Mendelian inheritance and genetic diseases

Question 1

4 types of range of influence of genetics in medicine

Answer 1

-Chromosome abnormalities

• Single genes that cause major, important effects (Mendelian inheritance – and non-mendelian inheritance)
• Complex inheritance
  Heart diseases, diabetes, schizophrenia, some birth defects (e.g.: spina bifida)
• Epigenetics modifications (expression of genes)

Question 2

what are the odds for a child to be affected by an autosomal recessive inheritance if both parents are carriers?

Answer 2

Question 3

What is PKU

Answer 3

Phenylketonuria (PKU)

Question 4

what causes PKU

Answer 4

increased level of phenylananine because of a deficiency of phenylalanine hydroxylase (PAH) (an enzyme)

Question 5

Characteristics of autosomosal recessive inheritance

Answer 5

• greatest reccurence risk among siblings of affected individuals
• males and females are equally likely to be affected
• if parents are both carriers of mutation in the same recessive gene, eache pregnancy has a 25% chance of inherited both gene mutations and being affected
• ethnic background and consanguinity may influence the likelihood of specific recessive disease

Question 6

What is the risk for the next sibling to have PKU?

Answer 6

25%

Question 7

What is the chance of the other 2 unaffected siblings to be carrier?

Answer 7

2/3

Question 8

Incidence of PKU in north america

Answer 8

1/12 000 - 5-6 cases in quebec in a year

Question 9

carrier frequency of Pku

Answer 9

1/55

Question 10

The maternal uncle’s partner is expecting a new infant (his sister is a carrier, meaning that he has 1/2 chances of being a carrier). What is the risk that this child will have PKU?

Answer 10

1/440 (0.2%)

Question 11

what means allelic heterogeneity

Answer 11

different mutation on the same gene

Question 12

What would locus heterogenity be?

Answer 12

When one disorder (phenotype) is caused by pathogenic changes in more than 1 gene

Locus=chromosomal location

Question 13

Synonym of locus heterogeneity

Answer 13

Genetic heterogeneity

Question 14

What is a dominant inheritance

Answer 14

if you are a carrier and pass down your gene, your child will be affected

Question 15

what is pleiotropy

Answer 15

defects in 1 gene will cause multiple sympton in multiple organ

Question 15

Characteristics of autosomal dominant inheritance

Answer 15

Multiple generations are affected
- males and females are equally likely to be affected
- male to male transmission occurs
- each offspring of an affected parent has a 50% chance of being affected and a 50% chance of being unaffected

Question 15

What means full penetrance

Answer 15

everyone who has the mutation will express the disease in one way or another

Question 16

What is variable expressivity

Answer 16

how the condition is expressed varies from 1 person to another

Question 17

What is a de novo mutation

Answer 17

A children affected by a new mutation (not inherited by parent, but is now at risk of passing it down to his/her kids)

Question 18

what is a mendelian (single gene) inheritance

Answer 18

X-linked inheritance - a mother passes down to its son

or

Y-linked inheritance

Question 19

Why are male more affected?

Answer 19

Because they only have 1 X, can’t compensate with another X, so can’t be carrier only and not affected

Question 20

Characteristics of X-linked Recessive inheritance

Answer 20

• The incidence of the condition is much higher in males than females
• all daughters of affected males will be carriers
• the condition is never transmitted directly from father to son
• sons of carrier females have a 50% chance of being affected and a 50% chance of being unaffected
• Daughters of carrier females have a 50% chance of being a carrier and a 50% chance of inheriting the normal copy of the gene

Question 21

In DMD: if there is 1/3 chance of being a de novo gene mutation, and a child is affected, what is the risk of the mother to be a carrier?

Answer 21

So Because a mutation can happen de novo in 1/3 cases (not inherited by the mother)

1-1/3=2/3

Question 22

how is passed down Y-linked traits

Answer 22

Never occur in females
it occurs in ALL male descendants of an affected male

Question 23

Why does the concept of dominant and recessive do not apply on y-linked trait?

Answer 23

Because there is only one allele (on the y) in a male