Basic Hematological Genetics Flashcards
All information required for the development of a complete adult organism is contained in a single cell (________)
zygote
DNA contain only four different bases
List them!
Adenine (A); Guanine (G); Thymine (T) and Cytosine (C)
DNA exists as a ______ in which ___ is paired to ___ and ___ to __
double helix
A; T
G; C
A linear strand of DNA has one end where the OH - group attached to the 5-carbon is free (ie ______ end or ___ stream end) while the other end in which the OH-group attached to the 3-carbon is free (_____ end or _____ stream end)
5 primer ; up
3-primer; down
the 51 end and the 31 end of each DNA strands are ALWAYS complementarily paired.
T/F
T
DNA
By convention, the strand shown at the top is the ______ or _____ strand but the strand at the bottom actually serves as _______
coding or sense
template
_____ bases are required to specify for ___ commonly occurring amino acids in proteins. Therefore the genetic code has to be in triplets (____)
Four
20
codon
Here each amino acid is specified by one or more sequences of codon but these sequences that specifies amino acid are interrupted by intervening sequence (______) that do not code for amino acids sequence of the proteins.
introns
CHROMOSOMAL IDENTIFICATION
Chromosome are identified at ______ under _____ microscope.
They are distinguishable by the relative _____ and the ___________ but these features alone is not easy to use in distinguishing different chrom
mitosis
Light
sizes
position of their centromeres
CHROMOSOME BANDING
_________ procedures that allows ______ along the _____ axis of a ____ chromosome is called chromosome-banding technique.
Cytological
differential staining
longitudinal; mitotic
TYPES of banding techniques
___-banding technique
___-banding technique
C
G
TYPES of banding techniques
C-banding technique:
_______ the chromosome and heat treating with _____, stains the _____ region only.
So we can identify types of chromosome
________,______,______,______
Denaturing; Giemsa
centromeric
Metacentric Sub-metacentric Accrocentric Telomeric
TYPES of banding techniques
G-Banding: _____ of mitotic chromosome with ______, followed by _____ stain will give differential staining reaction along the ____ of the chromosome reflecting the heterogeneity and complexity of the chromosome
Digestion; TRYPSIN
GIEMSA
length
Centromere location:
Metacentric
Submetacentric
Acrocentric
Telocentric
Middle
Between middle and end
Close to end
At end
Parts of an Acrocentric Chromosome
Satellite
P arm
Centromere
Q arm
P is the ____ arm
Q is the ___ arm
Short
Long
In 1976 A uniform nomenclature for human chromosome banding pattern was established based on G-banding
______,_________, and _________
REGION,BAND AND SUB- BAND
Even with G banding, chromosomes that are homologs can’t be distinguished
T/F
F
So precise is the banding pattern of each chromosome that homologs can be distinguished
With G banding, chromosome that are identical in size and centromere placement can be easily identified (______).
T/F
T
Karyotyping
GENE MUTATIONS
Definition
Any ______ in ______. It may comprise single base pair substitution, or a deletion or insertion of one or more base pairs, or a major alteration in the structure of a chromosome
alteration
DNA sequence
CLASSIFICATION OF MUTATIONS: Cell type
_______ mutation
_______ mutation
somatic
Germ line
CLASSIFICATION OF MUTATIONS: Cell type
somatic mutation: Occurs in ____ cell of the body except ____ cells.
Germ line mutation: occur in _____ only
any; germ
gametes
CLASSIFICATION OF MUTATIONS: Cell type
______ mutation: They are not transmissible
_______ mutation: this is transmissible
somatic
Germ line
CLASSIFICATION BASED ON TYPE OF MOLECULAR CHANGE
We can describe mutation further in terms of nucleotide change.
