Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

GENETICS M2M > Week 1 > Flashcards

Week 1 Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

Pharmacogenetics

A

the area of biochemical genetics concerned with the impact of genetic variation on drug response and metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two major physiological responses to drugs?

A

1) achieving desired effect

2) removing/inactivating the drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Pharmokinetics

A

rate at which the body absorbs, transports, metabolizes, and excretes drug
ATME
“whether/how much drug reaches target”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Pharmakodynamics

A

response of drug binding to its target and downstream targets
“what happens when drug reaches target”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Phase I drug metabolism

A

attach polar group onto compound to make more soluble - hydroxylation step

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Phase II drug metabolism

A

attach sugar/acetyl group to detoxify drug and make it easier to excrete

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Cytocrome P450

A

CYP450
responsible for phase I metabolism
Most are associated with inactivation of drug, but CYP2D6 is associated with activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CYP2D6

A

drug necessary to convert codeine into morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Frameshift mutation in CYP2D6

A

non function - no conversion to morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Splicing of CYP2D6

A

skin exons or alter reading frame - non functional - no conversion to morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Missence of CYP2D6

A

alter protein function - reduced activity - less conversion of morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Copy number alleles in CYP2D6

A

increased gene copies is increased activity!

Poor, Normal, or ultrarapid/ultrafast

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

CYP3A

A

Cyclosporine
Inhibitors: ketoconazole, grapefruit juice
Activators: rifampicin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CYP2D6

A

Codein, tricyclic, antidepressants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CYP2C9

A

warfarin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

TMPT

A

6-mercaptopurine
6-thioguanine
Chemotherapeutic, but bone marrow toxicity
ranges from high to virtually indetectaable enzymatic activity. Those with low (1:400) have extreme bone marrow suppression that causes fatality if not dosed correctly.
must give 1/10 of standard dose for those patients.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

G6PD

A

Sulfonamide, dapsone
X-linked enzyme
susceptible to hymolytic anemia after drug exposure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

VKORC1

A

Warfarin

blood thinner

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Warfarin

A

Both a CYP2C9 and VKORC1
Anti-coagulant
prescribed at standard dose of 5 mg and pt is watched over next few moths for excessive bleeding or clotting and dose id adjusted.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

NAT

A

isoniazid for TB
if quickly digested: no liver problems but not adequate TB treatment
if slowly digested: good TB treatment, but liver problems.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Haplotype

A

a group of allele sin coupling at closely linked loci, usually inherited as a unit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Pleitropic

A

multiple phenotypic effects due to a mutation(S) in a single gene. Often used when phenotypes are seemingly unrelated and/or in different tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Incomplete dominance

A

phenotype is intermediate between two homozygous phenotypes
trait inherited in dominant manner, but is more severe in homozygous than heterozygote.
semidominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

1st law of segregation

A

At meiosis, alleles separate (or segregate) from each other such that each gamete (egg or sperm) receives one copy from each allele pair.
have a 50:50 chance of getting the gene

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Mende’s 2nd law of independent assortment

A

At meiosis, the segregation of each pair of alleles is independent. [Note: genes physically near each other
(‘linked’) on the same chromosome violate this law]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Co-dominant traits

A

if both alleles/traits are expressed in heterozygous state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Hemizygous

A

male with mutated X

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

X-Inacivation

A

one chromosome is largely inactivated in somatic cells, to equalize expression of X-linked Genes between sexes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Penetrance

A

fraction of individuals with a trait genotype who manifest the disease
Can be either 100% penetrant or Incomplete penetrance.
Analogous to light switch

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Expressivity

A

degree to which a trait is expressed (measure of severity)
analogous to dimmer
influenced by sex, environmental factors, stochastic events, and modifier genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Phenocopies

A

Diseases that are due to non-genetic factors

ie. thyroid cancer due to radiation exposure vs. thyroid cancer due to RET mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Four factors that influence allele frequency

A

1) natural selection
2) genetic drift
3) nutation
4) gene flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Genome mutation

A

Due to chromosome missegregation

2-4 x 10^-2/cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Chromosome mutation

A

due to chromosome rearrangement

6x10^-4 / cell division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Gene mutation

A

due to base pair mutation

10^-5 to 10^-6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Polymorphism

A

genetic mutations that is common in more than 1% of the population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Genetic Drift

