Mcb Block 4:

Front 1

what is dichotomous characteristic?

Back 1

Either you have or do not have the disease

Front 2

What is continous chracteristic?

Back 2

characteristics everyone has but to different degree such as height, bp, weight

Front 3

Multifactoria diseases are

Back 3

combination of genetic and environmnetal causes which applies to most common diseases

Front 4

Define fully penetrant:

Back 4

Other genes and enrionmental factors have no effect---mendelian

Front 5

Define low penetrance

Back 5

plays a small part, along with other genetic and environmental factors

Front 6

Unique charcteristic of MS

Back 6

genetic factors play a major part in determining susceptibility but each individual factor has a low penetrance

Front 7

Wat is the chronic lifetime risk of a multifactorial disorder in western population?

Back 7

60%

Front 8

Polygenic is what?

Back 8

Caused by the presence of disease allele at mutliple genetic loci

Front 9

Polygenic inheritane is also known as what?

Back 9

quantitative inheritance

Front 10

What is polygenic inheritance determined by?

Back 10

It is determined by many genes each having a small, additive effect
ex: bp, height,

Front 11

What is regression to the mean?

Back 11

A simple genetic model in which the distribution of a certain chracter is the same in each generation

Front 12

Is regression to the mean also seen for non genetic factors?

Back 12

YES but does not prove that it is 100% genetic

Front 13

What is the sume of the variance of a phenotype?

Back 13

The sum of the genetically dtermined variation and environmentally determined variation

Front 14

What is heritability

Back 14

The proportion of the total phenotypic variance of a condition which cuased by additive genetic inheritance

Front 15

What is the value given to H when it is genetically determined?

Back 15

1

Front 16

What is the value given to H when it is environmental factors?

Back 16

0

Front 17

What is the range given to multifactorial diseases?

Back 17

0.4-0.7

Front 18

What is the liability/threshold model

Back 18

It isused to solve the apparent contradiction between a continuous distribution of a trai and the discontinous distribution of mutlifactoral disease

Front 19

What does that threshodld postulate?

Back 19

It postulates that susceptibility to the disease in a continous character

Front 20

What are three different studies done to determine that genes have a significant influence on a disease?

Back 20

familal aggregation, twin studies, and adoption studies

Front 21

What does the familal aggregration test for?

Back 21

It tets whether the disease prevalence in genetically related family members of affected individuals is increased over the prevalence of the disease in the general population

Front 22

What is degree of relationship?
first degree?
Second degree?
third Degree?

Back 22

50%
25%
12.5%

Front 23

What is used to test for familial aggregation/?
What does it quantify?

Back 23

Familial relative risk
should be less than 1.
It quantifies the degree of risk to relatives

Front 24

lambd r?

Back 24

is the risk to relative R of an affect proband compared with population risk

Front 25

What does teh twin study do?

Back 25

compared the disease concordance rates among MZ twin pairs with those of DZ twin pairs

Front 26

How much gens are shared between
MZ?
DZ?

Back 26

MZ: 100%
DZ:50%

Front 27

What is the bias in twin studies?

Back 27

they are dressed and treated the same in the same environment

Front 28

What is the ideal experiment for a twin study?

Back 28

To seperate MZ at birth

Front 29

What is signifacnt of the adoption study?

Back 29

It is used to determine if indiiduals are more concordant with their adoptive parents or with their biologic parents for a disease

Front 30

What is the value given to H when it is genetically determined?

Back 30

1

Front 31

What is the value given to H when it is environmental factors?

Back 31

0

Front 32

What are some characteristics of monogenic disorders?

Back 32

large familes
one disease gene/family
highlt penetrance genes
unaffected individuals also of use

Front 33

What are some characteristics of multifactorial diseases?

Back 33

small families
mutliple diseases genes/px
low penetrance genes
unaffected individuals can also carry
susceptibility disease

Front 34

What mapping do you use for monogenc disorder?

Back 34

parametric genetic mapping methods with lod score analysis

Front 35

What mapping do you use for multifactorial?

Back 35

Non-parametric genetic mapping methods with affected sibpair analysis
-uses large cohorts of cases and controls

Front 36

What is identical by descent?

Back 36

The same identical allele inherited from the same parent

Front 37

What is identical by state?

Back 37

The same allele but not identical..

Front 38

What are the problems associated with identical by state?

Back 38

becomes a problem when px are unavailable for genotyping

Front 39

When does IDS occur?

Back 39

1. when one of the parents is homozygous for a maker allele
2. when parents are heterozygoous for the sdame maker allele

Front 40

What do you do to conduct a sib pair study?

Back 40

1.Collect families with at least 2 affected siblings
2. perform a genome wide scan with regular spaced polymorphinc makers

Front 41

What is significant of hot spot mutation?

Back 41

Seen on many different haplotypes so px are usually unrelated
ex. 1138T>A in FGFR3 in achrondrodysplasia

Front 42

What is significance of founder mutations?

Back 42

If share a haplotype than share an ancestor.

ex. Cys282Tyr in HLA like gene on HSA6p21 in Haemochromastosis

Front 43

What is linkage disequilibrium?

Back 43

Shows that the percentange of haplotype should be a certain percentage but happens at a different percentage

ex C282Y Mutation cuasing hemochromastosis and HLA -a3
should be 3.3% but found at 15.6%

Front 44

What are haplotypes?

Back 44

Copy if the ancestral chromosomal region in which the mutation occurred.

identification of surrounding region indirectly detects the mutation

Front 45

What does the case control design test for?

Back 45

Test for differences in genetic marker frequency beetween affected cases and unaffected controls

Front 46

What is the percentage of DNa variation in affected cases?Unaffected controls?

Back 46

55% , 20%

Front 47

What is the odds ratio?

