Unit 5: Chromosomal Aberrations Flashcards
organization of chromosomes
linear DNA > looped around by histone protein > chromatin > (condensation) chromosome
defined by DNA
gene
refers to the arms of chromosomes
chromatids
chromosome in metaphase
2 sets of DNA / tetraploid (4n)
dark band and tightly packed by H1 in between 2 nucleosome
heterochromatin
why 2 versions of bands?
transcription factor cannot access heterochromatin so H1 needs to relax the structure para maaccess ang transcription factors
causes nucleosomes to tightly pack together. transcription factors cannot bind the DNA and genes are not expressed
methylation of DNA & histones (heterochromatin)
results in loose packing of nucleosomes. transcription factors can bind the DNA and genes are expressed
histone acetylation (euchromatin)
light band and loose
euchromatin
regions with high transcriptional activity are loosely packed
acetylation
regions with low or no transcriptional activity are densely packed
methylation
locus of the gene parts
located chromosome
arm
band
sub band
sub sub band
how are bands numbered?
numbered from the centromere going outward
made of hexameric repeats and protects the chromosomes
telomere
- These are variations from the wild-type condition in either chromosome structure or chromosome number.
- These arise spontaneously or induced by chemical or radiation mutagens.
chromosomal mutations
variation = ______; level of the chromosome = _________
mutation; aberration
an alteration of the nucleotide sequence of a gene
gene mutation
where does the alteration occur in gene mutation?
nucleotide sequence of a gene
caused by errors in DNA replication and mutagens such as UV and chemicals
gene mutation
any substance that can cause mutation
mutagens
a single gene is affected
gene mutation
influence is comparatively low
gene mutation
can cause sickle cell anemia, hemophilia, cystic fibrosis, huntington syncrome, tay-sachs disease and cancers
gene mutation
caused by errors in crossing over during meiosis
chromosomal mutations
alterations in the chromosome structure and number
chromosomal mutations
where does the alteration occur in chromosomal mutations?
in a segment of a chromosome
several genes are affected
chromosomal mutations
can cause klinefelter syndrome, turner syndrome, down syndrome
chromosomal mutations
can sometimes be lethal
chromosomal mutations
main difference between gene and chromosomal mutation
chromosomal mutation = may phenotypic expression
gene muta = wala
most common chromosome abnormality in spontaneous abortions
Trisomics (39k)
most common gender in sex chromosome aneuploids
males (1427)
Variation in Chromosome Structure
- Deletion
- Duplication
- Inversion
- Translocation
Variation in Chromosome Number
- Aneuploidy (Monosomics/Trisomics/Nullisomics/Tetrasomics)
- Polyploidy
the presence of an abnormal number of chromosomes
aneuploidy
loss of a single chromosome copy
monosomic
unbalanced set of chromosomes = relative gene dosage is upset (example: trisomy of chromosome 21)
aneuploid
the presence of more than 2 homologous chromosome sets
polyploidy
extra copies of single chromosomes
polysomic
T/F: Most chromosome abnormalities are lethal, frequently in spontaneous abortions
T
exceptions in spontaneous abortions
trisomy 13
trisomy 18
trisomy 21
sex chromosomes
An extra X or Y chromosome usually has a relatively mild effect. Why?
1) X chromosome inactivation/Dosage Compensation
2) Not much (essential) on the Y
EXAMPLES:
* Trisomy-X = 47, XXX (female)
* Double-Y = 47, XYY (male)
* Klinefelter Syndrome = 47, XXY (male,
sterile)
* Turner Syndrome = 45, X (female, sterile)
An extra or missing chromosome
aneuploidy
Extra chromosome sets
polyploidy
One chromosome absent
monosomy
One chromosome extra
trisomy
Part of a chromosome missing
deletion
Part of a chromosome present twice
duplication
Two chromosomes join long arms or exchange parts
translocation
Segment of chromosome reversed
inversion
A chromosome with identical arms
isochromosome
A chromosome that forms a ring due to deletions in telomeres, which cause ends to adhere
ring chromosome
nawala yung telomere kaya nagfuse
ring chromosome
what variation in chromosome structure is chronic myelogenous leukemia (9 & 22)?
translocation
two different chromosomes have exchanged segments with each other
reciprocal translocation
an entire chromosome attaches to another at the centromere
robertsonian translocation
the inverted segment includes the centromere (with both arms involved)
pericentric inversion
the two breaks appear on the same side of the centromere (in the same arm)
paracentric inversion
It involves the loss of a segment of a chromosome.
deletions
starts in breaks of chromosomes. These breaks maybe caused by agents (such as heat, ionizing radiation, viruses, transposable elements) or by errors in recombination.
deletion
where is the deleted segment located?
anywhere along the chromosome
If dominant dominant ‘A’ is lost in a deletion, then recessive ‘a’ will express itself. This expression of a recessive trait is called _________
Pseudodominance
T/F: If the missing genes are of physiological importance, the organism will not survive
T
an international standard for human
chromosome nomenclature, which includes band names, symbols and abbreviated terms used in the description of human chromosome and chromosome abnormalities.
