MGD S10 - Chromosome Abnormalities

Question 1

What are chromosomes made up off?

Answer 1

Chromosomes are made up of chromatin Chromatin is made up of:

• DNA
• Non-histone proteins
• RNA
• Histones (H1, H2A, H2B, H3, H4)

Question 2

What components make up chromatin?

Answer 2

Histones, RNA, DNA and non-histone protein

Question 3

List the types of histone and their characteristics

Answer 3

H1, H2A, H2B, H3, H4 H1 - Varies between species

H2A, H2B, H3 and H4 directly interact with the DNA H3 and H4 are highly conserved and are responsible for bead on a string structure

Question 4

What is euchromatin?

Answer 4

Lightly packed chromatin, often under active transcription

Question 5

What is heterochromatin?

Answer 5

Tightly packed chromatin and not under active transcription

Question 6

What are numerical chromosomal abnormalities?

Answer 6

Number of chromosomes other than 46

Question 7

What are the two types of numerical chromosomal abnormalities?

Answer 7

Polyploidy - cells containing more than two paired (homologous) sets of all chromosomes. Caused by polyspermy

Aneuploidy - (an abnormal number that is not a multiple of the haploid number) Monosomy is a loss of one chromosome i.e one chromosome pair missing Trisomy is a gain of one chromosome i.e one “chromosome pair” exists as a triplet

Question 8

What are structural chromosomal abnormalities?

Answer 8

Physical changes to one or more chromosome

Question 9

What are two types of structure abnormalities?

Answer 9

Balanced - Change does not result in missing or extra genetic information

Unbalanced - Change results in missing or extra genetic information

Question 10

List all the mutations that can occur within one chromosome

Answer 10

1) Deletion
2) Duplication
3) Inversion
4) Ring chromosome
5) Isochromosome; balanced - the arms are mirror images

Question 11

How does a ring chromosome form?

Answer 11

Loss of the telomeres at ends of both arms forming a ring

Question 12

List the mutations that occur between two chromosomes?

Answer 12

1) Inversion
2) Reciprocal Translocation
3) Robertsonian Translocation

Question 13

What is an inversion mutation?

Answer 13

No loss of genetic material, but as rearrangement of genetic material to a non-homologous chromosome

Question 14

What is reciprocal translocation (chromosome abnormality)?

Answer 14

No loss of genetic material, but an exchange of genetic material between two non-homologous chromosomes

Question 15

What is a robertsonian translocation?

Answer 15

Rearrangement of genetic material between two chromosomes; the q- arms (long arms) of two afrocentric chromosomes combine to form one ‘super-chromosome’ with the loss of both p-arms

Question 16

What is the difference between reciprocal and robertsonian translocation

Answer 16

Reciprocal is the exchange of genetic material between two non-homologous chromosomes whereas Robertsonian involves the exchange of genetic material produced two q arms from two acrocentric chromosomes to form a super chromosome and loss of the two small p arms

Question 17

What is a karyotype?

Answer 17

Picture of the systematic assortment of the complete set of chromosomes of an individual, starting with chromosome 1 and ending with the sex chromosomes

Question 18

How is a karyotype produced?

Answer 18

Produced by ‘cut and paste’ of chromosome pictures by hand or computer to make organised set of metaphase chromosomes

Question 19

Describe chromosome nomenclature

Answer 19

Number of chromosomes-comma-X chromosomes-Y chromosomes + or – for loss or gain of genetic material State whether in p or q arm

E.g. Normal Female = 46,XX and a Normal Male is 46,XY

E.g. 5p- means ‘missing a segment of the p-arm on chromosome 5

Question 20

Why would a patient be referred for karyotyping?

Answer 20

Congenital: - Prenatal screening e.g. family history

• Recurrent foetal loss
• Infertility
• Birth defects e.g. mental retardation
• Abnormal sexual development e.g. Klienfelter’s Syndrome
• Acquired Abnormalities - Leukaemia and related diseases

Question 21

What can be identified from FISH?

Answer 21

Rearranged chromosomes, marker chromosomes and microduplications and microdeletions

Question 22

What is microarray used for?

Answer 22

High resolution of 5-10 megabases means that microarray can be used to test for submicroscopic chromosome abnormalities Used for individuals with suspected unbalanced chromosomal abnormalities

Question 23

What is uniparental disomy? (UPD)

Answer 23

Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other paren

Question 24

Why is imprinting significant to UPD?

Answer 24

Imprinted chromosomes show differential expression of specific genes depending on the parental origin of the chromosome If chromosome involved is not imprinted then UDP has no phenotypic effect

Question 25

Name a UPD syndrome

Answer 25

Prader-Willi (15)

Question 26

What is the most common mechanism to generate UDP?

Answer 26

Trisomy rescue

Question 27

Describe non-invasive pre-natal testing (NIPT)

Answer 27

Cell free DNA is present in plasma fraction of maternal blood

Question 28

What can NIPT be used to test for?

Answer 28

Chromosome aneuploidy, foetal sex, single gene disorders

Question 29

What is the advantage of NIPT compared to invasive pre-natal testing

Answer 29

Removes miscarriage risk