Unit II B Flashcards
1
Q
In autosomal dominant inheritance, the odds of an offspring inheriting the disease allele is ____
A
50%
2
Q
In autosomal dominant inheritance, all affected individuals have ____ parent(s) with the disease allele
A
at least one
3
Q
In autosomal recessive inheritance, parents of an affected person must be either _____ or _____
A
carriers diseased
4
Q
Recessive diseases tend to _____ generations
A
skip
5
Q
Autosomal dominant diseases tend to _____ generations
A
be present in all
6
Q
In X-linked dominant inheritance, _____ can be affected
A
females and males
7
Q
In X-linked inheritance, an affected male will pass disease allele to _____ but not to _____
A
All daughters any sons
8
Q
In X-linked recessive inheritance, males with a single copy of disease allele are affected because _____
A
males are hemizygous for X-linked genes
9
Q
_____ describes whether a person with disease genotype will have disease phenotype
A
penetrance
10
Q
_____ describes the severity (variation) in phenotype when disease genotype is present
A
expressivity
11
Q
_____ describes when a single disease genotype results in multiple, unrelated disease phenotypes
A
Pleiotropy
12
Q
_____ diseases are associated with reduction of males in pedigree due to lethality
A
X-linked dominant
13
Q
In _____ inheritance, females are usually carriers
A
X-linked recessive
14
Q
The rate of SNPs between two people is _____
A
1/1000
15
Q
human genome sequencing focused on _____ regions of genome
A
euchromatic
16
Q
_____ percent of the genome is translated
A
1.5
17
Q
_____ percent of genome has genes (introns/exons)
A
20-25
18
Q
_____ percent of genome has single copy sequences
A
50
19
Q
_____ percent of genome has repeat sequences
A
40-50
20
Q
Tandem repeats are found in _____, _____, and _____
A
genome heterochromatic regions centromeric regions
21
Q
The 2 classes of repetitive DNA are _____
A
tandem repeats dispersed repetitive elements
22
Q
_____ describes genes that have high sequence similarity and that carry out similar but distinct functions
A
gene families
23
Q
gene families arise from _____ and facilitate genomic innovation
A
gene duplication
24
Q
CNVs increase genomic diversity but lead to many diseases because _____
A
they are unstable parts of genome
25
the major limitation of current sequencing/genotyping is \_\_\_\_
highly duplicated/repeated regions of genome are unexamined
26
\_\_\_\_\_ describes how in complex diseases, SNPs only account for a small fraction of expected genomic contribution
missing heritability
27
\_\_\_\_\_ describes presence of cells with different genotypes in a single organism
mosaicism
28
The clinical features of Trisomy 21 (down syndrome) are \_\_\_\_\_
distinct facial features short stature hypotonia (low muscle mass) intellectual impairment cardiac defects leukemia
29
The clinical features of Trisomy 18 (edward syndrome) are \_\_\_\_\_
small size rocker-bottom feet clenched fingers
30
The clinical features of Trisomy 13 (patau syndrome) are \_\_\_\_\_
distinct facial features intellectual impairment congenital malformations
31
What are the 5 possible mechanisms of structural chromosomal rearrangements?
