Biochem - Genetics (Part 2) Flashcards Preview

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Flashcards in Biochem - Genetics (Part 2) Deck (115)
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1
Q

What is true of genetic diseases with variable expression?

A

The nature and severity of the phenotype varies from one individual to another with the same disease

2
Q

What is true of genetic diseases with incomplete penetrance?

A

Not all individuals with the mutant genotype will show the complete mutant phenotype

3
Q

What is the significance of imprinting in genetic diseases?

A

A genetic disease has a different phenotype depending on whether the mutation is inherited from the mother or from the father

4
Q

What is meant by linkage disequilibrium?

A

Measured in a population, it is the tendency for certain alleles at two linked loci to occur together more often than expected by chance

5
Q

What term describes the situation in which cells in the body have a different genetic makeup?

A

Mosaicism

6
Q

What is the name of the phenomenon whereby a genetic disease has an earlier onset or worsening severity in each subsequent generation?

A

Anticipation

7
Q

What word describes the phenomenon of a single gene having more than one effect on an individual's phenotype?

A

Pleiotropy

8
Q

Prader-Willi and Angelman syndromes are the result of which genetic process?

A

Genetic imprinting

9
Q

Define Lyonization

A

The random inactivation of one X chromosome in females

10
Q

A patient has inherited a mutation in a tumor suppressor gene. Mutation of the remaining (previously normal) copy of the tumor suppressor gene represents a loss of _____, which may lead to the development of cancer.

A

Heterozygosity; the patient was previously a heterozygote for lost tumor suppressor gene and both genes must be lost for oncogenesis

11
Q

True or False? Oncogenes, in a manner similar to tumor-suppressor genes, must have a deletion/mutation in the complementary allele before cancer develops.

A

False; the mutation of a single oncogene can produce cancer

12
Q

A genetic disease that shows _____ _____ will have mutations at different loci that produce the same phenotype.

A

Locus heterogeneity

13
Q

True or False: Albinism is an example of a genetic disease that demonstrates locus heterogeneity.

A

TRUE

14
Q

What is an example of a genetic disease that displays anticipation?

A

Huntington's disease

15
Q

Define heteroplasmy.

A

The presence of both normal and mutated mitochondrial DNA, resulting in variable expression in mitochondrial inherited diseases

16
Q

What is the significance of a dominant negative mutation?

A

A nonfunctional altered protein that also prevents the normal gene product from functioning

17
Q

Name a disease whose pathogenesis involves loss of heterozygosity.

A

Retinoblastoma

18
Q

The tendency for certain alleles to be inherited together more often than is expected by chance is called what?

A

Linkage disequilibrium

19
Q

True or False? The Hardy-Weinberg law assumes that there are no mutations at the locus being studied.

A

TRUE

20
Q

What equation describes the disease prevalence in a population that is in Hardy-Weinberg equilibrium?

A

p2 + 2pq + q2 = 1; where q2 is the prevalence of an autosomal recessive disease

21
Q

What is the heterozygote prevalence in a population that is in Hardy-Weinberg equilibrium?

A

2pq

22
Q

In Hardy-Weinberg population genetics, what do p and q represent?

A

Alleles of a gene

23
Q

What are the four assumptions of the Hardy-Weinberg equation?

A

No mutation occurring at the locus; no selection for any of the genotypes at the locus; completely random mating; no migration

24
Q

The prevalence of which type of genetic disease is indicated by q in males and q2 in females in Hardy-Weinberg genetics?

A

X-linked recessive diseases

25
Q

How is Prader-Willi syndrome inherited?

A

It is inherited via the deactivation of paternal copies of genes on chromosome 15

26
Q

In genetics, what does the term imprinting refer to?

A

When, at a single locus, one allele is inactivated by methylation (an inherited condition) and one allele is not (disease occurs as the result of the loss of the active allele)

27
Q

How is Angelman syndrome inherited?

A

Via the deactivation of the maternal copies of genes on chromosome 15; via chromosomal deletion, faulty imprinting, or uniparental disomy

28
Q

Where is the gene located in Prader-Willi syndrome? In Angelman's syndrome?

A

Both syndromes are due to inactivation or deletion of genes on chromosome 15

29
Q

What are the signs of Prader-Willi syndrome?

