genetic disease Flashcards
(132 cards)
1
Q
how many chromosomes are in the human body
A
22 pairs of autosomes
1 pair of sex chromsomes
2
Q
how many genes encode Pr
A
20,000 protein encoding genes
3
Q
what is the roll of non protein encodeing genes
A
Control of the protein-encoding genes
4
Q
what is it when 1 chromsome is different from the other
A
Heterozygous
5
Q
when both chromosomes are affected at a given locus
A
Homozygous
6
Q
what is a mutation
A
a permant change in the DNA
7
Q
what happens if a mutation is in a germ cell
A
Can be inherited
8
Q
what happens if a mutation affects somatic cells
A
Results in tumor or developmental abnormality
- can be cancerous, death, sublethal, or change the cell
9
Q
what is a point mutation
A
Single base substituted
10
Q
what is a frameshift mutation
A
Insertion/deletion of 1-2 base pairs
11
Q
what is a trinucleotide repeat
A
amplification of a 3 nucleotide sequence
12
Q
what kind of mutation is a Fragile X syndrom
A
Trinucleotide repeat
13
Q
what is the ultimate result of a frame shift mutation
A
change in the reading frame
14
Q
what kind of mutation is sickle cell anemia
A
Point mutation (missense mutation)
15
Q
what are the types of polymorphisms
A
SNPS
Copy number variation
16
Q
what is the most common type of Polymorphism
A
SNPs
17
Q
where are most SNPs found
A
within exons, introns, or intergenic regions
18
Q
what can SNPs be markers for
A
Multigenic complex disease
19
Q
what is a copy number variation
A
Different number of large cont. stretch of DNA
20
Q
where is copy number variation found
A
1/2 gene-coding sequences
21
Q
what is the effect of copy number cariation being involed in gene coding sequences
A
Account for phenotypic variation
22
Q
what aside from mutations can inmpact Protein-coding gene function
A
Polymorphisms
Epigenetic
changes
Alterations in non-coding RNAs
23
Q
what are epigenetic changes
A
Modulation of gene expression without altering DNA sequence
24
Q
when are epigenetic changes important
A
Development
Homeostasis
25
what are epigenetic changes that occur to alter protein coding genes
methylation of promoter region makes inaccessible to RNA polymerase, ruducing PR synth
26
what is the action of MiRNA's
Inhibit translation of their target messenger RNAs into corresponding Proteins
- via suppression/ destruction
27
what are some alterations in non-coing RNA;s
microRNAs
| Long non-coding RNAs (IncRNA)
28
what are the actions of Lon non-coding RNAs
Control/repression/regulate DNA expression
29
what cleaves PRe-miRNA to 2 miRNA
Dicer
30
what does miRNA bind to after being cleaved
Silencing Complex
31
what happens if there is an imperfect match between miRNA and mRNA
represses by decreasing transcription
32
what happens if there is a perfect match between miRNA and mRNA
mRNA is cleaved leading to silencing
33
what are the types of Mendelian disorders
Autosomal Dominany
Autosomal Recessive
Sex-linked (x linked) disorder
34
what are the types of Genetic disorders
mendelian
Multifactoral (polygenic)
Cytogenetic (Chromsomal aberrations)
35
how many genes are affect in medelian disorders
Single gene
36
what do genes do
Contain info to produce proteins that perform specific functions
37
what does mutation lead to
Production of abnormal protein
| - may alter phenotype
38
does each mutation lead to a different phenotype
nope, may lead to the same phenotypic alteration
39
what chromsomes are affected in autosomal dominant disorders
one of the autosomes
40
what is the inheritance of autosomal dominant disordrs
Heterozygous state
- one parent affected
- half the offspring get disease
41
when does Autosomal dominant disorders show themsleves
outward physical change
| - delayed age of onset
42
what kind of disorder is huntingtons diseaes
Autosomal dominant
43
what is reduced or incomplete penetrace
Person has a mutant gene, but doesn't or only partially expresses it phenotypically
44
what is variable expressivity
trait seen phenotypically in all individuals ahving the mutant gene
- differntly expressed in individuals
45
what is a de novo mutation
affected individuals may not have affected parents because disease arose from new mutation
46
what kind of disease in Neurofibromatosis
AD disease
47
how often does Neurofibromatosis show it self
100% penetrance
| variable expressivity
48
Commonness of neurofibromatosis