A

random fluctuation of allele frequencies, usually in small populations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Gene Flow

A

when populations with different allele frequencies mix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Incidence rate of autusomal domiant

A

2* mutation rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Assumptions of Hardy-Weingberg

A

Large populations are randomly mating
Allele frequency remains constant because
1) there are no new mutations
2) no selection for/against alleles
3) no immigration/emigration with new allele frequencies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Stratification

A

populations containing two or more subgroups preferentially mate within own subgroup
(AA) with sickle cell anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Assortive Mating

A

Choice of mate is dependent on particular trait (ie height, intelligence, dwarfism, blindness)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Mitosis vs. Meiosis

A

1) paternally and maternally derived homologous chromosomes pair at onset of meiosis, where as they segregate independently in mitosis
2) reciprocal recombination events occur in meiosis, but are rare in mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

chiasmata

A

crossing of chromatid strands of homologous chromosomes

a physical linkage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Bivalent

A

pair of homologous chromosomes in association, as seen in metaphase of first meiotic division

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Synaptonemal complex

A

The synaptonemal complex is a protein structure that forms between homologous chromosomes (two pairs of sister chromatids) during meiosis and is thought to mediate chromosome pairing, synapsis, and recombination.
Disassembled during end of prophase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Reciprocal Recombination

A

generate physical linkages between homologs

2-3 crossover events occur per pari of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Genetic consequences of meiosis

A

1) reduction of chromosome number
2) recombination during meiosis I prophase giving 2^23 possibilities
3) independent assortment of maternal and paternal chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Non-disjunction in meiosis I

A

100% abnormal cells

2 (N+1) and 2(N-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Non-disjunction in Meiosis II

A

50% abnormal cells

2 N and 1 (N+1) and 1(N-1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What increases rates of non-disjunction?

A

1) Maternal Age
2) crossing over events that occur too near (entanglement) or too far from centromere (less effective in spindle attachments)
3) Reduction of recombination events

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

what percentage of genetic abnormalities cause first semester spontaneous abortions?

A

50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

what percentage of live born infants have congenital abnormalities?

A

3%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What percentage of sperm is abnormal?

A

1-3%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What percentage of ova are abnormal?

A

> 3%

increasing with advanced maternal age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

metacentric

A

central centromere

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

submetacentric

A

off center and arms are clearly of different lengths

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Acentric

A

centromere nearly at the end
includes 13, 14, 15, 21, 22
small masses of chromatin called Satellites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Satellites

A

a small mass of chromosome containing genes for rRNA at the end of the short arm of acentric chromosomes
Highly polymorphic and variable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Telocentric

A

centromere at one end and only a single arm

not observed in humans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

ploidy

A

number of homologous chromosome sets present in a cell or organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Euploidy

A

true ploidy

full sets of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Triploid

A

3 sets of chromosomes - 69

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Tetraploid

A

4 sets of chromosomes - 92

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

mechanism that causes tetraploidy

A

DNA duplication but not cell division (endomitosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Aneuploidy

A

abnormal chromosome number due to the extra or missing chromosome
arrises during meiosis I or II, could be paternal or maternal
or post zygotically

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Tolerated aneuploidies at conception

A

45,X

Trisomy 16, 21, 22

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Tolerated aneuploidies at live birth

A

trisomy 13, 18, 21

sex chromosome aneuploidy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

When should cytogenic studies be ordered?

A

1) multiple congenital abnormalities
2) developmental delay + minor abnormalities
3) historical familial chromosomal abnormality
4) intrauterine growth reduction
5) history of miscarriages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Postnatal cytogenic studies

A

peripheral blood

skin biopsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Cytogenic Studies with acquired cancer

A

Bone Marrow
tumor
peripheral blood
lymph node

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Trisomy 21 Phenotype:

A

1) brachycephaly (shorter head) 2) midface hypoplasia 3) up slanting palpebral fissures 4) spicanthal folds (extra skin on inside of eyes) 5) small ears 6) large appearing tongue 7) increased joint mobility 8) brushfield spots 9) incurving 5th finger 10) increased space between 1st and 2nd toe 11) horizontal fissure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Clinical Features of Down Syndrome: cardiac

A

50% have congenital heart defect

mostly atrioventricular canal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