A

Mental retardation, obesity, hypogonadism, and hypotonia

30
Q

What are the signs of Angelman's syndrome?

A

Mental retardation, seizures, ataxia, and inappropriate laughter (happy puppet syndrome)

31
Q

In Leber's hereditary optic neuropathy, vision loss is _____ (central/peripheral).

A

Central

32
Q

Autosomal-dominant patterns of inheritance are often found in diseases caused by defects in _____ genes.

A

Structural; as opposed to recessive diseases, which are often caused by faulty enzyme genes

33
Q

True or False: A mother with an X-linked dominant disease may pass the disease only to her sons.

A

False; both her sons and her daughters may be affected

34
Q

True or False? Patients with autosomal-dominant disorders often present clinically after puberty.

A

True; in order for the diseases to remain in the population, affected people must have offspring

35
Q

What is the pattern of inheritance of hypophosphatemic rickets?

A

X-linked dominant

36
Q

What is the mode of inheritance if a disease is present in many generations and affects both males and females in roughly equal proportions?

A

Autosomal dominant

37
Q

What is the mode of inheritance in a family in which a disease is transmitted only through the mother and all children (both boys and girls) are affected?

A

Mitochondrial inheritance

38
Q

Autosomal-recessive patterns of inheritance are often found in diseases caused by defects in _____.

A

Enzymes; as opposed to dominant diseases, which are often caused by faulty structural genes

39
Q

True or False? A mother may pass a disease with a mitochondrial pattern of inheritance to both her sons and her daughters.

A

TRUE

40
Q

What is the mode of inheritance if a gene is present in a single generation and 25% of the offspring from the same two parents have the disease?

A

Autosomal recessive

41
Q

What is the pattern of inheritance of Leber's hereditary optic neuropathy?

A

Mitochondrial inheritance

42
Q

Do patients with dominant or recessive diseases generally present at a younger age?

A

Autosomal-recessive diseases

43
Q

What would you expect to see on urinalysis in a patient with hypophosphatemic rickets?

A

You would expect an increased urine phosphate level since there is proximal tubule phosphate loss

44
Q

Variable expression of mitochondrial diseases can be accounted for by what phenomenon?

A

Heteroplasmy

45
Q

True or False? Hypophosphatemic rickets can be treated by vitamin D supplementation.

A

False; this disease is also known as vitamin D-resistant rickets

46
Q

What is the mechanism of phosphate wasting in hypophosphatemic rickets?

A

There is increased phosphate wasting at the proximal renal tubule

47
Q

Which cells are affected in Leber's hereditary optic neuropathy?

A

There is degeneration of retinal ganglion cells and their axons

48
Q

In general, are autosomal dominant or autosomal-recessive disorders more severe?

A

Autosomal recessive

49
Q

What is the mode of inheritance in a family in which 50% of sons are affected and there is no male-to-male transmission?

A

X-linked recessive

50
Q

What percentage of sons of a carrier mother are expected to inherit an X-linked recessive disease?

A

50%

51
Q

True or False? X-linked recessive diseases are commonly more severe in males than in females.

A

TRUE

52
Q

True or False? A mother with an X-linked dominant disease may pass the disease to either her sons or her daughters.

A

TRUE

53
Q

True or False? A father with an X-linked dominant disease will pass the disease to all of his daughters but none of his sons.

A

TRUE

54
Q

A mother with achondroplasia is pregnant; assuming that the father does not have this condition, what is the likelihood that her child will also have the disease?

A

50%; achondroplasia is an autosomal-dominant disease

55
Q

Achondroplasia is the result of a defect in the _____ receptor.

A

Fibroblast growth factor 3

56
Q

Describe the clinical manifestations of achondroplasia.

A

Patient has dwarfism with short limbs but a normally sized head and trunk

57
Q

What parental attributes are associated with achondroplasia?

A

Advanced paternal age

58
Q

What is the mode of inheritance of autosomal-dominant polycystic kidney disease?

A

Autosomal dominant

59
Q

Autosomal-dominant polycystic kidney disease is associated with what cardiac pathology?

A

Mitral valve prolapse

60
Q

A 50-year-old man has hematuria, hypertension, and progressive renal failure. His kidneys are both massively dilated as a result of multiple large cysts. What is the most likely diagnosis?