International System for Human Cytogenomic Nomenclature (ISCN)
abbreviation for deletions of parts of a chromosome
del
symbol for chromosome deletions
-
a deletion that occurs towards the end of a chromosome
terminal deletion
T/F: Micro-deletion is usually found in adults with physical abnormalities. A large amount of deletion would result in immediate abortion (miscarriage)
F; usually found in children
a deletion that occurs from the interior of a chromosome
Intercalary/interstitial deletion
a relatively small amount of deletion (up to 5Mb that could include a dozen genes)
microdeletion
cri du chat syndrome deletion
5p-
retinoblastoma deletion
13q
prader-willi syndrome deletion
15q-
wilms tumor deletion
11q-
Kidney tumors, genital and urinary tract abnormalities
Wilms tumor
Cancer of the eye, increased risk of other cancers
Retinoblastoma
Infants: weak slow growth; children and adults: obesity, compulsive eating
Affected infants have poor sucking reflex. By age 5-6, children become compulsive eaters. Other symtoms include poor sexual development in males, behavioral
problems and mental retardation
Prader-Willi syndrome
Infants have catlike cry, some facial anomalies, severe mental retardation
Mentally retarded, with defects on facial
development, gastrointestinal malformations, and abnormal throat structures.
Cri du chat syndrome
Deletions in the long arm of chromosome 15 between bands of q11 and q13.
Prader-Willi syndrome
s a genetic disorder. It causes delayed development, problems with speech and balance, intellectual disability, and sometimes, seizures.
angelman syndrome
T/F: People with Angelman syndrome often smile and laugh frequently, and have happy, excitable personalities.
T
first signs of angelman syndrome (months)
developmental delays which begin between about 6 & 12 months of age
at what age do children with angelman syndrome experience seizure?
2-3 yo
is located on the segment of chromosome 15 that is often deleted in people with this disorder.
OCA2 gene
In some people who have Angelman syndrome, the loss of a gene called _____ is associated with light-colored hair and fair skin
OCA2
It is a chromosomal mutation that results in the doubling of a segment of a chromosome.
duplication
the duplicated sections are adjacent to the original
tandem duplication
Forms of Chromosome Duplication
Tandem
Reverse Tandem
Terminal Tandem
the presence of extrachromosomal segment causing duplication of a set of genes on the same arm, but in reverse order, in the same chromosome.
reverse tandem
tandem duplication at the end of a chromosome
terminal tandem duplication
T/F: The duplications are deleterious.
F; not deleterious
T/F: The duplication is useful in evolution of new genetic material position such as reallocation of chromosomal material
without altering its quantity may result in an altered phenotype. Example: Position Effect in Drosophila
T
It is a chromosomal mutation that results when a segment of a chromosome is excised and then reintegrated in an orientation 180O from the original orientation.
Inversion
abbreviation for inversions
inv
chromosomes twist into a loop in the
region in which the gene order is inverted
Inversion heterozygote
T/F: Inversions do not alter the genetic content but change the linear sequence of genetic information
T
- Does not include centromere
- Crossing-over produces one acentric (no centromere) and one dicentric (two
centromeres) chromosome
paracentric inversion
what does paracentric inversion produce when crossing over?
1 acentric
1 dicentric
- Includes centromere
- Crossing-over results in duplications and
deletions of genetic information
Pericentric inversion
The ______ chromatids fail to move to either pole due to lack of centromere. The _______ chromatids have two centromeres and are connected by a bridge, breaks and contains duplications and deficiencies.
acentric; dicentric
T/F: When crossing over occurs within the inverted segment of a pericentric inversion, then acentric and dicentric chromatids are formed.
F; paracentric
change in position of a chromosome segment within the same chromosome.
intrachromosomal
- There is a change in position of chromosome segments and the gene
sequences they contain. - no gain or loss of genetic material
translocation
transfer of a chromosome segment from one chromosome into a nonhomologous chromosome.
interchromosomal
The broken piece gets attached to one end of the chromosomes.
simple translocation
The broken segment segment of one chromosome gets inserted interstitially in a chromosome.
shift translocation
A segment from one chromosome is exchanged with a segment from another non homologous one, so that in reality two translocation chromosomes are simultaneously achieved.
* Homozygotic and heterozygotic translocation
reciprocal translocation
T/F: Homozygotes do not have any cytological peculiarities and undergo regular pairing during meiosis and cannot be detected cytologically.
T
T/F: In translocation of heterozygotes, breaks occur on only one of the chromosomes of a homologous pair. In heterozygotic translocation a considerable degree of meiotic irregularities occur.
