequence , Cohort Studies , DNA Copy Number Variations/genetics , Family , Female , Humans , Male , Microsatellite Repeats/genetics , Molecular Sequence Annotation , Mutation/genetics , PedigreeABSTRACT
Satellite cell is a kind of myogenic stem cells, which plays an important role in muscle development and injury repair. Through proliferation, differentiation and fusion of muscle fiber can satellite cells make new myonuclear, leading to the hypertrophy of skeletal muscle and fiber type transformation, and this would further affect the meat quality. Here, we review the relationship between muscle fiber development and meat quality attributes as well as the influence of the satellite cell differentiation on muscle fiber character. Besides, we also summarize the classical signaling pathway (i.e., Notch etc.) and influence of epigenetic regulation (i.e. miRNA) on muscle quality.
