Basic genetics and patterns of inheritance
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Genes are composed of deoxyribonucleic acid (DNA) and are contained on the chromosomes. Each strand of DNA has a specific sequence of four nucleotides, each containing a different base, adenine, thymine, cytosine, or guanine. Adenine pairs with thymine and cytosine pairs with guanine as two complementary strands of DNA are wound together to form a double helix. Genes have a common basic structure (Fig. 20). First, there are upstream sequences that regulate transcription, known as promoters and enhancers. Then, there is a transcription initiation site, followed by a series of alternating exons and introns. The DNA sequence serves as a template from which messenger RNA (mRNA) is made; this process is known as transcription. As transcription proceeds, a primary mRNA is made from the DNA sequence of the gene, which includes the introns. The intron sequences are then spliced out and the exons are linked together to form the mature mRNA molecule. Thus, the exons are the only portions of the gene that specify the final protein product. The mature mRNA molecule is used to make the protein product by the process of translation. Groups of three nucleotides, called codons, code for specific amino acids. Transfer RNA (tRNA) and ribosomal RNA (rRNA) interact with the mRNA to assemble the amino acids into a polypeptide chain to form the final protein molecule.
Biochemical Markers in Ophthalmology
Ching-Yu Cheng, Tien Yin Wong in Ophthalmic Epidemiology, 2022
Initial attempts to identify genomic sequence variations that predispose humans to specific phenotypic traits made in the second half of the 20th century were met with mixed results. However, the completion of the sequencing of the human genome, soon after the dawn of the new century [2, 3], was a truly momentous achievement, marking the birth of genomic medicine. Human DNA is composed of over three billion nucleotide base-pairs distributed across 22 pairs of autosomal chromosomes and two sex chromosomes. In each human DNA sequence position only one nucleotide (adenine, cytosine, guanine, or thymidine) may be present at a time and their succession determines the properties of protein-coding mRNA transcripts. Across the world, the DNA sequence is almost identical and genomic positions that have polymorphic values (variance of nucleotides seen in that position in different individuals) is less than 1% of the genome length [4]. Most sequence polymorphisms are believed to be functionally neutral, but many have downstream consequences that result in the expression of unusual phenotypic traits.
Diagnosis: Nanosensors in Diagnosis and Medical Monitoring
Harry F. Tibbals in Medical Nanotechnology and Nanomedicine, 2017
As libraries of completed human genomes and polymorphisms are accumulating, the knowledge about relationships between genes, diseases, and therapies is being gathered as well. It is not necessary to completely sequence an individual genome to obtain much information that is relevant to health and disease—panels of sample DNA sequences can provide selected information focused on diseases or conditions. Many variations found in the human genome involve a single base substitution—single gene microchips with complementary DNA sequences that have been found to have significance can be used to screen for matches in samples taken from healthy and diseased tissues. This creates a huge potential for medical applications, in diagnostics, the development of drugs, and personalized medicine [330-334,366-369,381-383]. Gene array chips can be mass produced to screen for disease markers and SNPs. MALDI MS and capillary or microdrop elec-trophoresis can be used in laboratories to read and characterize extremely small samples separated and selected on chip targets for diagnoses.
Diagnostics in space: will zero gravity add weight to new advances?
Published in Expert Review of Molecular Diagnostics, 2020
Because next-generation sequencing instruments are often too large and complex for use in space, a newer and more compact system, such as nanopore sequencing technology developed by ONT, is highly suitable for future deployment in space applications. Nanopore sequencing enables direct, real-time analysis of long DNA or RNA fragments by monitoring changes to an electrical current as nucleic acids are passed through a protein nanopore. The resulting signal is decoded to provide the specific DNA or RNA sequence. Compared to other sequencing technologies, the nanopore system has several advantages: it does not require amplification if the template concentration is sufficiently high, it does not require labeling of nucleotides for fluorescent detection, it has relatively shorter sample preparation times, it has less sensitivity to temperature, and it has long read lengths (an average of 10,000 base-pairs) [1,10–13].
Cystic fibrosis – Ten promising therapeutic approaches in the current era of care
Published in Expert Opinion on Investigational Drugs, 2020
Ranjani Somayaji, Dave P Nichols, Scott C Bell
The best known gene-editing strategy is the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 whereby DNA is inputted using a specific technology to correct the mutated sequence of the CFTR gene [79]. The CRISPR/Cas9 system has been adapted from a host defense system that naturally occurs in bacteria whereby they obtain DNA fragments from invading viruses (i.e. bacteriophages) and create segments called CRISPR. These segments serve as a memory and can be used to target the virus upon re-infection to disable it. Similarly, in the lab, a small piece of RNA is created which can bind to a DNA sequence in the genome of human cells as well as to the Cas9 enzyme (or other enzymes in some cases) to cut at a specified location and edit accordingly. This approach has the potential advantages of life-long expression of the corrected gene in that cell or its progeny and reduced risk of insertional mutagenesis. The first studies using organoid-based methodology to explore CRISPR/Cas9 as a potential CF therapy were undertaken in 2013 and demonstrated that gene-editing led to corrected allele expression and a fully functioning organoid providing a proof of concept for this technology [80]. Subsequent studies of CRISPR/Cas9 as well as others including antisense-oligonucleotide-mediated and mRNA-mediated therapies have been conducted using various in vivo models and have demonstrated some success in relation to corrected allele expression and cell/organoid functioning [71,81,82,83].
RNA A-to-I editing, environmental exposure, and human diseases
Published in Critical Reviews in Toxicology, 2021
RNA editing is a post-transcriptional modification that finally induces changes in RNA sequence (Uchida and Jones 2018), which is different from its encoded DNA. In 1986, Benne et al. (1986) reported four extra nucleotides in the mitochondrial cytochrome oxidase (cox) subunit II gene’s transcript which was not encoded in the DNA in trypanosome species. The authors suggested that the RNA editing process was responsible for adding four nucleotides to RNA during or after transcription (Benne et al. 1986), showing a difference from its complementary DNA sequence. Currently, a few different types of RNA editing have been identified in mammalian cells, such as A-to-I and G-to-U. A-to-I is one of the RNA editing types occurring in various RNA species. The conversion of A-to-I that is defined as the editing of adenosine deamination to inosine, is catalyzed by ADAR (Adenosine Deaminase that Act on RNA) enzymes family. The members of the family can catalyze the reaction that converts A into I in double-stranded RNA. In the process of RNA editing, adenosine is converted to inosine after deamination at the C6 position (Nishikura 2016). Inosine can be recognized as guanosine by cell machinery (Bass BL 2002). Finally, it is paired with cytidine in a double-stranded configuration of RNA (Nishikura 2016).
Related Knowledge Centers
- Allele
- Directionality
- DNA
- Nucleobase
- Nucleotide
- Polymer
- Rna
- Sense
- Nucleic Acid Secondary Structure
- Nucleic Acid Tertiary Structure