25 Oral Exam Questions Flashcards
1
Q
- What are the two major disciplines within Behavioural Genetics?
A
-
Quantitative Behavioural Genetics (a study of phenotypic variation in populations, which aims to distinguish the (biologically) heritable portion from the nonheritable (or nonbiologically heritable) portion of that variation)
* Simply put, the phenotypic value (P) of an individual is the combined result of its genotype (G) and the effects of the environment (E):
P = G + E
- We can study Quantitative behavioural genetics using a number of research designs to undersatnd how traits are partly influeneced by genes and partly by environment
- Twin Design
- Adoption Design
- Sibling Design
- Genome-wide Complex Trait Analysis (GCTA) is an Additive genetics method - comparing DNA of unrelated individuals - comparing locus - see how much genes influence a phenotype
-
Molecular Genetics - studies the structure and function of genes at a molecular level. The study of chromosomes and gene expression of an organism can give insight into heredity, genetic variation, and mutations.
- The Human Genome Project was a molecular genetics project that began in the 1990s and was projected to take fifteen years to complete. However, because of technological advances the progress of the project was advanced and the project finished in 2003, taking only thirteen years.
- The quantitative trait locus (QTL) model for common complex disorders
- QTLs are mapped by identifying which molecular markers (such as SNPs or AFLPs) correlate with an observed trait.
- This is often an early step in identifying and sequencing the actual genes that cause the trait variation.
2
Q
- What is an association study?
A
- An examination of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait.
- Look for gene versions which are different in affected individuals and those in unaffected (case/ control studies)
- In genetics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, orWGAS
- Association study designs require:
- Large sample sizes
- Large numbers of genetic markers
- Not currently economically viable
- Gap between heritability and GWA identified associations = missing heritability problem
3
Q
- Is Heritability fixed at birth?
A
- Heritability is the extent to which genetic individual differences contribute to individual differences in traits
- The heritability of most traits is esitmated to be 40-60% (IQ controversially has been suggested as 40% heritable) and is fixed at birth
-
GCTA (Gene wide complex trait analysis) heritability estimates are substantial:
- Height & Weight
- Psychiatric and mediacal disorders
- General congnitive ability
- Use DNA of unrelated individuals, compare locus by locus and see if they are more similar in certain phenotypes etc., see how much of DNA influences a phenotype/ how heritable a phenotype is.
- This is a QUANTITATIVE genetics method, not a molecular genetics method
- Heritability of most traits ~ 40-60%
- Largest GWA associations ~ 1%
- Putting all known SNP associations together accounts for little variance
- Gap between heritability and GWA identified associations = missing
heritability problem
4
Q
- What are the aims of Molecular Genetics?
A
- understanding and treating genetic diseases
- closing the missing heritability gap - currenlty only a small proportion of genes have been found that influences for example educational attainment
- Extending QTLM to account for more genetic varience in traits
- studies the structure and function of genes at a molecular level. The study of chromosomes and gene expression of an organism can give insight into heredity, genetic variation, and mutations. This is useful in the study of developmental biology and in understanding and treating genetic diseases.
- The Human Genome Project is a molecular genetics project that began in the 1990s and was projected to take fifteen years to complete. However, because of technological advances the progress of the project was advanced and the project finished in 2003, taking only thirteen years.
5
Q
- What are the aims of Quantitative Genetics?
A
- to find quantitative traits (a measurable phenotype that depends on the cumulative actions of genes and the environment)
- estimates of G vs E using twins, siblings, parents and offspring, rather than from more distantly related (and therefore less similar) subjects.
- The standard error for heritability estimates is improved with large sample sizes.
- Quantitative Genetics is the study of the inheritance of traits that show a continuous distribution of phenotypes in a segregating (population of genes).
- Traits that are controlled by many genes also exhibit quantitative inheritance as each gene segregates in a Mendelian fashion. (Mendelian inheritance is a set of rules about genetic inheritance.
- Gregor Mendel, father of modern genetics. The basic rules of genetics were first discovered by a monk named Gregor Mendel in the 1850s, and published in 1866.)
*
6
Q
- Define A
A
From ACE we split varience into - : i) Additive Genetics,ii) Common Environment, iii) Environment specific to each twin (nonshared environment)
- Additive genetics (heritability)
- Individual differences caused by the independent effects of alleles (alternative form of a gene) or loci that “add up”. (In contrast to nonadditive genetic variance, in which the effects of alleles or loci interact.)
- A mechanism of quantitative inheritance such that the combined effects of genetic alleles at two or more gene loci are equal to the sum of their individual effects.
7
Q
- Define C
A
From ACE: i) Additive Genetics,ii) Common Environment, iii) Environment specific to each twin (nonshared environment)
Common Environment
- Environmental factors responsible for resemblance between family members
- urban environment
- parents divorcing
- low income or poverty
8
Q
- Define E
A
From ACE: i) Additive Genetics,ii) Common Environment, iii) Environment specific to each twin (nonshared environment)
Environment specific to each twin (nonshared environment)
- A traumatic experience
- A life event in one twin
- Different relationships in the family
- parenting can act as a nonshared einvironmental factor
9
Q
- List 5 facts about DNA (Deoxyribonucleic acid) - (GO for 9)
A
Deoxyribonucleic acid (DNA):
- A double-stranded molecule held together by weak bonds between base pairs of nucleotides.
