Chromosomal Abnormalities Flashcards
What is meant by the karyotype?
It is the chromosome set of an individual species in terms of number and structure of chromosomes
How many chromosomes do humans have?
22 pairs of normal chromosomes, 1 pair of sex chromsomes
What is a nucleosome?
When the DNA is wrapped around the histone proteins
When nucleosomes condense, what is formed?
A chromatin fibre
What is formed when chromatin condenses?
Chromosome
How do very long DNA molecules fit into the cell?
The DNA is wrapped around histones, forming nucleosomes which are then coiled into the chromatin fibre which is then further condensed to fit into the chromosome
Which cells do not contain chromatin?
Red blood cells
During what phase of mitosis are chromsomes usually karyotypes and why?
During metaphase, as the chromosomes are less condensed
Which cells are commonly chosen to be karyotyped and why?
White blood cells as they easily enter into mitosis
What is the short arm of a chromosome called?
The p arm
What is the long arm of the chromosome called?
The q arm
What connects the p arm with the q arm?
A centromere
What is added when karotyping to prevent mitosis from progressing past the metaphase?
Colchicine
How are the chromosomes released from the cell?
During karyotyping, a hypotonic solution is added, which causes the cell to swell and burst, releasing all the chromosomes
What is used during karyotyping to fix the chromosomes in place on the glass slide?
Carnoys fluid
what is carnoys fluid?
A combination of acetic acid and ethanol used to fix the chromosomes in place
What are the tips of the chromosome called?
Telomere
What staining technique is used in karyotyping?
Giemsa staining
What does giemsa staining produce?
Banding patterns on the chromosomes
How are the bands on chromosomes numbered?
The bands closest to the centromere is 1, and they increase in number the further you get from the centromere
What do dark bands on the chromosomes represent?
Heterochromatin - this is where the DNA is wrapped more tightly around the histone proteins and is more condensed
What do light bands on chromosomes represent?
Euchromatin - where the DNA is not packed as tightly around the chromatin so it is more open
What is meant by metacentric chromosomes?
Where the p arm and the q arm are the same length
What are submetacentric chromosomes?
Where the p arm is shorter than the q arm
What is meant by acrocentric chromosomes?
Where the short p arms have been reduced to a stump and replaced by non-coding satellites
What type of translocation can acrocentric chromosomes undergo?
Robertsonian translocations
What is a robertsonian translocation?
Where there is translocation between two acrocentric chromosomes which results in the formation of one chromosome with normal lengthed arms, and one where the two satellite sections have combined = loss of chromosome
Which chromosomes do Robertsonian translocations usually occur in?
13, 14, 15, 21 and 22
What is meant by a de novo abnormality?
A chromosomal abnormality which is not inherited from the parents
During what stage does cross-over occur?
During prophase of meiosis 1
What is the purpose of meiosis?
To reduce the diploid number to haploid so that diploid zygotes can be formed
To ensure there is genetic variation amongst offspring
What is the purpose of mitosis?
For growth, repair and replace exhausted daughter cells - helps to maintain diploid number
Describe how crossing over occurs?
The pairs of homologous chromosomes align, chiasma form and sections of DNA are exchanged
What is a recombinant chromatid?
A chromatid in which sections of DNA have been swapped during cross over
What is monosomy?
A loss of a chromosome - so now the chromosome only consists of one chromatid
What is trisomy?
Where there is a gain of a chromosome, 3 copies of chromosomes
What is the most common cause of numerical chromosomal abnormalities?
Non-dysjunction
What is non-dysjunction?
The failure of homologous chromosomes to separate properly during cell division
What term is used to describe abnormal chromosome numbers?
Aneuploidy
What are the three stages in which chromosomal abnormalities can occur?
Mitosis, meiosis 1 or meiosis 2
What is Trisomy 21?
Down syndrome
What causes trisomy 21?
failure of the 21s chromosome to separate during egg or sperm development
What can be used to rapidly detect pre-natal Trisomy?