GI defects in Down Syndrome

A

10-15% of DS babies
esophageal or duodenal atresias
Hirshprungs disease
non anatomical defects: feeding problems, gastro esophageal reflux disease, celiac

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

How are esophageal and duodenal atresias detected

A

extra amniotic fluid becuase baby can’t swallow

called polyhydramnios

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Ophthalmologic problems in Down Syndrome

A

60% of DS patients have there

1) conjuntivitis (blocked tear ducts) 2) myoptia (near sightedness) 3) lazy eye 4) nysagmus (jiggly eye) 5) cataracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Ear, nose and throat problems in Down Syndrome

A

Chronic ear infections
deafness (both sensorineural and conductive)
chronic nasal congestion
enlarged tonsil and adenoids leading to sleep apnea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Percentage of hearing loss in Down Syndrome

A

75%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Endocrine disorders in Down Syndrome

A 
25% Thyroid Disease (hypothyroidism)
Insulin dependent diabetes
Alopecia
Reduced fertility (normal puberty)
females can be fertile, but males are almost never
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Orthopedic problems in Down Syndrome

A

Hips and joint subluxation

Atlantoaxial subluxation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Blood issues in Down Syndrome

A

Myeloproliferation disorder
Increase risk of leukemia (12-20X) in perinatal period
iron deficiency due to feeding issues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Neurological/Psychiatric problems in down Syndrome

A 
Hypotonic
Seizures (infantile spasms)
Depression
Early onset AD
autism (1/10)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

Development and behavioral phenotype of Down Syndrome

A

Delayed gross motor development due to hypotonia
Intellectual disability IQ -50
Speech problems due to small mouth/large tongue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Recurrence risk of Down Syndrome

A

1/100 + risk of maternal age

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Risk for having DS child in 20s

A

1/1000

86
Q

Risk of having DS child at 35

A

1/200

87
Q

risk of having DS child at 40

A

1/100

88
Q

risk of having DS child at 45

A

1/20 to 1/10

89
Q

Types of trisomy 21

A

Complete 90%
Acentric translocation 3-4%
Mosaic: 1-2%

90
Q

Maternal Age effect

A

1) diminished recombination due to lack of chiasmata or mislocalization
2) decreased segregation
less able to overcome non-disjunction detection

91
Q

Prevalence of Trisomy 21

A

1/800 to 1/900 live births

Only 20-25% of conceptuses survive to birth

92
Q

Trisomy 18

A

Edwards Syndrome

93
Q

Trisomy 18 phenotype

A

small for gestation age, microcephaly, clenched hands/overlapping fingers, rocker bottom feet, heart/brain abnormalities

94
Q

Trisomy 13

A

patau syndrome

95
Q

Phenotype of Trisomy 13

A

growth retardation, severe mental retardaton, sloping forehad, misformed ears, cleft palate, clenched and overlapping fingers, rocker botton feet, congenital heart defects, urogenital defects, ocular abnormalities

96
Q

Turner Syndrome

A

45, X
most common abnormalities in spontaneous abortions
99% of fetuses do not survive to term
1/2500 female births

97
Q

Turner Phenotype

A

prenatal lymphedema, cystic hygroma, congenital heart defect, coarctation of aorta, gonadal dysgenesis, short stature, webbed neck, low set ears, normal intelligence, infertility due to non-functioning ovaries, hormone dysfunction(requires hormone replacement)

98
Q

karyotypes of Turners

A 
45, X (50%)
46, X, i(Xq) Three long arms 1 short
mos 45X/46 X i(Xq)
mos 45, X/ 46 XX (truncated long arm)
all surviving births are through to be mosaic
99
Q

Klinefelter Syndrome

A

47, XXY

common 1/1000 males

100
Q

Klinefelter syndrome phenotype

A

tall, hypogonadism, atrophic testis (infertile), underdevelopment of 2nd sexual characteristics, learning disability, poor psychosocial development, delayed speech and langauge, quiet, not broard shoulders, wide hips
At puberty: small tests, reduced facial and body hair, infertility, hypospadias (uretrha underside penis), gynecomastia (enlarged breasts)

101
Q

Origin of Klinefelter

A

50% due to paternal meiosis I (failure of Xp/Yp recombination)
50% de to maternal meiosis I errors (75% occur in meiosis I)

102
Q

Klinefelter Mosaicism

A

25% are mosaic
most common are 47, XXY/ 46 XY (with normal testicular development maybe)
48 XXYY, 48 XXXY, 49 XXXXY

103
Q

when are structural chromosomal abnormalities visible by cytogenetics?