- The four nucleotides in DNA contain the bases: adenine (A), thymine (T) & guanine, (G), cytosine (C)
- In nature, base pairs form only between A and T and between G and C.
- The base sequence of each single strand can be deduced from that of its partner (eg A->T T>A).
- 3 Billion base pairs (3,000,000,000) (approx 2% genes)
- 2 metres of DNA in each cell
- More than 99% of the DNA sequence is the same for everybody
- Only ~ 1% of the DNA sequence is variable (still a lot of variation!)
- There are several types of DNA variation (e.g., number of repeats of a particular stretch of DNA (copy number variations - CNVs); chromosomal abnormalities (deletions, duplications, substitutions); single nucleotide polymorphisms)
10
Q
- What are microarrays?
A
- A DNA microarray (also commonly known as DNA chip or biochip) is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome.
11
Q
- What is SNP?
A
- Single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide.
- For most of the DNA sequence we share the exact same sequence - they are specific sections in the DNA that can differ between humans - these are individual differences SNPS.
- For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA.
- About 10 million SNPs have been identified of which about 3 million are common.
- SNPs that may help predict an individual’s response to certain drugs, susceptibility to environmental factors such as toxins, and risk of developing particular diseases.
- SNPs can also be used to track the inheritance of disease genes within families.
- Future studies will work to identify SNPs associated with complex diseases such as heart disease, diabetes, and cancer.
- Ultimately the entire DNA sequence will be sequenced then there will be no need for genotyping - babies are predicted to be sequenced at birth
12
Q
- What is the ‘QTL model?’
A
- The Quantative Trait Loci Model - It is a probabilisitc model aiming to understand how genes influence perceived individual differences in traits
- Quantitative traits are phenotypes (characteristics) that vary in degree and can be attributed to polygenic effects, i.e., the product of two or more genes, and their environment.
- A quantitative trait loci (QTL) is a section of DNA (the locus) that correlates with variation in a phenotype (the quantitative trait). …
- Multiple QTL models are recommended as CONVENTIONAL methods for the detection of quantitative trait loci (QTLs) are based on a comparison of single QTL models with a model assuming no QTL
- There is evidence that many QTLs are additive - it may incerase risk if we are talking about disorders - the more genes we have that influence schizophrenia the more chance there is of it being observed
- However, with extroversion we would say there are alleles that increase the probablity of extroversion and alleles that decrease the probablity - all of these are additive..
- The model is powered to detect 1% effect sizes (useful as there are
- Two key genetic concepts underlie the ‘generalist genes’ action:
- Pleiotropy: a gene that affects many traits
- Polygenicity: many genes affect one trait
- QTL model:
- Quantitative: any trait that is continually distributed
- There are locations in our DNA that is related to the variability of a trait
- Each circle represents a person, the shape is a normal distribution with 70% of people in the middle
- The stripy circle is a person carrying one yellow and one red allele on a particular SNP
- Fundamental problem: every circle should be filled in
- The graph indicates that the yellow allele is a risk allele, but it also suggests you can also be a superb reader with a yellow allele
- The QTL problem
Association study designs require:
–Large sample sizes
–Large numbers of genetic markers
• Problem: not economically viable
–$0.1 per genotype
–1000 samples
–100,000 genetic markers
–$10 Million
13
Q
- Describe the Twin Method.
A
The twin method is used to try and understand the heritiability of traits by comparing the correlations between (monozygotic MZ) twins and (dizygotic Dz) twins.
The key rationale for the twin method is that idenitcal twins share 100% of the genes that can differ between humans (known as segregating DNA) wheras non-identical twins share 50%. Segregating DNA is ~ 1% of our genes.
- Recruit a large sample of identical twins and a large sample of non-identical twins.
- We compare the similarity between Mz twins on a particular trait as compared to the similarity between Dz twins
- Correlation between twin 1 and twin 2 in the sample is assessed on continuous traits - eg a score for mathematics..
- If it is a medical disorder it is called a concordance (i.e. if one twin has schizophrenia does the other one?) Higher concordence rates in Mz suggest more genetic influence
- Then we have these a correlation number of for example 0.6 for Mz twins and 0.3 for Dz twins.
- We compare these numbers - and based on these we can make claims about the proportion of the trait attributed to genes and the proportion attributed to environment. It will almost always be both nature and nurture.
Limitations of standard twin studies have led to studies of:
- Twins reared apart
- Offspring of twins
14
Q
- Describe the Adoption Method
A
Adoption studies are one of the classic tools of behavioral genetics.