Quantitative Flourescence PCR
What is the cause of 85-90% of trisomy 21?
Maternal dysjunction
What increases the risk of maternal dysjunction?
Increasing maternal age
Why does maternal non-dysjunction increase with age?
As you get older there is progressive degradation of factors which hold homologous chromatids together, meaning incorrect separation is more likely to occur
What is the karyotype of someone with trisomy 21?
47 + 21, or 47, XX+21
What causes turners syndrome?
X monosomy
What causes Kleinfelder’s disease?
XXY - trisomy where you have an extra X chromsome
What is the most common form of aneuploidy?
Sex chromosome imbalance
How does the body tolerate an imbalance in sex chromsomes?
The excess X chromsomes get inactivated and Y chromosomes do not contain many genes
How are excess X chromosomes silenced?
It is packed into a transcriptionally inactive heterochromatin
What is a Barr body?
An inactive X chromosome
If excess X chromosomes are silenced, why can some XXY and XXX have effects?
Some genes may be located in the PAR regions - genes in this region behave like autosomal genes and therefore are not inactivated like the rest of the X chromosome
What are PAR regions?
Pseudoautosomal regions - contain pseudoautosomal genes that behave like autosomal genes and therefore are not silenced when excess X or Y chromosomes are
What is it which allows crossing over between X and Y chromosomes?
Psuedoautosomal regions
What happens when unequal crossing over occurs?
Duplication and deletion
What translocation results in the formation of the Philadelphia gene?
t(9;22)(q34;q11)
What condition can the fusion of the ABL and BCR gene lead to?
Chronic Myeloid Leukemia
What is haploinsufficiency?
A dominant phenotype in diploid organisms that are heterozygous for a loss of function allele- one copy of a gene is inactivated or deleted and the remaining functional copy of the gene is not adequate to produce the needed gene product to preserve normal function
What is genomic imprinting?
Changes to the DNA or chromatin that are inherited but do not affect the DNA sequence
How is genomic imprinting achieved?
Through DNA methylation
Carriers of balanced translocations have increased risk of what?
Creating gametes with unbalanced chromosome translocations, leading to infertility, miscarriages or children with abnormalities
What is the severity of the phenotype dependant on?
The gene content of the affected segment
Is trisomy or monosomy usually more tolerated?
Trisomy
What are some signs and symptoms of patients with Williams syndrome?
Long philtrum - space between nose and lip
Short, upturned nose
Arched eyebrows
Funny, cocktail party personalities
Aortic Stenosis (narrowing)
Why is Williams syndrome detected using array Comparative Genome Hybridisation?
The deletion is too small to be detected using karyotyping
What are the three types of structural chromosomal abnormalities that can occur?
Deletion, duplication and inversion
What can be seen when higher levels of karotyping resolution is done?
Sub-bands and sub-sub bands
Most aneuploidy caused by non-disjunction arises in what process?
Oogenesis
Is paternal age a risk factor for aneuploidy?
No
What three conditions are affected by the paternal age effect?
Apert syndrome
Crouzon syndrome
Pfeiffer syndrome
Although paternal age is not a risk factor in aneuploidy, what is?
Smoking
How many times per chromosome per cycle of meiosis does cross over occur?
1-3 times
What are some signs and symptoms of 7q11.23 duplication syndrome?
Delayed speech development
Autistic behaviours that affect social interaction and communication
Dilatation of the aorta
Flat eyebrows
Broad nose and short philtrum
What is meant by mosacism?
The presence of two or more populations of cells with different genotypes eg a person has two sets of DNA so not all cells will have the same genetic material
what are the two causes of mosaicism?
Mitotic disjunction during embryonic development
Loss of extra chromosome in early development
What is paracentric inversion?
Inversion not around the centromere
What is pericentric inversion?
Inversion of a section of the chromosome, around the centromere
