Genetics Flashcards
(109 cards)
1
Q
Stages of meiosis
A
- Interphase
- Meiosis 1
- Meiosis 2
Meiosis 1 and 2 stages:
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis
2
Q
Prophase 1
A
Crossover between homologous chromosomes
2 pairs of homologous chromosomes (with 2 sister chromatids)
2n
3
Q
Chiasma
A
The region where crossover occurs so genetic recombination can occur
4
Q
Tetrads
A
Homologous chromosomes are organized in this manner
5
Q
Meiosis 1 is also called
A
Reduction division
6
Q
Meiosis interphase
A
Duplication of chromosome to form 2 sister chromatids
2n
7
Q
Metaphase 1
A
Tetrads align along the midline
2n
8
Q
Anaphase 1
A
Random segregation of the homologous chromosomes to opposite poles
2n
9
Q
Telophase + cytokinesis 1
A
separation into 2 cells
1 copy of each chromosome (with sister chromatid)
n
10
Q
Anaphase 2
A
Separation of sister chromatids
11
Q
Telophase and cytokinesis 2
A
4 haploid gametes that are genetically distinct
n
12
Q
Genetic diversity of the gametes in Meiosis happens at…
A
- Prophase 1 (crossover)
2. Anaphase 1 (random segregation)
13
Q
46, XY –>
A
23 X
23 X
23 Y
23 Y
14
Q
Male gametogenesis
A
Spermatogenesis
results in 4 genetically distinct spermatozoa
15
Q
Female gametogenesis
A
Oogenesis
results in one ovum and 3 polar bodies
16
Q
Fertilization
A
Haploid spermatozoa (23 chromosomes; n) join with haploid ovum (23 chr; n) to make diploid organism (23 pairs; 46 chr; 2n)
17
Q
Mitosis stages
A
- Interphase
- Mitosis
(PMAT)
18
Q
Interphase
A
Gap 1 (G1) S phase Gap 2 (G2)
19
Q
What’s special about G2?
A
It enlarges the cytosol
20
Q
Mitosis defintion
A
Cell division in somatic cells to form 2 new daughter cells that are identical genetically as the parent
Parent is diploid and daughter is diploid
21
Q
S phase
A
DNA replication
Each of the 46 chromosomes is duplicated and has a sister chromatid linked at the centromere
22
Q
G1
A
Cellular contents (not chromosomes) are duplicated
23
Q
G2
A
Cell double checks the duplicated chromosomes for error and makes any repairs needed
24
Q
Whats special about PMAT in mitosis?
A
There is a phase called prometaphase
25
Prophase (mitosis)
- Breakdown of nuclear membrane
- Spindle fibers appear
- Chromosomes condense
26
Prometaphase
Spindle fibers attach to the chromosomes
| - Chromosomes condense
27
Metaphase (mitosis)
Chromosomes align
| maximally condensed
28
Anaphase (mitosis)
- Centromeres divide
| - Sister chromatids move to opposite poles
29
Telophase (mitosis)
- Nuclear membrane reforms
- Chromosomes decondense
- Spindle fibers dissapear
30
Cytokinesis (mitosis)
- Cytoplasm divides
| - Parent cell becomes 2 daughter cells with identical genetic information
31
Whats the point of mitosis?
- responsible for growth and development
- important for cell replacement and healing
- genetically identical daughter cells are formed which re-enter the cell cycle
32
Cancer in regards to mitosis?
Result of uncontrolled mitotic divisions
33
Mendel's 3 laws and ratios
1. Law of dominance (3:1)
2. Law of segregation
3. Law of independent assortment
Dihybrid cross (9:3:3:1)
34
Wild type
Most frequently observed allele in a population
| - Usually used to identify the control allele that is found in the starting strain
35
Dominant autosomal traits are shown in what frequency to M and F
50%
| Equally in both sexes
36
Incomplete penetrance
The individual has the allele but they don't show the trait
37
Variable expressivity
The range of the severity of the trait shown
38
Autosomal dominant traits
- Only one allele for the trait to manifest
| - Vertical inheritance
39
Autosomal dominant disorders
Food Actually Hurts My Stomach Lining (FAHMSL)
1. Familal hypercholesterolemia
2. Achondroplasia
3. Huntingtons disease
4. Marfan syndrome
5. Sonic Hedgehog syndrome
6. Lynch syndrome
40
Familial hypercholestrolemia
Due to LDLR deficiency
LDLR needed to clear LDL cholesterol from blood into the liver
The deficiency means too much cholesterol stays in the blood
41
Familial hypercholestrolemia genetic principle
Haploinsufficiency
| One copy of the LDLR is nonfunctional
42
Haploinsufficiency
Both alleles are required to avoid disease but only one allele is functional
43
Achondroplasia
FGFR3 signals too early and is persistently active
FGFR3 encodes a receptor that responds to the hormone FGF (fibroblast growth factor)
The response is ossification and stop growing
Achondroplasia is premature ossification so dwarfism
44
Achondroplasia genetic principle
Gain of function
| FGFR3 gene is not regulated and persistently on
45
Gain of function
Protein does more than it should or acts in an unregulated manner
46
Achondroplasia extra facts
- Observable at birth
| - Fully penetrant disorder
47
Allelic heterogeneity
Different mutations on that same gene can lead to same or other disorders
Ex. FGFR3 gene mutation can lead to other disorders not just achondroplasia
Ex. Marfan syndrome
48
Locus heterogeneity
Mutations at different genes can cause similar presentation
Ex. Other genes can cause dwarfism
49
Huntington disease
CAG codes for glutamine
When there is an expansion of CAG codon it makes the Gln string too long causing neuronal death
50
Huntington disease genetic principle
Attainment of a novel function (a type of gain of function)
This new function is not understood
51
Huntington disease extra facts
- fully penetrant
- adult onset
- if you have the CAG expansion you will get the disorder if you live long enough
52
What is huntington disease due to?