Insertion Deletion Inversion Reciprocal Translocation Duplication
32
There is no loss of genetic material in _____ chromosomal rearrangements
balanced
33
In reciprocal translocation, _____ segregation results in balanced progeny, while _____ segregation results in unbalanced progeny
alternate (normal+abnormal) adjacent (abnormal)
34
The overall risk of balanced parents having unbalanced progeny is \_\_\_\_\_
0-30%
35
\_\_\_\_\_ describes variations in gene expression not due to DNA sequence changes
epigenetics
36
DNA and histone _____ mediates gene silencing (usually). These are both examples of \_\_\_\_\_
methylation epigenetics
37
DNA methylation marks are reset in _____ and reestablished during \_\_\_\_\_
primordial germ cells gametogenesis
38
This enzyme mediates propagation of epigenetic marks in somatic cells
Maintenance methyltransferase
39
When the maternal allele is imprinted, the _____ allele is expressed
paternal
40
Give 2 examples of disorders associated with genetic imprinting
Prader-Willi Angelman
41
PWS and AS are due to deletions in chromosome \_\_\_\_\_
15q11-13
42
PWS region of 15q11-13 is expressed only on \_\_\_\_\_
paternal chromosome
43
AS region of 15q11-13 is expressed only on \_\_\_\_\_
maternal chromosome
44
\_\_\_\_\_ determines sex-specific expression pattern on 15q11-13
imprinting center
45
\_\_\_\_\_ describes inheriting both alleles of a gene from a single parent
uniparental disomy
46
maternal uniparental disomy can cause \_\_\_\_\_
PWS
47
In childhood B-cell ALL, _____ is correlated with a good prognosis, while _____ is correlated with a poor prognosis
hyperdiploidy hypodiploidy
48
FISH uses fluorescently tagged _____ to target _____ or \_\_\_\_\_
single-stranded DNA specific chromosomes (identify #) regions/bands of chromosomes (identify translocations)
49
\_\_\_\_\_ (FISH probe) is used for _____ in \_\_\_\_\_
centromere (cen) enumeration ALL
50
\_\_\_\_\_ (FISH probe) is used for _____ in \_\_\_\_\_
dual fusion, fusion (DF/F) translocation BCR:ABL & PML:RARa
51
In APML, fusion of _____ (genes) codes for a novel transcription factor that ____ differentiation/transcription
PML:RARa represses
52
\_\_\_\_\_ is a treatment for APML because it recruits _____ that prevents repression of transcription
retinoic acid coactivators
53
In CML, fusion of _____ (genes) codes for a novel tyrosine kinase that results in \_\_\_\_\_
BCR:ABL cell proliferation
54
\_\_\_\_\_ is a treatment for CML because it binds to _____ of BCR:ABL and inhibits cell proliferation
Gleevec ATP-binding site
55
Describe how CMA works
Put probes on array, add target single-stranded DNA. detect CNVs. Compare to reference CNVs.
56
CMA cannot detect \_\_\_\_\_
balanced rearrangements mosaicism (
57
What are 3 examples of balanced rearrangements?
Inversions Reciprocal translocations Robertsonian translocations
58
\_\_\_\_\_ inversions include the centromere, while _____ inversions exclude the centromere
Pericentric Paracentric
59
\_\_\_\_\_ translocations result from breakage+rejoining of non-homologous chromosomes
Reciprocal
60
\_\_\_\_\_ translocations result in fusion of two acrocentric chromosomes within their centromeric regions (loss of both short arms)
Robertsonian
61
The chromosomal abnormality in DS is usually \_\_\_\_\_
Trisomy 21
62
The risk for errors of _____ increases with rising maternal age
nondysjunction
63
What are the physical features of DS?
midfacial hypoplasia upslanting palpebral fissures small ears large tongue hypotonia transverse palmar crease short fingers
64
What medical issues are associated with DS?
Cardiac (AV canal) GI (atresia, constipation, feeding, GERD) Ophthalmic (myopia, strabism, nystagmus, blocked tear ducts) ENT (deafness, apnea, ear inf., nasal congestion) Endocrine (thyroid disease, infertility, diabetes) Orthopedic (subluxation) Hematologic (leukemia, anemia)
65
What developmental/behavioral issues are associated with DS?
impaired motor development intellectual disability speed problems depression alzheimer's autism
66
What are the physical features of PWS?
dysmorphic (almond eyes, undescended testicles) hypotonia light pigmentation
67
What medical issues are associated with PWS?
