8-27 Multifactorial Complex Dz

Question 0

Continuous/Quantitative traits

Answer 0

Able to be quantified and vary numerically (height, weight, etc.)

Question 1

Qualitative/Dichocotomous traits

Answer 1

-Either Present or Absent and is predictable by simple rules

Ex. Mendelian Inheritance->ability to metabolize lactose, eye color/etc

Question 2

Complex traits are able to be ______ or _______

2)What’s the “catch with Complex traits”

Answer 2

Complex traits can be continuous/quantitative OR
qualitative/dichotomous [present or absent only]
2) simple rules used to calculate Mendelian inheritance CANT be used with CT since in CT multiple factors are involved

Question 3

Formula for variance

Answer 3

Variance = (Standard Deviation from the mean) ^2

Question 4

1) What is heritability (h^2)

2) How is this related to twin studies?

Answer 4

1) Heritability = Proportion of the Variance which is SOLELY GENETIC.
- –> [H^2 = V(genetic) / V(total) ]

2) [H^2 = V(DiZygotic Twins) - V(MonoZygotic Twins) ]
__________________________________
V(DZgotc Twins)

Question 5

1) How is the POLYGENIC THEORY For complex dzs[more than 1 gene playing a role] of quantitative traits modified to also incorporate the possibility of qualitative traits which can be complex as well
2) Who created this modification?

Answer 5

Those qualitative/dichotamous traits which are either absent or present can be complex in nature and have the Gaussian distribution like Quantitative traits BUT have to reach a certain THRESHOLD on that distribution curve in order for the dz to actually show up–>even with multiple genes playing a role

2)Douglas Falconer=Polygenic theory of
discontinuous/qualitative/dichotomous traits

Question 6

1) Familial Aggregation

2) How do we measure Familial Aggregation

Answer 6

when the occurrence of a dz is common in more family member relatives then what can be explained by just chance–>must b some genetic component…
2)Compare freq. of dz with a relative and the freq. of the dz of a person from general population
[relative and person general pop should have same freq. –>if freq. differ greatly=likely familial aggregation/genetics at hand!]

Question 7

1) Relative Risk Ratio
2) How is it calculated/formula
3) RRR > 1 means what………

Answer 7

1)A quantitative way to measure familial aggregation (AKA chance a disease is genetically caused)
2)RRR= Prevalence of dz in relatives of infected
___________________________
Prevalence of dz in general population
3) RRR>1= Higher RiSk a family member will acquire same dz due to genetics

Question 8

Concordance

Answer 8

Describes chance a person will share the
SAME PHENOTYPE and SAME DZ with a family member

2)Low Concordance=Dz is NOT all Genetic-based and has environmental factors playing at hand

Question 9

Higher Concordance in Monozygotic Twins vs. Dizygotic Twins implies what?

Answer 9

Strong evidence there must be some genetic factor playing a role in a specific disease.

[if there was no genetic factor playing a role in a specific disease, concordance rate for that dz would be THE SAME FOR BOTH MONOZY AND DIZYGOTC TWINS)

Question 10

How can you tell genetic factors are more important than environmental factors in a specific disease?

Answer 10

You’ll see similar concordance rates between monozygotic twins reared apart and monozygot twins placed together

Question 11

A) A Monozygotic twin should have ___% in common w/other twin
B)1st degree relatives[n=_]should have _% cmmon w/family member

C)2nd degree relatives[n=_]should have__%cmoon w/family member

Answer 11

A)Monozygotic twins have should have 100% cmmon w/other twin!!!

B)1st degree relative/n=1 should have 50%common w/family member

C) 2nd degree relative/n=2 should have 25%cmmon w/family member

Question 12

% of Alleles in common for Monozygotic twins=_____%. What does it mean when the dz Concordance Rate for Monozygotic twins is only 40%?

Answer 12

Proportion/% of Alleles in cmmon for Monozygotic twins SHOULD ALWAYS BE 100%. If Concordance rate is 40% then that means that dz has something OtHER than genetics playing a role in its manifestation —->environment!

Question 13

% of Alleles in common for DiZygotic twins=_____%. What does it mean when a dz Concordance Rate for DiZygotic twins is only 8%?

Answer 13

Proportion/% of Alleles in cmmon for DiZygotic twins SHOULD ALWAYS BE 50%. If Concordance rate is only 8% then that means there’s only 8% chance the other DiZgotc twin will get it=dz has something OtHER than genetics playing a role —->environment!

Question 14

1) What is Variance by definition?

2) What are the 3 Formulas for Variance??

Answer 14

Refers to the contribution genetics gives vs. contribution the environment gives to a specific trait or dz
A- [V= (Stndrd Deviation)^2]
B- [V(total)= V(genetics) + V(environment)]
C- [V(total)=STD^2genetics + STD^2environment ]

Question 15

A Relative Risk Ratio of x < 1 means….