A

Autosomal-dominant polycystic kidney disease

61
Q

What three nonrenal pathologies are associated with autosomal-dominant polycystic kidney disease?

A

Polycystic liver disease, berry aneurysm, and mitral valve prolapse

62
Q

Ninety percent of cases of adult polycystic kidney disease are associated with a mutation in what gene?

A

APKD1, which is located on chromosome 16 (remember: 16 letters in polycystic kidney)

63
Q

Adult polycystic kidney disease is inherited in an autosomal-_____ (dominant/recessive) pattern, whereas infantile polycystic kidney disease is associated with an autosomal-_____ (dominant/recessive) pattern.

A

Dominant; recessive

64
Q

What is the mode of inheritance of familial adenomatous polyposis?

A

Autosomal dominant

65
Q

What is the prognosis for a patient with familial adenomatous polyposis?

A

Adenomatous polyps will progress to colon cancer unless they are resected

66
Q

The defect that leads to familial adenomatous polyposis is found on chromosome ____.

A

5 (remember: 5 letters in polyp)

67
Q

The defect that leads to familial adenomatous polyposis is found in the ____ gene.

A

APC (remember, it stands for Adenomatosis Polyposis Coli)

68
Q

What is the mode of inheritance of familial hypercholesterolemia?

A

Autosomal dominant

69
Q

Familial hypercholesterolemia is the result of a defect in what type of receptor?

A

Low-density lipoprotein receptor

70
Q

In patients with familial hypercholesterolemia, heterozygotes can be expected to have a cholesterol level around ____ mg/dL, and homozygotes can be expected to have a cholesterol level around ____ mg/dL.

A

300; 700

71
Q

A middle-aged woman had a myocardial infarction 20 years ago, and has tendon xanthomas on her Achilles tendon. What is the most likely diagnosis?

A

Familial hypercholesterolemia

72
Q

What is another name for Osler-Weber-Rendu syndrome?

A

Hereditary hemorrhagic telangiectasia

73
Q

Why is recurrent epistaxis a common finding in Osler-Weber-Rendu syndrome?

A

Malformed blood vessels in the nose can break and cause frequent nosebleeds

74
Q

A patient has multiple telangiectasias, skin discolorations, and notes recurrent epistaxis; what other physical finding might be expected?

A

This constellation of symptoms is typical of hereditary hemorrhagic telangiectasia; can also see arteriovenous malformations

75
Q

What is the mode of inheritance of hereditary spherocytosis?

A

Autosomal dominant

76
Q

A patient has hemolytic anemia, increased mean corpuscular hemoglobin concentration, and spheroid erythrocytes. What is the most likely diagnosis?

A

Hereditary spherocytosis

77
Q

Why do patients with hereditary spherocytosis have elevated mean corpuscular hemoglobin concentration?

A

Red blood cells have less surface area and volume and therefore more concentrated hemoglobin

78
Q

Describe the clinical manifestations of hereditary spherocytosis.

A

Symptoms associated with anemia such as fatigue, shortness of breath, pallor, and dark urine

79
Q

In refractory cases, how can you cure hereditary spherocytosis?

A

A splenectomy is curative

80
Q

What is the mode of inheritance of Huntington's disease?

A

Autosomal dominant

81
Q

A 50-year-old patient develops depression, progressive dementia, and choreiform movements. What is the most likely diagnosis?

A

Huntington's disease; symptoms usually begin between 20 and 50 years of age

82
Q

You are performing an autopsy on a man who had Huntington's disease; what would you find on inspection of the brain?

A

Huntington's disease is associated with atrophy of the caudate

83
Q

The defect that leads to Huntington's disease is found on chromosome ____.

A

4 (remember: Hunting 4 food)

84
Q

What would a genetic analysis of a patient with Huntington's disease demonstrate on chromosome 4?

A

Trinucleotide repeats of (CAG)n in the Huntingtin gene

85
Q

Which neurotransmitters are most affected by Huntington's disease?

A

Decreased levels of γ-aminobutyric acid and acetylcholine

86
Q

What is the mode of inheritance of Marfan's syndrome?

A

Autosomal dominant

87
Q

Marfan's syndrome is the result of a mutation in the _____ gene.

