Exam 2; Genetic Disease Flashcards Preview

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Flashcards in Exam 2; Genetic Disease Deck (82):
1

How many protein encoding genes are there in the human genome

roughly 19,000

2

This refers to a permanent change in the DNA

mutation

3

What can become of a mutation that effects germ cells

it can be inherited/transmitted to progeny

4

What can become of a mutation that effects somatic cells

can result in tumor or developmental abnormalities

5

What is a point mutation

a single nucleotide base substituted (missence)

6

What is a frameshift mutation

insertion or deletion of one or two base pairs, altering the reading frame of the DNA

7

What is a trinucleotide repeat mutation

amplification of sequence of 3 nucleotides (Fragile X syndrome)

8

What is a single nucleotide polymorphism

variation in just one nucleotide at a single site on the DNA molecule, over 6 million have been identified

9

What is a copy number variation

different numbers of large contiguous stretches of DNA; may account for much phenotypic variation

10

What are epigenetic changes

modulation of gene expression without altered DNA sequence; important in development as well as normal homeostasis

11

This of a promoter region makes them inaccessible to RNA polymerase thus reducing protein synthesis

methylation

12

What can occur is there are alterations in non-coding RNAs

microRNAs inhibit translation of their target messenger RNAs into their corresponding proteins

13

This type of disorder implies that the altered gene locus is on an autosome and the disease will be evident clinically when only one of the chromosomes in the pair exhibits a mutation at the affected gene locus

autosomal dominant disorder (ADD)

14

True or False
autosomal dominant disorders are evident at birth since they create outward physical changes

False; many exhibit delayed age onset (Huntington's disease)

15

What is it when the person has a mutant gene (ADD) but does not express it phenotypically

reduce or incomplete penetrance

16

What is it when the trait is seen phenotypically in the individuals having the mutant gene but is expressed differently among the individuals (ADD)

variable expressivity

17

What is it when the affected individuals (ADD) may not have affected parents because their disease arose from a new mutation

de novo mutation

18

What are the chances of a person have (ADD) if only one parent is affected

50%

19

This disorder implies that the trait is expressed only in both gene at a given locus are affected (homozygous individuals)

autosomal recessive disorders (ARD)

20

True or False
The parents of an ARD child usually do not show the disease

True

21

Offspring of an heterozygous ARD carrier have what changes of having or being a carrier of the disease

1 in 4 chance of having it
2 in 4 (1 in 2) chance of carrying it

22

If the mutant gene is rare (ARD) there is a strong possibility that the affected child is the product of what

a consanguineous (from the same ancestor) relationship

23

What are three characteristics of ARD

two germline mutations (one from each parent) to develop the disease
equally transmitted by men and women
25% offspring; horizontal pattern in family

24

Many ARD disorders present how

with enzyme defects that produce inborn errors of metabolism; in heterozygous individuals, this may not be evident clinically but would have reduced numbers

25

What is the age of onset of ARD compared to ADD

more frequently early in life

26

The expression of the defect of ARD is what compared to ADD

expression is more uniform and complete penetrance is common

27

Which is more common, ARD or ADD

ARD

28

How many Y-linked disorders have been discovered

None (except the trait "hairy ears"), all sex-linked diseases are X-linked

29

Almost all X-linked disorders are this

recessive, therefore females are usually heterozygous

30

Who is typically affected by X-linked disorders

homozygous females and males (only have 1X; homozygous) i.e. hemophilia

31

What is lyonization

16 days after conception, all but one X-chromosome is the nucleus of each cell is inactivated; either the maternal or paternal X, all progeny will have the same inactivated X chromosome

32

What are the cell types of a lyonization female

a mixture; those with active paternal X and those with active maternal X; typically proportionally equal

33

This refers to inactivation of an abnormally high percentage of normal X chromosomes leading to clinical evidence of the disease in a heterozygote

unfavorable lyonization

34

This ADD has nearly 100% penetrance, even though the gene has quite variable expressivity among the affected individuals

neurofibromatosis

35

These disorders are inherited in a variety of patterns; mutation of genes that encode proteins necessary for formation of normal bone and connective tissue

diseases caused by mutations in structural proteins

36

This is an ADD due to the mutation of FBN1 gene resulting in abnormal fibrillin; a glycoprotein necessary for normal elastic fiber production

marfan syndrome

37

What is the prevalence of Marfan syndrome

1 in 5,000

38

What are the clinical manifestations of Marfan syndrome

tall, thin body
abnormally long legs
arachnodactyly (long fingers)
dislocation of lens of the eye
aortic aneurysm and dissection, leading to heart failure and aortic rupture

39

This syndrome is highly variable (at least 6 clinical variants) and deals will a problem in collagen synthesis (30 types of collagen)

Ehlers-Danlos Syndrome

40

What are the clinical manifestations of Ehlers-Dalos syndrome

hyper extensible skin and hyperbole joints
skin fragility and delayed wound healing
rupture of the colon and large arteries
hernia

