MGD S10 - Chromosomal abnormalities Flashcards Preview

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Flashcards in MGD S10 - Chromosomal abnormalities Deck (40):
1

What are chromosomes made out of?

Chromatin

2

What is Chromatin made out of?

DNA
Histones
Non-histone proteins
RNA

3

What are the different varieties of Histones called?

H1
H2a
H2b
H3
H4

4

Describe the structure of the nucleosome core

Hint: What histones? How many?

H2a/b
H3
H4

Contains 8 polypeptides/histones molecules - Heterooctomeric protein

5

How many base pairs are contained within each nucleosome?

166bp

6

What is the function of H1?

Stabilises the nucleosome

7

What is Euchromatin?

Lightly packed DNA often under active transcription

8

What is Heterochromatin?

Tightly packed DNA that is not being expressed

9

What are the levels of packing present in chromosome?

DNA packed into nucleosomes

Which are folded into solenoid fibres

Which are in turn folded tightly and then coiled to form the chromosome fibres

10

How many pairs of chromosomes are present in a human cell?

23 pairs

11

What are the two categories of numerical chromosomal abnormality?

Polyploid
Aneuplodiy

12

What is an numerical chromosomal abnormality?

Having a number of chromosomes that isn't 46

13

Give examples of types of polyploidy

Trisomy
Tetraploidy

14

What are the two types of Aneuploidy?

Monosomy
Trisomy

15

What is an Aneuploidy?

An abnormal number of chromosomes that is not divisible by haploid number (23 in humans)

16

What is a monosomy?

Loss of one chromosome i.e. One chromosome pair exists as a single chromosome

17

What is a triploid?

Trisomy is the gain of one chromosome i.e. One chromosome pair exists as a triplet

18

Describe how Aneuploidy comes about

Non-disjunction during meiosis in the parent organism/s

This leads to trisomy or monosomy when gametes fuse

19

Which Autosomal Aneuploidies might result in a viable pregnancy to term what do these Aneuploidies result in?

Trisomy 21: Down Syndrome

Trisomy 18: Edwards Syndrome

Trisomy 13: Patau syndrome

No monosomy is viable (Except Turner syndrome)

20

What are the sex chromosome aneuploidies and what conditions result?

Turner syndrome: 45,X

Triple X syndrome : 47,XXX

Kleinfelter syndrome: 47 XXY

47,XYY

21

What is X chromosome Inactivation?

Only one X chromosome is ever active in a human cell

The others are inactivated and form condensed structures around the periphery of the cell nucleus known as 'Barr bodies'

22

What is the most common cause of Polyploidy?

Fertilisation of an Ovum by more than one Sperm

23

What is the prevalence of triploidy and tetraploidy in humans and what is the fate of any foetus with polyploidy?

Triploidy occurs in 2-3% of pregnancies

Tetraploidy occurs in 1-2% of all pregnancies

All pregnancies with polyploidy result in miscarriage or in the case of triploidy, death shortly after delivery

24

How might mosaicism come about?

Non-disjunction in mitosis can lead to two separate populations of cells with different karyotypes

Mosaicism can result, especially if this occurs early in development

25

What is structural chromosomal abnormality?

What are the two major categories of Structural chromosomal abnormality?

Physical changes to one or more chromosomes

Balanced
Unbalanced

26

What is the difference between balanced and unbalanced structural chromosomal abnormalities

Unbalanced changes cause missing or extra genetic information to be deleted/introduced

Balanced abnormalities do not result in missing or extra genetic info

27

What are the types of structural chromosomal abnormality that affect only one chromosome?

Give a breif description of each

Deletion - Loss of genetic info

Duplication - Some genetic info is doubled

Inversion - Rearrangement of genetic info without loss or addition

Ring Chromosome - Loss of telomeres or ends of both arms resulting in a ring being formed

Isochromosome - Creation of two non-identical chromosomes, one is a combination of two short arms, one is the combination of two long arms

28

What are the p and q arms of a chromosome?

p arm = short arm
q arm = long arm

29

What are the types of structural chromosomal abnormality that can affect two chromosomes?

Give a brief description of each

Inversion - No loss of genetic material, genetic material is rearranged to a non-homologous chromosome

Reciprocal translocation - Exchange of genetic material from non-homologous chromosomes, no loss of genetic material occurs

Robertsonian translocation - The q arms of two acrocentric chromosomes combine to form one super-chromosome, the p arms are lost

30

What are the consequences of a translocation?

Breakpoints will often be between genes, so often have a normal phenotype

Derivative chromosomes may be passed onto offspring who will probably be unbalanced/ have disease phenotype

The phenotype will vary depending on where the offspring is monosomic and trisomic

31

What are the two types of deletion?

Give a brief description of each

Interstitial - Region of chromosome deleted is internal to chromosome

Terminal - Region of chromosome deleted at the end of a chromosome

32

What are the consequences of a deletion?

Deletions will be unbalanced and there will have a disease phenotype

Deletions may be large enough to see via light microscopy

33

What is Karyotyping?

Cut and pasting pictures of metaphase chromosomes into homologous pairs

34

How are chromosome pairs organised in a karyotype?

From Largest (chromosome pair 1) to smallest (chromosome pair 22)

23rd pair is the sex chromosomes

35

How does position of the centromere vary in humans?

Hint: Give names and short descriptions for each position

Metacentric - centromere in the middle of the chromosome

Sub-metacentric - Centromere found between telomeres and middle of chromosome

Acrocentric - Centromere found very close to the telomeres, leaving only very short p arms

Telocentric chromosomes with no p arms and centromere joined at the telomeres are not seen in humans

36

How is a normal karyotype formula expressed?

Give examples of a normal male and female.

Number of chromosomes
Followed by a comma
Then X chromosomes
Then Y chromosomes

Eg.
Normal Male = 46,XY
Normal Female = 46,XX

37

How are chromosomal abnormalities expressed in a karyotype formula?

Give an example of the karyotype formula for an otherwise normal female with a deletion on the q arm of chromosome 4

A plus or minus sign denotes extra or missing sections from a chromosome

A chromosome number followed by a p/q and a +/- indicate which chromosome arm is affected

Eg.
46,XX 4p-

38

Why might we refer a patient for karyotyping?

Congenital abnormality:

Prenatal screening
-Down's Syndrome, especially if high maternal age (>35)
-Family history of chromosomal defects
-Abnormal foetal ultrasound scan

Birth defects
-Malformations
-Mental retardation

Abnormal sexual development
- E.g. Klienfelter Syndrome

Infertility

Recurrent foetal loss

Acquired abnormalities:

Leukaemia and related disorders

39

Describe how Fluorescent In-situ Hybridisation (FISH) is performed

Fluorescently labelled single stranded nucleic acids (Normally DNA, sometimes RNA) are permitted to interact with DNA In-situ.

Labels can be monochrome or multicoloured (multicoloured labels can be used to band a chromosome)

They form complexes or hybrids with sufficiently complementary sequences of the patient's DNA

40

What is useful about Fluorescent In-situ Hybridisation?

Excellent for spotting gross alterations easily

Multicolour FISH can be used to band chromosomes to identify abberant sequences