A

changes greater than 5 megabases

104
Q

Reciprocal Translocation

A

translocation between two non-homologous chromosomes

105
Q

Quadrivalent

A

structure that forms the gametocyte in meiosis I, divides chromosomes of one daughter cell and chromosomes to the other daughter cell.

106
Q

Alternative segregation

A

alternate centromeres to the same pole
centromere of homologues to opposite poles
always leads to normal and balanced translocation
occurs 50% of the time

107
Q

Adjacent 1 Segregation

A

adjacent nonhomologous centromeres to the same pole
Top from bottom
each contains duplications and deletions,
50% of the time
results in trisomy or monosomy

108
Q

Adjacent 2 segregation

A

adjacent homologous centromeres to same pole
seldom occurs
Separation from right and left

109
Q

Reciprocal Translocation

A

BALANCED
partner homologues arrnges themselves to maximize pairing to from quadravalent and separated by alternate and adjacent separtion

110
Q

Robertsonian

A

Structural chromosomal rearrangment that cuases acrocetnric chromsome to fuse to make double centromere or single centromere
almost always leads to unbalanced because they have 45
can be homologous or non homologous

111
Q

Human acrocentric chromosomes

A 
13, 14, 15, 21, 22
most common is 13:14 75%
also 14:21
and 21:21
can be de novo or familial
112
Q

Homologous acrocentric chromosomes

A

pairing of both of the same sister chromatids

ie. 13 with 13

113
Q

Non-Homologous Acrocentric chromosomes

A

between two different acrocentric chromatids

13 and 14

114
Q

how many trisomy 13 are due to roberstonian translocation

A

20%

115
Q

Pericentric Inversion

A

inversion that include the centromere
non-consequential unless break in gene
Familial
not associated with increased SAB, infertility, or recombinant offspring

116
Q

Crossing over in pericentric inversion

A

if crossing over occurs between two non-sister chromatids gives rise to:

1) two complimentary recombinants
2) duplication of long arm, deletion of short
3) deletion of long arm, duplication of short arm

117
Q

Gamete possibilities of pericentric inversion

A

1) normal, unrearranged
2) inversion, balanced (combined about 50%)
3) two complimentary recombinants (one compatible one lethal)

118
Q

Paracentric Inversion

A

Excludes centromere

Familial and Sporadic

119
Q

Crossing over in Paracentric Inversion

A

results in 1/2 balance and 1/2 unbalanced
Products are either dicentric (two centrosomes) or acentric
both unstable.

120
Q

Anirdia

A

poor iris development due to paracentric inversion of 11

121
Q

Balanced Translocation Carriers

A

Risk of having unbalanced progeny of 0-30% depending on type of translocation
risk of unbalanced is due to: Size of exchange material, tolerated monosomies or trisomies, maternal translocations are more likely to have unbalanced offsprings

122
Q

TBX-1

A

due to a deletion and duplication in chromosome 22
Disturbance in migration of neural crest cells in pharyngeal arches and pouches results in cleft lip, palate, heart defects
influence parathyroid, thyroid, and thymus.

123
Q

Isochromosome

A

abnormal chromosomes in which one arm is duplicated (forms two arms of equal length with the same loci in reverse sequence) and the other arm missing.

124
Q

AML

A

Acute myelogenous Leukemia
seem mostly in adults
Diagnosed by Auer Rod in Bone Marrow and elevated Blast in Bone marrow and peripheral blood.
Two main fusion proteins: PML-RARalpha and BCR-ABL

125
Q

How is AML diagnosed

A

Auer rod in Bone Marrow

Elevated blasts in bone marrow and peripheral blood

126
Q

CML

A

Chronic Myeloid Leukemia
Night sweats, fatigue, weightloss, anemia, splenomegaly
diagnosed by longulated large cells in peripheral blood and bone marrow is hypocellular
characterized by BCR-ABL protein (9 and 22)

