Chromosomal Aberrations

Question 1

Down, Edwards and Patau Sydrome

Answer 1

• -Edwards: trisomy 18
• -Patau: Trisomy 13
• -Down: Trisomy 21
• -All other aneuploidies are not compatible w/ life

Question 2

Turner Syndrome

Answer 2

• -Monosomy of X (45X)

- - Pt. is female

Question 3

Klinefelter Syndrome

Answer 3

• -47XXY

- -Pt. is male

Question 4

Other Sex Chromo Abnormalities w/ mild phenotypes

Answer 4

• -47XYY: Pt. is male

- -47XXX: Pt. is female

Question 5

Prevalence of Structural Chromo Abnormalities in pregnancies and live births

Answer 5

• -pregnancies: 0.5%

- -live births: 0.2%

Question 6

Two processes that generate structural chromosomal aberrations

Answer 6

• -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)

Question 7

Cri-du-Chat Syndrome

Answer 7

• -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

Question 8

Di George Syndrome

Answer 8

• -1/4,000
• -microdeletion on chromo 22
• -auto dominant inheritance
• -wide variety of phenotypes
• -congenital heart defects, immunodeficiency, mental retardation, cleft palate, parahypothyroidism

Question 9

Which are worse deletions or duplications?

Answer 9

• -deletions because you are getting rid of part of the chromosome completely
• -duplications tend to have much more mild phenotype

Question 10

Translocation vs. Insertion

Answer 10

• -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

Question 11

Carriers of Insertions/Translocations

Answer 11

• -asymptomatic
• -however, will be a problem when they undergo meiosis since meiosis requires the chromosomes to be exactly correct to align

Question 12

Philadelphia Chromosome

Answer 12

• -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

Question 13

Robertsonian Translocation

Answer 13

• -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)

Question 14

Inversion and Possible Problems of it

Answer 14

• -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)

Question 15

Balanced vs Unbalanced Alterations

Answer 15

• -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

Question 16

Possible Cause of Reduced Fertility?

Answer 16

• -balanced alteration in carrier (dosent know they have it) gives way to possibly unbalanced alteration during meiosis
• -smaller chance of meiosis producing normal viability

Question 17

Robertsonian Translocation and Meiosis

Answer 17

• -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

Question 18

of Pregnancies w/ Abnormal Chromosomes (out of 10,000), # Unbalanced Rearrangements, # Balanced

Answer 18

• -800 pregnancies w/ abnormal chromosomes (94% spontaneously aborted)
• -27 w/ unbalanced rearrangements (85% spontaneously aborted)
• -19 balanced rearrangements (16% spontaneously aborted)

Question 19

of Live Births w/ Trisomy 21, 47XXY (XXX or XYY), Balanced Rearrangements (out of 8,500)

Answer 19

• -Trisomy 21 = 10
• -Extra X’s or Y’s = 15
• • Balanced Rearrangments = 16

Question 20

Circumstances in which karyotype analysis is used?

Answer 20

• -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

Question 21

Karyotype preparation

Answer 21

• -culture live cells from Pt. (lymphocytes from blood)
• -arrest cells in metaphase
• -lyse cells
• -put on slide and stain

Question 22

Chromosomal aberrations–recognizable inheritance

Answer 22

• -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

Question 23

Genome Instability and Cancer

Answer 23

• -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