Chromosomal Aberrations Flashcards
1
Q
Down, Edwards and Patau Sydrome
A
- -Edwards: trisomy 18
- -Patau: Trisomy 13
- -Down: Trisomy 21
- -All other aneuploidies are not compatible w/ life
2
Q
Turner Syndrome
A
- -Monosomy of X (45X)
- - Pt. is female
3
Q
Klinefelter Syndrome
A
- -47XXY
- -Pt. is male
4
Q
Other Sex Chromo Abnormalities w/ mild phenotypes
A
- -47XYY: Pt. is male
- -47XXX: Pt. is female
5
Q
Prevalence of Structural Chromo Abnormalities in pregnancies and live births
A
- -pregnancies: 0.5%
- -live births: 0.2%
6
Q
Two processes that generate structural chromosomal aberrations
A
- -healing of DNA double strand breaks (non-homologous end joining can create chimeric chromosomes)
- -unbalanced recombination (can occur at any loci that share a certain degree of sequence homology–causes mostly deletions and duplications)
7
Q
Cri-du-Chat Syndrome
A
- -microcephaly, hypertelorism, micrognathia, severe mental retardation, heart defects, cat-like cry
- -1/25,000
- -deletion on chromo 5 (del5p)
- -developmental gene so dominant phenotype
- -many systems affected since many genes are affected
- -new mutation since dominant and large gene
8
Q
Di George Syndrome
A
- -1/4,000
- -microdeletion on chromo 22
- -auto dominant inheritance
- -wide variety of phenotypes
- -congenital heart defects, immunodeficiency, mental retardation, cleft palate, parahypothyroidism
9
Q
Which are worse deletions or duplications?
A
- -deletions because you are getting rid of part of the chromosome completely
- -duplications tend to have much more mild phenotype
10
Q
Translocation vs. Insertion
A
- -translocation: attaches piece of chromosome from one to another’s end
- -insertion: inserts fragment from one chromosome into middle of another
- -both result in NO loss of genetic material
11
Q
Carriers of Insertions/Translocations
A
- -asymptomatic
- -however, will be a problem when they undergo meiosis since meiosis requires the chromosomes to be exactly correct to align
12
Q
Philadelphia Chromosome
A
- -translocation between chromo’s 9 and 22
- -moves ABL tyrosine kinase gene from 9 to the BCR region of chromo 22
- -chimeric ABL/BCR protein functions as a dominant oncogene causing myelogenous leukemia
13
Q
Robertsonian Translocation
A
- -translocation that puts two q (short) chromo arms together and two p (long) arms together
- -if no essential genetic material is on 2 short arm chromo than it is lost in cell division
- -most common is 13q and 14q (1/1,300)
14
Q
Inversion and Possible Problems of it
A
- -chromosome suffers 2 breaks and the broken off fragment re-inserts intself in opposite orientation
- -balanced alteration and asymptomatic in carrier
- -however, in offspring the inverted region will form a loop in order to pair w/ normal homolog in meiosis and if crossover occurs at/near that region, the genetic material is translocated (inviable w/ life)
15
Q
Balanced vs Unbalanced Alterations
A
- -balanced= no loss of genetic material
- -unbalanced = reduction/addition of genetic material
- -unbalanced (deletions/duplications) will likely affect carrier since gene dosage is changed
- -those w/ balanced alterations likely dont know they have it, will only show up at reproduction since balanced alterations greatly reduce success of meiosis
- -carrier of balanced will lead to unbalanced alterations in offspring
16
Q
Possible Cause of Reduced Fertility?
A
- -balanced alteration in carrier (dosent know they have it) gives way to possibly unbalanced alteration during meiosis
- -smaller chance of meiosis producing normal viability
17
Q
Robertsonian Translocation and Meiosis
A
- -double short armed chromo will be lost if no essential genetic material on it
- -chimeric chromosome (both long arms) will align w/ both homologs and the 3 aligned chromos can split in 3 different ways
- -one balanced and 2 unbalanced outcomes
18
Q
of Pregnancies w/ Abnormal Chromosomes (out of 10,000), # Unbalanced Rearrangements, # Balanced
A
- -800 pregnancies w/ abnormal chromosomes (94% spontaneously aborted)
- -27 w/ unbalanced rearrangements (85% spontaneously aborted)
- -19 balanced rearrangements (16% spontaneously aborted)
19
Q
of Live Births w/ Trisomy 21, 47XXY (XXX or XYY), Balanced Rearrangements (out of 8,500)
A
- -Trisomy 21 = 10
- -Extra X’s or Y’s = 15
- Balanced Rearrangments = 16
20
Q
Circumstances in which karyotype analysis is used?
A
- -problems of early/growth development
- -stillbirth/neonatal death
- -fertility problems
- -pregnancy w/ advanced maternal age
- -also used for cancer and family history of chromosomal aberration
21
Q
Karyotype preparation
A
- -culture live cells from Pt. (lymphocytes from blood)
- -arrest cells in metaphase
- -lyse cells
- -put on slide and stain
22
Q
Chromosomal aberrations–recognizable inheritance
A
- -cause multiple abnormalities (usually involving developmental delay, presence of several individuals w/ multiple abnormalities in a pedigree points to chromosomal inheritance
- -aberrations frequently cause spontaneous abortions (or multiple miscarriages)
- -frequently cause infertility
23
Q
Genome Instability and Cancer
A
- -in most cancers, genome instability leads to multiple aneuploidies
- -genome instability contributes to progression of cancer by amyplifying oncogenes and deleting tumor supressor genes
- -genome instability also results from progression of cancer due to loss of cell cycle control over genome integrity