Point mutations/sustitutions: A change in ______ to _____ in a DNA molecule.
one base pair to another
CLASSIFICATION BASED ON PHENOTYPE
Depending on type and location, mutation can have a wide range of phenotypic effect from non to severe
1.________ mutation
2.________ mutation
3.______ mutations
Loss of function
Gain of function
Lethal
CLASSIFICATION BASED ON PHENOTYPE
Depending on type and location, mutation can have a wide range of phenotypic effect from non to severe
1. Loss of function mutation:_____ or ______ the function of the gene product (____ mutations)
reduces or eliminate
null
CLASSIFICATION BASED ON PHENOTYPE
Depending on type and location, mutation can have a wide range of phenotypic effect from non to severe
2.Gain of function mutation: Mutation resulting in a gene product with ______ or ______ function and may result from mutation in _____ region of the gene resulting in expression at a higher level
enhanced or new
regulating
CLASSIFICATION BASED ON PHENOTYPE
Depending on type and location, mutation can have a wide range of phenotypic effect from non to severe
Lethal mutations: mutations interrupting a process that is _____________ of the organism
essential to the survival
A transition is said to occur when a _____ replaces _______
A transversion occurs when a _______ replaces a ________
pyrimdine
another pyrimdine
pyrimdine
purine or vice versa
ABO blood group
I gene encodes ________ which modifies substance ___.
3 alleles are known ___,___, and ___
glycosyltransferase
H
IA,IB and IO.
ABO blood group
DNA sequence IA and IB when compared show _____ consistent single nucleotide _____ , and these changes result in different ______ functions leading to different ——— modification.
four
substitution
glycosyltransferase
H-substance
ABO blood group
DNA of IO show _____ of a single nucleotide early in the coding sequence thus resulting in a ______ mutation at the point of the ______.
This then causes a ______ to arise after about _____ nucleotide sequence thus leading to chain termination of the enzyme product leading to non-functional product.
There is gain of function in _____
deletion; frame shift; deletion
stop codon
100
CML
CHROMOSOMAL ANOMALIES
Can be:
__________ (numerical)
__________
Quantitative
Qualitative
CHROMOSOMAL ANOMALIES
Quantitative Chromosomal abberations:
Can be __________ of one or more
chromosome (_______ ) or even addition of one or more complete set of chromosomal (_____)
addition or loss
aneuploidy
Euploidy
Aneuploidy
Monosomy –___of ___ chromosome from a ___________
Trisomy -_____ of ____ additional chromosome to _________
Tetrasomy: ___ of two additional chromosomes
loss; one; single haploid set
Gain; one; a single haploid
gain; two
Aneuploidy generally result from ________
Non-dysjunction
Euploidy
polyploidy- ___,______,_____
As in:
______ = 3n
_________= 4n
————— = 5n
3n, 4n,5n
Triploidy
Tetraploidy
Pentaploidy
Qualitative chromosom anomalies: usually results when a chromosome ______________________
breaks in one or more places
Qualitative chromosom anomalies:
- a portion can be ___ (______e.g 5q-)
- Chromosomal ______
- ______
4.__________
5._________ (mirror image)
lost; deletion
Duplication
Inversion
Translocations
Isochromosome
Qualitative chromosom anomalies:
- a portion can be lost (deletion e.g 5q-)
This loss we can be:
_______ deletion
__________ deletion
Terminal
intercalary
Qualitative chromosom anomalies:
- a portion can be lost (deletion e.g 5q-)
This loss we can be:
Terminal deletion: occurring near _____of the chromosome
intercalary deletion: Occurring ____ the chromosome
one end
within
Note: in chromosomal deletion , The segment that ________ are usually retained after cell division while the other part is lost e.g cri du chat loss of small terminal part of p arm of chrom 5
has the centromere
Inversion (inv): Involves simultaneous ____ with _____ of the intervening segment
breaks
rotation
Translocations: could be
_________
_________
__________
Reciprocal
Non-Reciprocal
Robertson
KARYOTYPING:
________ of chromosomes from a particular cell according to a well established system such that the ______ chromosome are first and _______ are last to form an ________
Arrangement
largest; smallest
idiogram
further molecular technique
_________ analysis of DNA
__________ (FISH)
_______ methods
___________ methods
Southern blot
Florescent insitu hybridization
PCR
Nucleotide sequencing
APPLICATION OF FISH
Detection of ______ and _______________
Identification of __________ (rearranged chromosome of uncertain origin)
numeric and structural chromosomal abnormalities
marker chromosome
APPLICATION OF FISH
Monitoring of the ________ and detection of ______ or _____
Identification of the ____ of marrow cell following marrow transplantation
effects of therapy; MRD or early relapse
origin
APPLICATION OF FISH
Identification of the _________
Examination of the _____ pattern of non –diving or _____ cells
Detection of gene _______
neoplastic cell linage
karyotypic; interphase
amplification
FISH
Efficiency of hybridization and detection is (low or high?)
