Genetic analysis of complex disease

Question 1

what is monogenic inheritance?

Answer 1

inherited from one locus and produces one phenotype

Question 2

what is pleiotropy?

Answer 2

inherited from locus that produces several phenotypes

Question 3

what is oligogenic inhetitance?

Answer 3

inherited from a few loci that gives one phenotype

Question 4

what is polygenic inheritance?

Answer 4

inherited from nany loci that produces one phenotypoe

Question 5

what is complex disease or

multifactorial inheritance

Answer 5

inhjeroted from one loci + multiple factors causing multiple phenotypes

Question 6

how do you call when diseases is caused by one locus and produces?

• one phenotype
• several phenotypes

Answer 6

• one phenotype - monogenic inheritance (Sorsby)
• several phenotypes - pleiotropy (ABCA4

Question 7

who do you call when on elocus causes multiple phenotypes such as RDS or ABCA4?

Answer 7

pleiotropism

Question 8

how do you call when one phenotype is cause by:

• few loci
• many loci

Answer 8

• few loci — oligogenic inheritance
• many loci —- polygenic inheritance

Question 9

give an example of

• pleiotropism and
• polygenic inheritance

Answer 9

• pleiotropism (ABCA4) one loci - multiple phenotypes
• polygenic inheritance (RP) many loci, one phenotype

Question 10

what is the difference between discrete trait or continious trait?

Answer 10

discrete (qualitative) yes or no

continuous (measured)

Question 11

explain the formula

p² + 2pq + q² = 1

Answer 11

p = AA

1pq = Aa

q2 = aa

Question 12

how to grade in numbers AA, Aa and aa?

Answer 12

AA -1

Aa 0

aa 1

so 1 for the disease (one disease) we are quantifying the disease

Question 13

what is alleles identical by descent and by state?

give some examples

Answer 13

• by descent if the person s are related ( 2 or more people in a family with blue eyes will have an allele for blue eye that is identical by descent because they are family)
• by state ( 2 or more people with blue eyes but not related)
  
  • examples
    
    • monozygotic identical twins HAVE ALL GENES IDENTICAL BY DESCENT
    • Parents and offspring SHARE ONE-HALF OF GENES IDENTICAL BY DESCENT
    • sibblings ALSO SHARE ONE-HALF OF GENES BUT ON AVERAGE
    • UNREALATED INDIVIDUALAS share NONE of their genes by descent (but some maybe by state)

Question 15

what is concordance?

Answer 15

if a pair of relatives have SAME PHENOTYPE for a given trait

-you can calculate the CONCORDANCE RATE if in 10 pairs you see how many have diabetes and 70 pairs have the concordance rate is 70%

THIS HELPS YOU TO DETERMINE IF A CONDITION IS GENETIC OR NOT - YOU MEASSURE THE CONC-RATE IN DZ AND MZ AND TRHE DIFFERENCE TELLS YOU SOMETHING

Question 16

in addition to concordance what other meassure of similarity can you obtain?

Answer 16

CONCORDANCE AND CORRELATION

CORRELATION its a measure of degree of similarity of a trait

trait:

identical = 1

no relaitonship = 0

opposite = -1

Question 17

what is heritability?

Answer 17

• tells you if some trait is very genetic or not very genetic
• its the proportion of phenotypic variation due to additive genetic deffects
  
  • estimated from the parent off-spring
    
    • h² = 2p _po
  • or from MZ and DZ
    
    • h2 < 2 (pMZ - pDZ)
• heritability frequency
  
  • h2 = 2pq a²
  • a is allelic effect
  • pq is gene frequency (common or not common)
  • so to look for rare diseases look in families

Question 18

if the gene frequency is 1 (max) what is the heritability?

Answer 18

ZERO

Question 19

table for allele association with phenotype

Answer 19

Question 20

what is the difference between Linkage and Association?

Answer 20

• Association —–Allele specific
• Linkage ——–Locus specific

Association has to be with the SAME ALLELE so in one pedigree the affected person has always the same allele (either A or a)

Linkage has the same LOCUS so in a pedigree the affected individual has to have always the 1 or 2

Linkage does not always imply association and viceversa

Example:

• trait locus: allele D (disease), d (wild type), genotypes DD, Dd, dd
• marker locus: allele 1, allele 2, genotypes 11, 12, 22
  *

Question 21

what is the association of Ankilosing spondilitis and HLA B27 and what does it mean?

Answer 21

87% association

means that 87% of people with AS has HLAB27 but

most carriers of B27 don’t have AS

HLA associations are population specific (so mention in what population)