orphan genes, de novo genes

Life begins with a switch in genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA). Despite its importance, the essential regulators of ZGA remain largely unknown in mammals. Based on de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse 2-cell embryos. Nr5a2 is required for progression beyond the 2-cell stage. It binds to its motif within SINE B1/Alu retrotransposable elements found in cis -regulatory regions of ZGA genes...

Escherichia coli can use allantoin as its sole nitrogen source under anaerobic conditions. The ureidoglycolate produced by double release of ammonia from allantoin can flow into either the glyoxylate shunt or further catabolic transcarbamoylation. Although the former pathway is well studied, the genes of the latter (catabolic) pathway are not known. In the catabolic pathway, ureidoglycolate is finally converted to carbamoyl phosphate (CP) and oxamate, and then CP is dephosphorylated to carbamate by a catabolic carbamate kinase (CK), whereby ATP is formed...

BACKGROUND: Fetal skeletal dysplasia (SD) is a common congenital disability comprising a complex group of skeletal disorders with substantial clinical and genetic heterogeneity. Many of these defects are detected prenatally using ultrasound (US). However, the diagnostic accuracy of the US is limited. METHODS: We recruited 55 unrelated fetuses with US-detected skeletal anomalies and performed sequential tests using copy number variation sequencing, targeted skeletal gene panel sequencing, or whole exome sequencing...

Identification of cis -regulatory sequences controlling gene expression is an arduous challenge that is being actively explored to discover key genetic factors responsible for traits of agronomic interest. Here, we used a genome-wide de novo approach to investigate preferentially located motifs (PLMs) in the proximal cis -regulatory landscape of Arabidopsis thaliana and Zea mays . We report three groups of PLMs in both the 5'- and 3'-gene-proximal regions and emphasize conserved PLMs in both species, particularly in the 3'-gene-proximal region...

Leveraging innovative tools to speed up prebreeding and discovery of genotypic sources of adaptation from landraces, crop wild relatives, and orphan crops is a key prerequisite to accelerate genetic gain of abiotic stress tolerance in annual crops such as legumes and cereals, many of which are still orphan species despite advances in major row crops. Here, we review a novel, interdisciplinary approach to combine ecological climate data with evolutionary genomics under the paradigm of a new field of study: genome-environment associations (GEAs)...

BACKGROUND: Fever of unknown origin (FUO) has been difficult to diagnose in pediatric clinical practice. With the gradual change in the disease spectrum, genetic factors have received increasing attention. Limited studies have shown an association between FUO and chromosomal abnormalities. In this study, we investigated the clinical and genetic characteristics of patients with FUO presenting with chromosomal abnormalities in a Chinese pediatric cohort. RESULTS: Chromosomal abnormalities were detected in 5...

BACKGROUND: Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p...

Most vertebrate sex-determining genes (SDGs) emerge as neofunctionalized genes through duplication and/or mutation of ancestral genes that are involved with sexual differentiation. We previously demonstrated dm-W to be the SDG in the African clawed frog Xenopus laevis and found that a portion of this gene emerged from the masculinization gene dmrt1 after allotetraploidization by interspecific hybridization between two ancestral species around 17-18 million years ago. dm-W has four exons consisting of a noncoding exon 1, dmrt1-derived exons 2 and 3, and an orphan exon 4 (Ex4) of unknown origin that includes coding sequence...

Perilla , also termed as purple mint, Chinese basil, or Perilla mint, is a flavoring herb widely used in East Asia. Both crude oil and essential oil are employed for consumption as well as industrial purposes. Fatty acids (FAs) biosynthesis and oil body assemblies in Perilla have been extensively investigated over the last three decades. Recent advances have been made in order to reveal the enzymes involved in the fatty acid biosynthesis in Perilla . Among those fatty acids, alpha-linolenic acid retained the attention of scientists mainly due to its medicinal and nutraceutical properties...

BACKGROUND: Skeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal deformities and may complicate the diagnostic odyssey of patients. In this study, we report the molecular and phenotypic characteristics of patients with dual molecular diagnosis and variable skeletal deformities...