Feeding issues (need tube, become obese) Opththalmic (strabismus, nystagmus) Orthpedic (scoliosis) ENT (apnea)
68
What developmental/behavioral issues are associated with PWS?
intellectual disability antagonistic behavior insatiable desire to eat
69
List 2 other chromosomal abnormalities associated with 15q11-13
IDIC 15 (supernumerary marker) 15q interstitial duplication (maternally inherited)
70
\_\_\_\_\_ is the study of differences in drug response due to allelic variation in genes affecting drug metabolism, efficacy, and toxicity
pharmacogenetics
71
\_\_\_\_\_ is concerned with the assessment of common genetic variants in the aggregate for their impact on the outcome of drug therapy.
pharmacogenomics
72
\_\_\_\_\_ is the rate at which the body absorbs, distributes, metabolizes, or excretes drugs/metabolites.
pharmacokinetics
73
\_\_\_\_\_ is the response of the drug binding to its targets and downstream targets. (i.e. what happens)
pharmacodynamics
74
Phase I metabolism involves attaching a _____ group to compound to make it more \_\_\_\_\_
polar soluble
75
Phase II metabolism involves attaching a _____ group to compound to make it more \_\_\_\_\_
sugar/acetyl easily excreted
76
The CYP450 complex is active mainly in the _____ and to some extent in the \_\_\_\_\_
liver intestinal epithelium
77
Most CYPs function to _____ drugs, but _____ is an exception
inactivate CYP2D6 (codeine--\>morphine)
78
CYP3A: _____ (substrate), _____ (mechanism), _____ (activators/inhibitors)
cyclosporine genetically less important rifampin (activator) ketoconazole+grapefruit juice (inhibitor)
79
CYP2D6: _____ (substrates)
codeine
80
CYP2C9: _____ (substrate)
warfarin
81
NAT: _____ (drug)
isoniazid for TB
82
TMPT: _____ (drugs), _____ (notes)
6-mercaptopurine + 6-thioguanine for ALL
83
G6PD: _____ (drugs), _____ (mechanism), _____ (notes)
sulfonamide+dapsone X-linked enzyme deficiency causes anemia
84
VKORC1: _____ (drug)
warfarin
85
What are the assumptions of Hardy-Weinberg?
large population random mating no mutations no selection no population movement
86
Increased variation through sexual reproduction occurs via _____ and \_\_\_\_\_
haploid gametes recombination in meiosis
87
Gonad determination is \_\_\_\_\_
chromosomal (presence/absence of Y)
88
describe embryology of dimorphic reproductive organs
wk4: primordial germ cells form in wall of yolk sac. wk5: coelomic epithelium becomes genital ridge wk6: primordial germ cells migrate to dorsal mesentary of hindgut and enter gonad. epithelium of gonadal ridge form primitive sex cords.
89
What are the clinical features of Turner Syndrome (45, XO)?
short webbed neck cystic hygroma puffy hands/feet infertility low-set ears broad chest cubitus valgus
90
What are the clinical features of Kleinfelter Syndrome (47, XXY)?
tall small testes infertility gynecomastia reduced hair
91
What are the clinical features of Jacobs Syndrome (47, XYY)?
tall autism learning/developmental issues behavioral/emotional issues
92
What are the clinical features of Triple X Syndrome (47, XXX)?
tall learning/developmental issues seizures kidney issues
93
what are the characteristics of multifactorial inheritance traits?
incomplete penetrance variable expressivity heterogeneity (allele+locus) phenocopies
94
A higher concordance rate for disease in monozygotic twins than in dizygotic suggests that \_\_\_\_\_
genetic variation is a more significant risk factor than non-genetic factors
95
\_\_\_\_\_ describes the proportion of total variance in a trait that is due to variation in genes
heritability
96
What are the 3 types of DNA polymorphisms used for finding disease genes?
