Lecture 5 Genes and chromosome alterations Flashcards
Genetic Recombination and Linkage
A. Methods to study Chromosomes
1. Karyotype (Chromosome morphology)
2. Array CGH (deletions, duplications)
B. Chromosome mutations
1. Chromosome rearrangements
● Duplications
● Deletions
● Inversions
● Translocations
2. Aneuploidy
3. Polyploidy
● Autoploidy
● Alloploidy
● Significance and importance in evolution
4. Genomic Imprinting
A. Studying chromosomes
EUKARYOTIC CHROMOSOME MORPHOLOGY – REVIEW
●CENTROMERE: attachment point for spindle microtubules
●2 TELOMERES: tips of a linear chromosome
●ORIGINS OF REPLICATION: where the DNA synthesis begins
Four types of chromosomes based on the position of the centromere
Submetacentric - centromere towards end creating long arm (q) and short arm (p)
Metacentric - centromere in middle
Telocentric - centromere at end of
chromosome
Acrocentric - centromere near one end
creating a long arm and a
knob or satellite
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- WHAT is a KARYOTYPE
COMPLETE SET OF CHROMOSOMES POSSESSED BY AN ORGANISM
● Metaphase chromosomes treated with colchicine (prevents disjunction)
● Lined up in descending order of size
● Prepared from actively dividing cells (WBC, bone marrow cells, meristematic
tissues of plants
● Revealed by staining techniques - Banding patterns (reveals difference in
genes)
The Process of Karyotyping
Colchicine is added to the culture to arrest the cells in metaphase
Colcemid works by preventing the formation of the microtubules
slide 6-7
G-(Giemsa)-banding
● Heterochromatic regions rich with adenine and thymine
(AT-rich) DNA and relatively gene-poor, stain more darkly in
G-banding.
● Euchromatin regions —which tends to be rich with guanine and
cytosine (GC-rich) and more transcriptionally
active—incorporates less Giemsa stain
- Array Comparative Genomic Hybridization (Array CGH)
● Compares the patient’s genome against a reference genome
● Identifies the differences between the two genomes
● Deletion/loss or a duplication/gain (quantitative results)
slide 9
Array CGH Analysis
slide 10
B. BASIC TYPES OF CHROMOSOME MUTATIONS
- Rearrangements – abnormal structure of chromosomes
●Duplication
●Deletion
●Inversion
●Translocations - Aneuploidy – abnormal number of chromosomes
- Polyploidy – alter the complete sets of chromosomes (3n, 4n, 5n)
- REARRANGEMENTS
- Alteration of chromosome structure
a. Deletion
b. Duplication
c. Inversion
d. Translocations
slide 12
Chromosome rearrangements
Alter the structure of chromosomes
Two sources of rearrangements
●Double strand DNA break (DDIT)
●Errors in crossing over
4 types of rearrangements
*Duplication
*Deletion
*Inversion
* Translocations
Human Conditions Due to Chromosomal Alterations
- CRI DU CHAT SYNDROME (1/50,000)
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Human Conditions Due to Chromosomal Alterations
- Chronic Myelogenous leukemia (CML)
● Physically link genes that were separate
● Affect gene expression by linking to new promoter
● Chronic Myelogenous leukemia or CML and Philadelphia chromosome (#22)
Bcr promoter is always ON!! cell divides uncontrollably (cancer)
Bcr-abl fusion protein
● Disrupt function of the gene during chromosome break
Aneuploidies
abnormal number of chromosomes
Caused mainly by nondisjuntion during meiosis
slide 16
Examples of Aneuploidies
- Nullisomy - Loss of both members of homologous pair 2n-2 (Humans = 44 chromosomes)
- Monosomy - Loss of a single chromosome 2n-1(Humans = 45 chromosomes)
- Trisomy - Gain of a single chromosome 2n+1(Humans = 47 chromosomes)
- Tetrasomy - Gain of two homologous chromosomes 2n+2 (Humans = 48 chromosomes)
Aneuploidy of Autosomes
Down Syndrome
●Less common - No dosage compensation for autosomes
●Most embryos are spontaneously aborted
●Trisomy 21 or Down Syndrome (1/700 births)
○Primary Down syndrome (aneuploidy) - 75%
○Familial Down syndrome (translocation) - 25%
●Other human Trisomies
○ Trisomy 18 or Edward syndrome (1/8000 births)
○ Trisomy 13 or Patau syndrome (1/15,000)
○ Trisomy 8 (1/25,000 – 1/50,000)
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Translocation can cause Down syndrom
Carriers have increased risk of producing Down syndrome children
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Patau’s Trisomy Syndrome
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Trisomy 18 (Edward’s Syndrome)
-unusally small head
-back of the head is prominent
- ears are malformed and low-set
-mouth and haw are small (may also have a cleft lip or cleft palate
-hands are clenched into fists, and the index finger overlaps the other fingers
0club feet (or rocker bottom feet) and toes may be webbed or fused
Aneuploidy of Sex Chromosomes
More common
○ Dosage compensation for X
chromosomes (Barr bodies)
○ Y chromosome has few genes
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Turners syndrome
slide 24
Klinefelter syndrome
slide 25
Polyploidy Alteration of complete sets of chromosomes
● Common in plants
o triploids (3n)
o tetraploids (4n)
o pentaploids (5n)
o higher numbers of chromosome sets
● Major mechanism for new plant evolution (wheat, oats, cotton, potatoes, sugarcane)
● Two major types
Autoploidy - From single species
■ Caused by accidents of meiosis/ mitosis that produce extra sets■ Artificially induced by chemicals that halt microtubules colchicine, no spindle formation
Alloploidy - From two species
Colochicine treatment prevents spindle formation and results in doubling of chromosome numbers
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