1/3000 live births
49
what is the largest group of mendelian disorders
Autosomal recessive disorders
50
what is the inheritance of autosomal recessive disorders
Homozygous
- parents usually appear unaffected
- 25% offspring affected
- 50% offspring carriers
51
what happens if the recessive gene is rare in a population
disorder may be a result of being from the same blood line (incest)
52
what does an autosomal recessive disorder do to the proteins
Enzyme defect, leading to metabolic dysfuntion
53
what is the effect of an autosomal recessive disorder on a carrier
Unaffected clinically, but may have reduced but adequate leaves of normal functional enzyme
54
how does autosomal disorders show themselves
early in life
complete penetrance
little variability
55
what chromosome are sex-linked disorders found on
All on the X chromsome
56
what is the only important gene on the Y chromsosme
SRY - sex determining region
| - also hairy ears possibly
57
do X-linked diseases tend to be dominant or recessive
Dominant
58
why might heterozygous females show X-linked diseases
Unfavorable lyonization
59
when do X-linked diseases tend to express themselves
Earlier
60
what is Lyonization
either X chromosome may be inactivated at 16 days after conception. all progeny of that cell will have the same inactivated X chromosome.
61
what does the inactivated chromosome in females become
Barr body
62
who and when was lyonization found
mary lyon in 1962
63
what is unfavorable lyonization
inactivation of an abnormally high percentage of normal X chrosomes leading to clinical evidence of recessive disease in a heterozygous females
64
what is the heritability of margan syndrome
Autosomal Dominant dissorder
65
what does margan syndrome do
Connective tissue disorder of FBN1 gene leading to abrnoaml fibrilin
66
what is the use of fibrillin
Glycoprotein needed for elastic fiber production
67
commonness of marfan syndrom
1:5000
68
what are the clinical signs of marfan sydrome
Thin, tall body habitus with abnormally long legs, arms, and fingers (arachnodactyl)
Dislocation of lens of eyes
69
what is the problem with marfan syndrome
Aortic aneurysm/dissection leading to heart failure and aortic ruption
blood vessels lack strength
70
what are the types of EHlers-Danlos syndromes
6 clinical types with dominant and recessive forms
71
what is the problem caused by Ehlers-danlos syndromes
problem with collagen synthesis
72
clinical signs of ehlers-Danlos syndromes
```
Hyperextensible skin and hypermobile joints
Skin fragility and delayed wound healing
Rupture of colon, large arteries
Hernias
- problem with wound healing
```
73
commonness of Familial hypercholesterolemia
1:500 (Common)
74
what mutation causes Failial hypercholesterolemia
LDL receptor mutation
75
what does the LDL receptor mutation in familial hypercholesterolemia lead to
impaired metabolism and increased LDL cholesterol in the plasma
- xanthomas of skin
- premaure atherosclerosis
76
hertability of Familial hypercholesterolemia
heterozygous: 2-3x more cholesterol level
Homozygous: 5x more cholesterol
- autosomal dominant
77
what is used to treat Familial hypercholesterolemia homozygous individuals
lomitapide
78
what are xanthomas
yellow papulomas at joints
79
what is the problem with homozygoud familial hypercholesterolemia
Leads to heart attacks at 20 years old
80
what is the problem with cysteic fibrosis
Chloride channel protein
81
heritability of phenylketonuria
Autosomal recessive
82
how prevelant is phenylketonuria
1:10,000 caucasian babies
83
what enzyme is affect from phenylketonuria
lack of phenylaninine
84
what does phenylketonuria lead to
Hyperphenylalanimia
| PKU
85
how does Phenylketonuria manifest during life
- Infants are normal at birth
- elevated phenylalanine impair brain development
- metal retardation at 6months
86
who do we prevent phenylketonuria in the USA
screen newborns at birth is mandated
restrict diet of phenylalanine
- will live a normal life then
87
how are storage disease transmitted
Autosomal recessive
88
who is affected by storage disease
Infants and young children
89
what does a storage disease lead to
Accumulation of large insoluble molecules (sphingolipids, mucopolysaccharides) in macrophages
- leads to hepatosplenomegaly
90
what system may get affected by storage disease
CNS
91