41

This is one of the more common inherited disorders (ADD) resulting from a mutation of the gene that encodes the LDL receptor

familial hypercholesterolemia

42

What is the frequency of familial hypercholesterolemia

1 in 500

43

What results from familial hypercholesterolemia

impaired metabolism and increased LDL cholesterol in the plasma

44

What are two clinical manifestations of familial hypercholesterolemia

xanthomas of the skin
premature atherosclerosis

45

Heterozygotes have what in regards to familial hypercholesterolemia

2-3x increase LDL

46

Homozygotes have what in regards to familial hypercholesterolemia

over 5x normal LDL levels, typically die of MI by age 15/20

47

This drug can be used to treat familial hypercholesterolemia

lomitapide

48

This is an ARD that affects 1 in 10,000 caucasian infants and is caused by a lack of phenylalanine hydroxylase leading to hyperphenylalaninemia and PKU

phenylketouria

49

What is the clinical manifestation of phenylketouria

affected infants are normal at birth but elevated phenylalanine levels impair brain development leading to mental retardation by 6 months

50

What steps are taken to prevent phenylketouria

screening of newborns in mandatory in the US
restricting dietary sources of phenylalanine will prevent the development of mental retardation

51

This AR transmission commonly affects infants and young children and is characterized by accumulation of insoluble large molecules (sphingolipids, mucopolysaccharides) in macrophages leading to hepatosplenomegaly

Lysosomal storage diseases

52

What is also frequently involved with lysosomal storage diseases

CNS involvement, mental retardation and/or early death i.e. Tay-Sachs, Niemann-Pick, Gaucher, Mucopolysaccharidoses

53

Most of these are AR traits and is due to the lack of any one of several enzymes necessary to degrade mucopolysaccharides; 7 variants

mucopolysaccharide storage disease

54

What are the clinical manifestations of mucopolysaccharide storage diseases

coarse facial hair
clouding of the cornea
joint stiffness
mental retardation

55

This is caused by a deficiency of alpha-L-iduronidase (laronidase); life expectancy is only 6-10 years if untreated

Hurler syndrome

56

What are some treatment options for Hurler syndrome

bone marrow transplant
enzyme therapy that may improve the outlook, but not completely correct it, costs >$300,000/annually
treatment can extend the life expectancy to +/- 30 years

57

This is caused by a deficiency of L-iduronate sulfatase and is in a X-linked inheritance pattern

Hunter syndrome

58

What are the clinical manifestations of Hunter syndrome

coarse facial hair
joint stiffness
mental retardation
milder than Hurler syndrome

59

Disorders with multifactorial inheritance has what two characteristics

many physiologic trains (height, weight, BP, etc.)
may underlie common diseases such as diabetes, hypertension, gout, etc.

60

What characterizes a disorder with multifactorial inheritance

two or more genes responsible, plus environmental, non-genetic influences

61

What is the frequency of inheriting a disorder with multifactorial inheritance

2-7%

62

It is estimated that what percentage of newborns have a chromosome abnormality

1 in 200

63

In as many as what percentage of 1st trimester spontaneous abortions, the fetus has a chromosome abnormality

50%

64

What is a euploid

a normal chromosome count (2 x 23 = 46)

65

What is a polyploid

an increase chromosome count that is a multiple of that normally seen (3 x 23 = 46) it generally results in a spontaneous abortion

66

What is an aneuploidy

any number that is not an exact multiple of the normal chromosome, like a trisomy or monosomy

67

What is a structural abnormality of a chromosome

chromosome breakage followed by loss or rearrangement of material

68

This is a translation of a part of one chromosome to another non homologous chromosome

translocation

69

What is reciprocal translocation

fragments exchanged between two chromosomes

70

This is when a chromosome breaks in two points, then the released fragments are reunited after a complete turnaround

inversion

71

This is the most common chromosomal disorder; due to meiotic non-disjunction of chromosome 21 during formation of the ovum - associated with advanced maternal age

trisomy 21; Down Syndrome

72

What are the chances of having a child with down syndrome at 45

45 1:25

73

What are the clinical manifestations of down syndrome

mental retardation
epicanthic folds
flat facial profile
cardiac malformation
increases susceptibility to infection (periodontal disease)
large tongue
increase prevalence of acute leukemia

74

This is defined as male hypogonadism that develops when there are at least two X chromosomes and one or more Y chromosomes

Klinefelter

75

This is due to partial or complete absence of one of the X chromosomes

Turner syndrome

76

What is the phenotype of some one with Klinefelters

male

77

What are the clinical manifestations of Klinefelters

increased length of lower limbs
reduced body hair
gynecomastia
hypogonadism
male sterility (most common cause)

78

What occurs dentally involving Klinefelters

taurodontism (weird molars and elongated pulp chambers)

79

What are the clinical manifestations of Turners syndrome

markedly short stature
webbing of the neck; low posterior hairline
"shield-like" chest
high arched palate
variety of congenital cardiovascular malformations
failure to develop secondary sex characteristics; primary amenorrhea (no menstruation)

80

What are three ways to diagnose a genetic disease

FISH
comparative genetic hybridization
molecular diagnosis; PCR, restriction enzymes, comparison of the order, fluorescently labeled nucleotides

81

What are four PRE-NATAL indications for genetic analysis

mother age >34
parent who is a carrier of a chromosomal translocation
Hx of previous child with chromosomal abnormality
parent who is a carrier of an X-linked disorder

82

What are the six POST-NATAL indications for genetic analysis

multiple congenital anomalies
unexplained mental retardation and/or developmental delay
suspected aneuploidy
suspected sex chromosomal abnormality
infertility
multiple spontaneous abortions