GIM2 - Clinical Genetics Basics

Question 1

what are the 3 factors which makes up the aetiology of disease

Answer 1

environmental, single gene, polygenic

Question 2

what is somatic mutation

Answer 2

when the disease is caused by the gene mutation during the life of the person but not born with the mutated gene

Question 3

what are the 4 different modes of single gene modes of inheritance?

Answer 3

autosomal dominant, autosomal recessive, X-linked, Mitochondrial

Question 4

what are some examples for autosomal dominant inheritance

Answer 4

marfan syndrome, huntington disease, myotonic dystrophy

Question 5

what kind of defects do AD normally affect?

Answer 5

structural proteins, receptors, transcription factors (extra-cellular)

Question 6

what is penetrance

Answer 6

frequency with which a specific genotype is expressed by those individuals that possess it, usually given as a percentage.

• may vary with age
• can be incomplete penetrance - not all who has the genes will have the condition

Question 7

what is expressivity?

Answer 7

variation in expression - the extent to which a heritable trait is manifested by the individuals

Question 8

what is anticipation

Answer 8

symptoms of a genetic disorder become apparent at an earlier stage in comparison to the previous generation as the gene is passed on

Question 9

what is de novo/new dominant

Answer 9

new mutation that has occurred during gametogenesis or in early embryonic development

Question 10

what is the risk of the offspring contracting the an autosomal recessive condition by parents who are both carrier

Answer 10

25%

Question 11

what is compound heterozygous ?

Answer 11

Compound heterozygous is when the parents have different gene mutation of the same disease (cystic fibrosis one in the beginning and 1 in the end of the gene mutated) then the compound effect of the 2 different gene will contribute to the generation of the disease as they produce a non-functioning protein

Question 12

what are some examples for autosomal recessive inheritance

Answer 12

CF, haemachromatosis, sickle cell disease

Question 13

what is X-linked inheritance

Answer 13

only the X chromosome is affected ie male is for sure affected

female can also be affected but with varied degree of affectance

Question 14

how is X-linked transmitted?

Answer 14

from mother to son

Question 15

what are some examples for XL inheritance

Answer 15

duchenne muscular dystrophy, fragile X syndrome, red/green colour blindness, haemophilia

Question 16

what is the risk of offspring having the condition if the condition is X-linked

Answer 16

25% affected boy, 25% carrier girl

Question 17

what is the risk of offspring having the condition if the condition is X-linked and the father is affected

Answer 17

all daughters are carriers, all sons unaffected

Question 18

what are the 2 factors which causes XL female carrier to have severe symptoms of the condtion

Answer 18

X inactivation & XL condition being dominant

Question 19

what is another name for X-inactivation?

Answer 19

lyonisation

Question 20

what is x-inactivation?

Answer 20

Occurs in early embryogenesis

random inactivation of one of the X chromosomes in cells with more than one X chromosome.

Compensates for the presence of the double X gene dose.

Question 21

what is skewed X inactivation

Answer 21

random favouring of one chromosome over the other - leading to significantly more cells with one particular X chromosome

Question 22

what is tissue variability

Answer 22

– random preference for the X chromosome with the mutation to be active in crucial tissue group – eg muscle in Duchenne Muscular dystrophy

Question 23

what are some examples for XL dominant

Answer 23

Rett syndrome (lethal in males, phenotype only in female)

FragileX syndrome - females:- asymptomatic to fully symptomatic ( due to X-inactivation pattern)

Question 24

what are some examples for XL recessive

Answer 24

Red-green colour blindness
Haemophilia
Duchene Muscular dystrophy
Carrier girls usually unaffected BUT can have significant symptoms because of X-inactivation (switches off normal X)

Question 25

what are some examples for mitochondrial inheritance

Answer 25

maternally inherited diabetes and deafness

Question 26

where does all our mitchondrial genes come from

Answer 26

maternal