Back 47

ad/bc

Front 48

What are the advantages of a case-control study? disadvantages?

Back 48

advantages:
easy to collect cases and controls
detection of risk alleles with small
lamda values
disadvantages:
matched control group needed
sample size is important
Genes with small relativevrisks require large numbers

Front 49

SNP

Back 49

small nucleotide polymorphism

Front 50

What is the mutation rate of SNP?

Back 50

10^-7 to 10^-8 per generation
mutationally stable

Front 51

What are some characterisitics of linkage studies?

Back 51

families
known pedigree/relationship btw px
no of recombination evens btw px is low
large regions of DNa shared
limited number of genetic makers required

Front 52

What are some chracteristics of association studies?

Back 52

population
unknown population
no of recombination events between unrelated px is high
small regions of DNA shargin btw unrelated px
larger no. of genetic markers required
Strength of association depends on age and number of mutation

Front 53

What is the transmission disequilibrium test?

Back 53

analyses affected individuals plus parents
(a-b)^2/(a+b)
a= number of times a heterozygous parent trasmits allele 1 to an affected child
b= number of times the ther allele is transmitted

Front 54

What is celiac disease?

Back 54

most common food tolerance in western population
abnormal immune response to gluten proteins

Front 55

What is concordance study on MZ and DZ on celiac disease?

Back 55

MZ: 86%
DZ: 20%

Front 56

What are the results of CD on general population and in siblings of CD px?

Back 56

gen pop: .5%
in sibling: 10%

Front 57

95% of CD px express this allele:

Back 57

HLA-DQ2 or HLA-DQ8 heterodimer

Front 58

25% of CD px express this allele:

Back 58

HLA-DQ2/DQ8

Front 59

What is the percentage of the general population expressing CD?

Back 59

0.5-1%

Front 60

What chromsome linkages are there with CD?

Back 60

6 (lod aorund 7) and 19 (lod around 3)

Front 61

What haplotype is associated with Chromsome 19

Back 61

MYO9B

Front 62

What does the MYO9b do?

Back 62

encodes an inconventiional myosin molecule that has a role in actin remodeling of epithelial enterocytes
- immunogenic gluten peptide can enter the deeper mucosal layer- initiating the inflammatory response

Front 63

What is Hirschsprung disease?

Back 63

Absense of nerve cells in the large bowel, no bowel movement causing abdominal distension

Front 64

What is the recurrence risk?

Back 64

3-4%

Front 65

What is the sex ratio for hirschspring disease?

Back 65

4:1
males:females

Front 66

What is the gene and ligand involved in system 1 of the hirschspring disease?

Back 66

RET-promotes neural crest stem cell migration to the intestine

GDNF and NRT

Front 67

What is the penetrance percentage for RET in famililal caes and sporadic cases?

Back 67

50-70%; 15-35%

Front 68

What role does GDNF and NRTN have?

Back 68

GDNF has a role in migration of neural crest cells and NRTN promotes their survival

Front 69

What genes are involved in system 2 of HD?

Back 69

EDNRB: recessive, invovled not only ins pread of neual precursors from the small bowel to the large bowel, but also of melanocytes

Front 70

What is diabetes mellitus?

Back 70

autoimmune disorder wish destroys pancreatic islet beta cells

Front 71

what MHC complex accounts for 40% of the familial aggregration?

Back 71

MHC 6p21.3

Front 72

HLA-DQ2/DQ8 is present in how many type 1 px?

Back 72

30%

Front 73

What is absent in type px?

Back 73

HLA-DQ6

Front 74

What is the population risk and siblings risk for type 1 diabetes?

Back 74

.2-2.5%
7-20to25%

Front 75

What is the reccurence risk for an offspring from an affected female?affected male?

Back 75

2-2.5%
5%

Front 76

How many people have type 2 diabetes mellitus:

Back 76

8% with a first degree relatives increases to 10-15%

Front 77

What inheritance is maturity onset diabetes of the young (MODY)

Back 77

AD

Front 78

What are the three type of gene affiliated with MODY?

Back 78

MODY 2: glucokinase def.
50% of heterozygous women develop gestational diabeted
MODY 1 and 3: hepatocyte nuclear factor 1A and 4A respectively

Front 79

What does HNF 1A and HNF 4a do?

Back 79

HNF 1 A activator of HNF 4a: activation of liver specific genes in glucose, cholesterol and FA metabolism

Front 80

What does peroxisome proliferator-activated receptor gamma do?

Back 80

ligand dependent TF regulating gene involved in lipid and glucose metabolism and adipocyte differentiation

Front 81

What did they find in type 2 diabetes when performed a whole genome association

Back 81

transcription factor 7 like 2
and
Zine transporter SLCC30A8
and
two coromosomal loci containing genes involved in beta cell development of function

Front 82

What is strongest risk factor for AD?

Back 82

age
5% over the age of 65
20% of the age of 80

Front 83

What are the three genes associated with early onset AD

Back 83

1. amylod precursor protein (<1%)
2. Presenilin 1 (50% of AD)
4. Presenilin 2 (<1%)

Front 84

What is APP?

Back 84

cell surface protein and is highly conversed in evolution

Front 85

What are functions of P1 and P2?

Back 85

involved with proteolytic cleavage of APP

Front 86

What does abnormal cleavage of APP result in ?

Back 86

Abeta42 which results in aggregation

Front 87

What is the importance of ApoE4?

Back 87

linkage analysis in late onset AD
increased association of E4 in AP px
apoE in AD amylod plauqes

Front 88

What is the freq of apoE4 in ad px

Back 88

40% w/ a risk of 30-50%

Front 89

What are the effects of apoE4?

Back 89

can inc lifetime risk from 9% to 29%
E4/E4: 15 fold increase
E4/E1,2,3: 3 fold increase