Genetic Basis Of Disease Flashcards
What is a gene?
A functional DNA that is used to make a valuable product (RNA or protein)
A factor that controls a phenotype and segregates in pedigrees according to mendels laws
What is an allele?
Individual version of a gene of DNA sequence at a locus on a single chromosome
What is a loci / locus?
A unique chromosomal location defining the position of an individual gene or DNA sequence
How do we know a disease has a genetic basis?
-If it has a clear Mendelian inheritance pattern (dominant / recessive inheritance pattern)
- if two people sharing more genetic material with affected people are more likely to have the disease
How do we know a disease has a genetic basis?
-If it has a clear Mendelian inheritance pattern (dominant / recessive inheritance pattern)
- if two people sharing more genetic material with affected people are more likely to have the disease
What does it mean if lambda is increased?
Increased risk of disease
What is the odds ratio?
A statistic that quantifies the strength of the association between two events (A and B)
A with B / A without B
Eg number of people with the allele and with disease / number of people with allele without disease
What are monogenic conditions?
High odds ratio, an allele extremely likely to associate with a disease so effectively sufficient by itself
- caused by a single gene
What are polygenic conditions?
Multiple alleles each with a modest odds ratio (each allele not sufficient to cause condition)
Cumulative effect
What is polyphagia?
Abnormally strong, incessant sensation of hunger or desire to eat, often leading to over eating
Does not subside after eating
Symptom of an underlying medical condition - not a condition itself
How is obesity defined?
Using BMI
Equation for BMI? What number would mean obese?
Weight / height^2 (kg/m^2)
Obese = >30kg/m^2
What is the beta value / effect size for genetic risk?
The effect each allele has on a phenotype
What does it mean if:
B > 0
B = 0
B < 0
For genetic risk
B > 0 - positive value indicates increased risk
B = 0 - no risk (OR = 1)
B < 0 - negative value indicates reduced risk (protection) OR < 1
Polygenic risk score equation? What does each part mean?
PRSj - (sum of) Bi * dosage ij
B = risk associated with a particular allele
Dosage = number of each allele the person has (0, 1, 2)
How to calculate the risk contributed by each allele?
B x dosage
How to calculate the overall risk? (PRS)
Polygenic risk score calculated by adding risk for all the alleles
=allele1 (B x dosage) + allele2 (B x dosage) + allele3 (B x dosage) + allele n (B x dosage)
What is a feature of MC4R mutations?
Can have opposite effects on obesity
What does GLP-1 do?
Helps to regulate blood sugar levels —> makes you feel less hungry and prevent cravings. Also slows the emptying of the stomach
What do complex diseases result from?
The interactions between alleles of several genes, and between genotype and the environment
What happens if two loci are close together?
Less likely they are to be separated by meiotic recombination over the generations
What are a and A alleles associated with?
A = red
a = blue
What is a SNP?
Single nucleotide polymorphism
= DNA base which varies between Individuals in a population
What is an effect allele?
DNA sequence which causes a particular condition. Eg by altering a protein