CNS involvement in storage disease leads to what
neuronal damage
mental retardation
early death
92
what are types of lysosomal storage disease
Tay-sachs disease
Niemann-Pick disease
Gaucher disease
Mucopolysaccharidoses
93
what is the hertability of mucopolysaccharides storage disease
Autosomal recessive (mostly)
94
what causes Mucopolysaccharide storage disease
Lack of any one of the enzymes needed to degrade mucopolysaccharides
95
what is the clinical signs of mucopolysaccharide storage disease
coarse facial features
clouding of cornea
Joint stiffness
mental retardation
96
how is Hurler disease (MPS type 1) transmitted
Autosomal recessive
97
what causes Hurler Disease (MPS type I)
Deficiency of alpha-L-iduronidase (Iaronidase)
98
how long can you live with Hurler disease (MPS type I) if untreated
6-10 years
99
how to treat hurler disease (MPS type I)
bone marrow transplant
enzyme replacement
- won't fix all of the disease
100
cost of enzyme for Hurler disease(MPS type I)
greater than 300k
101
how is Hunter sdnrome passed down
X-linked
102
what cuases Hunter syndrome
deficiency of L-iduronate sulfatase
103
what are the symptoms of hunter syndrome
Absence of corneal clouding and milder clinical course
| similar to Hurler syndrome
104
what are multifactorial (polygenic) disorders
2+ genes respondible
| environmental also
105
what disease do multifactorial disorders tend to cause
```
Diabetes
hypertension
gout
schizophrenia
bipolar...
```
106
what is found in a normal karyotype
22 autosome pairs
1 sex chromosome pair
46 total
107
how common is a chromosomal abnormality
1:200
108
how often does chromosomes cause 1st trimetster spontaneous abortions
50%
109
what is a normal chrosomsal count
euploid
110
what is an increase in the number of chromosomes by multiple of the number normally seen (i.e 23x3 or 23x4)
polyploidy
111
what does polyploidy lead to
Spontaneous abortion
112
any number of chromosomes that is not a multiple of the normal chrosome
Aneuploidy
113
extra chromosome
Trisomy
114
absence of a chromsome
Monosomy
115
what do structural abnormalities often result from
when chromosome breakage is followed by a loss or rearrangement of material
116
what is the transfer of a part of one chromsome to another nonhomologous chromosome
Translocation
117
when fragments are exchnaged between 2 chromosome
reciprocal translocation
118
loss of a part of a chromosome
deletion
119
when a chromosome breaks in two points, then the release fragment is reunited after a complete turnaround
Inversion
120
what disease does trisomy 21 causes
Down sydnrome
121
what is the most common chromosomal disorder
trisomy 21
122
what causes downs to increase
advanced maternal age
<20 1:1550
>45: 1:25
123
what causes trisomy 21
meiotic non-disjunction of chromosome 21 during ovum formation
124
clinical signs of trisomy 21
mental retardation
epicanthic folds
flat facial profile
cardiac malformations
increased susceptibility to infection (including severe periodontal disease in children)
large tongue
increased prevalence of acute leukemia(10-20 times more likely)
125
what is klinefelter syndrome
Male hypogonadism when there are at least 2 X chromosomes and Y+ you chromosome (47 XXY)
126
what is turner syndrome
Female hypogonadism partial or complete absence of one of the X chromosomes (45, X)
127
are klinefelter patients phenotypically male or female
Male
128
clinically how does klinefleter affect people
Increased length of lower limbs
reduced body hair
gynecomastia
Hpogonadism (most common cause of male sterility)
129
how does klinefleter affect dental
Taurodontism ( enlarged tooth pulps)
130
clinical sings of turner syndrome
Markedly short stature
webbing of neck
low posterior hairline
shield like chest
high-arched palate
variety of congenital cardiovascular malformations
failure to develop secondary sex characteristics; primary amenorrhea
131
when should you do prenatal genetic analysis
mother's age greater than 34 years
parent is a carrier of a chromosomal translacation of X linked disorder
History of a perivous child with chromosmal abnormality
132
when should you do a postnatal genetic analysis
```
Multiple congenital anomalies
unexplained mental retardation and/developmental delay
suspected aneuploidy
suspected sex chromosomal abnromality
infertility
multiple spontaneous abortions
```
