11/6 8-9a Chromosomal Abnormalities II Flashcards
Two major types of chromosomal structural abnormalities
Balanced and Unbalanced
3 types of balanced chromosomal structural abnormalities
Inversions, reciprocal translocations, Robertsonian translocations
4 types of unbalanced chromosomal structural abnormalities
Deletions, duplications, isochomosomes, marker (ring) chromosomes
Balanced structural abnormalities have normal or abnormal complement of chromosomal material?
Normal, leading to normal phenotypic presentation
Unbalanced structural abnormalities have normal or abnormal complement of chromosomal material?
Abnormal
2 types of inversions (balanced chromosomal structural abnormality)
Pericentric and paracentric
Structural rearrangements require what kind of DNA break?
Two double stranded DNA breaks
What type of abnormality is shown here: 46, XX inv(5)(p12q14)
Pericentric inversion on chrom 5 from p12 to q14, in a female with 46 chromosomes
4 types of gametes resulting from pericentric inversion
1 normal, 2 duplication/deletion, 1 inversion
What does “pericentric” refer to in pericentric inversion?
Inversion that includes the centromeric DNA sequences
What is the meiotic structure with two chromosomes called?
Bivalent
What is the meiotic structure with three chromosomes called?
Trivalent
What is the meiotic structure with three chromosomes called?
Quadravalent
4 types of gametes resulting from paracentric inversion
1 normal, 1 deletion/duplication, dicentric, 1 deletion/duplication, acentric, 1 inversion
Likelihood of parent with paracentric inversion producing live offspring with unbalanced chromosomal content?
Essentially zero, any potential fertilization would likely lead to spontaneous abortion.
What type of abnormality is shown here: 46, XY inv(3)(q22q24)
Paracentric inversion on chrom 3 from q22 to q24, in a male with 46 chromosomes
What type of abnormality is shown here: 46, XX t(3;21)
Reciprocal translocation between chromosomes 3 and 21, in a female with 46 chromosomes
3 segregation patterns during meiosis of reciprocal translocation carriers
Alternative, Adjacent-1, Adjacent-2
2 types of gametes produced by an alternate segregation of reciprocal translocation carriers
1 normal, 1 balanced
Type of gametes produced by an adjacent (-1, -2) segregation of reciprocal translocation carriers
Unbalanced
Partial trisomy and partial monosomy result after fertilization of a wt gamete with gamete produced from what type of segregation with reciprocal translocations?
Adjacent-1 or -2
Balanced reciprocal chromosome translocations of chromosomes 9 and 22 can lead to what type of leukemia?
Chronic Myelogenous Leukemia or CML
CML involves reciprocal translocations of which two chromosomes?
Chromosomes 9 and 22
What is the name of chromosome 22 after its reciprocal translocation with chromosome 9?
Philadelphia chromosome
What are the two components of the fusion gene resulting in chronic myelogenous leukemia?
BCR (breakpoint cluster region) on chromosome 22 and ABL on chromosome 9
Why is ABL called an proto-oncogene?
Its reciprocal translocation onto chromosome 22 creates a fusion gene with BCR that can lead to chronic myelogenous leukemia (CML)
What type of abnormality is shown here: 46, XX t(9;22)(q34;q11.2)
Reciprocal translocation between chromosomes 9 and 22 at the q34 and q11.2 regions, in a female with 46 chromosomes
What disease is likely to occur with this abnormality: 46, XX t(9;22)(q34;q11.2)
Chronic myelogenous leukemia or CML
What type of abnormality does the Philadelphia gene arise from?
Reciprocal translocation between chromosomes 9 and 22
What type of translocation involves acrocentric chromosomes losing their short arms?
Robertsonian translocation
What occurs in a Robertsonian translocation?
Fusion of long arms of two acrocentric chromosomes, with deletion of the short arms
Is a Robertsonian translocation balanced or unbalanced?
Balanced, because there are 5 acrocentric chromosomes in the human karyotype, which all contain repetitive satellite DNA and copies of rRNA. Loss of 2 short arms can be compensated for
What type of abnormality is shown here: 45, XY, der(14;21)(q10;q10)
Robertsonian translocation between chromosomes 14 and 21 at origin of the long arms (q10), in a male with 45 chromosomes
Why does Robertsonian translocation result in 1 less chromosome?
2 acrocentric chromosomes fuse, deleting the short arms and forming one chromosome with the two long arms
What type of abnormality and disease is shown here: 45, XY, der(14;21)(q10;q10) +21
Down syndrome due to Robertsonian translocation
How many different gametes can be produced by a parent with Robertsonian translocation?
6
What proportion of the gametes produced by a parent with Robertsonian translocation (45, XY, der(14;21)(q10;q10)) are viable?
3/6 or half
Of the viable gametes produced by a parent with Robertsonian translocation (45, XY, der(14;21)(q10;q10)) , what proportion would have a normal phenotype?
2/3, one normal, one balanced
Of the viable gametes produced by a parent with Robertsonian translocation (45, XY, der(14;21)(q10;q10)) , what proportion would have an abnormal phenotype? What would that be?
1/3, Down syndrome
