Chromosomes and Chromosomal Abnormalities - Genetics 2

Question 1

How is a chromosome recognised?

Answer 1

• Banding pattern with specific stains
• Length
• Position of the centromere

Question 2

What can the short arm of the chromosome be written as?

Answer 2

p

Question 3

What can the long arm of the chromosome be written as?

Answer 3

q

Question 4

What is an acrocentric chromosome?

Answer 4

• Doesn’t really have a short arm (little bit that encodes satellite ribosomal genes, tRNAs etc)
• Has a centromere and a long arm
• Only chromosomes 13, 14, 15, 21 and 22

Question 5

What is a balanced chromosomal rearrangement?

Answer 5

• All chromosomal material is present

Question 6

What is an unbalanced chromosomal rearrangement?

Answer 6

• Extra or missing chromosomal material, usually one or three copies of the same gene
• Developmentally ‘bad news’

Question 7

What is aneuploidy

Answer 7

When there is a whole extra or missing chromosome

Question 8

What is Translocation?

Answer 8

Rearrangement of chromosomes

Question 9

What is Aneuploidy usually caused by?

Answer 9

Nondisjunction in meiosis in either meiosis 1 (resulting in two gametes having 3 chromosomes and two having one) or in meiosis 2 (resulting in two gametes being normal and one having 3 and the final having only one)

Question 10

What is Down syndrome?

Answer 10

Trisomy 21 (3 copies of chromosome 21)

Question 11

What is Edward syndrome?

Answer 11

Trisomy 18

Question 12

What is Patau syndrome?

Answer 12

Trisomy 13

Question 13

How can chromosomal defects be tested before birth?

Answer 13

• Interphase chromosome counting using FISH (fluorescence In situ Hybridization)
• Chromosome will fluoresce and then can be counted, for example: a trisomy will show 3 fluorescent chromosomes instead of 2

Question 14

How can chromosomal defects be tested (not before birth)

Answer 14

Array CGH (comparative genome hybridisation)
• Patient DNA and Control DNA of an equal amount and normal chromosome complement are mixed
• Hybridise them into a gene chip and if the control DNA and the patients DNA match, it should produce an even graph with equal amounts of the control and patient DNa
• If there is less or more of the patient DNA/chromosome this will be shown as a slight dip or a peak in the graph

Question 15

What is Turner syndrome?

Answer 15

45X: only one sex chromosome

Question 16

Why is X chromosome aneuploidy better tolerated?

Answer 16

Because of X inactivation

Question 17

What are the X chromosome aneuploidies?

Answer 17

• Turner syndrome: 45 X
• Triple X: 47 XXX
• Klinefelter syndrome 47 XXY (male)

Question 18

What is chromosomal insertion?

Answer 18

• Area of one chromosome is inserted into another
• Usually not known or recognised until they go on to have children (as long as the insertion doesn’t cut through a gene)

Question 19

What is Robertsonian translocation?

Answer 19

• Only affect the acrocentric chromosomes (13, 14, 15, 21 and 22)
• 2 Acrocentric chromosomes get stuck end to end
• An example would be 45 XY t(14:21)
• Prior to testing they may not be aware of this translocation

Question 20

What are the different chromosomal results for the children of a mother with a roberstonian translocation (45 XX t(14:21) and a father with normal chromosomes

Answer 20

• Normal - inherits the normal versions of each gene from both parents
• Balanced translocation - inherits the normal versions from the father and the translocated version from the mother: 45XX/XY t(14:21)
• Trisomy 14 - inherits the normal versions from the father and one normal 14 from the mother and the translocated chromosome (results in miscarriage)
• Trisomy 21 (Down syndrome) - inherits the normal version from the father and the translocated chromosome and a normal 21 chromosome

Question 21

How can the chromosomal pattern for someone with Down syndrome that has been caused by an inherited Roberstonian translocation be written (boy)?

Answer 21

46 XY der(14:21) + 21

Question 22

What is a reciprocal translocation?

Answer 22

• Can happen with any of the autosomes
• Exchange of 2 eccentric fragments of a chromosome (stable)
• Exchange of eccentric and centric fragments- dicentric and not stable in mitosis

Question 23

What are the different chromosomal results for the children of a mother with normal chromosomes (1 and 9) and a father with one set of reciprocal translocated chromosomes (one normal 1, one normal 9, one pair of reciprocally translocated 1 and 9)?

Answer 23

1. Normal - inherit normal chromosomes from both parents
2. Balanced 1;9 translocation - normal set from mother, both reciprocally translocated chromosomes from father
3. Partial Trisomy 9 and monosomy 1 - normal from mother, one reciprocally translocated from father and one normal chromosome 9
4. Partial Trisomy 1 and monosomy 9 - normal set from the mother, one translocated chromosome from father and one normal chromosome 1

Question 24

If a mothers chromosomal pattern is written as 46, XX, t(12:17) (p13;p13), what is the son’s if he has inherited the translocation?

Answer 24

46, XY, der(17) t(12;17) (p13;p13)mat

Question 25

What are the reproductive risks of reciprocal translocations?

Answer 25

• 50% chance no effect: either balanced translocation or normal
• 50% unbalanced: if large segment, miscarriage and if a small segment, dysmorphic delayed child

Question 26

What is a Philadelphia chromosome?

Answer 26

• Reciprocal translocation between Ch 9 and Ch 22
• Forms a bcr-abl gene (an oncogene)
• 46, XY, t(9:22) (q34;q11.2)
• 95% of patients with chronic myeloid leukaemia (CML) have this gene

Question 27

What is the Charcot Marie Tooth Disease?

Answer 27

• Duplication (happens in 39 genes, 70-80% of the time on Ch 17 on p)
• Results in damage to the myelin sheath