L73 – Genetics of Respiratory Diseases Flashcards Preview

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Flashcards in L73 – Genetics of Respiratory Diseases Deck (40):
1

Effect of cystic fibrosis on airways?

Buildup of thick, sticky mucus in lungs

>> clogging, infection of bronchial passages

>> impede breathing, destroy lungs

2

Effect of cystic fibrosis on pancreas?

pancreatic insufficiency,
diabetes

occlusion of ducts prevents pancreas from delivering critical digestive enzymes to bowel

3

Effect of cystic fibrosis on skin?

malfunctioning of sweat glands
>> perspiration contains excessive salt

4

Which chromosome is the CF gene located on?

7

5

What does the CF gene translate?

CFTR

Cystic fibrosis transmembrane conductance regulator protein

6

What does CFTR do?

Membrane protein > controls passage of chloride ions in and out of the cells

7

What type of mutation occurs in CF?

Deletion of phenylalanine in position 508 in CTFR

8

What are the domains of CFTR?

 TMD-1, TMD-2 = transmembrane domains

 NBF-1, NBF-2 = nucleotide-binding folds

 R = regulatory domain

9

What are the 2 ways of CFTR defect ?

Mutation > CFTR in membrane but doesnt work

Mutation > completely missing CFTR

10

Explain how CFTR normally functions in sweat glands?

Cells secrete water into duct from tangled end of gland

As sweat rises towards skin, cells lining UPPER DUCT reabsorb Na+, Cl-, other molecules

>> Cl- move from sweat into cells, create electrical gradient > draw Na+ into cell

>> Decrease salt conc. in sweat

11

Explain the normal function of CFTR in pancreas?

Normally: CFTR pumps Cl- into duct
>> water slurry follows (osmosis)

>> flows out into intestine carrying digestive enzymes

12

Explain the defective function of CFTR in pancreas?

CFTR is missing >> Cl-, water stay in cells (no slurry to carry enzymes away)

>> enzymes begin to digest pancreas itself
>> inflammation
>> thick mucus plugs duct (pancreatic insufficiency)

13

What is the treatment for CF lungs?

inhale recombinant human deoxyribonuclease I (Dornase Alfa) to reduce mucus viscosity

Mechanical suction

14

What kind of gene defect is CF?

Single gene defect

Autosomal recessive

15

What are the chances of carrier, affected and unaffected when CF carrier x CF carrier?

carrier x carrier
25% unaffected,
50% carriers,
25% affected

16

What are the chances of carrier, affected and unaffected when CF affected x CF carrier?

50% carriers

50% affected

17

Rank the frequency of carrier and carrier of White, Asian , Black and Hispanic?

White > Hispanic > Black > Asian

18

Why CF mutation exists in such high frequency?

heterozygote advantage against diarrhea (e.g. cholera), pulmonary tuberculosis, thalassemia

19

What is the Molecular diagnosis of CF?

PCR: specific primer against CF gene
>> stain DNA by ethidium bromide
>> visualize as a band

20

What are the hallmarks of a multifactorial disease? (2)

Healthy parents can have son / daughter with
asthma

A (more) severely affected parent is (more) likely to
produce an affected child

21

Explain in multifactorial disease, why 2 affected parents are more likely to produce an affected child?

Explanation:
assume liability for traits is additive
>> one disease gene with large effect vs. multiple genes (small proportion gets all the good / bad genes)

>> Continuous / quantitative distribution of severity

22

List some common Non-Mendelian trait / disease?

intelligence, height, asthma, hypertension, diabetes mellitus, cleft lip, cleft palate

>> regression to mediocrity

23

What does polygenic mean?

multiple genes:

Each of the genes has a relatively small effect on the phenotype

> these traits/ diseases reflect the cumulative effect
of genetic variation at these loci

24

What is the difference between polygenic and multi-factorial?

multi-factorial:
Multiple genes interplay with environmental factors

polygenic:
Determined by many genes at different loci, without the influence of the environment

25

How to tell whether a disease in influenced by genetics?

Adopted vs natural children:

- Influenced by genetics: adopted = no disease
natural = disease

- Influenced by environment:
adopted and natural both affected

26

What is familial tendency?

higher frequency of specific disease among relatives of affected individuals

27

Does familial tendency depend solely on genetics?

No

families share common environments

28

Is asthma genetic or environmental?

Both

29

What are the chances of asthma if two parents are:
-neither have asthma
-One parent affected
- both parents affected

Neither - 6%
One - 20%
Both - 60%

30

Compare the environment and genome of identical an fraternal twins?

Identical: same genome
Fraternal: half genome same

For both, environment factors are not exact

31

How is concordance rate calculated?

Both affected/ (one affected + both affected) x 100

32

What is the concordance rate if the disease is totally genetic?

Both affected/ (one affected + both affected) x 100

one affected = 0, therefore concordance rate = 1

33

What is the expected correlation between genetics and phenotype in MZ and DZ twins for a totally genetic disease?

Expected correlation

MZ = 1.00
DZ = 0.50

34

WHy is the concardance rate of asthma in MZ and DZ not 1.00 and 0.50?

Because environmental factors matter

35

What would the concordance rate be if asthma is only caused by environment?

MZ and DZ concordance rates are the same

36

What produces susceptibility to asthma?

Combined effects of several weak genes add up to produce susceptibility to asthma

37

What are the environmental factors involved in asthma?

Tobacco smoke, pollution, chemical fumes in certain jobs, dust mites, temperature, humidity of air

Amount of salt in diet

Lung infections

38

Does genetics = disease?

NO

Genetics = susceptibility to the disease

39

Is it easier to influence genetics or environment?

Environment

40

Development of polygenic disease is determined by?

Interplay between genetic factors and environment

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