Unstable repeat regions
This area is sometimes unstable but:
- The longer the more unstable
- Anticipation
53
Anticipation
Disease gets worse in coming generations
Ex. huntingtons disease the disease might be more severe or have and earlier onset in later generations
54
Marfan syndrome
Caused by mutation in fibrillin gene --> produces diff protein
*Both alleles are expressed but only need one allele with mutation for this disease
Leads to connective tissue problems like:
- Chest wall deformity
- Tall stature
- Risk of heart defect
- Eye lens subluxation
55
Marfan syndrome genetic principles
1. Haploinsufficiency
Loss of expression from one of the fibrillin alleles
2. Double negative
Both alleles expressed but DN leads to the disorder (autosomal dominant)
3. Allelic heterogeneity
Different types of mutation in the same gene (fibrillin) can cause MS
56
Sonic hedgehog mutation
SHH signalling is required for many things including the midline of the body and brain formation
Loss of one functional copy of SHH can cause holoprosencephaly (inability for brain to separate)
57
SHH extra facts
- Incomplete penetrance for some people who have on SHH mutation
- Variable expressivity
58
SHH genetic principles
- Haploinsufficiency
- Incomplete penetrance
- Variable expressivity
59
Lynch syndrome
Hereditary non-poyposis colon cancer
Caused by a mutation in one allele of a gene that that are part of the DNA mismatch repair system
called "care takers"
Genetic principle: 2 hit hypothesis
60
2 hit hypothesis in Lynch syndrome
Heterozygosity is lost after second mutation occurs
Loss of both copies leads to accumulation of mutations in the cell
61
Why are dominant disease alleles typically not inherited in the homozygous state?
1. Very rare so its rarer to have 2 people with the same dominant disorder to mate and have offspring
2. Dominant disease alleles are more severe when homozygous
62
Lynch syndrome genetic principle
Loss of heterozygosity
63
Autosomal recessive trait
- Individual must inherit a non functional allele from each parent
- Functional allele is haplosufficient
- horizontal inheritance
- mainly enzyme deficiencies
64
Autosomal recessive disorders
TAPSC
- Tay Sachs disease
- Phenylketonuria
- Cystic fibrosis
- Alpha 1 antitrypsin deficiency
- Sickle cell disease
65
Tay Sachs disease
Deficiency of HEXA (hexosaminidase A activity) enzyme
Loss of both HEXA alleles
Decline of CNS starts at 6 months due to accumulation of a specific ganglioside in the lysosomes
66
Tay Sachs disease genetic principle
Founder effect in Ashkenazi Jewish populations
67
Founder effect
Lack of genetic diversity due to population rising from small number of ancestors
68
Phenylketonuria (PKU)
Deficiency of phenyalanine hydroxylase enzyme
Inability to degrade Phenylalanine which builds up and goes to the brain (too much) so other amino acids dont get into the brain
Diagnosed at birth
69
PKU treatment
- Special diet
| - Formula
70
PKU genetic principle
Genetic disease (inborn error of metabolism)
71
Cystic fibrosis
Deficiency of ion channel by CFTR gene mutation
Causes mucus to accumulate in the luminal space:
- Pancreatic insufficiency
- Frequent pulmonary infections
- High salt water content in sweat
- Males may have congenital absence of vans deferens
Usually the channel allows Cl --> Na --> water
72
CF genetic principle
Ion channel
73
Explain 2/3 carrier risk
If disorder is fully penetrant and both parents are carriers then we can deduce a 2/3 carrier risk in a healthy child
74
Alpha 1 antitrypsin deficiency (AATD)
Deficiency of a protease inhibitor (elastase)
75
Neutrophils
Work to fight infections in the lungs and secrete elastase (protease enzyme) to degrade elastin so they can migrate and get to the invading bacteria
76
AAT
Liver cells secrete AAT to travel to the lungs to protect from elastase
Gene that encodes called SERPINA1
77
Alpha 1 antitrypsin name
Trypsin is the founding member of the serine protease enzyme (bc serine in the active site)
AAT inhibts trypsin
78
2 alleles of AAT
1. M allele (functional)
| 2. Z allele (leads to AATD when homozygous)
79
Z allele
- Doesn't bind well to elastase (loss of function)
- Degraded more quickly (loss of function)
- Polymerizes in liver when synthesized (attainment of novel function)
80
AATD genetic principles
1. Loss of function
| 2. Attainment of novel function
81
