GENES AND HOW TO RESEARCH THEM
Scientists use specialised methods to explore the links between genes and individual differences. Many different research methods are used to test genetic theories, which I have detailed below. First, ensure you understand the following key terms.
KEYWORDS
GENOTYPE:
The genes on the 23 pairs of human chromosomes represent a person's genetic makeup.
A genotype never changes; phenotype can change over time.
An example to illustrate the difference between them.
About intelligence, they may explain that an individual might have an intellectual potential (genotype), but they require environmental stimulus such as education for this to develop.
PKU is an example of a disorder caused by a defective gene resulting in severe learning difficulties. However, if identified early and treated with a special diet, individuals show normal levels of intelligence. Other examples, e.g., schizophrenia
PHENOTYPE:
Genetics and the environment determine a person’s actual/observable characteristics. e.g., physical appearance, behavioural characteristics, personality.
THERE ARE TWO TYPES OF TWINS:
MONOZYGOTIC TWINS: MZ or Identical twins. Twins share the same genetic makeup because they develop from a single sperm fertilising a single egg to create a single zygote, which then divides into two separate embryos before continuing to grow. MZ twins have the same genotype / DNA.
DIZYGOTIC TWINS: DZ twins: non-identical twins – or fraternal twins).DZ twins result from two different eggs being fertilised by two different sperm, resulting in two zygotes that grow in parallel. Non-identical twins are no more closely genetically related than any pair of full siblings (that is, sharing, on average, 50 per cent of the DNA that can differ between two people). However, they (conveniently for researchers) happen to be born simultaneously, so we do not need to worry about differences between twins within a pair due to age differences.
NON-EXPERIMENTAL RESEARCH METHODS THAT ANALYSE THE FREQUENCY OF MENTAL ILLNESS IN FAMILIES
PEDIGREE ANALYSIS: A GENETIC FAMILY TREE
A pedigree is a genetic diagram representing a family tree that shows how traits or diseases are passed down through multiple generations. Geneticists use pedigree analysis to trace the inheritance patterns of specific family characteristics, such as genetic disorders. Pedigrees help determine if a trait follows a dominant, recessive, X-linked, or mitochondrial inheritance pattern.
Process: In pedigree analysis, researchers construct a family tree that charts which members are affected by a trait or disease across generations. This allows them to spot inheritance patterns, such as whether the trait skips generations (suggesting recessive inheritance) or is passed more frequently through one sex (suggesting X-linked inheritance). By identifying these patterns, researchers can hypothesise whether a specific gene is responsible and use genetic testing to confirm it.
Example: Before discovering the CFTR gene, which causes cystic fibrosis, pedigree analysis was used to track how the disease was passed down through families, helping researchers understand its recessive inheritance pattern.
LINKAGE ANALYSIS
Linkage analysis is a more specific method for locating the region of a chromosome where a gene associated with a trait or disease is likely to be found. This method builds on pedigree analysis but focuses on tracking genetic markers and DNA sequences with known locations inherited alongside the disease. The principle is that genes located close together on the same chromosome are likely to be inherited together or linked.
Process: In linkage analysis, researchers study families with multiple affected members and analyse the inheritance of genetic markers. They look for markers passed down more frequently with the disease than expected by chance, indicating that the gene causing the disease is near those markers on the chromosome. This narrows down the potential location of the disease-causing gene.
Example: Linkage analysis was crucial in identifying the gene responsible for Huntington’s disease by tracking genetic markers in families with multiple generations affected by the disorder.
KEY DIFFERENCES
The pedigree analysis focuses on identifying patterns of inheritance in families and helps determine whether a trait follows a dominant, recessive, or X-linked pattern. It is more about understanding how the disease moves through generations.
Linkage analysis builds on pedigree data but goes further by identifying genetic markers inherited from the disease, helping to locate the specific region of the genome where the disease-causing gene is likely to be.
GENOME-WIDE ASSOCIATION STUDIES (GWAS)
A Genome-Wide Association Study (GWAS) is used to identify genetic variants across the entire genome that are associated with a particular trait or disease. This method involves comparing the DNA of individuals with the disease (affected group) and those without (unaffected group).
