Chromosomal Aberrations Flashcards
What are chromosomal aberrations?
Abnormalities in structure and number of chromosomes
What is meant by the term aneuploid?
uneven number of chromosomes (e.g. 1 or 3)
What are the three trismonies that can be observed in practice?
13 patau
18 Edwards
21 down
A person with only one X chromosome and no Y has what syndrome?
Turner’s syndrome
What is the genotype of someone with Klinefelter syndrome?
XXY
What are the two ways in which structural chromosomal abnormalities occur?
Non-homologus end joining
Unbalanced recombination
Which are generally more severe: duplications or deletions?
Deletions
What is CRI-Du-Chat syndrome?
Arises from a deletion on chromosome 5
What is Di George syndrome?
microdeletion on chromosome 22. Results are very variable but include: Immunodeficiency Hypoarathroidism MR cleft palate
What is an insertion?
Taking a part of one chromosome and inserting it into another
What is a translocation?
Taking a part of one chromosome and attaching it onto the end of another
A translocation between chromosome 9 and 22 produces what disease?
The Philadelphia chromosome–Ber/Abl protein—chronic myeloid leukemia
What is a Robertsonian translocation?
When two chromosomes simultaneously exchange material via translocation. Results in the longs pairing, and the shorts pairing
How do inversions happen?
When a chromosome is damaged and the broken fragment is attached upside down
True or false: inversions of chromosomes are almost always lethal for the carrier.
False
True or false: inversions of chromosomes are almost always lethal for the carrier’s offspring. Why/why not?
True, because the inverted regions have to loop around in meiosis to pair with the homologous chromosome. If crossover occurs, then this is a translocation
What is a balanced alteration?
A chromosomal rearrangement that does not change the amount of DNA in the affected cell
What is an unbalanced alteration?
A chromosomal rearrangement that changes the amount of DNA in the affected cell
True or false: carriers of balanced alterations are usually aware of their condition?
False
True or false: carriers of balanced alteration usually produce viable offspring
False
What is karyotyping?
Studying the composition of the chromosomes in a cell
What are the six indications for examining a karyotype?
Problems of early growth/development Still birth/neonatal death Fertility problems Pregnancy with advanced maternal age Cancer Family h/o chromosomal aberrations
Out of 10000 pregnancies, how many live births are there? Spontaneous abortions?
8500, 1500
Out of 10000 pregnancies, how many will have normal chromosome? Abnormal?
9200 normal (92%), 800 abnormal
Of the 8500 live births, how many children will have down syndrome?
10
A deletion of chromosome 5 results in what disease? Symptoms?
Cri-du-chat syndrome. MR, microcephaly, micrognathia, heat defects, cat-like-cry
A microdeletion on chromosome 22 results in what disease? Symptoms?
Di George syndrome. Congenital heart defects, MR, cleft palate, immunodeficiency
A traslocation between chromosome 9 and 22 produces what disease/new chromosome?
Philadelphia chromosome produced, chronic myeloid leukemia due to overexpression of Abl1 gene due to translocation to Bcr. (Abl/Br tyrosine kinase)
What type of crossover occurs when two entire arms are switched?
Robertsonian translocation
What is the term that describes the translocation of a chromosome and a reinsertion of the gene backwards? When is this a problem?
Inversion
Problem for individual’s offspring, not usually individual them self.
What are the three things to look for in a pedigree that is suggestive of chromosomal inheritance?
- MR, multiple symptoms
- Multiple spontaneous abortions
- infertility
How do chromosomal abberrations result in CA?
Genomne instability deletes tumor suppressors/ amplifies oncogenes
Loss of cell cycle control
What is the karyotype for Turner’s syndrome?
45, X
What is the karyotype for Klinefelter syndrome?
47, XXY
What is the karyotype for Edwards, patau, and down syndomes?
47, 13 = Patau
47, 18 = Edwards
47, 21 = Down
Of 10000 pregnancies, how many balanced rearrangements will there be? How many of these will spontaneously abort? How many survive?
19/10000 pregnancies
3/19 die
16 survive
Of 10000 pregnancies, how many unbalanced rearrangements will there be? How many of these will spontaneously abort? How many survive?
27/10000 pregnancies
23 die
4 survive
Of 10000 pregnancies, how many will have normal chromosomes? How many of these will spontaneously abort? How many survive?
9200/10000 will have normal chromosomes
750 die
8450 survive
Of 10000 pregnancies, how many will have ABnormal chromosomes? How many of these will spontaneously abort? How many survive?
800/10000 will have abnormal chromosomes
750 die
50 survive
Of 10000 pregnancies, how many will have extra X chromosomes? How many of these will spontaneously abort? How many survive?
19/10000 pregnancies
4 die
15 survive
Of 10000 pregnancies, how many will have Down syndrome? How many of these will spontaneously abort? How many survive?
45/10000 pregnancies
35 die
10 survive
What percentage of children are born with recognizable birth defects?
2-3%
What is the rate of child death due to birth defects? To premature birth?
20% 20%
Give data for HPNOC (my acronym)?
Heart defects 1/100-1/200 Pyloric stenosos 1/300 Neural tube defects 1/1000 Orofacial clefts 1/700 - 1/1000 Clubfoot 1/1000
What percent of birth defects have complex inheritance?
50%
What percent of births are caused by single chromosomal defects?
25%
What percent of birth defects are caused by single GENE mutations?
20%
What percent of birth defects are caused by non-genetic factors?
5%
Chromosomal and genomic disorders affect what percent of the population?
0.38%
Single gene disorders affect what percent of the population?
2%
Disorders with multifactorial inheritance affect what percent of the population?
60%
What is the prevalence of Down? Edward? Patau?
1/800 for Down
1/8000 for Edward
1/25000 for patau
What is the prevalence of Turner syndrome?
1/2500
