Chap 7- Genetic variation causing disease Flashcards
(49 cards)
1
Q
pathogenic mutation
A
- changes function of gene
- usually do not randomly occur, we have “hot spots” for mutations
- i.e. CpG islands
2
Q
male germ line and mutations
A
- has higher probability of getting mutated
- with each cell division there is increased risk of mutation
- sperm cells continuously undergo division
- likelihood of mutation increases with males age
3
Q
degeneracy of genetic code
A
- most AA have more than one codon to specify them for protein synthesis
- change in nucleotide does not always result in new codon
4
Q
synonymous/ silent mutation
A
- result of redundancy of genetic code
- mutated codon often specifies same AA so no phenotype change
5
Q
nonsynonymous substitution
A
- causes change in AA
- replace purine with pyrimidine or vice versa
- aka missense mutation
- severity of mutation ranges
6
Q
stop-gain mutation
A
- AKA nonsense mutation
- mutation makes premature stop codon
7
Q
stop- loss mutation
A
- stop codon is lost due to mutation
- results in translation of untranslated regions
8
Q
what is the stop codon?
A
- UAG
- UAA
- UGA
9
Q
frameshift mutation
A
- when nucleotide is inserted or deleted that is not a multiple of 3
- frame completely changes
- can indirectly cause nonsense mutation
- can also occur from some mutations that produce altered splicing
10
Q
what is the usual result of a frameshift mutation?
A
nonfunctional protein
11
Q
karyotyping
A
- staining of chromosomes
- usually occurs and metaphase or prometaphase
- examined to identify chromosome abnormalities
12
Q
germ cell abnormality
A
- aka constitutional abnormality
- present in all nucleated cels
- present very early in development
- earlier a mutation starts the more severe consequences
13
Q
somatic abnormalities
A
- aka acquired abnormalities
- present in only certain cells or tissues
- acquired after child is born or anytime during their life
14
Q
structural abnormality
A
- problem with structure of chromosome
- i.e. breakage or new parts added
15
Q
numerical abnormalities
A
- change in number of chromosomes
- usually due to errors in chromosome segregation
16
Q
inversion
A
- deletion happens in just one arm
- material switched around in reverse direction
17
Q
paracentric inversion
A
- double break in just one arm of chromosome
- does not involve centromere
18
Q
pericentric inversion
A
- involves centromere which connects both arms
19
Q
ring chromosome
A
- occurs when both ends/ arms of chromosome are broken
- ends become sticky
- stick together to form ring
- rare
20
Q
role of centromere in mitosis and meiosis
A
- mitosis looks for one centromere, even if rest of chromosome is mutated
- if there is a dicentric or acentric centromere will not undergo mitosis
- meiosis cannot handle translocation
21
Q
translocation
A
- two different chromosomes each sustain a single break
- incorrect joining of broekn ends -> chromosome material exchange
- must occur between two close chromosomes
- can include the centromere but does not always
22
Q
euploid
A
- normal chromosomal makeup of individual
23
Q
aneuploid
A
- loss or gain of one or more chromosomes (not entire set)
- often in cancers
- i.e. trisomy 21
24
Q
polyploid
A
- extra set of chromosomes
- i.e. 3n or 4n rather than the normal 2n
25
trisomy
- three copies of a particular chromosome are present
| - usually autosomal changes are less tolerated than sex chromosome changes
26
monosomy
- chromosome is lacking
- i.e. turner syndrome
- autosomal monosomies are more severe than trisomies
27
how can aneuploid cells arise?
- nondisjunction
| - anaphase lag
28
what is nondisjunction?
- failure to separate paired chromosomes during meiosis anaphase I
- sister chromatids fail to disjoin at meiosis II or mitosis
29
what is anaphase lag?
- "lazy chromosome"
- all sisters have already crossed line
- nuclear division will not wait for lagging chromosome to get to opposite pole
- can result in abnormal distribution of chromosomes
30
what happens if there is a chromosome in cytoplasm?
- it gets degraded
| - can happen with anaphase lag
31
hypomorph
- mutant gene is incapable of carrying normal function
- can be reduced function or total loss of function
- usually involve change in protein structure
32
neomorph
- mutant gene has new acquired function that is toxic to cells
- usually involve change in protein structure
33
loss-of-function mutations
- severe mutation leads to deletion of an entire gene
- can lead to complete degradation of mRNA so no protein is produced
- includes nonsense mutations, frameshift mutations, and RNA splicing mutations
34
gain of function mutation
- common in cancer
| - many arise from chromosomal translocations and other rearrangements that make chimeric genes
35
chimeric genes
- due to translocation
- can have genes that are partly one gene and partly other gene
- can cause many problems
36
what is the result of a mutation in a regulatory gene?
- indirectly effects expression of many target genes controlled by the regulator
- genes themselves will not be mutated
37
what happens in a mutation in the enhancer?
get too much gene product
38
what happens in a mutation in the silencer?
not enough gene product
39
point mutation
- due to protein misfolding
- protein should be degraded
- in some diseases misfolded proteins are not degraded
- hydrophilic side must be outside, hydrophobic side must be inside
40
beta- thalassemia
- problem with adult Hb
- Hb normally has two alpha chains and two beta chains
- when balance is skewed, leads to aggregation of Hb in cell
- reduced beta production -> more alpha production -> cells aggregate and are lysed
41
environmental factors and phenotype
- environmental factors can sometimes influence phenotype
- exposure can be at various levels: at a distance, direct exposure, or contact with microbes/toxins
- especially important in triggering cancers
42
neurofibromatosis type 1
- autosomal dominant
- mutation in gene neurofibromin
- orginate from nonmyelinating schwann cells
- normal gene is tumor supressing gene
43
duchenne muscular dystrophy
- caused by mutation in dystrophin gene
- x linked recessive
- dystrophin gene should normally repair plasma membrane damage
- in DMD muscle membrane is progressively damaged and not repaired
- marked elevation of serum CK
44
what is turner syndrome?
- females lose one X chromosome
- 45 X, is a form of monosomy
- many live normal life with no signs showing until puberty
45
what are clinical features of Turner Syndrome?
- short stature
- primary ovarian failure
- cubitus valgus
- webbed neck
- broad chest with wide spaced nipples
- coartication of aorta *
- horseshoe kidney *
- does not affect intelligence
46
what is Klinefelter syndrome?
- when males have an extra X chromosome
| - 47 XXY
47
what are clinical features of Klinefelter syndrome?
- primary testicular failure
- gynecomastia, infertility, smaller testicles
- lower IQ
- tall stature
- poor muscle tone
- reduced secondary sex characteristics
48
down syndrome
- extra chromosome 21 aka trisomy 21
- flattened facial profile
- small nose
- epicanthal folds and bushfield spots
- short fifth fingers, wide gap between 1st and 2nd toes
- transverse palmar creases
- low IQ*
- hypotonia, vision and hearing problems
- Congenital heart malformations*
- increased risk for leukemia
49
how does maternal age effect down syndrome?
- 70% of down syndrome cases are due to issues at meiosis I in mother
- due to increased maternal age
- the longer the egg is at rest, the "lazier" it becomes, result is nondisjunction