BACKGROUND: Epilepsy is a neurological disorder characterized by the potential to induce seizure and accompanied by cognitive, psychological, and social consequences. CACNA1A gene is a voltage-gated P/Q-type Cav2.1 channel that is broadly expressed in the central nervous system, and the pathogenic variants within this gene may be associated with the epileptic phenotype. In the present study, we collected clinical and molecular data related to epileptic patients with CACNA1A pathogenic variants and investigated possible meaningful relationship between age at onset, neurodevelopmental disorders, type of seizures, brain imaging abnormalities, genotype, and protein domains...

Wild plants serve as a large reservoir of known and yet-unknown viruses and as a source of viral pathogens of cultivated plants. Yellow mosaic disease of forest shrub Ligustrum vulgare (privet) was recurrently observed in Europe for more than 100 years. Using a universal virus identification approach based on deep sequencing and de novo assembly of viral small interfering (si)RNAs we identified a causative agent of this disease in Switzerland and reconstructed its complete 3-segmented RNA genome. Notably, a short 3'-terminal common region (CR) attached to each segment via a ∼53-71 nucleotide poly(A) tract, as determined by RT-PCR sequencing, was initially identified as an orphan siRNA contig with conserved tRNA-like secondary structure...

As drivers of evolutionary innovations, new genes allow organisms to explore new niches. However, clear examples of this process remain scarce. Bamboos, the unique grass lineage diversifying into the forest, have evolved with a key innovation of fast growth of woody stem, reaching up to 1 m per day. Here, we identify 1,622 bamboo-specific orphan genes that appeared in recent 46 Million years, and 19 of them evolved from non-coding ancestral sequences with entire de novo origination process reconstructed. The new genes evolved gradually in exon-intron structure, protein length, expression specificity and evolutionary constraint...

BACKGROUND: Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD. METHODS: Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020...

The "dark transcriptome" can be considered the multitude of sequences that are transcribed but not annotated as genes. We evaluated expression of 6,692 annotated genes and 29,354 unannotated open reading frames (ORFs) in the Saccharomyces cerevisiae genome across diverse environmental, genetic and developmental conditions (3,457 RNA-Seq samples). Over 30% of the highly transcribed ORFs have translation evidence. Phylostratigraphic analysis infers most of these transcribed ORFs would encode species-specific proteins ("orphan-ORFs"); hundreds have mean expression comparable to annotated genes...

Orphan genes are characteristic genomic features that have no detectable homology to genes in any other species and represent an important attribute of genome evolution as sources of novel genetic functions. Here, we identified 445 genes specific to Populus trichocarpa. Of these, we performed deeper reconstruction of 13 orphan genes to provide evidence of de novo gene evolution. Populus and its sister genera Salix are particularly well suited for the study of orphan gene evolution because of the Salicoid whole-genome duplication event (WGD) which resulted in highly syntenic sister chromosomal segments across the Salicaceae...

BACKGROUND: Collagen VI-related dystrophy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy. This disease is caused by causative variants in COL6A1, COL6A2, or COL6A3. Most reported causative variants are de novo; therefore, to identify possible associated causative variants, comprehensive large cohort studies are required for different ethnicities. METHODS: We retrospectively reviewed clinical information, muscle histology, and genetic analyses from 147 Japanese patients representing 130 families, whose samples were sent for diagnosis to the National Center of Neurology and Psychiatry between July 1979 and January 2020...

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population. METHODS: With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families...

The bicaudal D homolog 2 ( BICD2 ) gene encodes a protein required for the stable complex of dynein and dynactin, which functions as a motor protein working along the microtubule cytoskeleton. Both inherited and de novo variants of BICD2 are reported with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). Here, we report a male patient with a novel mutation in the BICD2 gene caused by a heterozygous substitution of arginine with cysteine at residue 162 (Arg162Cys); inherited from his asymptomatic mother...

The estrogen-related receptor (ERR) family of orphan nuclear receptors are transcriptional activators for genes involved in mitochondrial bioenergetics and metabolism. The goal of this study was to explore the role of ERRα in lipid metabolism and the potential effect of inhibiting ERRα on the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). In the current study, three experimental mouse models: high-fat diet, high-carbohydrate diet, and a genetic model of hepatic insulin resistance where the liver hyperinsulinemia signal is mimicked via hepatic deletion of Pten (phosphatase and tensin homolog deleted on chromosome 10), the negative regulator of the insulin/phosphatidylinositol 3-kinase signaling pathway, were used...