Process: Researchers look for single nucleotide polymorphisms (SNPs) and minor genetic variations. By scanning the entire genome, they can identify SNPs more common in the affected group than in the unaffected group. These SNPs may be linked to the genes responsible for the disease.
Example: GWAS has been used to find genetic variants associated with diseases like diabetes, schizophrenia, and Alzheimer's.
CONCORDANCE RATES OF FAMILIES
Family-based concordance studies examine the genetic material of affected individuals and their close relatives, such as parents and siblings, to see whether specific genetic variants are inherited along with the disease. FAMILY STUDIES Investigate how much a characteristic runs in the family, e.g., the concordance/correlations of rates in 1st, 2nd, and 3rd-degree relatives (correlations essentially).
Process: Researchers look for genetic variants transmitted more often than expected by chance from parents to affected children. This helps identify genetic factors involved in the disease while accounting for family relationships and shared environments.
Example: This method is often used in studying complex disorders like autism, where many genetic factors may be involved.The percentage likelihood that if one individual in a pair has a trait, the other individual also has that trait.
More specifically, Concordance rates are a statistical measure used in genetics and psychology to determine the likelihood that two individuals (often twins) will exhibit a particular trait or disorder. Concordance rates are especially useful in twin studies, where researchers compare the similarities between monozygotic twins (identical, sharing 100% of their genes) and dizygotic twins (fraternal, sharing about 50% of their genes). If the concordance rate is higher in monozygotic twins than in dizygotic twins, it suggests that genetic factors play a significant role in the trait or disorder being studied.
For example, if 60% of identical twins both have a particular trait (like schizophrenia) while only 15% of fraternal twins share that trait, it indicates a genetic influence on schizophrenia.
CONCORDANCE VERSUS CORRELATION
Concordance rates are similar to correlations in that both are measures of how two variables (or individuals) relate to one another:
Correlations measure the strength and direction of a relationship between two continuous variables, such as height and weight. Correlation coefficients range from -1 to +1, where +1 indicates a perfect positive relationship (as one variable increases, the other increases), and -1 indicates a perfect negative relationship (as one increases, the other decreases).
Concordance rates, on the other hand, measure the presence or absence of a specific trait in two individuals, such as the presence of a mental disorder in both twins. Concordance is usually reported as a percentage or a probability rather than a coefficient.
KEY DIFFERENCES:
Concordance focuses more on matching traits (such as "yes or no" outcomes), whereas correlation typically looks at continuous relationships between variables.
Concordance rates are specific to genetic and behavioural traits, often in twin studies, while correlation coefficients are used broadly across various fields to describe relationships between measurable variables.
EXAMPLE
If identical twins have a high concordance rate for a condition like depression (say 70%), it suggests that genetics play a vital role. A high positive correlation between environmental stress levels and the severity of depression (say +0.75) would mean that environmental factors also play a significant role. Both measures help understand how traits or conditions arise from genetics, environment, or a combination.
TWIN CONCORDANCE STUDIES
In twin studies, researchers often compare monozygotic (MZ) twins (identical twins who share 100% of their DNA) raised together with dizygotic (DZ) twins (fraternal twins who share about 50% of their DNA) raised in the same environment. By looking at how similar these twins are for a particular trait (known as the concordance rate), researchers can estimate the influence of genetics on that trait. If MZ twins show a higher concordance rate for a trait than DZ twins, this suggests a genetic basis for that characteristic.
For example, a trait entirely due to genetics, such as blood type, would have a 100% concordance rate in MZ twins, meaning both twins would always have the same blood type. On the other hand, if a trait were not influenced by genetics, the concordance rate between MZ and DZ twins would be similar, indicating that other factors (like environment) are responsible.
Researchers compare the concordance rates between MZ and DZ twins to estimate how much genes influence a trait. Since the only significant difference between these two types of twins is the amount of shared DNA, a more remarkable similarity in MZ twins indicates a more substantial genetic influence. If a trait were entirely heritable, MZ twins would always be identical for that trait, while DZ twins would show less similarity. Conversely, if a trait had no genetic component, MZ and DZ twins would show similar levels of resemblance.
In reality, we rarely see these extremes. For most traits, the influence of genetics is somewhere in between. A well-known meta-analysis of twin studies, often called the "Heritability of Everything" paper, reviewed data across various traits. It found that, on average, the correlation between MZ twins for various traits was 0.6, while the correlation between DZ twins was 0.3.
