Structural Chromosomal abnormalities

Question 1

Balanced

Answer 1

No gain or loss of genetic material

Question 2

Unbalanced

Answer 2

Gain or loss of genetic material

Question 3

Reciprocal translocation

Answer 3

Exchange of genetic material between non-homologous chromosomes

attach image from slide 8

Question 4

What is this an image of ?

Answer 4

Balanced reciprocal translocation (chromosome 2 & 8)

Question 5

What are the effects of reciprocal translocation in carriers?

Answer 5

May have no effect (silent)

Transformation to cancer and increased growth rate of cells

Question 6

What if the reciprocal translocation is located in the germ line cells?

Answer 6

There is a higher incidence of spontaneous abortions in the carrier

Question 7

Reciprocal translocation

Answer 7

Segregation at Meiosis

Question 8

Reciprical Translocation creating a fusion gene

Answer 8

slide 13

t(9;22) –> Chronic Myelogenous Leukemia–> activation of an oncogene–> Cancer Philadelphia chromosome t(9;22)–> Activation of BCR-ABL tyrosine kinase which is a proto-oncogene in hematopoietic cells

Question 9

Reciprocal translocation changing gene expression

Answer 9

t(8;14) —> Burkitt lymphoma Dysregulation of c-Myc gene expression, leading to cancer

Question 10

Robertsonian translocation

Answer 10

• Occurs between acrocentric chromosomes
  
  • Chromosomes 13,14,15,21,22
• There is loss of the short arms of the two chromosomes
  
  • The satellite structures in the acrocentric chrome. contain multiple copies of genetic material for RNA
• Fusion of the long arms of the two chromosomes

Question 11

What is this an image of ?

Answer 11

Robertsonian translocation- Effects during Meiosis

Question 12

Robertsonian translocation alternate segregation

Answer 12

Normal gamete (gamete 1)

Gamete with the derivative chromosome(gamete 2) that results in a Robertsonian translocation carrier on fertilization

Question 13

Robertsonian translocation: adjacent segregation

Answer 13

Results in trisomy of the respective chromosome on fertilization

Gamete 3 would result in trisomy 14, that is compatible with survival, and results in spontaneous abortion

Gamete 4 would result in trisomy 21(down syndrome) on fertilization

Question 14

What accounts for 2-5% of children with Downs syndrome?

Answer 14

Robertsonian Translocation

Question 15

Cri-du-chat Syndrome

Answer 15

Deletion of Chromosome 5p

46,XX,del(5)(p15.3)(pter)

46,XY,del(5)(p15.3)(pter)

Question 16

Features of Cri-du-chat Syndrome

Answer 16

High pitched, cat like cry

micrognathia which influences the cat-like cry and speech problems later in life

microcephaly

hypertelorism(widely spaced eyes)

Question 17

What is this Karyotype showing?

Answer 17

Cri-du-chat Syndrome

Question 18

What is this CGH showing?

Answer 18

Cri-du-chat Syndrome

Question 19

22q11.2 Deletion syndrome

Answer 19

Microdeletion of chromosome 22q11.2

DiGeorge syndrome, Velocardiofacial

Question 20

Features of 22q11.2 Deletion syndrome

Answer 20

congenital heart defects

absence of thymus- can cause immunological problems

Cleft lip and palate- can lead to speech difficulty

learning disability

Increased risk of schizophrenia

Question 21

Facial anomalies of 22q11.2 deletion syndrome

Answer 21

Long midface

narrow palpebral fissures

prominent nasal root

bulbus nasal tip

ear dysmorphology

Question 22

What is this CGH showing?

Answer 22

Microdeletion of chromosome 22q11.2

Question 23

What is this a FISH of ?

Answer 23

Microdeletion of chromosome 22q11.2

Question 24

Wolf-Hirschhorn syndrome

Answer 24

Deletion of ch 4p

seizures

skeletal abnormalities and congenital heart defects

spectrum of intellectual and developmental delay(mild to severe)

Question 25

what are the facial anomalies of Wolf-Hirschhorn syndrome

Answer 25

Widely spaced eyes

high arched eyebrows,

broad and flat nasal bridge (similar to roman helmet)

short philtrum

downturned mouth

small chin

Question 26

Deletions in Chromosome 15q11-13

Answer 26

A few genes on chromosome q5 are monogenic( only one allele is expressed)

SNRPN and UBE3A

Prader willi and Angelman syndrome

Question 27

Prader-willi syndrome

Answer 27

Deletion of Paternal chromosome 15q11-13 SNRPN

Question 28

Angelmans syndrome

Answer 28

Deletion of maternal chromosome 15q11-13 UBE3A

Question 29

Features of Prader willi

Answer 29

Eating disorder-hyperphagia

Developmental delays

hypotonia at birth

hypogonadism

distinctive facial features

Question 30

Features of Angelmans syndrome

Answer 30

inappropriate laughing and smiling

jerky uncoordinated movement

lack of speech

hypotonia

severe developmental delay

Question 31

Inversion abnormality

Answer 31

May be pEricentric ( involves the cEntromere)

paracentric (does not involve the centromere)

Usually result in a change in the banding pattern of the chromosome and can be identified by karyotype analysis

Question 32

what is this an image of?

Answer 32

Pericentric inversion

Question 33

what is this an image of?

Answer 33

paracentric inversion

Question 34

Effects of inversion during meiosis

Answer 34

results in duplication or deletion of segments of the chromosome -unbalanced genetic material

The gametes with acentric and dicentric chromosomes are not viable

carriers of inversions may be asymptomatic but have a high risk of spontaneous abortions

Question 35

Isochromosome

Answer 35

There is a loss of one arm of a chromosome and duplication of the other arm

Typically results in chromosomal and gene dosage imbalance

isochromosome of an autosome is lethal

Question 36

x-isochromosome

Answer 36

Long arms of the X chromosome join to form an isochromosome

Question 37

ring chromosome

Answer 37

Forms when a chromosome loses genetic material at the terminal portions and the ends fuse to form a ring like structure