Genetics of Common Disease

Question 1

What is mutated in cystic fibrosis?

Answer 1

→ F delta 508

→ phenylalanine codon is removed

Question 2

What is the inheritance pattern like in mendelian disease?

Answer 2

→ Recessive loss of function
→ Autosomal dominant
→ X linked

Question 3

How can you measure intermediate phenotype?

Answer 3

→ Electrocardiogram

Question 4

What is the intermediate phenotype in people with sudden cardiac death?

Answer 4

→ Heart rate might be slower than it is supposed to be

→ heart is larger than usual - cardiomyopathy

Question 5

What is the relationship between conduction and heart size?

Answer 5

→ The larger the heart muscle the longer it takes for conduction because the surface area is larger

Question 6

What does a quivering signal on an ECG look like and why?

Answer 6

→ Ventricular fibrillation

→ Heart muscle gets tired and there is no electrical output

Question 7

What do the P wave and QRS wave mean?

Answer 7

→ P wave - going across the atria

→ QRS - going across the ventricle

Question 8

What is the QT interval associated with?

Answer 8

→ Highly associated with risk of sudden cardiac arrest

Question 9

What does it mean if the QT interval is longer?

Answer 9

→ Increased susceptibility of a heart attack

Question 10

Why are twin studies used?

Answer 10

→ twins are genetically identical
→ non identical twins are not genetically identical but the environment is the same
→ this enables you to eliminate the environment as a confounding factor

Question 11

What percentage is the variation in heart rate due to genetics?

Answer 11

→ 58%

Question 12

What percentage is the variation in QRS down to genetics?

Answer 12

→ 54%

Question 13

What does high heritability imply?

Answer 13

→ Strong resemblance

Question 14

What is concordance?

Answer 14

→ How similar a phenotype is

Question 15

What does it mean if there are big differences between MZ twins and DZ twins?

Answer 15

→ Trait is more genetic than environmental

Question 16

What are SNPs?

Answer 16

→ Variations in a single nucleotide

→ DNA sequence variations that occur when a single nucleotide is altered

Question 17

What is the most common form of variation in the genome?

Answer 17

→ SNPs

Question 18

What is a genotype?

Answer 18

→ A pair of alleles at a locus

Question 19

What is a haplotype?

Answer 19

→ Sequence of alleles along a single chromosome

Question 20

What is a qualitative measure example?

Answer 20

→ Disease status

→ Presence or absence of congenital defect

Question 21

What is a quantitative measure example?

Answer 21

→ Blood glucose levels
→ % body fat
→ heart rate

Question 22

What is the short term goal of genetic association studies?

Answer 22

→ Identifying genetic variants that explain differences in phenotype among individuals

Question 23

What is the long term goal of genetic association?

Answer 23

→ Inform the process of identifying and delivering better prevention and treatment strategies

Question 24

Why can the SNPs for cardiovascular disease not be in essential parts of the genome?

Answer 24

→ They do not manifest from birth

Question 25

What is the relationship between linkage disequilibrium and SNP distance?

Answer 25

→ Linkage disequilibrium between two SNPs decreases with physical distance

Question 26

When do you need fewer SNPs to capture variation?

Answer 26

→ When LD is strong

Question 27

Why are some variants not recombined?

Answer 27

→ The regions are physically together

Question 28

How many SNPs does an SNP chip have?

Answer 28

→ 317,000 SNPs

Question 29

Describe how an SNP microarray works?

Answer 29

→ Run 12 samples
→ Each of the wells has tags for 300,000 variants
→ they are stuck to the base of the chip
→ DNA is run across the chip
→If the DNA has the variant it binds to it
→ fluorescent dye binds

Question 30

What are the axes of the graph for testing genetic association?

Answer 30

→ X axis is genotype

→ Y axis is phenotype

Question 31

What do the dots on the manhattan plot represent?

Answer 31

→ A variant

Question 32

What do the peaks on the manhattan plot show?

Answer 32

→ statistical test has a significant effect

Question 33

Why do you need a lot of people in a GWAS study?

Answer 33

→ If the genes are numerous and small in effect

Question 34

What are the 3 possibilities when finding a SNP associated with a disease?

Answer 34

→ Causal relationship between SNP and disease
→ Marker is in linkage disequilibrium with a causal locus
→ false positive

Question 35

How is the P value set?

Answer 35

→ 0.05/n

→ n is the number of tests

Question 36

What is linkage disequilibrium?

Answer 36

→linkage disequilibrium is the non-random association of alleles at different loci in a given population.