Lecture 9

Question 1

what is a complex genetic disease?

Answer 1

a polygenic disorder and a multifactorial cause, so the role of different genes associate to the pathological phenotype and the involvement of the environmental factors can influence the phenotype

Question 1

what is a complex genetic disease?

Answer 1

a polygenic disorder and a multifactorial cause, so the role of different genes associate to the pathological phenotype and the involvement of the environmental factors can influence the phenotype

Question 1

what is a complex genetic disease?

Answer 1

a polygenic disorder and a multifactorial cause, so the role of different genes associate to the pathological phenotype and the involvement of the environmental factors can influence the phenotype

Question 2

what are some main features of complex diseases?

Answer 2

1. do not show a classical mendelian pattern of inheritance
2. moderate to high evidence of genetic involvement
3. we don’t have causative genes, but susceptibility genes

Question 3

describe susceptibility genes:

Answer 3

we have interacts of two or ore loci that are associated to the phenotype

Question 4

what is the additive effect?

Answer 4

when the effect of loci is equal to the sum of their independent effect

Question 5

what is the multiplicative effect?

Answer 5

when the loci interact in a way that results in an even greater risk than generated independent by each locus

Question 6

what is a qualitative trait?

Answer 6

any trait measured by its presence or absence → yes or no question

Question 7

what is a quantitative trait?

Answer 7

a trait that can be measured in a continuous fashion

Question 8

can a disease / trait be measured as both qualitative and quantitative?

Answer 8

yes → diabetes: is a qualitative disorder, but we can slo measure the level of glucose in the blood

Question 9

what is one of the mahout public health concerns in the world?

Answer 9

obesity

Question 10

what physiological parameters must be considered when thinking about the cause of obesity?

Answer 10

level or hormones, criteria associated with the lifestyle, and molecular phenotypes such as metabolic or genomic features

Question 11

what is known for sure about obesity?

Answer 11

1. obesity tends to occur within a family - could be genetic or shared environmental factors / lifestyle
2. about 70% of the variance in BMI is genetic factor-dependent

Question 12

several loci in other syndromic conditions have been linked to obesity?

Answer 12

Prader-Willi and Bardet-Biedl syndrome

Question 13

what is leptin?

Answer 13

an important receptor for the hormone system by which adipose tissue signals its state and regulates appetite (mice with a leptin deficiency were morbidly obese)

Question 14

what is responsible for controlling the balance between food intake and energy expenditure?

Answer 14

hypothalamus

Question 15

what are the two different types of neurons in the hypothalamus?

Answer 15

orexigenic neuron and anorexigenic neuron

Question 16

what does an orexigenic neuron control?

Answer 16

promotes food intake

Question 17

what does an anorexigenic neuron control?

Answer 17

suppressed appetite

Question 18

what is obesity caused by?

Answer 18

by an altered perturbation of the balance between orexigenic and anorexigenic neurons

Question 19

in genetic studies to identify loci associated with obesity, what was used?

Answer 19

positional cloning

Question 20

what was the issue with the majority of the GWAS studies that have been performed on genes related to obesity?

Answer 20

• a huge amount of data was obtained, but it is important to have a very high number of participants to have a statistically significant result and it is very difficult to conduct a study based on common variance
• it is necessary to have a well-characterized population, defied in a clear way possibly by the same clinician or at least with the same criteria
• different populations may have different genetic variations
• in most cases the GWAS were not able to be validated or replicated

Question 21

what type of variants may be associated to a multifacgtorial disorder, making them hard to identify?

Answer 21

rare variants with low pathogenic effect

Question 22

why is it difficult to get a clear characterization of obesity through genetic counseling?

Answer 22

we may have different family members with the same phenotype but a lot of different factors may influence that phenotype

Question 23

what is thrombophilia?

Answer 23

an abnormal blood coagulation which increases the risk o developing clots at early onset, in atypical sites of the body → opposite of hemophilia (tendency to bleed)

Question 24

what are the main clinical features of thrombophilia?

Answer 24

1. thrombosis at age <45 2. repeated thrombosis 3. positive family history for thrombosis 4. unusual location of thrombus such as cerebral veins, mesenteric veins (abdominal veins), spleen, portal, liver, and kidney

Question 25

what factors play a role in thrombophilia?

Answer 25

both environmental and genetic

Question 26

what is genetic disposition in thrombophelia due to?

Answer 26

due to alteration on genes that encode for important proteins in the coagulation cascade

Question 27

what is the most important factor in the coagulation cascade?

Answer 27

factor X → converted to thrombin which activated fibrinogen into fibrin clots

Question 28

what other two factors besides factor X are important players involved in the coagulation cascade?

Answer 28

factor II and Leiden factor (factor V) → are the most important factors associated with the genetic forms of thrombophelia

Question 29

how many genetic types of thrombophelia are there?

Answer 29

2

Question 30

describe type I thrombophelia:

Answer 30

the most severe form with more frequent thrombotic events

Question 31

what is type I thrombophelia caused by?

Answer 31

a deficit of anticoagulants such as antithrombin III, protein C, and S protein

Question 32

what us type II thrombophelia?

Answer 32

most common form, caused by the hyperactivation of coagulation factors

Question 33

what factors are associated with type II thrombophelia?

Answer 33

factor II, factor V, and MTHFT

Question 34

what type of genetic effects are seen in thrombophilia?

Answer 34

additive or multiplicative effects: we have multiplicative effects we have the presence of specific environmental factors coupled with the genetic predisposition

Question 35

what can we do to reduce the risk of thrombophilia?

Answer 35

we cannot eliminate the genetic predisposition, but we can modulate the environmental factors to reduce the risk

Question 36

what category does the genetic test for thrombophilia fall into?

Answer 36

screening → it can also be performed in completely healthy individuals regardless of symptoms or family predisposition = the identification of the genetic predisposition I very well described and lifestyle changes can be suggested based on the obtained results

Question 37

how is thrombophilia different from other genetic disorders?

Answer 37

we have the ability to help control the exhibition of the disease through alteration of the lifestyle and environmental factors