Lecture 24

Question 1

What is a euploid ploidy?

Answer 1

A euploid ploidy means having an exact multiple of the haploid number of chromosomes. Normal gametes have the haploid number of chromosomes for humans: N = 23. A normal somatic cell is Diploid 2N = 46

Question 2

What is polyploid ploidy?

Answer 2

Polyploid cells and organisms are those containing more than two paired sets of chromosomes.
3N = triploid: Meiosis division failure
4N = tetraploid: 1st mitotic division failure

Question 3

What is aneuploid ploidy?

Answer 3

Any non-euploid number of chromosomes, resulting from nondisjunction of a single pair of homologous chromosomes during meiosis (ex: Trisomy, monosomy)

Question 4

What is trisomy ploidy?

Answer 4

The presence of an extra copy of a single chromosome in a zygote

Question 5

What is monosomy ploidy?

Answer 5

The absence of a single chromosome in a zygote

Question 6

When does meiotic aneuploidy occur?

Answer 6

During an error in meiosis 1 or meiosis 2

Question 7

What is the result of meiotic 1 aneuploidy?

Answer 7

1) Two Disomic gametes (each have 2 sets chromosomes instead of 1)
2) Two Nullosomic gametes (each have 0 sets chromosomes instead of 1)

Question 8

What is the result of meiotic 2 aneuploidy?

Answer 8

1) Two normal gametes (each have 1 set of chromosomes)
2) One disomic gamete (2 sets of chromosomes instead of 1)
3) One nullosomic gamete (0 set of chromosomes instead of 1)

Question 9

What is the most common trisomy among live born children?

Answer 9

1) Trisomy 21 - Down Syndrome

2) Frequency of about 1/600 to 1/1000 live births are down syndrome

Question 10

What is the most common trisomy among live born children?

Answer 10

1) Trisomy 21 - Down Syndrome

2) Frequency of about 1/600 to 1/1000 live births are down syndrome

Question 11

Autosomal monosomy results in ______

Answer 11

1) Underexpression of the genes on that chromosome

2) All prenatal lethals

Question 12

Autosomal trisomy results in _______

Answer 12

1) Overexpression of the genes on that chromosome

2) Perinatal lethal except trisomy 21

Question 13

Why do sex chromosomal trisomies have very mild if any phenotypic effects?

Answer 13

X-chromosome inactivation

Question 14

What is Turner syndrome caused by?

Answer 14

A female is missing one of her two X chromosomes

Question 15

What are indications that one should go for prenatal diagnosis of aneuploidy?

Answer 15

1) History of spontaneous abortion
2) Advanced maternal age (>35 years)
3) Family history of mental retardation/developmental delay
4) Fetal anomalies on ultrasound

Question 16

What are indications for prenatal diagnosis of an aneuploidy?

Answer 16

1) History of spontaneous abortion
2) Advanced maternal age (>35 years)
3) Family history of mental retardation/developmental delay
4) Fetal anomalies on ultrasound

Question 17

How is a Karyotype made and what can it be used for?

Answer 17

1) Amniocytes cultured for 7-10 days
2) Mitotic chromosomes are arrested at metaphase
3) Staining with Giemsa dye results in distinctive banding patterns (G-banding)
4) Aneuploidy (trisomy, monosomy), translocations, large duplications/deletions can be observed under the microscope

Question 18

What is Fluorescence In Situ Hybridization (FISH)?

Answer 18

FISH is a cytogenetic technique that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes

Question 19

How does Fluorescence In Situ Hybridization (FISH) work?

Answer 19

1) FISH uses DNA probes tagged with fluorescent nucleotides that bind to only those parts of the chromosome with which they show a high degree of sequence complementarity
2) Fluorescence microscopy can be used to find out where the fluorescent probe is bound to the chromosomes

Question 20

What is Fluorescence In Situ Hybridization (FISH) most commonly used for?

Answer 20

1) FISH is often used for finding specific features in DNA for use in genetic counseling, medicine, and species identification
a) Can be used to look for specific microdeletion or contiguous gene syndroms like Prader-Willi, Angelman or DiGeorge
b) Can be used to look carefully near the ends of chromosomes (subtelomeres) for a child with learning difficulties, mental retardation or autism
2) FISH can also be used to detect and localize specific RNA targets (mRNA, lncRNA and miRNA) in cells, circulating tumor cells, and tissue samples
a) Can be used to target oncogenes and tumor suppressor genes to identify amplified oncogenes or deleted tumor suppressor genes in tumors

Question 21

What are advantages of Fluorescence In Situ Hybridization (FISH) over a Karyotype?