T
exchange of segments between two chromosomes
reciprocal interchromosomal translocation
used to denote a translocation between chromosome A and chromosome B
t(A;B)(p1;q2)
transfer of segment in one direction from one chromosome to another
non-reciprocal interchromosomal translocation
the short arms and/or the long arms of
the same chromosome join at the centromere
isochromes
creates two copies of a large genetic
region
isochromes
show characteristic mirror image appearance of banding patterns extending in both directions from centromere
isochromes
- special cases of joining at centromeres
- occur between chromosomes that have tiny short arms (acrocentrics)
- no obvious lost in genetic information because the short arms contain repeated rRNA genes
- forms a very recognizable and long product
robertsonian translocation
It involves reciprocal translocation between the long arm of chromosome 22 and chromosome 9.
chronic myelogenous leukemia
- Transition of c-abl within the bcr
- It results to uncontrolled replication of myeloblasts
chronic myelogenous leukemia
Leukemic cells have ________ __________
Philadelphia chromosome
- Common disease in Africa
- Virus-induced tumor; malignant B cells secrete antibodies
burkitt’s lymphoma
T/F: Chromosome mutations may occur which results in variation in the number of individual chromosomes or in variation in complete sets of chromosomes.
T
Organism or cell has one or exact multiple of complete set(s) of chromosomes
euploidy
⦿ It involves reciprocal translocation between chromosome 8 and 14.
⦿ Activation of c-myc
burkitt’s lymphoma
One or several chromosomes are lost from or added to the normal set of chromosomes.
aneuploidy
aneuploidy results from?
nondisjunction
irregular distribution of sister chromatids during mitosis or of homologous chromosomes during meiosis
nondisjunction
Phenotypic effects range from minor physical symptoms to devastating and lethal deficiencies in major organ systems.
aneuploidy
involves a loss of one homologous pair; 2N-2
nullisomy
involves a loss of a single chromosome; 2N-1
monosomy
involves a single extra chromosome; 2N+1
trisomy
Phenotypic features – wide skull that is flat at the back; eyelids have an epicanthic fold; iris contains spots; tongue are furrowed & protruding; physical growth, behavior and mental development are retarded; some have congenital heart defects.
Down Syndrome / Trisomy 21
*It occurs when there are three copies of chromosome 21.
*Condition named as mongolism (but not used anymore)
Down Syndrome / Trisomy 21
involves an extra chromosome pair; 2N+2
tetrasomy
Phenotypic features – cleft lip and palate; small eyes; polydactyly (extra fingers and toes); mental and developmental retardation; severe malformations of the brain and nervous system
Patau Syndrome / Trisomy 13
- Three copies of chromosome 13
- Most affected infants die before the age of three months.
Patau Syndrome / Trisomy 13
- Most affected infants are female.
- Average survival time is 2-4 months
Edward Syndrome / Trisomy 18
why is maternal age the leading risk factor for autosomal trisomy?
- The integrity of primary oocytes decreases as the woman age.
- Maternal selection becomes less effective.
T/F: Maternal age is the leading risk factor for autosomal trisomy
T
Phenotypic features – have multiple congenital malformations affecting almost every organ system; clenched fists; elongated skull; low-set malformed ears; mental and developmental retardation.
Edward Syndrome / Trisomy 18
- Monosomy for the X chromosome
- Complete absence of X chromosome in the absence or presence of Y chromosome is always lethal.
Turner Syndrome (45 X)
Phenotypic features do not develop until puberty.
Klinefelter Syndrome (47 XXY)
Phenotypic features – short and wide chested; extra folds of skin on the neck, underdeveloped breasts and rudimentary ovaries, absence of Barr body, color blindness, narrowing of aorta
Turner Syndrome (45 X)
Phenotypic features – poor sexual development; very low fertility; with breast development
Klinefelter Syndrome (47 XXY)
- Phenotypic features – above average height, suffered personality disorders, below normal intelligence
- Early studies associate violent criminal behavior with the presence of extra Y chromosome.
XYY Syndrome (47 XYY)
T/F: X chromosome is essential for survival.
T
involves variations from the normal state in the number of complete sets of chromosomes.
Polyploidy
Abnormalities in the number of haploid
chromosomal sets can arise in several ways
- Errors in meiosis during gamete formation
- Events in fertilization
- Errors in mitosis following fertilization
The basic chromosome set, from which all the other genomes are formed, is called the _____ ____
monoploid set
Through the formation of unreduced gametes that have double the normal complement of chromosomes or through abortive mitotic division, called _________
endoreduplication
T/F: Polyploids can arise from genome duplications occurring before or after fertilization
T
T/F: Polyploid species have multiple complete sets of chromosomes
T
most common form of polyploidy
triploidy
Forms of triploidy
69 XXY
69 XXX
69 XYY
T/F: triploid infants have only limited survival, and most die within a month.
T
A male with a translocation between the short arm of chromosome 7 at band 21.1
and the long arm of chromosome 9 at band 34.1
46, XY t (7;9) (p21.1; q34.1)
Indicates the number, the chromosome
sex chromosome constitution, and the nature of the specific abnormality
chromosomal shorthand
A male missing part of the long arm of chromosome 7
46, XY del (7q)
A female with trisomy 21 Down Syndrome
47, XX, +21
Triplo-X syndrome (female)
47, XXX
A male or female with Trisomy 13 or Patau Syndrome
47, XY +13 or 47, XX +13
A male or female with Trisomy 18 or Edward Syndrome
47, XY +18 or 47, XX +18