Sensitivity and specificity is (low or high?)
High
High
FISH is a slow technique
T/F
F
It is a rapid technique
FISH
Large number of cells can be analysed in a short time
T/F
T
FISH
cytogenetic data can be obtained from ________ or ________ cells or from _____ with (low or high?) mitotic index (e.g CLL), or poor samples that contain too few cells for routine cytogenetic study.
non- dividing or terminally differentiating
tumors
Low
With FISH, Automation of analysis is also possible
T/F
T
ERYTHROCYTE ANTGENES AND ANTIBODIES
A blood groups system is a group of _______ encoded by alleles at a ______ or _______ so closely linked that ___________
antigens
single gene locus or at gene loci
cross over does not occur
ERYTHROCYTE ANTGENES AND ANTIBODIES
An antigen collection is a group of antigens that are _____,_______, or ______ related but their genes are _____________
phenotypically, biochemically or genetically
not known to be allelic
International Society of Blood Transfusion has recently recognized ____ blood group systems.
34
_____ antigen collection have been defined generally.
7
Immunology of the blood group system.
An antigen is a substance that can ___________ when introduced into an immuno competent host and can ____________
evoke an immune response
react with the antibody.
Most blood group antigens are _______ and their specificity is mostly determined either by the _________ (e.g. ABO) or __________ (e.g. MN, Kell, Duffy, Kidd, Diego)
glycoproteins
oligosaccharide
amino acid sequence
An antigen can have several epitopes
An antigen can have several antigenic determinant with each epitope capable of eliciting an antibody response.
T/F
T
T
Specificity of an antigen is determined by its _______ and ________ with its antibody
structure and stereochemical fit
The ability of an antigen to stimulate an immune response is called _____
immunogenicity
An antigen’s ability to react with the antibody is called its ________
antigenicity
Most erythrocyte antigen are detected early in fetal development
T/F
T
all erythrocyte antigens are fully developed at birth
T/F
F
Not all are fully developed at birth
_____,______, and ______ blood group antigens are examples of Carbohydrate antigens
P, ABO and Lewis
PABLO
RED CELL ANTIBODIES
Classification
______ antibodies
_____ antibodies
Auto
Allo
RED CELL ANTIBODIES
Classification: In terms of mode of sensitization
________
___________
Naturally occurring
Immune antibodies
RED CELL ANTIBODIES
Classification: In term of optimal temperature
Cold – __-__oc
Warm – ___oc
2-4
37
IgG is the ______ type red cell antibody,
immune
receptors or macrophage in the liver and spleen removes Ig__ coated red cell from circulation.
G
IgG anti RBC antibody are not capable of complement fixation
T/F
F
They are
Binding to complement by IgG antibody is determined by
______ and ______
Surface density
Location of the recognised antigen
C1q requires that at least _______ molecule bind to a red cell within a span of ________ to initiate the complement cascade
two IgG
20-30nm
IgG-anti-D rarely bind complement because ____________________; and the epitope is __________________
most D sites are spaced too far apart
so small that only one anti –D molecule per epitope can bind
Most IgG anti ABH antibody do not agglutinate saline suspended red cell
T/F
If T, what do they do
If F, why?
T
rather they sensitize red cell at 37oc and can be detected with the help of AHG.
Ig__ antibody crosses placenta.
G
IgM is a pentamer
IgM cross the placenta.
T/F
T
F
IgA is the primary antibody in _____
IgA Exist predominately as _____ with a _____ component there in
secretion
dimers
secretory
IgA Does not cross placenta m
IgA can fix complement
T/F
T
F
aggregated IgA can activate _____ pathway of complement
alternate
Naturally occurring allo-antibodies are mostly associated with carbohydrate antigen
T/F
T
Haemolytic Disease of the newborn
_____ and ____ which crosses placenta are mostly implicated
IgG1 and IgG3
