Chapter 24: Medical Genetics Flashcards

1
Q

Many genetic diseases exhibit __ __, which means that they may be caused by mutations in more than one gene

A

locus heterogeneity

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2
Q

What are autosomal recessive diseases usually caused by?

A

loss-of-function mutations

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3
Q

What are three explanations for autosomal dominant diseases?

A

haploinsufficiency
gain-of-function mutations
dominant-negative mutations

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4
Q

Be familiar with the seven observations that determine a disease is genetic

A
  1. An individual who exhibits the disease is more likely to have genetic relatives with the disorder than of someone in the general population
  2. Identical twins share the disease more than nonidentical twins
  3. The disease does not spread to individuals sharing a similar environment
  4. Different populations tend to have different frequencies of the disease
  5. The disease tends to develop at a characteristic age (age of onset)
  6. The human disorder may resemble a disorder that is already known to have a genetic basis in animals
  7. A correlation is observed between a distance and a mutant human gene or a chromosomal alteration
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5
Q

Define autosomal in terms of disease

A

gene associated with disease is on an autosome, not a sex chromosome

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6
Q

What are the four characteristics of an autosomal recessive inheritance?

A
  1. Frequently, an affected offspring has two unaffected parents
  2. When two unaffected heterozygotes have children, the percentage of an affected child on average is 25%
  3. Two affected individuals have 100% affected children
  4. The trait occurs within the same frequency in both sexes
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7
Q

What are the five common characteristics of an autosomal dominant inheritance?

A
  1. An affected offspring usually has one or two affected parents
  2. An affected individual with only one affected parent is expected to produce 50% on average affected off spring
  3. Two affected, heterozygous individual have on average, 25% unaffected off spring
  4. The trait occurs with the same frequency in both sexes
  5. For most dominant, disease-causing alleles, the homozygous is more severely affected with the disorder, in some cases dominance may be lethal
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8
Q

What is haploinsufficency?

A

a copy does not produce a normal phenotype (50% of functional protein is not enough to produce a normal phenotype)

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9
Q

Define gain-of-function mutations

A

changes a gene product so that it gains a new/ abnormal function

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10
Q

Define dominant-negative mutation

A

alters the gene product in a way that acts antagonistically to the normal gene

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11
Q

Why are males more affected when it comes to x-linked diseases?

A

Because they are hemizygous (only have a single copy)

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12
Q

What are the three characteristics of an x-linked recessive inheritance?

A
  1. Males are much more likely to exhibit the trait
  2. Mothers of affected males often have brothers/fathers who are also affected
  3. Daughters of affected males, on average, produce 50% affected sons
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13
Q

What are two characteristics of an x-linked dominant inheritance?

A
  1. Only females exhibit the trait when it is lethal to males
  2. Affected mothers have a 50% chance of passing the trait to their daughters
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14
Q

Define a prion

A

disease-causing agent composed entirely of protein

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15
Q

Why can a prion cause disease?

A

Prion protein in the abnormal conformation (PrP^Sc) can convert a protein in the normal form (PrP^C) to the abnormal conformation

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16
Q

What is the difference between monozygotic (MZ) twins and dizygotic (DZ) twins?

A

monozygotic- formed from the same sperm and egg

Dizygotic - formed from separate pairs of sperm and egg

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17
Q

Define concordance

A

degree to which a trait is inherited, refers to the percentage of twin pairs in which both twins exhibit the disorder or trait

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18
Q

Define age of onset

A

characteristic age a disease develops

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19
Q

What is an example of an autosomal dominant disorder?

A

Huntington’s disease

mutation in gene that encodes a protein termed huntingtin - adds polyglutamine tract to protein - causes an aggregation of proteins in neurons

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20
Q

What are four autosomal dominant disorders?

A

Huntington’s
Achondroplasia
Polydactyly
Brachydactyly
Syndactyly

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21
Q

Disorders that involved __ __ typically have an autosomal recessive mode of inheritance

A

defective enzymes

22
Q

What are examples of autosomal recessive disorders?

A

Albanism
Cystic Fibrosis
Tay-Sachs Disease

23
Q

What is the most common lethal genetic disease among caucasians?

A

Cystic fibrosis (CF)

24
Q

Describe cystic fibrosis

A

gene encodes CFTR which regulates ion transport across the cell membrane

Mutant allele creates an altered CFTR protein leading to ion imbalance

25
Q

Describe Tay-Sachs disease (TSD)

A

develop symptoms at 4 to 6mo.

result of mutation in gene the encodes enzyme HexA which breaks down lipids called gangliosides

excess accumulation of lipid of cells in CNS causes neurodegenerative symptoms

26
Q

What are four examples of X-lined dominant disorders?

A

Duchenne muscular dystrophy
Hemophilia A and B
Androgen insensitivity syndrome

27
Q

What are examples of x-linked recessive disorders?

A

red-green color blindness
Rett syndrome
Vit-D resistant ricketts

28
Q

Describe Vitamin-D resistant rickets

A

softening and weakening of bones primarily caused by Vit-D deficiency

caused by lack of phosphate

29
Q

What are two characteristics of Y-Linked traits?

A
  1. Trait only affects males
  2. Affected males get it from their fathers and give it to their sons
30
Q

What is an example of a y-linked trait?

A

Hypertrichosis of the ear

31
Q

Define locus heterogeneity

A

phenomenon that a disease can be caused by mutations in two or more different genes

32
Q

What is an example of locus heterogeneity?

A

hemophilia

33
Q

How is hemophilia a locus heterogeneity?

A

Defect in any proteins of blood clotting cascade can cause disease

34
Q

Hemophilia A is a defect in clotting Factor

A

VIII

35
Q

Hemophilia B is caused by a defect in clotting factor

A

IX

36
Q

Hemophilia C is caused by a defect in clotting factor

A

XI

37
Q

Define penetrance

A

proportion of individuals with a specific genotype who manifest the corresponding phenotype

38
Q

What are three examples of disorders that can avoid complete penetrance?

A

neurofibromatosis
polydactyly
ABO blood group - rarely

39
Q

In complete penetrance may cause a phenotype to ?

A

skip a generation

40
Q

Define expressivity

A

degree to which a penetrant gene is phenotypically presented

41
Q

If neurofibromatosis penetrates, it may be exhibited in various forms including?

A

spots (mildest)
freckling (intermediate)

42
Q

Penetrance and expressivity are used most often with __ __ traits

A

autosomal dominant

43
Q

What are the reasons for incomplete penetrance and variable expressivity?

A

Gene interactions
Environmental effects

44
Q

What is phenylketonuria?

A

an autosomal recessive disorder that is a defect in the gene that encodes phenylalanine hydroxylase

45
Q

Describe what causes issues in PKU

A

Unmetabolized phenylalanine will accumulate as phenylpyruvic acid which causes mental and physical abnormalities

46
Q

Define phenocopy

A

an organism whose phenotype has been modified to resemble the phenotype of a different mutant organism

47
Q

What is an example of a phenocopy?

A

Phocomelia
Thalidomide

48
Q

What is Phocomelia?

A

supression of limb development caused by a dominant allele with variable expressivity

49
Q

What is Thalidomide?

A

sedative - children with shortened limbs due to pregnancy drug use

50
Q

Thalidomide is a ?

A

stereoisomer!