127
Q

Symptoms of CML

A

night sweats, fatigue, weight loss, anemia, splenomegaly

128
Q

diagnosis of CML

A

longulated large cells in blood, bone marrow in hypocellular

129
Q

BCR-ABL

A

in CML

translocation between Ch 9 (ABL) and Ch 22 (BCR)

130
Q

What is other characteristics of CML

A

BCR-ABL fusion
gain of ch 8
deletion of 22

131
Q

Treatment of CML

A

Gleevec
targets BCR-ABL fusion protein and inhibits by binding to ATP binding site
tyrosine kinase inhibitor

132
Q

APL

A

Acute Promyelocytic leukemia
PML-RARAlpha
translocation of 15:17

133
Q

PML-RARalpha

A

PML (ch15) and RARalpha (Ch 17)
creates novel transcriptionf actor that prevents differentiation of myeloid hematropeoetic precursors past promyloctypic stage.

134
Q

Treatment of APL

A

with trans-retinoic acid (vitamin A) overcomes inhibition and allow differentiation and APL goes into remission.

135
Q

Types of leukemia that Down Syndrome patients develop

A

ALL, AML, 20 to 100 fold increase

AMKL 500x more likely

136
Q

ALL

A

hyperdiploidy in bone marrow and peripheral blood

137
Q

FISH

A

specific clones >200 bp DNA sequences are covalent bound to Fluorescent dye.
hybridized in either interphase or metaphase conditions
can be used to identify number of specific chromosomes or identify translocation

138
Q

Various types of probes for FISH

A

1) centromere
2) locus specific
3) dual Fusion/fusion
4) break Apart
5) whole chromosome pain

139
Q

Centromere probes

A

used for enumeration

140
Q

Locus Specific probes

A

used to detect deletions or duplications

141
Q

Dual Fusion and Fusion probes

A

used to detect translocation

142
Q

Break Apart Probes

A

used in detecting translocation rearrangements

143
Q

Whole Chromosome Pain Probes

A

used to identify markers and translocations

144
Q

Two types of translocations

A

1) right next to strong promoter and enhancer that up regulates expression
2) novel fusion

145
Q

Chromosomal Microarray

A

high volume, automated analysis of many pieces of DNA at once.
CMA chips use labels or probes that bond to specific chromosome regions.
can detect deletions, duplications (great than 200 kbases) , but not translocations

146
Q

Cytogenetics:

A

genome screen; mitotic selected cells, gain/loss, balanaced rearrangements, highly dependent on technological expertise.

147
Q

CMA

A

genome screen, interphase on all cells, gain or loss only, technology dependent, detects runs in homozygosity by detecting SNPs.

148
Q

Copy Number Variants

A

structural variation that results in the cell having an abnormal or normal variation in the number of copies of one or more sections of DNA.
Specific duplications
may be inherited or de novo

149
Q

Runs of Homozygosity

A

indicates that child is born from a father and mother who are first degree relatives.

150
Q

Procedure for testing children with developmental and learning disorders, autism, dysmophic features, failure to thrive

A

1) CMA detects deletion or duplciation
2) parental FISH to determine if finding is rare, normal or family variant
3) if found in parents, test family to see if genetic component
4) if not found in parent, look in genetic variants databse

151
Q

Epigenetics

A

mitotically and meiotically heritable variations in gene expression that are not caused by changes in DNA sequence but by

1) reversible post-translational modifications of histones by DNA methylation
2) Generalized, not sex specific

152
Q

Genetic Imprinting

A

1) normal process due to alterations chromatin structure that occur in the germ line that is unique to one of your parents.
2) methylation of cytoseine, modification of histone code
3) effects expression
4) reversible gene inactivation
5) occurs in less than 10% of genome

153
Q

MeCP2

A

interacts with methylated DNA and undergoes ATP hydrolysis to promote continued histone de-acytylation and histone methylation.

154
Q

Methylation is..

A

1) established in the gamete
2) stably maintained after fertilization
3) reversible, so that it can be reset during gametogenesis to transmit appropriate sex-specific imprinting to progeny

155
Q

Hemi-methylated DNA

A

during DNA replication, when the old strand is methylated but new strand is not

156
Q

Methyltransferase

A

enzyme that methylates the new strand to create fully methylated DNA

157
Q

Where does epigenetic programming occur

A

in germ cells sex specific methylation of imprinted loci is specific to sperm or egg.
when fertilized, zygote has unique methylation pattern from both mom and dad
somatic cells maintain this methylation pattern for the remainder of life.