Answer 21

1) Rapid diagnosis relative to routine karyotype: FISH can be performed on interphase cells, so it does not require growth and metaphase arrest in cell culture
2) Can identify small, submicroscopic changes on chromosomes invisible to karyotyping as well as aneuploidies and large duplications/deletions (Prader-Willi, Angelman or DiGeorge)

Question 22

What are advantages of Fluorescence In Situ Hybridization (FISH) over a Karyotype?

Answer 22

1) Rapid diagnosis relative to routine karyotype: FISH can be performed on interphase cells, so it does not require growth and metaphase arrest in cell culture
2) Can identify small, submicroscopic changes on chromosomes invisible to karyotyping as well as aneuploidies and large duplications/deletions

Question 23

When is it helpful to use FISH on metaphase chromosomes rather than interphase chromosomes?

Answer 23

When looking for a particular deletion on a particular chromosome that may be small (DiGeorge)

Question 24

Why is FISH important in breast cancer diagnosis?

Answer 24

1) FISH can determine how many copies of Her 2-neu genes (oncogenes) are overexpressed in an individual
2) 1/3 of women with breast cancer overexpress Her 2-neu genes
3) Herceptin can be prescribed to particularly target Her 2-neu and reduce overexpression

Question 25

What are SINES and LINES?

Answer 25

1) SINEs are short internuclear elements and LINEs are long internuclear elements
2) Both are repeat sequences that make up parts of introns

Question 26

What are two types of intra-chromosomal rearrangements?

Answer 26

1) Deletions

2) Inversions

Question 27

What are three types of inter-chromosomal rearrangements?

Answer 27

1) Deletions
2) Duplications
3) Translocations

Question 28

How can one describe the two chromosomes produced from unequal crossing over in meiosis (interchromosomal recombination)?

Answer 28

1) Deletion of genes (the loss of genes are transferred to the other chromosome)
2) Duplication of genes (the gain of genes are from the other chromosome)

Question 29

How can one describe the result of an intrachromosomal recombination of a chromosome?

Answer 29

1) Deletion with a lost deleted fragment

2) Paracentric inversion (if it occurs on an arm) or Pericentric inversion (if it occurs with the centromere)

Question 30

What is an inversion?

Answer 30

1) Form by intra-chromosomal recombination between repetitive sequences (lines and sines)
2) Usually no abnormal phenotype in balanced carriers (unless breakpoints interrupts important genes)

Question 31

What is an inversion?

Answer 31

1) Form by intra-chromosomal recombination between repetitive sequences (lines and sines)
2) Usually no abnormal phenotype in balanced carriers (unless breakpoints interrupts important genes)

Question 32

What are two types of inversions?

Answer 32

1) Paracentric - within one arm

2) Pericentric - includes centromere

Question 33

What is the result of meiotic recombination within a paracentric inversion?

Answer 33

1) 2 inviable gametes (0 or 2 centromeres with deletion/duplication)
2) 2 viable gametes (one normal and one inversion carrier)
(1/4 normal, 1/4 inversion carriers/ 1/4 acentric, & 1/4 dicentric)

Question 34

What is the result of meiotic recombination within a pericentric inversion?

Answer 34

1) 2 gametes carrying complementary duplication/deletions (possibly viable)
2) 2 viable gametes, 1 normal and one inversion carrier
(1/4 normal, 1/4 inversion carrier, 1/4 each of two dup/del gametes)

Question 35

What are two types of inter-chromosomal translocations (between non-homologous chromosomes)?

Answer 35

1) Reciprocal translocation

2) Robertsonian translocation

Question 36

What is a Robertsonian translocation?

Answer 36

1) Rare form of chromosomal rearrangement that in humans occurs (non-lethally) in the five acrocentric chromosome pairs, namely 13, 14, 15, 21, and 22
2) During a Robertsonian translocation, the participating chromosomes break at their centromeres and the long arms fuse to form a single chromosome with a single centromere
3) The short arms also join to form a reciprocal product, which typically contains nonessential genes and is usually lost within a few cell divisions

Question 37

What are the results from a Robertsonian translocation once meiosis has finished and gametes are formed?

Answer 37

1) 1/3 Meiosis - normal and balanced translocation carrier gametes - normal phenotype kids
2) 2/3 meiosis - unbalanced defective or inviable gametes - spontaneous abortion or birth defects

Question 38

What is recommended for women who have multiple unexplained miscarriages?

Answer 38

Recommended to have karyotype or FISH analysis to identify balanced translocation/inversion carriers