Disease features of AATD caused by homozygosity of the Z allele
1. COPD
- Adult onset
- Increased by smoking
- loss of function of protease inhibitor
2. Liver disease
- often paediatric (10%)
- polymerization in the rough ER causes liver damage
- polymerization can be thought of as attainment of novel function
82
Sickle cell disease (SCD)
Single base pair change in DNA causes structural variation in hemoglobin (transport oxygen)
Glutamate 6 to valine change causes the Hb to polymerize and change the shape of the red blood cells
83
Glu6Val
Normally Glu is at position 6 which is the outer surface and soluble
switched to Val makes it hydrophobic and causes Hb proteins to polymerize
84
Sickle cell disorder and malaria
Heterozygous advantage for malaria due to selection pressure
Pseudodominance
85
Pseudodominance definition
SCD is autosomal recessive but the allele can be found in high frequency because of selective pressure from malaria
1/8 chance for carrier
86
Pseudodominance reasons we may see it
1. High frequency of the recessive allele
2. Consanguinity
3. Luck
87
Codominace
- Both alleles are expressed
- Both are equally detected
Ex. sometimes sickle cell trait
88
Karyotype
- Staining metaphase stage chromosomes
| - Metaphase stage chromosomes are condensed
89
X chromosome inactivation
- one of the X chromosomes are inactivated
- occurs during fetal development
- usually random
90
How is the X chromosome inactivated?
- Expresses RNA from gene called XIST
- XIST RNA coats the chromosome that expressed it
- other proteins help
- then the genes on that x chromosome are silenced
91
Why are males hemizygous
Due to XY
92
Why are males hemizygous for the genes on the X chromosome
Due to XY
93
X linked disorders
- Glucose 6 phosphate dehydrogenase deficiency
- Red-green color blindness
- Hemophilia A and B
- Lesch-Nyhan syndrome
- Duchenne muscular dystrophy
94
Glucose 6 phosphate dehydrogenase deficiency
| (G6PD deficiency) caused by:
exposure to:
1. Sulfa drugs
2. Primaquine
3. Fava beans
4. Other
95
Glucose 6 phosphate dehydrogenase deficiency
| G6PD deficiency
Anemia due to oxidative damage in red blood cells
People with this are sensitive to oxidizing agents
96
G6PD
1. is an enzyme that puts glucose in the pentose phosphate shunt (NADH and ribose sugar) and is needed for NADPH production
2. NADPH needed to maintain glutathione in a reduced active form
3. Glutathione is needed to protect RBC from oxidative damage
97
Why is complete loss of G6PD activity lethal?
All proteins packaged into the RBC must function for the lifetime of the cell
But decrease in protein stability or reduction will impact the red blood cell
98
G6PD Deficiency genetic principle
Some mutations can be driven to high frequency in the population due to environmental pressures
99
Red- green color blindness
More common in males because it is X linked
Caused by inappropriate crossing over because of unequal intragenic recombination during meiosis that may lead to loss of gene
100
R + G color blindness genetic principle
Deletion/duplication mutation can occur due to repetitive regions
1 red gene and 1,2,3 green gene
101
Hemophilia A and B
Bleeding disorder
Lack of blood clotting
Mainly in males
Females may show symptoms
if they are carriers but less then men
If a carrier female is affected it could be bc of non random x inactivation
102
What pathogenic variants in the gene cause hemophilia A
Factor 8 (F8) and Factor 9 (F9)
103
Lesch-Nyhan syndrome
Caused by mutation of gene encoding hypoxanthine guanosine phophoribosyl transferase (HGPRT) enzyme
Inability to salvage purines (A and G) increased reliance on de novo synthesis --> causes excessive disposal of uric acid
104
What is the symptoms of Lesch-Nyhan syndrome?
- Intellectual disability
- Seizure
- Self destructive behaviour
105
2 routes for purine bases
1. Synthesized de novo
| 2. Salvaged
106
Duchenne muscular dystrophy (DMD)
- Encodes the dystrophin protein
- required for muscle fiber integrity
- links actin cytoskeleton of the muscle fiber to the plasma membrane --> links to extracellular matrix
107
Lesch-Nyhan syndrome genetic principle
X linked disorder caused by deficiency of an enzyme
108
DMD genetic principle
Boys have genetic fitness to 0 = they cant reproduce
109
What is the 2/3 rule?
When your sibling is affected by an autosomal recessive then theres a 2/3 chance you are a carrier?