158
Q

Erasure of genetic imprinting

A

in germ cells this methylation is erased until you have kids, where the methylation pattern will persist based on sex of baby.
if erasure does not occur, there will be an imbalance because you will either have no active copies or two active copies. you need the alteration.

159
Q

Prader Willi Syndrome

A

excessive eating, short stature, hypogonadism, some degree of intellectual disability
due to deletion in paternal p15, uniparental disomy, imprinting center mutation

160
Q

what are the causes of Prader Willi syndrome

A

70% due to deletion in paternal p15
28% due to maternal uniparental disomy
2% imprinting error to cause maternal allele to be persistant

161
Q

Angelman Syndrome

A

short stature, severe intellectual disability, spasticity, seizures
maternal gene methylation/deletion on Ch15

162
Q

Causes of Angelman syndrome

A

70% deletion of maternal gene on qch15
4% due to paternal uniparental disomy
8% imprinting center mutation to make paternal persistent
8% mutation in UBE3A mutation

163
Q

How do deletions in imprinting centers occur?

A

presence of low copy repeats near common breakpoints that arise from large genomic duplications of HERC2. These make it more likely to have inter and intra-chromosomal misalignments and homologous recombinations resulting in deletions.

164
Q

Uniparental disomy

A

presence of a disomic cell line containing two chromosomes or portions of either parental imprinted allele.

165
Q

trisomic conceptus

A

when you have 2 paternal allels and 1 from the other during fertilization. Normally this inviable, but then undergoes trisomy rescue that removes one of chromatids. to leave with either two maternal or paternal chromosomes.

166
Q

Testing for Prader-Willi

A

Methylation testing of Ch15

FISH or microarray

167
Q

Prader Willi physical features in infancy

A

hyptonic, almond shaped eyes, lighter pigmentation, undescended testicle, severe feeding problems (need G tube)

168
Q

Phenotype of Prader Willi in toddlers

A

feeding becomes voracious, obescity, strabismus (lazy eye), nysagmus

169
Q

medical problems with PWS

A

strabismus, nystagmus, scoliosis, sleep apnea, obesity

170
Q

Development and behavioral phenotype of PWS

A

mild/moderate cognitive diabilites
behavioral issues
motor delays due to hypotonia
excessive compulsion disorders

171
Q

Other disorders with Ch 15q

A

1) marker chromosome - inverted duplications
2) interstitial duplications
3) linkage disequilibrium

172
Q

Marker Chromosome - inverted duplicaiton of Ch15q

A

forms extra tiny chromosome that is made up of part of p and q so you have 4 copies of gene.
Autism, NOT dysmporphic, hypotonic, seizures

173
Q

Interstitial duplications of 15q

A

to make a partial trisomy

autism, not dysmorphic, sqizures, hypotonia

174
Q

how does genetic variation beneif organisms?

A

1) allows them to exist in constantly changing environment
2) encounter and need to fend off bacteria, viruses, parasites
3) need to purge deleterious mutations

175
Q

Sexual dimorphism

A

1) phenotypic differences between male and female

2) induces reproductive organs as well as body habitus differences

176
Q

X-inactivation

A

no matter how many Xs in you have, there is still only one active X.
The other X is turned off but phenotypes occur in Aneuploidy because of pseudo-autosomal regions that remain active in inactivated X.

177
Q

Post-Puberty signs of Kleinfelter

A

Small testes, reduced facial hair and body hair, infertility, hypospadias (urethra underside of penis), gyneocmastia (enlarged breasts)

178
Q

47, XYY

A

Jacob’s Syndrome
learning diabilities, speech delay, developmental delay, behavior and emotional difficulties, autism, tall, still fertile!
1/1000

179
Q

Triple X

A

47,XXX
Tall, increased risk of learning disabilities, delayed speech, delayed motor dvpt, seizures, kidney abnormalities.
1/1000

180
Q

Primary Sex Determination

A

determined by gonads
Presence of Y - male
Presence of X is female
we have the potential to be both, and testes and ovaries result from common biopotenail gonad and are differentiated.