- An example: Comparison of adoptive and biological sibling pairs
- We can compare adoptive vs biological siblings to conclude about genetic and environmental influences on traits:
- Adoptive sibling pairs similar? - shared environment only
- Biological siblings - genes 50% + shared environment
- NB// Other comparisons can be made using this design (e.g. resemblance between adopted child and birth parents is due to genetics; resemblance between adopted child and adoptive parents is due to shared environment)
- These studies are used to estimate the degree to which a trait varies in response to environmental and genetic variation.
- Adoption studies are typically used together with twin studies when estimating heritability.
Assumptions of the adoption design
- Representativeness:
- of general population? - Yes in general
- Prenatal environment:
- only genes make mother same as child
- Selective placement:
- adoptive vs biological parents only similar due to genes
- Assortative mating:
15
Q
- How can we estimate the influence of non-shared environment?
A
We can extimate by looking at what makes identical twins different as this can only be non-shared environment as they share 100% genes.
We can find E the Environment specific to each twin (nonshared environment) by undertaking a simple set of calculations:
By comparing DZ (dyzygotic twins) with MZ (monozygotic) twins we have as a starting point:
rMZ = A + C
rDZ = .5A + C
rMZ - rDZ = 0.5A
WE therefore get A = 2(rMZ - rDZ)
C = rMZ - A
E = 1 - rMZ
The varience in non-shared environment E = 1 - rMZ
E = 1 - A + C
17
Q
- What is epigenetics?
A
- Epi - above - beyond the genes.. Our DNA is in every cell of our body but depending on its locations different genes will be expressed or silenced
- It is both a field of study and a continuous process our bodies go through linked to house keeping genes (within the DNA) and environmental factors
- For example in the skin only genes relevant to the skin will be expresed - genes relevant to neurons would be silent (methelenated).
- The same DNA sequence gives rise to different expressions at different times in different organs..
- The study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself
- Such effects on cellular and physiological phenotypic traits may result from external or environmental factors that switch genes on and off and affect how cells express genes
- These gene espressions may or may not be heritable and to say they are heritiable is controversial
- The Epigeonome regulates gene expression. It describes all possible expressions of my genes (biological prcesses etc). The epigenome can be dynamically altered by environmental conditions and regulates many processes.. digestion etc..
19
Q
- What does menthyl do to genes?
A
- DNA methylation is an epigenetic mechanism that occurs by the addition of a methyl (CH3) group to DNA
- Methylenatied genes can not be expressed - they are silenced
- Nonmethylinated genes permit genes to be expressed..
- Methylation modifies the function of the DNA.
- When located in a gene promoter, DNA methylation typically acts to repress gene transcription.
- Yellow mouse – un-methylated mutation in the Agouti gene (can be manipulated with high methylinated diet)
methyl-rich diet)
20
Q
- Define the following concepts: Genome- Epigenome – Transcriptome – Proteome - Phenome
A
The concepts are all linked in a chain of relationships. The ome at the end referes to an entirity of the information being desribed. So to give a clear definition I will define the concepts using myself..
- The genome describes the full sequence of my DNA - (both coding and noncoding that make up approx. 3 billion base pairs - mainly static).
- The Epigeonome regulates my gene expression. It describes all possible expressions of my genes (biological prcesses etc). The epigenome can be dynamically altered by environmental conditions and regulates many processes.. digestion etc..
- Transcriptome - This is where the genes (coding only) are coded into proteins via RNA (a different language to DNA) under the influence of all the epigenetic processes. It is a collection of all the gene readouts present in a cell
- Proteome - a collection of all possible proteins that my genome is cabable of and all possible amounts of proteins at different times
- Phenome - collection of all possible phenotypes that my genome can produce.
The sequence of the DNA will determine which proteins I am capable of producing. How much and when these proteins are produced is a continuously regulated process by epigenetic processes.
22
Q
- Give an example of a gene-environment interaction.
A
- Gene–environment interaction (or genotype–environment interaction or G×E) is when two different genotypes respond to environmental variation in different ways.
- We can think of this as how sensitive people are - some are more sensitive to the gene-environment interaction and can be affected more by it -
- We should not confuse with gene-environment correlation
- Phenylketonuria (PKU) is a human genetic condition caused by mutations to a gene coding for a particular liver enzyme.
- Newborns found to have high levels of phenylalanine in their blood can be put on a special, phenylalanine-free diet. If they are put on this diet right away and stay on it, these children avoid the severe effects of PKU.
- This example shows that a change in environment (lowering Phenylalanine consumption) can affect the phenotype of a particular trait, demonstrating a gene-environment interaction.
- In the absence of this enzyme, an amino acid known as phenylalanine does not get converted into the next amino acid in a biochemical pathway, and therefore too much phenylalanine passes into the blood and other tissues.
- This disturbs brain development leading to mental retardation and other problems. PKU affects approximately 1 out of every 15,000 infants in the U.S. However, most affected infants do not grow up impaired because of a standard screening program used in the U.S. and other industrialized societies.
- IMG in question - This norm of reaction shows lines that are not parallel indicating a gene by environment interaction. Each genotype is responding to environmental variation in a different way.