This means that although identical twins are more similar to each other than fraternal twins, they are not identical (a correlation of 1.0), and fraternal twins are not entirely dissimilar (a correlation of 0.0). Across many studies, this pattern consistently shows that most traits have partial heritability—genes play a significant role, but environment and other factors are also important. Heritability is neither 100% nor 0%, but falls somewhere in between for most characteristics we study.
CONCORDANCE RATES OF SEPARATED MZ TWINS
Studies on twins, particularly monozygotic (MZ) twins, provide a unique opportunity to estimate how much genetics contribute to psychological traits. Since MZ twins share identical genomes, high concordance rates for traits in these twins are often attributed to genetics. However, one limitation is that MZ twins raised together may also experience similar environments and treatment (due to their identical appearance), which can inflate concordance rates.
Researchers conduct studies on MZ twins who were separated at birth and raised apart to better separate the influence of nature (genetics) from nurture (environment). These studies allow researchers to examine how similar twins are for specific traits despite growing up in different environments. Although these studies are rare, they help clarify the genetic vs environmental contributions to various characteristics, which may not be apparent from studies of MZ twins raised together.
CHILDREN OF DISCONCORDANT MZ TWINS
Even studies on separated MZ twins cannot eliminate the influence of environmental factors. One way to further distinguish between genetic and environmental influences is by studying the offspring of discordant MZ twins—twins where one develops a condition like schizophrenia but the other does not. By examining the children of the unaffected twin, researchers can explore whether the risk of the condition is passed on genetically despite the parents not displaying it themselves.
This approach helps control for environmental factors that may influence the development of a condition and can offer more substantial evidence for the genetic basis of a trait. However, such studies are challenging to conduct due to the difficulty of finding sufficient cases of discordant MZ twins, making them a niche but essential research area.
ADOPTION STUDIES
Adoption studies provide another way to disentangle genetic and environmental influences. In these studies, researchers compare traits or characteristics in adopted children with both their biological relatives (whom they share genes with but not environments) and their adoptive parents (whom they share environments with but not genes).
If a trait is highly heritable, adopted children should resemble their biological parents more than their adoptive parents. For instance, if an adopted child’s traits show higher concordance or similarity with their biological parents, it indicates a more substantial genetic influence. Conversely, if they resemble their adoptive parents more, this suggests environmental factors play a more significant role.
Adoption studies thus provide valuable insights into the balance of nature and nurture, controlling for environmental influences that can confound other family studies.
GENETIC RESEARCH USING PEDIGREES
Researchers studying the genetic basis of diseases, including mental illnesses, often use family histories to trace how a disorder runs through families. By constructing pedigrees, they can observe patterns of inheritance and assess whether specific individuals in the family are more likely to be affected by the trait or disease. Here’s a step-by-step look at the process:
Grouping Family Members: The family is divided into two groups: those affected by the trait or disease and those unaffected. This allows researchers to compare genetic material between the two groups.
DNA Analysis: Researchers compare the DNA sequences of family members, looking for regions on chromosomes that are more commonly found in the affected group than the unaffected group.
Identifying Genes: The researchers focus on chromosomal segments that appear to be linked to the disease, narrowing these down to specific genes that may be involved in the condition. Once identified, these genes can be studied further to understand how they contribute to the disease.
EXPERIMENTAL RESEARCH METHODS THAT SEQUENCE GENES
PHYSIOLOGICAL TECHNIQUES
Physiological techniques are used to explore organisms' functional properties, such as their physical and biochemical processes. These techniques allow researchers to observe how genetic variation affects the function of different biological systems.
GENE SEQUENCING
Gene sequencing involves analysing DNA to investigate whether specific genes are associated with traits or diseases. Researchers can pinpoint genetic variations linked to inherited conditions or behaviours by mapping and comparing DNA sequences.
CANDIDATE GENE STUDIES
Candidate gene studies focus on specific genes suspected of playing a role in a disease based on prior knowledge of the gene’s function.
Process: Researchers select specific genes thought to be involved in the disease (due to their known biological roles) and test whether mutations or variations in these genes are more frequent in individuals affected by the disease than unaffected ones.
