Mendelian disorders and multifactorial disease

Question 1

def. single gene disorders (mendelian)

Answer 1

• single gene mutations

- follow specific pattern of inheritance that can be followed in pedigree

Question 2

what does pattern depend on

Answer 2

1. function of protein

2. how mutation affects the protein

Question 3

3 ways mutatation affects function

Answer 3

1. gain of function
2. loss of function
3. disruption of multiprotein complex

Question 4

features of auto. dom.

Answer 4

• passed from generations
• male and female
• male to male transmission

Question 5

4 reasons disease occurs in autosomal dominant despite one normal gene

Answer 5

1. haploinsufficiency - more than 50% needed
2. dominant negative effect - abnormal protein interferes with normal protein
3. mutation may enhance function of protein
4. random somatic loss/mutation of other gene may occur

Question 6

def. penetrance

Answer 6

proportion of indivs. with a mutation causing a disorder that show clinical signs of the disorder

Question 7

how does penetrance work

Answer 7

• all or nothing

- may be explained by modifier genes in the individual

Question 8

def. variable expressivity

Question 9

example of ADs

Answer 9

FAP, marfans, polycystic kidney, achondroplasia

Question 10

example of a reccesive

Answer 10

CF

Question 11

features of recessive

Answer 11

• tend to be single sibship
• not usually in multiple generations
• both males and females
• both parents not usually affectes

Question 12

why are heterosygotes normal when they have one abnormal gene in recessive dis. (2)

Answer 12

1. half normal amount of product is enough

2. often enzymes, structural proteins without critical thresholds

Question 13

X linked to know

Answer 13

duschenne muscular dystrphy

• muscle weakness
• calf hypertrophy

Question 14

patho. of DMD

Answer 14

• gene encodes dystropin - role in maintenance of muscle membrane integrity

Question 15

what will be seen in mother with germ cell mutation of DMD

Answer 15

germ-line mutation in all their cells

50% risk of son having

Question 16

what will be seen in mother with germ-line mosaicsm

Answer 16

mutaiton in some of her eggs

- blood test will not show

Question 17

features of X linked dis.

Answer 17

• all males affected
• no male to male transmission
• rarely expressed in females

Question 18

what is hemophillia A

Answer 18

def. in factor VIII

- X linked mutation in 98%

Question 19

what is X-inactivation in females

Answer 19

• only one X active in cells
• some early stage an X is inactivated and all daughter cells have this inactivatiokns
• 50-50 chance of paternal or maternal cells

Question 20

how does X-linked disease occur in females (2)

Answer 20

1. X linked dom.

2. skewed X-inactivations - most of the cells carrying the mutation have this one as active

Question 21

what are multifactorial disorders

Answer 21

multiple genes interacting with the environment

Question 22

what do mutlifactorials look like on pedigree

Answer 22

cluster in families, but without clear patterns

Question 23

2 ways multifactorial are different

Answer 23

1. lower heritability

2. no single factor is responsible

Question 24

3 ways to determine if there is a genetic componeent

Answer 24

1. family studies
2. twin studies
3. adoption studies