Answer 15

If RRR is x < 1 then dz most probably NOT related to GENETICS and the RISK for a family member getting it is low

Question 16

h^2 = 1 means……

Answer 16

h^2=1 means ALL Variability is coming from Genetics in twin studies!

Question 17

• h^2 (heritability) should have a value between _____.

* *h^2= 0 means……..

Answer 17

*h^2 (heritability) should have a value between 0 and 1

• *h^2=0 means NONE of variability in twins comes from GENETICS/hardwiring—–> all variability you see must have came from Environment only!
• *V(monozygotic) and V(DiZygotic) = V[environment]

Question 18

What is a normal or Gaussian distribution curve?

Answer 18

Distribution of values for quantitative traits (and polygenic traits/dz) that complex traits usually take the shape of.

Question 19

What did Ronald Fisher demonstrate?

Answer 19

Demonstrated that dz governed by Polygenic (more than 1 gene) factors ALSO took the shape of a normal or Gaussian distribution curve JUSt like Quantitative traits such as height, weight..

Question 20

1)What is the cause and pattern of inheritance for the polygenic digenic Retinitis Pigmentosa?

Answer 20

1)RP requires you to have a mutant[mut] allele present in both the
peripherin gene AND the ROM1 gene in order to have RP dz
—These genes are on different loci of the chromosome

2)Photoreceptor membrane proteins are mutated –>loss of vision & Blindness by middle age

Question 21

1) What is the gene most commonly mutated in Hirschprung dz?

2) Why does HSCR(Hirschsprung) have mendelian AND complex forms? WHat is this known as? [3]

Answer 21

1) the RET gene is commonly mutated and functionally inactive
2)A-HSCR can arise from a mutation/loss in 3 different genes of 3 different loci–>dominant, recessive or multigenic outcomes! =loci heterogeneity
B-Also..Mendelian HSCR usually comes from complete loss of function/mutation in the RET gene

Question 22

1) IN regards to (HSCR/Hirschsprung) what would happen if there was “partial” loss or reduced expression of the RET gene?
2) What’s the catch to this?

Answer 22

other mutations in RET gene can cause reduced/partial function of RET protein (allelic heterogeneity) which confers SUSCEPTIBILITY for HSCR

2)Even though ur more susceptible you’ll still need specific alleles of modifier genes from other locations to actually create HSCR dz

Question 23

1) What is MHC?
2) What is MHC relationship to Type I DM
3) Is Type I DM genetic-based?

Answer 23

1)MHC=large genomic region with families of related genes inside of it that work to present antigens for immune cells
2)specifically, a MHC class 2 locus (HLA-DR3 and 4 haplotype) are inherited as a group [1 from each parent] and are known to cause
Type I DM!
3)Type I DM is genetic based BUT there is a significant portion of environmental stuff at hand–>MonozygTwins concordance=40%

Question 24

1) What are the genetic causes for Idiopathic Cerebral Vein Thrombosis [2]?
2) What are the ENVironmental factors for ICVT?

Answer 24

1) A-Mutations in the 3’untranslated region of prothrombin mRNA [G>A] INC its stability & plasma levels
B-mutant allele of Factor 5 DEC Fac 5A degradation by Protein C–>Factor 5 continues to participate in clotting process
(Factor 5 breaksdwn Prothrombin)

2) BCP INC Factor X, Prothrombin AND clotting factors by itself———–>OVERALL INC RISK BY 20 FOLD!

Question 25

How is the E-allele apolipoprotein and Alzheimer dz related?

Answer 25

People with at least 1 copy of the EAP are 2-3 times more likely to have Alzheimer. Mechanisms unknown. BOTH copies=HIGH RISK!

Question 26

Discuss the RARE/least common Mendelian form of Alzheimer

Answer 26

Inherited in a DOMINANT manner and is due to mutations in genes which code for precursor proteins–>insoluble aggregate complex

Question 27

A. What are the 5 most common types of congenital malformations

B. What are congential malformations?

Answer 27

1. Congential heart defects(Ventricular)/MOST cmmon
2. Neural tube defects
3. Cleft lip w/or without palate
4. Pyloric stenosis
5. Hip dysplasia

B. When ISOLATED defects seem to reoccur in families

Question 28

What 2 highly prevalent mental disorders are genetics based?

Answer 28

1. Schizophrenia
2. Bipolar

**thought to be caused by multigenic factors

Question 29

1) What causes Anencephaly (NTD)?

2) What was it first thought to be caused by?

Answer 29

1)Anencephaly (incomplete development of brain) AND spinal bifida “leading” cause is Deficiency of Vitamin Folic Acid! Reduces dz by 75%!

**it was first thought to be caused by multiple genetic and environmental factors