CNVs SNPs microsatellites
97
describe candidate gene association studies
need prior hypothesis/markers prone to false-positives used for common alleles with small/moderate ORs done in case-control studies can't do multiple-testing correction, can't ethnically match cases/controls, stratification effects
98
Describe genetic linkage studies
no hypothesis needed search genome for regions co-inherited with disease in families used for mendelian traits
99
Degree of recombination per meiosis event is measured in \_\_\_\_\_
centiMorgans (cM)
100
\_\_\_\_\_ is a statistical measure of genetic linkage
LOD (\>3 = proof of linkage)
101
Describe GWASs
search for SNPs across entire genome used for common alleles with small/moderate ORs can do multiple-testing correction and stratification correction done in case-control studies requires follow-up study for specific SNPs of interest
102
In Autosomal Recessive diseases, the majority of mutant alleles are present in \_\_\_\_\_
carriers
103
\_\_\_\_\_ describes multiple, different mutant alleles of a single gene
allelic heterogeneity
104
A _____ carries two different mutant alleles of a single gene. The phenotype is usually \_\_\_\_\_
compound heterozygote moderate
105
Describe biochemical defects of PKU
mutation in PAH or mutation in BH4 (coactivator) that result in excess Phe buildup and damage to CNS
106
PKU screening is done via \_\_\_\_\_
mass spect
107
Newborns must be screened for PKU _____ so that _____ is no longer present to give false negative result
a few days after birth maternal PAH
108
Treatment for PKU is \_\_\_\_\_
low Phe diet for entire life
109
describe phenotype and ecogenetics of ATD
emphesyma+liver problems (bc of misfolded protein buildup) smoking increases severity and causes earlier onset
110
normally, α1-antitrypsin inhibits \_\_\_\_\_, thus a mutation causes degradation of too much \_\_\_\_\_
elastase elastin
111
The _____ mutant allele for ATD is the most severe, while the _____ allele is the least severe.
Z S
112
describe biochemical defects of T-S
mutation in HexA (α subunit) prevents degredation of GM2 ganglioside in neuronal lysosomes.
113
In Sandhoff disease, mutation in _____ affects both HexA and HexB
β subunit
114
In AB variant of T-S, HexA and HexB are _____ but GM2 accumulates due to mutation in \_\_\_\_\_
GM2 activating protein (GM2-AP) that mediates binding between HexA and GM2
115
carrier and prenatal screenings for T-S are done for _____ population using \_\_\_\_\_
Ashkenazi Jew enzyme assay
116
\_\_\_\_\_ controls expression pattern of globin genes
Locus Control Region (LCR)
117
What is the expression order for α cluster of globin genes?
ζ --\> α2 + α1
118
What is the expression order for β cluster of globin genes?
ε (embryonic) γG + γA (fetal) δ + β (adult)
119
HBA2 is _____ form of hemoglobin in adults and HBA is the _____ form
minor major
120
In sickle cell, mutation in _____ creates \_\_\_\_\_, which is less soluble and forms fibers that cause sickle shape in RBC
β globin (E6V) HbS
121
In hemoglobin C, mutation in _____ creates \_\_\_\_, which is less soluble and form crystals that don't change shape of RBC
β globin (E6K)
122
Sickle cell is diagnosed using \_\_\_\_\_
RFLP (loss of restriction site)
123
α-Thalassemia 1 is most prevalent in _____ and its genotypes are _____ and \_\_\_\_\_
southeast asia αα/-- (mild. α-thal 1 trait) --/-- (hydrops fetalis)
124
α-Thalassemia 2 is most prevalent in _____ and its genotypes are _____ and \_\_\_\_\_
africa, med, asia α-/α- (mild. α-thal 2 trait) αα/α- (silent carrier)
125
The compound heterozygote genotype for α-thalassemia is \_\_\_\_\_
α-/-- (severe. HbH disease)
126
Thalassemia major vs. thalassemia minor
major: severe disease phenotype minor: mild disease / carrier
127
Simple thalassemia vs. complex thalassemia
simple: mutations/deletions affect only β globin gene complex: mutations/deletions affect multiple genes in β cluster
128
β+ thalassemia vs. β0 thalassemia
β+: some β globin is made. some HbA present. β0: no β globin made. no HbA.
