3.7.1 Basic concepts of genetics
Cell Division
When a parent cell divides into two or more daughter cells, this process is known as cell division. Usually, cell division happens as part of a longer cell cycle. Each parental cell produces two daughter cells, which is how all cells reproduce.
A new cell population might be generated by the division and growth of a single parental cell and its progeny, which would result from the division and growth of the newly formed daughter cells.
In other measures, repeated cycles of growth and division enable the formation of structures made up of millions of cells from a single cell.
Types of Cell division:
The first form of cell division is vegetative division, in which each daughter cell divides to produce two copies of the parent cell, a process known as mitosis. Meiosis is the second, and it produces four haploid daughter cells.
Mitosis: The method by which cells create perfect duplicates of themselves. Mitotic division results in two identical diploid daughter cells. Almost all of the body’s cells, including those in the eyes, skin, hair, and muscles, undergo mitosis.
Meiosis: Instead of producing identical daughter cells as in mitosis, sperm or egg cells are produced in this method of cell division. Meiotic division results in four genetically different haploid daughter cells.
Binary Fission: Bacteria and other single-celled species reproduce by copying themselves (Scholey et al., 2003).
Gene
A gene is a functioning genetic component that produces proteins from nucleotides. Genes are the basic units of hereditary and are sequences of DNA within a chromosome. Chromosomes hold the locations of genes.
Since genes are formed of nucleotide chains, they are truly DNA strands. Nucleotides make up a gene’s chemical structure. Genes are formed of A, T, G, and C nucleotides, which make up a portion of DNA. It forms hydrogen bonds with the nucleotides of the opposing strand and phosphodiester bonds with the nucleotide next to it.
Two categories of components, called core and regulatory, make up the majority of the gene structure.
The core parts or sequences do participate in the production of proteins. While the regulatory components keep gene expression in check (Pearson, 2006).
Transcription and Translation
Proteins are synthesised in a two-step process of transcription to mRNA followed by translation to an immature protein.
The process of making an RNA strand from a DNA strand is called transcription. DNA is once more used as a template during transcription, just as it is during DNA replication. A new RNA molecule is “transcribed” with the information previously contained in DNA molecules.
In order to make proteins, mRNA molecules must go through a process known as translation. A protein with a specified sequence of amino acids can be produced using the nucleotide sequence found in the mRNA molecule (Burmann et al., 2010).
Human Genome
The human genome is made up of 20,000 genes spread across 23 linear chromosomes. A small percentage codes directly for protein sequences, whilst the remaining genes include non-coding single-copy sequences and repetitive DNA.
Humans have two genomes: a nuclear genome and a mitochondrial genome. From the beginning of life (about 4.5 billion years ago) to the emergence of the Homo sapiens species, both of them show the molecular evolution of humans. Because of this, the human genome has traits that are particular to Homo sapiens and traits that are shared by several groups of species. The human nuclear genome contains 3.2 x 10(9) base pairs and is divided into 23 chromosomes of various sizes. The 21st chromosome is the smallest, with 5 x 10(7) base pairs, and the 1st chromosome is the largest, with 2.63 x 10(8) base pairs. Although the nucleotide sequence of each chromosome has been determined, uncertainties remain regarding how the nuclear genome is organized. The exact number of genes encoded by the human genome, for instance, is still unclear, with estimates ranging from 30 to 150 thousand genes. A small percentage of the human nuclear genome is made up of coding sequences. Repeated sequences make up around 50% of the genome, together with non-coding unique sequences. It’s common to incorrectly refer to this region of the genome as “junk DNA.” Genes are distributed unevenly across chromosomes; DNA fragments with low percentages of GC pairs code for fewer genes than those with high percentages of GC pairs (Pennisi, 2001).
Penetrance: the degree to which a specific gene or collection of genes is expressed in the phenotypes of persons carrying it, as assessed by the proportion of carriers exhibiting the distinctive phenotype.
Expressivity: is the amount to which a genotype manifests its phenotypic expression is measured by expressivity. Individuals with a specific mutation can differ in illness severity, but they can also differ in many other features of their phenotypes, such as the age at which disease symptoms appear.