181
Q

Mesonephric ducts

A

Wolffian
results in male structures
under influence of testosterone, elongate to form epididymis, seminal vesicles, ductus deferens
Promoted by SRY gene and SOX9

182
Q

SOX 9

A

on autosomal Ch.
a TF that produces anti-mullerian hormone.
cause regression of mullerian ducts and progression of mesonephric or wolffian duct

183
Q

FGF9

A

chemotactic factor that causes tubules to form mesonephric duct to penetrate gonadal ridge
testis differentiation

184
Q

SF1/NF5A1

A

stimulates differentiation of sertoli and leydig cells

185
Q

Paramesonephric Duct

A

Mullerian ducts
result in female structures
estrogen stimulates formation of uterus, cervix, broad ligament, fallopian tubes, upper 1/3 of vagina

186
Q

WNT4

A

protein
extracellular signaling factor
differentiation of ovary
inhibited by SOX9

187
Q

DHH

A

gene
nuclear hormone receptor
unregulated by WNT4
down regulates SOX9

188
Q

RSPO1

A

gene

coactivator of WNT

189
Q

Week 3 embryology

A

mesenchymal cells in primitive streak migrate to form genital tubercle and genital swellings

190
Q

Males secondary genetalia

A

androgen exposure and dihydrotestoserone from testis results in formation of glands, shaft and scrotum

191
Q

what forms glands of penis

A

genital tubercle

192
Q

what forms shaft of penis

A

urogential folds

193
Q

Female secondary genetalia

A

estrogen from mother and father results in formation of clitoris, labia major and minora

194
Q

labia minora

A

urogential folds

195
Q

labia majora

A

labioscrotal swellings

196
Q

Prader Scale

A

0 is no virilization and 5 is full virilization

197
Q

AIS

A

46 XY
normal or elevated testosterone or DHT
X linked androgen receptor
mild under virilization to full sex reversal

198
Q

5-alpha reductase deficiency

A

46 XY
normal/elevate testosterone or DHT
mutation causes decreased ability to convert testosterone into DHT
under virilized male, but increased at time of puberty.

199
Q

Disorders of SRY gene

A

either 46 XY or 46 XX (when SRY is transposed on X)
Decreased Testosterone or DHT in male, increased in female
under virilization of male if deleted or mutated
male phenotype if ectopic presence in 46 XX

200
Q

Denys Drash and Fraiser

A 
46 XY
decreased DHT or Test
sex reversal
mutation in WT1 gene 
chronic kidney disease, increase wilms tumor risk
WT1 is TF for SRY
201
Q

Congenital Adrenal hyperplasia

A

ambiguous genitalia 46, XX

12-hydroxylase deficiency

202
Q

Type I Gaucher

A

most common, non-neuropathic, childhood-adulthood
9/10 cases
prevalent in ashkenazi jews

203
Q

Phenotype of Type I Gaucher

A

anemia, hepatosplenomegaly, osteopneia, bone p ain, osteoprosis, thrombocytopenia, epixaxis (nose bleeds)
less than 30% glucocerebrosidase activity

204
Q

Type II Gaucher

A

infantile
rare, sever, neurological
1/100,000 births
severe brainstem abnormalities

205
Q

Type II gaucher phenotype

A

same as I, but also mental retardation, apnea, dementia, seizures, rigidity

206
Q

Type III gaucher

A

presents after infancy, some neuro components

all phenotype of I, but also mental retardation, dementia, convlusions

207
Q

Thrombocytopenia

A

abnormal drop in platelets involved in clotting.
pts bruise easily
due to:
1) decreased production of platelets by bone marrow
2) increased destruction of circulating platelets
3) increased trapping in spleen
4) loss due to hemorrhage

208
Q

How is Gaucher diagnosed?

A

1) Glucocerebrosidase activity
2) Genotyping
3) bone marrow for glycolipid laden macrophages
4) prenatal testing

209
Q

How are RBC removed?

A

1) 90% are removed by phagocytic activites in liver, spleen and lymph
2) 10% hemolyze in circulation
3) macrophages break down chemical components

210
Q

Clincial manifestation of Gacher

A

in absence of glucerebrosidase, glucocerebroside accumulate in macrophages and lysosomes fill up. IT gives it a wrinkled cigarette paper appearance. These build up in the liver, spleen and bone marrow.

GENETICS M2M (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions