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Flashcards in Single gene disorders Deck (59):
1

Recessive inheritance is mostly observed in defects of what?

Enzymes
Proteins involved in transport and storage

2

Dominant inheritance is mostly observed in defects of what?

Structural proteins
Proteins involved in growth
Receptor and signalling proteins

3

What is haploinsufficiency?

When half of gene cannot carry out cell function (explanation of dominant mode of inheritance)

4

What is the dominant negative effect?

When mutational protein competes with normal form, or destabilizes a structure composed of normal and mutated (explanation of dominant mode of inheritance)

5

What is the gain of function explanation for dominant inheritance?

Change in the function of the mutated protein compared to normal (signal proteins usually)

6

What is the lack of back up explanation of dominant inheritance?

Like two-hit model of CA

7

What is the psuedoanasomal region of Y?

Part of the Y chromosome that is similar to X

8

True or false: the X chromosomes in females are both expressed simultaneously by each cell

False--each cell expresses one, but varies between cells

9

What is the coefficient of inbreeding?

Describes the degree of homozygosity of a child

10

What is the most prevalent IEM?

PKU--defect in F hydroxylase

11

What recessive disease (that we discussed) is characterized by a defective Cl transporter?

Cystic fibrosis

12

Why is the sweat of someone with cystic fibrosis salty/more electrically conductive?

Loss of Cl transporter and effects on Na transporter

13

What are the two major types of cystic fibrosis discussed?

Pancreatic sufficient
Pancreatic insufficient

14

What are two possible explanations as to why there is heterogenity in cystic fibrosis?

1. Different allele mutations
2. Modification of other proteins (different ion channel may take over)

15

Why aren't patient found with homozygous dominant alleles of a disease?

This is usually fatal
(also less probable)

16

What is the term that describes when someone who has a mutated genotype does not express the phenotype?

incomplete penetrance

17

What accounts for the "skip" in generations seen in inherited diseases?

incomplete penetrance

18

What is the term that describes how strong a phenotype shows?

Expressivity

19

NF1 has highly variable expressivity. What does this mean?

The symptoms expressed by individuals with the disorder vary widely

20

NF1 has complete penetrance. What does this mean?

ALL individuals with NF1 will express some sort of symptoms at some point

21

Why is examining the parents crucial in determining if their next child (after having one who is affected) will be affected with a disease?

To determine whether the parents are carriers with overlooked symptoms, or if the mutation in the child is new.

22

True or false: if a parent has an inherited disease, but has only mild expression of it, then his/her affected offspring will also have mild expression

False

23

What is the cause of Huntington's disease?

Triplet expansion of a CAG triplet leading to the expansion of polyglutamine stretches

24

What is the number of CAG repeats in a normal individual? In someone with huntingons?

9-35 is normal
>40 huntingtons

25

What is a premutation?

A propensity to transmit a mutation to one's offspring without carrying the disease--Huntington's is the classic example (note this is NOT a recessive gene)

26

What is the term describing the increasing severity of a disease as it is transmitted through a pedigree?

Anticipation

27

What is the gene that is the cause of Achomdroplasia?

FGFR3

28

What is FGFR3?

A Y-kinase that inhibits chondrocyte proliferation

29

What is a mutational hotspot?

An area where new mutations form readily

30

Why are older male sperm more likely to produced offspring with genetic mutations?

Higher chance of developing spontaneous mutations since they are produced from cells that have had a longer time to mutate

31

What are the two ways collagen defects can develop

1. Problem with the primary structure of collagen
2. Problem with the enzymes that make collagen

32

The dominant form of Ehlers-Danlos syndrome is due to what?

Mutation in collagen

33

The recessive form of Ehlers-Danlos syndrome is due to what?

Mutation in enzymes that process collagen

34

Familial hypercholestremia is a recessive or dominant disorder?

Dominant

35

How does Familial hypercholestremia demonstrate the gene dosage effect?

Homozygotes have 4x higher LDL levels--heterozygotes have only x2

36

What are the surface regions that LDL receptors are found in?

coated pits

37

What is the protein that LDL receptor binds to?

Apoprotein B

38

The LDL receptors are internalized and are turned into what structure?

Lysosomes

39

What happens to the LDL receptor when it is in the lysosome?

Bud off into vesicles to be recycled back to cell surface

40

What is the action of acyl-coa:cholesteryl acyltransferase?

Esterifies excess cholesterol that is released by the LDL receptor lysosomes

41

Why is it notable that the LDL receptor is a heavily glycosylated protein?

Room for error in glycosylation

42

What is the RET gene's function?

Receptor and signalling molecule in development

43

What are the two types of mutation that the RET protein can undergo?

gain-of-function (increased signal)
Loss-of-function (loss of signal)

44

A LOF in the RET protein leads to what disease?

Hirschsprung disease (impairment of neuron development)

45

A GOF in the RET portein leads to what disease?

Multiple endocrine neoplasia (proliferation of neuroendocrine cells)

46

Why are both Hirschsprung disease and MEN dominant diseases?

Hapaloinsufficiency

47

What is Duchenne muscular dystrophy?

Defect in the dystrophin gene

48

What does dystrophin do?

it is a protein that is essential for attachment of muscle cells to the ECM

49

What type of inheritance is DMD?

X-linked recessive

50

True or false: the mutational rate of mitochondrial DNA is much lower than the nuclear DNA

False

51

What is heteroplasmy?

cells contain varying fractions of defective mtDNA (due to the fact that there is >1000 mtDNA in a cell)

52

What is LHON?

Mutation in the ND1 gene the encodes complex I of the ETC

53

What is a compound heterozygote?

When an individual has two mutant alleles

54

What is allele heterogeneity?

different mutations in the same gene causing different phenotypes

55

What is locus heterogeneity?

Mutations in different genes cause the same phenotype

56

What are modifier genes?

Genes specific to an individual that modify a mutated gene's effects

57

What is pleiotrophy?

A mutation that causes multiple phenotypes--not all carriers of same mutation display the same phenotype

58

What type of mutations do ova contribute?

non-disjunction

59

What type of mutations do sperm contribute?

Replication errors