Gene mutations:
Gene mutation happens via four main mechanisms: substitutions, deletions, insertions and frameshift.
| Type of gene mutation: | Summary: |
| Point mutation | A point mutation or substitution is a genetic mutation where a single nucleotide base is changed. Inserted or deleted from a sequence of DNA or RNA. Point mutations have a variety of effects on the downstream protein product. Consequences that are moderately predictable based upon the specifics of the mutation. |
| Substitutions | A substitution is a mutation in which one base is exchanged for another (i.e., a change in a single “chemical letter,” such as changing an A to a G). |
| Insertions | Insertion mutations are the addition of one or more nucleotide base pairs into a DNA sequence. Insertions can vary in size from one base pair incorrectly inserted into a DNA or a section of one chromosome inserted into another chromosome. |
| Deletions | A deletion mutation occurs when part of a DNA molecule is not copied correctly during DNA replication. This uncopied part can vary in size, from a single nucleotide or an entire chromosome. The loss of DNA during replication can lead to a genetic disease. |
| Frameshift | A frameshift mutation is a type of mutation involving the insertion or deletion of a nucleotide in which the number of deleted pairs if not a divisible number of three (codons). The divisible by three is important due to the cell reading a gene in groups of three bases. |
Patterns of Inheritance
An individual’s genotype governs his or her phenotype. Alleles inherited from the person’s parents determine their genotype (one from the maternal and one from the paternal). These alleles regulate the “dominant” or “recessive” nature of a trait. Additionally, whether a trait is “autosomal” or “X-linked” depends on where the alleles are located in the genome. If just one copy of an allele is necessary for the manifestation of a trait, it is said to be dominant. If two copies of an allele are necessary for the expression of a trait, the trait is recessive. In contrast to autosomal traits, which are governed by alleles found on any chromosome other than the X or Y, X-linked traits are those that are governed by an allele that is carried on the X chromosome. The gender of the progeny and the presence or absence of a dominant or recessive allele are two factors that affect the expression of X-linked traits. A Punnett square can be used to calculate the likelihood of simulating a given trait in a child. The use of a Punnett square enables two persons to visualise the potential genotypes of their progeny and assess the likelihood of trait expression, assuming they are aware of their genotype for the trait (Gropman & Adams, 2007).
| Inheritance Pattern | Characteristics | Disease Examples |
|---|---|---|
| Autosomal Dominant | Every affected person usually has an affected parent; it occurs in every generation. | Huntington’s disease, neurofibromatosis, achondroplasia, familial hypercholesterolemia |
| Autosomal Recessive | Both parents of an affected person are carriers, which is rarely common in every generation. | Tay-Sachs disease, sickle cell anaemia, cystic fibrosis, phenylketonuria (PKU) |
| X-linked Dominant | Females are more frequently impacted because all daughters and no sons of an infected father will be affected; males and females in the same generation can be affected if the mother is diseased. | Hypophatemic rickets (vitamin D resistant rickets), ornithine transcarbamylase deficiency |
| X-linked Recessive | Males are more frequently affected; affected males often present in each generation | Hemophilia A, Duchenne muscular dystrophy |
| Mitochondrial | Can affect both males and females, but is only passed on by females because all mitochondria of all children come from the mother; can appear in every generation | Leber’s hereditary optic neuropathy, Kearns-Sayre syndrome |
Bear in mind that most psychiatric disorders show non-mendelian patterns of inheritance. The interplay between genetic factors and the environment is key.
Family, Twin and Adoption Studies
Family studies:
Even while family studies are not as frequently cited as twin and adoption studies, they are nonetheless a relevant and significant element of the heredity vs environment puzzle. Family studies are mostly used to determine the degree of risk that relatives would experience the same mental illnesses as other family members do. Case-control family studies are used, along with population-relative risk estimates for mental disease. The term “relative risk” refers to the difference between the relative risk of a person with a mental disorder and the relative risk of a person without a mental disorder (Shih et al., 2004).
Affective disorder studies noted that the relative risk of developing bipolar disorder is significantly increased in 1st-degree relatives of those with the disorder. Alongside this, the risk of unipolar depression is also increased in families with bipolar disorder.
Autism has a strong genetic aetiology as shown in both family and twin studies.
Twin studies:
Twin studies are a crucial tool for analysing the nature vs. nurture debate. Monozygotic twins, sometimes known as identical twins, are siblings whose genotypes are identical. They are probably the best measure of whether biology influences human qualities and psychopathology. For instance, the idea of identical genes would ideally distribute itself toward the phenotypes of conduct and personality of identical twins if one twin had dark hair, the other twin will also have dark hair. Dizygotic twins, often known as fraternal twins, share exactly half of their genes. They are a very excellent point of reference for identical twins, albeit they are not as ideal as identical twins for determining the levels of genetic influence. Identical twins and fraternal twins both share the exact same age, which distinguishes them from first-degree relatives. Identical and fraternal twin samples are typically used in twin studies; if biology predominates over the environment, identical twins should behave or have more psychopathology in common than fraternal twins.
