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
