Complex disease & pharmacogenetics

Question 1

What is an allele?

Answer 1

An alternative form of the gene occupying the same locus

Question 2

What is a locus?

Answer 2

Specific position on a chromosome, whereby a gene responsible for a particular trait is located.

Question 3

What is codominance?

Answer 3

Two different alleles of a heterozygote are both expressed in the phenotype

Question 4

What is sex-linkage?

Answer 4

Results when genes are located on the sex chromosomes, whereas autosomal linkage is the converse

Question 5

What is polygenic inheritance?

Answer 5

A single feature is determined by more than one interacting genes
A particular feature can significantly be influenced by environmental factors during development

Question 6

What is a chi-squared test?

Answer 6

A statistical test to evaluate whether the observed phenotypic ratios differ significantly from the theoretical frequencies.

Question 7

What is gene mapping?

Answer 7

A technique used to locate the specific position of a gene occupies on a chromosome

Question 8

What is a phenotype?

Answer 8

Description of the character manifested by a gene

Question 9

What is a genotype?

Answer 9

The genetic constitution of an individual at a particular locus

Question 10

How many blood group allelic forms exist?

Answer 10

3, IA, IB, and IO

Question 11

What are the mendelian traits?

Answer 11

Phenotype is controlled by a single gene, inheritance abides Mendelian principles; homozygous (identical genes); double homozygous cross breed results in single expressed phenotype and genotype within the first filial generation

Question 12

How are Mendelian diseases studied?

Answer 12

Analyzing genetic pedigrees

Question 13

What are the complex traits?

Answer 13

Phenotype is controlled by multiple genes, in addition to environmental influences

Question 14

How are complex diseases studied?

Answer 14

Studied by evaluating affected individuals within a sampled population

Question 15

What are SNPs (Genetics)?

Answer 15

Single nucleotide polymorphisms
DNA sequence variations that occur when a single nucleotide is altered; a common form of variation within the human genome.

Question 16

What is association analysis?

Answer 16

Stratified population-based on genotype groups; identify whether the genotype can distinguish pathology of the disease, conduct a statistical tests to calculate significant difference of results.

Question 17

What are GWAS?

Answer 17

Genome-wide association studies is an observational study of a genome-wide set of genetic variations in different individuals and identifying any variant associated with a trait.

Question 18

What does a genome-wide association study require to be effective?

Answer 18

Requires large sample size, and multiple testing

False positives may occur, thus conduct an agnostic search

Question 19

How is a genome-wide association study conducted?

Answer 19

DNA samples collected from healthy individuals, and those with expressed phenotypic disease traits
DNA and sequences & genotypes are identified, the population is stratified into respective genotype groups.

Question 20

What is a risk allele?

Answer 20

The allele that is associated with the genetic predisposition of the disease; the allele that is evidently most frequency within the population and thus attributed to developing pathogenesis

Question 21

What is an additive model?

Answer 21

The addition of each risk allele will increase the risk of disease to an extent.

Question 22

What are the risk conditions for CVD?

Answer 22

Type 2 diabetes, obesity, high cholesterol, and high blood pressure

Question 23

What are modifiable risk factors?

Answer 23

Risk factors are conditions that increase the risk of developing a disease. Modifiable factors are concerned with precautionary measures that can be undertaken to change and reduce the risk associated with the factors

Question 24

What are some examples of modifiable risk factors?

Answer 24

Diet, sedentary lifestyle, smoking, and exercise

Question 25

What is a risk factor analysis?

Answer 25

Regarding the study of complex disease, identifying modifiable risk factors are pertinent in establishing preventative public health measures and schemes aimed at targeting high-risk groups and lowering the potential for pathology.
Altering habits
Identifying genetic factors can be used to model and predict diseases - strategies can be implemented to facilitate individual lifestyle
Lifestyle habits are observed and collecting within the population, and correlated with risk & frequency of developing CVD.

Question 26

What is heritability?

Answer 26

The level of phenotypic variations attributed to genetic factors

Question 27

How can traits be established through twin studies?

Answer 27

Monozygotic twins have a 100% shared genetic component
Dizygotic twins have 50% shared genetic component
Twins have shared environmental conditions, therefore phenotypic variations can be compared to establish a relationship with the hereditary trait
Significant differences compared with monozygotic twins

Question 28

What is missing heritability?

Answer 28

Single genetic variations cannot account for much of the heritability of diseases, and phenotypes

Question 29

What are the explanations for missing heritability?

Answer 29

Rare single nucleotide polymorphisms (Risk alleles infrequent)
Low-frequency variants with intermediate effect; inability to be recognized during GWAs, gene interactions (not investigated); miscalculated estimation of heritability diagnosis; reproducibility of results

Question 30

What is the definition of pharmacogenetics?

Answer 30

The study of variability in drug responses, due to genetic differences concerned with drug reactions, understanding the principles of pharmacogenetics on a patient individual basis can be used to improve drug therapy and prescription

Question 31

How does genetics influence pharmacology?

Answer 31

Specific medications can be prescribed for the same condition to different patients, patients express degrees of variability in terms of inadvertent drug effects; the concept of personalized medicine

Question 32

What factors effect phenotypic difference?

Answer 32

Genetic differences
Unique environment
Shared environment

Question 33

List some benefits and limitations of a GWAS

Answer 33

Benefits:
1. Can identify SNP-variant associations i.e. risk loci for complex disease
2. Identify at risk individuals
3. Discovery of novel biological mechanisms
4. Inform drug discovery or repurposing
5. Identify ethnic differences

Limitations:
1. Doesn’t identify causal variants – further testing required
2. Can’t identify all heritability (‘missing heritability’)
3. Thresholds – won’t identify rare variants
4. Environmental influence - epigenetics

Question 34

What is the major advantage of WGS(Whole genome sequencing)?

Answer 34

Entire genome scrutinised – every SNP can be identified

Clear identification of disease and disease risk