Lecture 5 Genes and chromosome alterations

Question 1

Genetic Recombination and Linkage

Answer 1

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

Question 2

A. Studying chromosomes

Answer 2

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

Question 3

Four types of chromosomes based on the position of the centromere

Answer 3

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

slide 4

Question 4

1. WHAT is a KARYOTYPE

Answer 4

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)

Question 5

The Process of Karyotyping

Answer 5

Colchicine is added to the culture to arrest the cells in metaphase
Colcemid works by preventing the formation of the microtubules

slide 6-7

Question 6

G-(Giemsa)-banding

Answer 6

● 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

Question 7

2. Array Comparative Genomic Hybridization (Array CGH)

Answer 7

● 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

Question 8

Array CGH Analysis

Answer 8

slide 10

Question 9

B. BASIC TYPES OF CHROMOSOME MUTATIONS

Answer 9

1. Rearrangements – abnormal structure of chromosomes
   ●Duplication
   ●Deletion
   ●Inversion
   ●Translocations
2. Aneuploidy – abnormal number of chromosomes
3. Polyploidy – alter the complete sets of chromosomes (3n, 4n, 5n)

Question 10

1. REARRANGEMENTS

Answer 10

• Alteration of chromosome structure
  a. Deletion
  b. Duplication
  c. Inversion
  d. Translocations

slide 12

Question 11

Chromosome rearrangements
Alter the structure of chromosomes

Answer 11

Two sources of rearrangements
●Double strand DNA break (DDIT)
●Errors in crossing over

4 types of rearrangements
*Duplication
*Deletion
*Inversion
* Translocations

Question 12

Human Conditions Due to Chromosomal Alterations

Answer 12

1. CRI DU CHAT SYNDROME (1/50,000)

slide 14

Question 13

Human Conditions Due to Chromosomal Alterations

Answer 13

2. 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

Question 14

Aneuploidies

Answer 14

abnormal number of chromosomes

Caused mainly by nondisjuntion during meiosis
slide 16

Question 15

Examples of Aneuploidies

Answer 15

• 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)

Question 16

Aneuploidy of Autosomes
Down Syndrome

Answer 16

●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)

slide 20

Question 17

Translocation can cause Down syndrom
Carriers have increased risk of producing Down syndrome children

Answer 17

slide 23

Question 18

Patau’s Trisomy Syndrome

Answer 18

slide 24

Question 19

Trisomy 18 (Edward’s Syndrome)

Answer 19

-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

Question 20

Aneuploidy of Sex Chromosomes

Answer 20

More common
○ Dosage compensation for X
chromosomes (Barr bodies)
○ Y chromosome has few genes

slide 23

Question 21

Turners syndrome

Answer 21

slide 24

Question 22

Klinefelter syndrome

Answer 22

slide 25

Question 23

Polyploidy Alteration of complete sets of chromosomes

Answer 23

● 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

Question 24

Colochicine treatment prevents spindle formation and results in doubling of chromosome numbers

Answer 24

slide 27

Question 25

Polyploidy in plant species

Answer 25

slide 28

Question 26

Error in Meiosis - polyploid plant

Answer 26

slide 29