Example: In studying mental illnesses like depression, researchers might examine genes involved in neurotransmitter pathways, such as the serotonin transporter gene, to assess their contribution to the disorder.
WHOLE-EXOME SEQUENCING
Whole-exome sequencing targets the exons (protein-coding regions of all genes), the most critical areas for producing proteins. This method is more efficient than whole-genome sequencing because it focuses on the areas most likely to affect biological functions.
Process: Researchers compare the exomes of individuals affected by a disease to those of unaffected individuals, searching for mutations unique to the affected group. This technique is effective in identifying rare mutations responsible for genetic disorders.
Example: Whole-exome sequencing has been instrumental in discovering mutations linked to rare genetic disorders, such as Rett syndrome.
WHOLE-GENOME SEQUENCING
Whole-genome sequencing is a comprehensive method that sequences the entire genome, including coding (exons) and non-coding regions. This approach allows researchers to detect all forms of genetic variation, including rare mutations, structural changes, and non-coding sequences that may contribute to diseases.
Process: By sequencing the genomes of affected and unaffected individuals (often family members), researchers compare the results to find genetic changes associated with the disease.
Example: Whole-genome sequencing has been crucial in identifying genetic variations linked to cancers and neurodevelopmental disorders.
SEGREGATION ANALYSIS
Segregation analysis is a statistical approach used to study how family traits are inherited. It helps determine whether a trait follows a particular genetic model, such as dominant, recessive, or multifactorial inheritance.
Process: Researchers analyse large families or groups of families, tracking the inheritance of a trait over generations. Statistical models are then applied to assess whether the inheritance pattern aligns with a specific genetic model.
Example: Segregation analysis has been used to study the inheritance of psychiatric disorders like bipolar disorder, which involves complex genetic and environmental interactions.
ANIMAL MODELS AND GENE KNOCKOUTS
Animal models, such as mice, are used in controlled lab settings to study the effects of specific genes. These models offer a simplified system for maintaining genetic and environmental factors, providing insights into gene functions and disease mechanisms.
In gene knockout experiments, researchers "knock out" or disable a specific gene to observe the effects of its absence on the organism.
Process: Animals are genetically engineered to lack a particular gene (or express a mutated version), and researchers then observe changes in physical, behavioural, or developmental traits. This helps determine the gene’s role in health and disease.
Example: BRCA1 knockout mice are used to study breast cancer, as mutations in the BRCA1 gene increase cancer risk in humans.
EXPERIMENTAL BREEDING
Experimental breeding involves crossing genetically diverse lines of organisms to examine how genetic variation influences traits such as behaviour or physiology. By breeding organisms with different genetic backgrounds, researchers can study the inheritance of specific characteristics and identify the genes responsible.
Example: Breeding two genetically distinct strains of mice can produce offspring with varying behaviours, allowing researchers to explore how genetic differences influence these behaviours.
HAPLOTYPE MAPPING
Haplotype mapping identifies specific combinations of genetic markers or inherited haplotypes. This technique helps locate disease-associated genes by determining whether particular haplotypes are more common in individuals with a disease than in unaffected individuals.
Process: Researchers study families and look for haplotypes consistently inherited with a disease trait. These haplotypes serve as genetic signposts, helping narrow genome regions that might contain disease-causing genes.
Example: Haplotype mapping was a critical method in the Human Genome Project, aiding in identifying genomic regions associated with specific diseases.
CYTOGENETIC TECHNIQUES
Cytogenetic techniques involve microscopic examination of cells' genetic components, particularly chromosomes. These methods help detect chromosomal abnormalities, such as deletions, duplications, or rearrangements, that can be linked to genetic disorders.
Example: Cytogenetic techniques are often used in diagnosing conditions like Down syndrome or various cancers, where chromosome number or structure changes play a crucial role.
BIOCHEMICAL TECHNIQUES
Biochemical techniques focus on examining the molecular and chemical processes within cells. Researchers typically work with cell extracts to analyse proteins, enzymes, or other molecules involved in cellular functions.
These techniques are vital for understanding how genes are expressed and how they interact with cellular processes. They provide insights into gene regulation, disease mechanisms, and metabolic functions.