A

Fibrillin

88
Q

What physical signs are associated with Marfan's syndrome?

A

Marfan's syndrome is associated with a tall habitus and long, tapering fingers and toes

89
Q

True or False? Marfan's syndrome is associated with hyperflexible joints.

A

TRUE

90
Q

What pathology of the cardiovascular system is seen in Marfan's syndrome?

A

Cystic medial necrosis of the aorta, aortic incompetence, and dissecting aortic aneurysms

91
Q

Marfan's syndrome is associated with what ocular pathology?

A

Subluxation of the lenses

92
Q

What is the inheritance pattern of multiple endocrine neoplasias?

A

These syndromes are inherited in an autosomal dominant fashion

93
Q

How many syndromes are considered multiple endocrine neoplasias?

A

Three, known as MEN I, MEN II, and MEN III

94
Q

Name 5 endocrine organs that develop tumors in the multiple endocrine neoplasia syndromes.

A

Pancreas, pituitary, parathyroid, thyroid, and adrenal medulla

95
Q

Which gene mutation causes multiple endocrine neoplasias 2A and 2B?

A

ret gene

96
Q

A tall male patient enters the emergency room with the combination of a dissecting ascending aorta and acute mitral valve prolapse; what disorder might explain these findings?

A

Marfan's syndrome is associated with cystic medial necrosis of the aorta which may lead to a dissection, as well as a floppy mitral valve prone to prolapse

97
Q

What is the mode of inheritance of neurofibromatosis type 1?

A

Autosomal dominant

98
Q

What is another name for neurofibromatosis type 1?

A

von Recklinghausen;s disease

99
Q

Neurofibromatosis type 1 (von Recklinghausen's disease) is associated with a mutation on which chromosome?

A

Chromosome 17 (remember: there are 17 letters in von Recklinghausen)

100
Q

A patient has caf-au-lait spots, Lisch nodules, scoliosis, neural tumors, and pheochromocytoma. What is the most likely diagnosis?

A

Neurofibromatosis type 1 (von Recklinghausen's disease)

101
Q

What is another term for the pigmented iris hamartomas associated with neurofibromatosis?

A

Lisch nodules

102
Q

What are the dermatologic findings in neurofibromatosis type 1?

A

Caf au lait spots and axillary freckling

103
Q

What neoplasms are associated with neurofibromatosis type 1?

A

Neural tumors, optic pathway gliomas, pheochromocytoma, and overall increased tumor susceptibility

104
Q

What is the mode of inheritance for neurofibromatosis type 2?

A

Autosomal dominant

105
Q

A patient has bilateral acoustic neuroma, optic pathway gliomas, and juvenile cataracts. What is the most likely diagnosis?

A

Neurofibromatosis type 2

106
Q

True or False? Neurofibromatosis type 2 is associated with skin findings that are similar to those of neurofibromatosis type 1.

A

False; neurofibromatosis type 2 is not associated with abnormal skin findings

107
Q

Neurofibromatosis type 2 is a result of a mutation in the gene _____ found on chromosome _____.

A

NF2, 22 (remember: Type 2 = 22)

108
Q

What is the mode of inheritance of tuberous sclerosis?

A

Autosomal dominant

109
Q

A patient has adenoma sebaceum on his face, ash leaf spots on his trunk, mental retardation, and seizures. What the most likely diagnosis?

A

Tuberous sclerosis

110
Q

What renal findings might distinguish a patient with tuberous sclerosis from a patient with adult polycystic kidney disease ?

A

While both will have renal cysts, tuberous sclerosis is associated with renal angiomyolipomas

111
Q

What is a cardiac manifestation of tuberous sclerosis?

A

Cardiac rhabdomyoma

112
Q

Compared to the general population, patients with tuberous sclerosis have an increased incidence of which brain tumor?

A

Astrocytoma

113
Q

True or False? All patients who inherit the gene in tuberous sclerosis will display very similar signs and symptoms.

A

False; although autosomal dominant, this disease has incomplete penetrance and a variable presentation

114
Q

What is the mode of inheritance of von Hippel-Lindau disease?

A

Autosomal dominant

115
Q

A patient has hemangioblastomas of the retina and cerebellum, as well as bilateral renal cell carcinoma. What is the most likely diagnosis?

A

von Hippel-Lindau disease