W1_03 Mendelian Disorders Flashcards Preview

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Flashcards in W1_03 Mendelian Disorders Deck (28)
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1
Q

what are 3 mechanisms by which mutations lead to disease?

A

gain of function;
loss of function;
disruption of a multiprotein complex

2
Q

what’s a missense mutation?

A

single base change, resulting in an amino acid change

3
Q

what’s a nonsense mutation?

A

single base change, resulting in a stop codon in the AA sequence

4
Q

what’s a frameshift mutation?

A

an insertion or deletion in the DNA that shifts the codons and changes all the amino acids downstream

5
Q

if the father transmits a genetic disease to his son, which type of single gene disease is ruled out?

A

it can’t be x-linked

6
Q

why does disease occur in AD conditions despite the presence of the normal gene product?

A

haploinsufficiency;
dominant-negative effect;
function-enhancing mutation;
random/somatic loss of other copy may occur

7
Q

define penetrance

A

an all-or-nothing phenomenon, describing the fraction of people with the mutation that show symptoms

8
Q

define expressivity

A

describes the range and severity of symptoms an affected individual may have

9
Q

polycystic kidney disease, achondroplasia, marfan’s syndrome, FAP, hereditary breast/ovarian cancer, myotonic dystrophy, and huntington’s are examples of which kind of single gene mutation?

A

autosomal dominant

10
Q

cystic fibrosis is caused by which gene?

A

mutation in the CF transmembrane conductance regulator gene (CFTR)

11
Q

what kind of single gene mutation is CF?

A

autosomal recessive

12
Q

sickle cell anemia, non-syndromic deafness (connexin 26), inborn metabolism errors (PKU, MPS, gaucher’s, tay-sachs), and thalassemia are which kind of single gene mutation?

A

autosomal recessive

13
Q

what are major phenotypic features of DMD?

A
age of onset - childhood;
muscle weakness;
calf hypertrophy;
moderate intellectual compromise;
elevated serum creatine kinase levels
14
Q

the DMD gene codes for which protein?

A

dystrophin, which maintains muscle integrity and assembly of the synaptic junction

15
Q

note: males with DMD don’t typically reproduce

A

ok

16
Q

note: about 2/3 of DMD patients are the result of carrier mothers

A

recall, it’s an x-linked disease

17
Q

define germline mosaicism

A

where a fraction of germ cells can have mutations. e.g. germline mosaicism in DMD

18
Q

which x-linked condition was common among the descendants of britain’s queen victoria, who was a carrier?

A

hemophilia a

19
Q

what is hemophilia a?

A

it’s a factor VIII activity deficiency that has variable expressivity. treated with IV replacement of factor VIII

20
Q

what’s x-inactivation?

A

in females, when the embryo is about 100 cells, each of those cells will inactivate one of the x chromosomes for itself and all future progenitors of that cell. thus, a female will have 50% paternal x and 50% maternal x in her body

21
Q

what’s skewed x-inactivation

A

when the x that has the mutation is active in most cells and the female gets clinical symptoms of the disease

22
Q

how can x-linked diseases occur in females?

A

skewed x-inactivation;

x-linked dominant

23
Q

rett syndrome, chronic granulomatous disease, fabry disease, x-linked hypophosphatemic rickets are which kind of single gene mutation?

A

x-linked

24
Q

heart disease, autism, obesity, cancer, congenital anomalies (cleft lip, neural tube, CHD, etc) are examples of what?

A

multifactorial genetic disease

25
Q

note: multifactorial diseases are less heritable than single gene disorders

A

ok

26
Q

name 2 autosomal dominant disorders

A

FAP;

achondroplasia

27
Q

name 2 autosomal recessive disorders

A

cystic fibrosis;

sickle cell anemia

28
Q

name 2 x-linked disorders

A

hemophilia A;

duchenne muscular dystrophy

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