Flashcards in MGD S10 - Chromosomal abnormalities Deck (40):
What are chromosomes made out of?
What is Chromatin made out of?
What are the different varieties of Histones called?
Describe the structure of the nucleosome core
Hint: What histones? How many?
Contains 8 polypeptides/histones molecules - Heterooctomeric protein
How many base pairs are contained within each nucleosome?
What is the function of H1?
Stabilises the nucleosome
What is Euchromatin?
Lightly packed DNA often under active transcription
What is Heterochromatin?
Tightly packed DNA that is not being expressed
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
How many pairs of chromosomes are present in a human cell?
What are the two categories of numerical chromosomal abnormality?
What is an numerical chromosomal abnormality?
Having a number of chromosomes that isn't 46
Give examples of types of polyploidy
What are the two types of Aneuploidy?
What is an Aneuploidy?
An abnormal number of chromosomes that is not divisible by haploid number (23 in humans)
What is a monosomy?
Loss of one chromosome i.e. One chromosome pair exists as a single chromosome
What is a triploid?
Trisomy is the gain of one chromosome i.e. One chromosome pair exists as a triplet
Describe how Aneuploidy comes about
Non-disjunction during meiosis in the parent organism/s
This leads to trisomy or monosomy when gametes fuse
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)
What are the sex chromosome aneuploidies and what conditions result?
Turner syndrome: 45,X
Triple X syndrome : 47,XXX
Kleinfelter syndrome: 47 XXY
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'
What is the most common cause of Polyploidy?
Fertilisation of an Ovum by more than one Sperm
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
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
What is structural chromosomal abnormality?
What are the two major categories of Structural chromosomal abnormality?
Physical changes to one or more chromosomes
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
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
What are the p and q arms of a chromosome?
p arm = short arm
q arm = long arm
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
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
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
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
What is Karyotyping?
Cut and pasting pictures of metaphase chromosomes into homologous pairs
How are chromosome pairs organised in a karyotype?
From Largest (chromosome pair 1) to smallest (chromosome pair 22)
23rd pair is the sex chromosomes
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
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
Normal Male = 46,XY
Normal Female = 46,XX
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
Why might we refer a patient for karyotyping?
-Down's Syndrome, especially if high maternal age (>35)
-Family history of chromosomal defects
-Abnormal foetal ultrasound scan
Abnormal sexual development
- E.g. Klienfelter Syndrome
Recurrent foetal loss
Leukaemia and related disorders
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