Transcript Chromosomes

Chromosomes
Cytogenetics
• A subdiscipline within genetics
• Focuses on chromosome variations
• Abnormal number of copies of genes or
chromosomes can lead to genetic
abnormalities
• Human genome sequence information is
used to identify genes that contribute to
the chromosome-related syndromes
Portrait of a Chromosome
• Primarily DNA and protein
• Described by size and shape
• Heterochromatin (dark)
• Euchromatin (light)
• Contains:
– Telomeres
– Origin of replication sites
– Centromere
Chromosomes
• Heterochromatin is darkly staining, contains
mostly repetitive DNA
• Euchromatin contains more protein encoding
genes
• Telomeres are chromosome tips composed of
many repeats of TTAGGG and shorten with
each cell division
• Centromere is the largest constriction of the
chromosome and where spindle fibers attach
Centromere Position
• At tip  telocentric
• Close to end  acrocentric
• Displaced from center  submetacentric
– Long arm q
– Short arm p
• At midpoint  metacentric
Karyotype
• Chromosomal chart
• Chromosomes arranged
by size and structure
• Arranged by largest to
smallest
Visualizing Chromosomes
Fetal tissue:
amniocentesis
chorionic villi sampling
fetal cell sorting
Adult tissue:
blood (white blood cells)
cheek swab (buccal cells)
skin cells
tissue biopsy
Amniocentesis
Figure 13.5a
Chorionic Villi Sampling
Figure 13.5b
Fetal Cell Sorting
Figure 13.5c
FISHing
• Fluorescence in situ hybridization
– in situ =in tissue
– in vivo =in living organism
– in vitro =in a dish
• Uses a fluorescent probe to detect specific
sequences of DNA
Chromosomal Abnormalities
Abnormal Chromosome # Polyploidy
• Polyploidy
– An entire extra set of
chromosome
• Example: Triploidy
– One egg fertilized by 2
sperm
OR
– A diploid egg fertilized by
one sperm
– A diploid sperm fertilizes an
egg
Abnormal Chromosome # Aneuploidy
• Missing a single chromosome (monosomy)
– OR -
• Having one extra chromosome (trisomy)
• Euploid =“good set”
• Aneuploid =“not good set”
• Caused by nondisjunction during meiosis
Nondisjunction at Meiosis I
Nondisjunction at Meiosis II
Nondisjunction at Mitosis
• Results in a mosaic
– Some cell populations are
affected while others are
not
• Severity of symptoms
depends on how early in
development the
nondisjunction occurs.
Autosomal Aneuploids
• Usually lethal
• Those that survive often have mental
retardation
• Most common for chromosomes 13, 18,
and 21. Why?
Trisomy 21
• October is Down
Syndrome Awareness
Month!
Table 13.6
Figure 13.7
Oogenesis
Before birth
Arrested in Prophase I
After puberty (each month)
Arrested in Metaphase II
Upon fertilization
Trisomy 18
• Edward syndrome
• Severe physical and mental
disabilities
• Development stops at the 6
month level
• Oddly clenched fists
• Low-set ears
• Small mouth
• Unusual or absent fingerprints
• Liver and heart problems
Trisomy 13
• Patau syndrome
• Fusion of the eyes or a
small or absent eye
• Cleft lip and palate
• Extra fingers and toes
• Mental retardation
Sex Chromosome Aneuploidy
Sex Chromosome Aneuploids:
Female
• Turner syndrome (XO)
– Delayed puberty
– 99% are not born
– Infertile
• Triplo-X (XXX)
– Tall stature
– Menstrual abnormalities
– All but 1 X is inactivated
Sex Chromosome Aneuploids:
Male
• Klinefelter Syndrome (XXY)
– Sexually underdeveloped
• Small testes
• Sparse facial and pubic hair
– Long arms and legs and big
feet and hands
– May develop breast tissue
– Often infertile
Sex Chromosome Aneuploids:
Male
• XXYY Syndrome
– Slightly delayed childhood development
– Behavioral problems
• ADD, OCD, and learning disabilities
–
–
–
–
–
Leg ulcers due to poor circulation
Sexual development is delayed
Testes do not descend
Infertile
Abnormal (YY) sperm AND abnormal (XX) egg
Sex Chromosome Aneuploids:
Male
•
•
•
•
•
Jacobs Syndrome (XYY)
1/1000 males has an extra Y
96% of XYY males are normal
Tall height and acne
Criminals with chromosomal abnormalities
tend to have XYY
Abnormal Chromosome Structure
• Deletion =missing genetic
material
– Can range in size (the
more genes deleted, the
worse the phenotype)
• Duplication =a region of
the chromosome where
genes are repeated
• Inversion =the DNA
sequence in a region of
the chromosome is
inverted
• Translocation =a piece of
the chromosome is
moved to another
chromosome
Translocation
• Nonhomologous chromosome exchange segments
Two major types:
• Robertsonian translocation
• Two nonhomologous acrocentric chromosomes
break at the centromere and long arms fuse. The
short arms are often lost.
• 5% of Down syndrome results from a Robertsonian
translocation between chr 21 and chr 14.
• Reciprocal translocation
• Two nonhomologous chromosomes exchange a
portion of their chromosome arms.
Segregation of a Robertsonian
Translocation
Reciprocal Translocation
• Exchange of material from one
chromosome arm to another
• Some individuals carry a translocation but
are not missing any genetic material unless
a translocation breakpoint interrupts a gene
Inversions
• Inverted chromosomes have a region flipped in
orientation
• 5-10% cause health problems probably due to
disruption of genes at the breakpoints
• Inversions may impact meiotic segregation
• Two types of inversions occur:
• Paracentric
– inverted region does NOT include centromere
• Pericentric
– inverted region includes centromere
Segregation of a Paracentric
Inversion
Figure 13.21
Segregation of a Pericentric
Inversion
Figure 13.22
Isochromosomes
• Chromosomes
with identical arms
• Form when
centromeres divide
along the incorrect
plane during
meiosis
Figure 13.23
Ring Chromosomes
• Chromosomes shaped like a ring
• Occur in 1 in 25,000 conceptions
• May arise when telomeres are lost
and sticky chromosome end fuse
– Radiation exposure