Where the rate of monozygotic twin concordance is high relative to the rate of dizygotic twin concordance, strong genetic aetiology for the condition can be suggested.
Schizophrenia accumulates in families. In discordant twins, the offspring of both affected and unaffected twins display the same risk of developing schizophrenia.
Adoption studies:
Adoption studies make up a sizable section of research on how genes and environment affect human traits and psychopathology. Studies on adoption are crucial because they take into consideration both biological parents and environmental parents, two sets of variables that could explain variations in behaviour, personality, and psychopathology. Of course, any genetic connections between biological parents and children who are given away are typically explained by genetics, and any environmental connections between adoptive parents and children who are adopted are typically explained by environment.
Direct Gene Analysis
In both basic and pharmacological research, the direct examination of single biological molecules is becoming increasingly significant (e.g. for gene expression analysis). Particularly fascinating new opportunities to examine biological processes in unprecedented depth are offered by single-molecule fluorescence detection. In order to directly identify and analyse RNA and DNA molecules, various academic and corporate research groups are currently working on the development of single-molecule detection-based technologies. When compared to techniques like real-time PCR or DNA arrays, these newly discovered approaches clearly outperform them because they are characterized as homogeneous assays and do not involve any amplification of the target or the signal.
Gene Tracking Analysis
A process for figuring out how one gene is passed down through a family. It is utilised in the diagnosis of hereditary illnesses like Huntington’s disease and cystic fibrosis. Using gene probes, it is possible to identify and choose appropriate molecular markers, such as single nucleotide polymorphisms (SNPs) or restriction fragment length polymorphisms (RFLPs), that are located in or close to the locus of interest. These can then be followed through family members and utilised to identify the illness locus prenatally in upcoming at-risk pregnancies (Jones et al., 2013).
What is a Genetic Marker?
Any change in the nucleic acid sequence or other genetic feature that is easily detectable and used to identify people, populations, or species, or to pinpoint the genes responsible for inheritable diseases, is referred to as a genetic marker (Davey et al., 2011).
What is Linkage Studies?
An investigation into the relationships between genes. The potential for genes and other genetic markers to be inherited together as a result of their close proximity on the same chromosome is known as linkage (Teare & Barrett, 2005).
Linkage association studies can pinpoint the genomic position of a variant that contributes to the likelihood of acquiring a condition.
What is a LOD Score?
A LOD score is a measure of the probability that two genetic characteristics are linked. If the score is high, the qualities are likely to be tightly related and typically inherited jointly. On the other side, low scores show a weak relationship. For a variety of reasons, including the need to comprehend specific genetic disorders and the desire to uncover a gene using knowledge of known genes, geneticists find it crucial to grasp these figures (Abreu et al., 2002).
A LOD score greater than 3.0 is considered evidence for linkage.
A LOD score less than -2.0 is considered evidence to exclude linkage.
Genome-Wide Association Studies
A research strategy known as a genome-wide association study (abbreviated GWAS) is used to find genetic variations that are statistically linked to a risk for a disease or a certain trait. The approach entails scanning the genomes of a large number of individuals in search of genetic variants that are more prevalent in persons with a particular disease or trait than in people without the disease or trait. These genomic variants are often utilised to look for neighbouring variants that are directly responsible for the disease or trait once they have been found.
Genetic Variants
A gene variation is an alteration to a gene’s DNA sequence that takes place throughout time. Gene variation is regarded to be a more accurate word for this type of genetic change than gene mutation because changes in DNA do not necessarily result in disease. A gene’s nucleotides—the building units of DNA—can be affected by one or more variations.
Genetic Influences on Development Including Gene-Environment Interactions
The genetic makeup acquired from the parental egg and sperm as well as environmental elements influences the proper growth of an individual. Our environment affects how our genes are expressed, and our genes affect how our environment affects them. Additionally, helpful for understanding some disorders are environment-gene interactions.
References:
(1) Genetic Alliance (2009). Inheritance Patterns. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK115561/.
(2) ib.bioninja.com.au. (n.d.). Pedigree Charts | BioNinja. [online] Available at: https://ib.bioninja.com.au/standard-level/topic-3-genetics/34-inheritance/pedigree-charts.html.
(3) P Mcguffin, Owen, M.J. and Gottesman, I.I. (2002). Psychiatric genetics and genomics. Oxford: Oxford University Press.