129
describe HPFH
no β or δ globin synthesis. Instead, γ globin synthesis continues bc 1) deletions cause enhancers to be closer to γ-globin gene or 2) mutations in promoter of γ-globin prevent repression of its synthesis
130
HPFH patients do not have disease because \_\_\_\_\_
HbF replaces action of HbA and HbA2
131
Describe Achondroplasia
AD (80% de novo) small stature short limbs GoF mutation in FGFR3. Enhances limitation of bone formation from cartilage. paternal age effect.
132
Describe Neurofibromatosis Type 1
AD (50% de novo), Var Exp. neurofibromas Lisch nodules cafe-au-lait spots LoF mutation in NF1. lose tumor suppression activity. Need both alleles to be mutant.
133
Describe Tuberous Sclerosis
AD (66% de novo), Var Exp. angiofibroma cortical dysplasia cardiac rhabodmyoma LAM lung disease Shagreen patch Ungual Fibroma LoF mutation in TSC1 or TSC2. lose cell growth/division regulation (hamartin+tuberin).
134
Describe Osteogenesis Imperfecta Type 1
AD, Var Exp. multiple bone fractures blue sclera LoF mutation in COL1A1. reduces type 1 collagen by 50%.
135
What are the 3 characteristics of Trinucleotide Repeat Disorders?
Slipped misparing (in germ cells) anticipation parental transmission bias
136
Describe Huntington Disease
AD, Trinuc Rep Disorder (CAG) early onset (paternal) or late onset (maternal). progressive neural degeneration. expansion of CAG repeat in HTT gene.
137
X chromosome inactivation occurs during 1st week of _____ and is functionally \_\_\_\_\_
embryogenesis mosaic
138
Describe Fragile X Syndrome.
XD, Trinuc Rep Disorder (CGG) intellectual disability dysmorphic features aggression maternal transmission bias. expansion of CGG repeat in FMR1 gene.
139
Describe Duchenne Muscular Dystrophy.
XR mutation in DMD gene (loss of Dystrophin). progressive muscle weakness calf hypertrophy dilated cardiomyopathy
140
Describe Hemphilia A
XR, 10% carrier females affected. bleeding bruising mutation in F8 gene. deficiency of Factor VIII.
141
mosaicism is analogous to mitochondrial \_\_\_\_\_
replicative segregation
142
Describe 4 mitochondrial inheritance disorders.
Kearns-Sayre (eye issues, ataxia, deafness) MELAS (stroke-like) MERRF (ragged-red fibers) LHON (vision failure)
143
Describe the 4 characteristics of epigenetics
1. different gene expression pattern (phenotype) from the same genome 2. generational inheritance through cell division 3. On/off state. no intermediate. 4. eraseable/interconvertable
144
Describe Waddington's epigenetic hill thing
Stability of differentiated states of cells is maintained due to being at "lowest energy state" (bottom of valley)
145
Give 3 examples of epigenetics
X-inactivation imprinting heterochromatin domains
146
Give 3 examples of LoF disorders
Duchene (loss of dystrophin) HNPP (loss of PMP22 gene) Osteogenesis Imp I (reduced collagen I)
147
Give 2 examples of GoF disorders
HbK (tighter O2 binding) CMT1A (duplication of PMP22 gene)
148
Give an example of novel property mutation disorder
Hubs' (sickle shape, but normal function)
149
What are the 8 steps at which mutations can affect protein function?
Transcription (thalassemia) Translation (thalassemia) Protein folding (Hb disorders) Post-Trans Mod (I-Cell) holomer assembly (Ost Imp I) localization (fam hypercholestrolemia) cofactor binding (homocystinuria) function (HbK)
150
Trinucleotide Repeat Disorders can occur in \_\_\_\_\_
5' UTR (Fragile X) Intron Exon (Huntington) 3' UTR
