Exam #5: Chromosomal Aberrations Flashcards
Frequency of Chromosomal Aberrations
The majority of fetuses w/ chromosomal aberrations are spontaneously aborted i.e. chromosomal aberrations are much more frequent at conception than at birth
For 10,000 pregnancies:
- 800 w/ chromosomal aberrations, BUT only 50 live births
- 47, XXY, XXX, & XYY, and then Trisomy 21 had the most live births of the numerical aberrations (15 & 10)
- Balanced rearrangement has more live births than those two numerical aberrations
- Unbalanced rearrangements were spontaneously aborted 85% of the time
Two Sources of Mutation Affecting Chromosomes
1) Numerical Aberrations = Nondisjunction during meiosis
2) Structural Chromosomal Alterations = rearrangements, loss, & duplication of parts of a chromosome
Balanced Alteration
- Move a fragment of DNA from one chromosome to another i.e. Translocations & Insertions (Inversion too)
- No loss or gain of genetic material
Unbalanced Alteration
- Deletions & Duplications
- BOTH change the amount of DNA in the cell
- BOTH have an impact on the carrier
- Deletions are typically more severe
Cri-Du-Chat Syndrome
- Caused by a deletion on chromosome 5 (del5p)
- Face symptoms: Microcephaly, Hypertelorism, Micrognathia
- Brain/CNS: Severe mental retardation
- Cardiovascular: Heart Defects
- Other: “Cat-like cry”
Di George Syndrome
- Caused by a microdeletion on chromosome 22
- Autosomal dominant inheritance
- Symptoms: heart defects, immunodeficiency, hypoparathyoridism, mental retardation, cleft palate
Why do balanced chromosomal alterations cause infertility in otherwise healthy carriers?
- Unbalanced alterations affect the carrier b/c the gene dosage is changed
- Balanced typically DO NOT
- However, balanced alterations greatly reduce the success of meiosis & subsequent pregnancy
Philadelphia Chromosome
- Translocation between chromosomes 9 & 22
- Moves ABL tyrosine kinase gene from chromosome 9 next to the BCR region of chromosome 22
- BCR/ABL chimeric protein is the dominant oncogene in CML
Robertsonian Translocation
- Long & short arms of a chromosome are exchanged
- Result is one chromosome w/ both long arms & one chromosome w/ both short arms
- Most common with chromosomes 13 & 14 in humans
CML
- Chronic Myelogenous Leukemia
- BCR/ABL protein from translocation of chromosome 9 & 22
Inversion
- Chromosome suffers two breaks
- Broken-off fragment is reinserted in the wrong orientation/ upside-down
- Balanced alteration
- Often asymptomatic in carrier BUT problems arise in offspring
Karyotype
- Studying the chromosome composition under light microscopy
- From cultured living cells of the patient that are arrested in metaphase
Turner Syndrome Karyotype
- Monosomy of X (45,X)
- Patient is female
Klinefelter Karyotype
- 47, XXY
- Patient is male
Down Syndrome Karyotype
- Trisomy 21
Edwards Karyotype
- Trisomy 18
Patau Karyotype
- Trisomy 13
Aneuploid
Uneven number of chromosomes
What are the two sources of structural chromosomal aberrations?
1) Healing of ds-DNA breaks with nonhomologous end joining
2) Unbalanced recombination
Hypertelorism
Increased distance between two organs, typically the eyes
Micrognathia
A condition where the jaw is undersized
Insertion
Moves the DNA fragment into the middle of another chromosome
Translocation
Moves the DNA fragment to the end of the another chromosome
How do you make a Karyotype?
1) Obtain live cell culture
2) Arrest in metaphase
3) Lyse in hypotonic solution
4) Fix to microscope slide
5) Stain
What are the indications for a karyotype?
- Problems of early growth/development
- Stillbirth/ Neonatal death
- Fertility problems
- Pregnancy with advanced maternal age (>35)
