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 birthArrested 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 segmentsTwo 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
